Term
| What did Louis Pasteur do? |
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Definition
First immunological experiment- ued B. antracais- heat/chemically inactivated bacillus in experimental sheep, live bacillus in control sheep
Inactivated sheep were protected, live sheep died |
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Term
| Define: Immunology, Immune System, Immunity |
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Definition
Immunology: study of immune system and its response in diseases and in health
Immune System: encompass the cells/organs of body that are involved in generating specific responses to invading microbes or any other insult to provide protection against those challenges
Immunity: Ability of human body to resist against microbes and other challenges is call immunity |
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Term
| What did Robert Koch do? What were his postulates? |
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Definition
First to introduce concept of microbial origin of diseases
Postulates
1. Microorganism must be isolated from diseased host and grown in pure culture
2. Microorganism must be detectable in infected host at every stage of disease
3. When susceptible, healthy animals infected with pathogens from pure culture, the specific symptoms of the disease must occur.
4. The microorganism must be re-isolated from diseased/deceased animal and correspond to original microorganism in pure culture |
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Term
| At what stage does innate immunity work? |
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Definition
| entry of microorganism and establishment of infection |
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Term
| What are the differences between innate and adaptive immunity? |
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Definition
Innate/natural immunity: determined genetically, inherited and is passed on to progeny
Adaptive- cell mediated immunity (T cells), developed by individual during lifetime on basis of exposure to different immune challenges and concomitant changes in their immunological make up, tailored to particular organisms involved, includes cell mediated and humoral immunity- mediated by antibody, produced by B cells differentiate into plasma cells in response to antigenic stimulation |
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Term
| What does clearance of pathogens depend on? |
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Definition
| Prompt microbial recognition by group of cells called antigen presenting cells (dendritic cells, macrophages, B cells); efficient function of effector cells which destroy/eliminate the pathogens (neutrophils, macrophages, NK cells, and effector T/B cells |
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Term
| How is a pathogen recognized by receptors on cells of innate immunity? |
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Definition
Group of germline encoded receptors on cell surface are involved in recognizing pathogens in innate immune response, several different structural types/bind to diverse array of ligands including peptide, proteins, glycoproteins, peptidoglycan, cars, glycolipids, phospholipids, nucleic acids
Receptors recognize specific pattern/molecular signature of particular group of organisms hence PRR- Pattern Recognition Receptors
Mannonse and LPS are specific molecular signature for many fungi/Gram negative bacteria respectively and are recognized by mannose receptors and TLR4 receptors |
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Term
| What is the inflammatory response with pathogen recognition? |
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Definition
Inflammation is co-ordinated response to cellular injury characterized by heat, pain, redness, and swelling- inflammation is induced by variety of inflammatory mediators released as consequence of pathogen recognition by macrophages- cytokines, complements, prostaglandins, leukotrins, platelet activating factor
Mediators function to: deliver effector molecules/cells to site of infection to augment destruction of invading organisms by tissue macrophages, provide physical barrier to prevent spread of infection, promote repair |
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Term
| What does the damage tissue do? |
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Definition
Release cytokines, chemokines and mediators also activate complements
cytokines- induce dilation of blood capillaries- increase blood flow
Cytokine/Chemokine- increase cell recruitment at site of injury by upregulated adhesion molecule expression on endothelium |
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Term
| What does the vasodilation due at the site of inflammation?> |
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Definition
| induces gap b/w endothelial cells, increase leak of blood plasma into interstitial cells, increase local fluid volume- edema/swelling, increase fluid volume put pressure on nerve endings/cause pain- prostaglandin also potent pain inducer |
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Term
| What is the effector mechanism of innate immune response? |
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Definition
| Tissue resident macrophages engulf pathogen and produce cytokines/chemokines- induce inflammatory response, neutrophils/NK cells recruited at site of infection to enhance immune response, complement functions as molecular tag and enhance performance of effector cells, complement also form protein complexes to damage pathogen cell membrane (membrane attack complex) |
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Term
| Characteristics of innate immunity |
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Definition
Fixed- doesn't adapt
Immediate- does not require time to amount an immune response
Non specific or limited specificity- responds to all type of infections
Do not improve over time- encounter w/ same pathogen for second time elicit response of similar intensity
Self/non-self discrimination- through PRR and pathogen associated molecular patterns- not precise |
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Term
| How is the pathogen recognized by receptors on cells of adaptive immunity? |
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Definition
Receptors on T/B lymphocytes specific for precise antigenic components, receptors generated as a result of random somatic recombination and somatic hypermutation (B cells only), Ig on B cells of T cell receptor on T cells recognize/bind molecules, macromolecules, virus particles or cell that contains a structure specific for them- called antigen
Particular part of antigen bound by Ig/TCR is known as antigenic determinant or epitope
Interaction b/w antigen and Ig/TCR is specific |
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Term
| What do the variable region and constant region of Ig recognize? |
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Definition
Variable: at amino terminus, variability in AA sequence, contains antigen binding site
Constant:AA sequences are identical b/w different Igs, binding site for cell-surface receptors on phagocytes and inflammatory cells/complement proteins- Igs have 5 different isotypes (IgM, D, G, A, E) M/D are Ag receptors
Antibodies are secreted by Ig which lack transmembrane region |
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Term
| What does the TCR consist of? |
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Definition
Alpha chain/beta chain anchored to T cell membrane
alpha/beta both consist of variable region/constant region
variable forms antigen binding site |
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Term
| How is the rearrangement of germline DNA segments enhance diversity of Ig and TCR? |
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Definition
Germline configuration refers to form of DNA present in germ cells: eggs/sperm
Variable regions of Ig/TCR are encoded at different gene segments
Rearrangement of different gene segments of Ig/TCR generate functional genes in various combos- somatic recombination
Various alternative forms of genes encoding variable region can rearrange, of light/heavy chain to assemble an Ig molecular adds to diversity |
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Term
| What is the process by which the Ig can become Ab-secretion plasma cell? |
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Definition
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Term
| What do the Ig/TCR recognize? |
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Definition
| TCR binds ONLY short peptides presented to them in form of complex w/membrane glycoprotein MHC- derived from breakdown of pathogen molecule w/in cell expressing MHC molecules- antigen processing and these cells are antigen-presenting cells |
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Term
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Definition
| Bound peptide transported to cell surface recognized by CD8 T cells which will kill the virus- infected cells- cytotoxic T cells |
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Term
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Definition
| Recognized by CD4 T cells which after interacting w/ APC will augment functions hence Helper T cells- macrophages interact w/ TH1 cells, B cells interact w/ TH2 cells |
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Term
| What are the three parts of the antibody-mediated immune response? |
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Definition
Neutralization: antibody can bind intact pathogen/toxins can neutralize their function by inhibiting microbial growth, replication, or interaction w/ human cells
Opsonization:IgG coats the surface of extracellullar pathogens/toxins and then facilitate their engulfment by phagocytes, which carry specific receptors for constant region of Ab molecules
Complement activation: Ag:Ab complex activate complement proteins, which opsonize the pathogen/facilitate engulfment by phagocytes which have specific complement receptors
When Ab involved- IgG opsonization in both ways, Ab w/ IgM- opsonization by complement is only mechanism as phagocytes do not have receptor for IgM constant region |
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Term
| How does TCR selection work? |
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Definition
Thymocytes w/ different TCR interact w/ MHC I/II molecules on cortical epithelia, cells that interact strongly are saved- positive selection
Cells the bind too strongly w/ self MHC molecules are signaled to die by apoptosis- negative selection (thus generated T cells are self-tolerant) |
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Term
| How does B cell selection work? |
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Definition
| Clones of B cells w/ Ig receptors that bind strongly to bone marrow constituent cells are eliminated by apoptosis |
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Term
| What are the characteristics of adaptive immunity? |
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Definition
Adaptive- tailored to particular pathogen involved
Slow to develop- requires a few days to mount reponse
Specific- response to any particular pathogen
Immunological memory- encounter w/ same pathogen for second time elicits a much faster/stronger secondary immune response
Self/non-self discrimination- rejection of skin/organ graft from another host of same species
Diverse- respond to variety of immune challenges in specific ways |
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Term
| What happens if you lack innate or adaptive immune response? |
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Definition
Innate- uncontrolled infection as adaptive immunity cannot be deployed w/out preceding innate response
Adaptive- controlled by innate immunity but fail to clear eventually |
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Term
| What is the allergy response? |
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Definition
Secondary response when re-exposure to Ag causes Ag to bind to IgE formed from previous exposure and bound to receptors on mast cells via constant region
Results in degranulation of mast cells, releasing histamine, cytokines, leukotreins, bradykinins, etc. |
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Term
| Define hematopoiesis and hematopoietic stem cell |
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Definition
Hematopoiesis- formation/development of blood cells, including proliferation/differentiation from stem cells
Hematopoietic stem cell- pluripotent specialized cells in bone marrow which gives rise to blood cells and cells of immune systems |
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Term
| Where does hematopoiesis occur in fetus? Adult? |
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Definition
Fetus- yolk sac, fetal liver, spleen/bone marrow
Adult- bone marrow of long bones |
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Term
| Define spatial regulation and temporal regulation |
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Definition
Spatial regulation: HSC must physically interact w/ additional cell types in bone marrow/thymus in order to become responsive to locally produced cytokines
Temporal regulation: Differentiation occurs through several distinct stages, which are identified by unique CD molecule expression and responsiveness to certain cytokines |
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Term
| What does the common lymphoid progenitor differentiate into? |
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Definition
In bone marrow/thymus- developed cells in lymph nodes/effector sites
T cell- effector T cell (helper and cytotoxic)
NK cells- activated NK cells
B cell- plasma cells (antibody producing) |
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Term
| What does the myeloid progenitor differentiate into? |
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Definition
In Bone marrow- mature cells in blood/effector sites
Neutrophil
Eosinophil
Basophil
Monocyte-macrophages (tissue only)
Unknown- mast cells (tissue only)
Dendritic cell precursor- dendritic cell (matured DC only in LN) |
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Term
| What does the erthyroid progenitor differentiate into? |
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Definition
In bone marrow- mature cells in blood/effector site
Erythroblast- erythrocyte (blood only)
Megakaryoctye- platelet |
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Term
| What are the cells of the innate immune system? |
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Definition
Cells which do not have receptors specific for antigen
Monocyte/macrophage, granuloctyes, DC, NK cells, B1 cells |
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Term
| What are characteristics of monocytes? |
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Definition
2-10% of WBC, peanut shaped nucleus, large cytoplasm w/ numerous cytoplasmic granules, surface molecules: MHC II, Fc receptors, complement receptors, CD14 (16, 32, 64); differentiate into macrophages in tissue- Kupffer cell (live), microglia (brain)
Characteristic macrophage functions: highly phagocytic, cytokine production, antigen presenting, microbicidal, scavenger cell of body
Maturation: SC- monoblast- promonocyte- monocyte (blood)- macrophage(tissue) |
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Term
| What are the characteristics of dendritic cell? |
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Definition
<1% in blood/tissue, mature initially along same pathway as macrophages, pleomorphic cell w/ numerous pseudopods on plasma membrane, characteristic surface molecules: high expression of MHC II, characteristic function: antigen presentation to cells of adaptive immune system
Activation of T cells and initiation of adaptive immune responses |
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Term
| What are the characteristics of neutrophils? |
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Definition
Predominant in WBC, numerous light/dark cytoplasmic granules, azurephilic granules (light) contain hydrolytic enzymes, myeloperoxidase, microbial factors; secondary specific granules (dark) contain lysozyme, lactoferrin, alkaline phosphatase
charactersitc surface molecules: Fc receptors, complement receptors
Characteristic functions: highly phagocytic, microbicidal
Maturation scheme: SC- myeloblast- myelocyte- neutrophil (blood)
Large BM reserve, short lived, die in fight w/ pathogen-pus, phagocytosis and killing of microorganisms |
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Term
| What are professional and non-professional phagocytes? |
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Definition
Professional: monocytes, macrophages, neutrophils, dendritic cells
Non-professional: fibroblasts and epithelial cells |
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Term
| What are the characteristics of eosinophils? |
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Definition
cytoplasmic granules are basic and bind to acidic dye eosin
1-6% of WBC
distinct eosinophilic granules in cytoplasm, contain "major basic protein" in addition to hydrolytic enzymes
Maturation similar to neutrophils
Characteristic functions: phagocytic, but not primary function- killing of antibody coated parasites through release of granule contents
Cytotoxic to worms, initiation of allergic reactions through activation of mast cells |
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Term
| What are the characteristics of basophils? |
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Definition
<1% of WBC, cytoplasmic granules are acidic and bind to basic dye hematoxylin
Mast cells found in all types of CT especially abundant near epithelial surfaces
Both mast/basophil have large purple cytoplasmic granules which contain histamine, heparin, protease enzymes
Basophil maturation- similar to neutrophils, mast cells have unique pathway
Characteristic surface molecules: both have Fc Receptor and IgE receptor
Characteristic functions: major placyes in allergic reactions, may contribute to resistance to parasitic infections, also contribute to inflammatory reactions |
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Term
| What are the characteristics of NK cells? |
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Definition
Releases lytic granules that kill come virus-infected cells
Larger than T/B cells often called Large Granular Lymphocytes (LGLs)
Characteristic surface molecules: Fc receptor and CD56
Do not have TCR/immunoglobulin on surface
Characteristic functions: kill virus infected cells and tumor cells
Complete maturation in BM from common lymphoid precursor, but distinct maturation pathway |
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Term
| What are the characteristics of gamma:delta T cells? |
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Definition
unlike alpha:beta consist of gamma:delta chains, about 1-5% of T cells, ligands for these receptos are not well defined- MIC-A, organic P, alkylamine bind to these receptors
Release cytokines in event of infection/strengthen power of innate immune response |
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Term
| What are the characteristics of B1 cells? |
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Definition
| Develop during early embryonic stage, surface receptor is IgM, recognizes polysaccharide antigen, produce only IgM- no class switching, no cognate help from T cells, characteristically found in peritoneal cavity |
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Term
| What are the cells of the acquired immune system and what state are they usually found? |
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Definition
| Lymphocytes- T/B cells, small cells w/ little cytoplasm apparent, most existing as resting cells (not activated) |
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Term
| What are the characteristics of T cells? |
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Definition
Characteristic surface molecules: T cell receptor and CD3
Maturation in BM- completes in thymus
Lymphoid progenitor- T progenitor- Pre T- T cells
2 major subsets: CD4 and CD8
Both subsets mature from same precursor cell |
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Term
| What are the characteristics of CD4+ T lymphocytes? |
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Definition
Function primarily as helper T cells
Express TCR and CD4 surface molecules
Recognizes processed antigen when bound to platform molecule: MHC II on professional APC
Secretes cytokines that activate effector cells (IL-2, IFNg, IL-4, IL-5)
2 types: Th1- secretes IL-2 and IFNg, help CTLs and macrophages
Th2- secrets IL-4, IL-5; help B cells |
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Term
| What are the characteristics of CD8+ T lymphocytes? |
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Definition
Function primarily as cytotoxic T cells (CTL)
Express TCR and CD8 surface molecules
Recognizes processed antigen when bound to platform molecule MHC I found in almost all cells of body
Upon activation killer function is mediated by inducing apoptosis of target cells (via death receptors/granules) |
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Term
| What are the characteristics of B lymphocytes? |
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Definition
Complete maturation in BM, production of antibodies
lymphoid progenitor- Pro B (early/late)- Pre B (large/small; XLA, defective Btk gene, susceptible to extracellular bacteria/virus)- B cell
Characteristic surface molecules: BCR (surface immunoglobulin), MHC II
Recognizes soluble, unprocessed antigen
Can act as professional APC
Upon activation by antigen, B cell differentiates into plasma cell, which secretes high amounts of immunoglobulin, hence B cell mediated immunity is called antibody-mediated (humoral) |
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Term
| What are primary and secondary lymphoid tissues? |
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Definition
Primary: central- BM, thymus: site of cell maturation
Secondary: peripheral- spleen, lymph nodes, mucosa-associated tissues: site of mature cell residence and initiation of immune response |
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Term
| Where do cells of the immune system develop primarily? |
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Definition
Bone marrow- most immature cells reside nearest to bone
cells migrate toward central sinus as maturation occurs then exit
Ribs, sternum, iliac crest and vertebra remain cellular throughout life
Central sinus lined by endothelial cells and reticular cells which are sources of growth factors and cytokines
Reticular cells provide reticular fibers to create microenvironments and provide cell contact signals and developing cells |
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Term
| What are the characteristics of thymus? |
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Definition
Bilobed under sternum, develops from 3/4 pharyngeal pouches, multiple lobules w/in lobes each consisting of outer cortex and inner medulla, maturation in cortex
Cortical epithelial cells provide cell contact signals, growth factors and cytokines to developing thymocytes
Scattered macrophages in cortex help eliminate apoptotic thymocytes
Mature T cells migrate into medullary region and eventually enter the blood via venules in corticomedullary junction
Positive selection-cortex, negative selection- medulla |
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Term
| What are the primary and secondary lymphoid follicles of the spleen? |
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Definition
Primary- all resting B cells indicating no antigenic stimulation
Secondary- outer mantle of resting B cells with a central germinal center containing proliferating B cells, indicative of an ongoing immune response |
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Term
| What are the characteristics of the spleen? |
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Definition
Site of immune responses to blood-borne antigens, covered by tough fibrous capsule w/ trabeculae which penetrate organ carrying blood vessels
Arteries exit trabeculae enter white pulp via arterioles and dump into sinuses of red pulp, blood percolates through red pulp and exits via trabecular veins
Both pathogens/lymphocytes enter/leave spleen in blood
Periarteriolar lymphoid sheath (PALS) area surrounding arterioles which is rich in T cells
Lymphoid follicle- out pocketing of lymphocytes form PALS which is rich in B cells |
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Term
| What are the characteristics of the lymph nodes? |
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Definition
Site of immune response to tissue-borne antigens, ovals covered by fibrous capsule which act as filtration units for lymphatic drainage
Has outer cortex and inner medulla
Cortex- primary/secondary follicles (B cell rich) interspersed by paracortical region (rich in T cells)
Medulla rich in macrophages and plasma cells
Lymphocytes/draining antigen enter subcapsular sinus via afferent lymphatic vessels, also enter through post-capillary venules
Lymphocytes/antigens percolate through outer cortex and inner medulla of lymph lymph nodes
All lymphocyte exit via efferent lymphatic in hilus of node
DC (paracortical) and follicular DC (follicles) bind antigen and activate antigen-specific T cells (paracortical) and B cells (follicles) which become effector cells
Some T cells leave node and some stay back to help B cells differentiate into plasma cells
Plasma cells move to medulla and secrete AB which is taken to site of infection via efferent lymph and blood |
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Term
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Definition
Gut-associated lymphoid tissue, similar organized lymphoid tissues in RT are called bronchial-associated lymphoid tissue (BALT)and also MALT
GALT- tonsils, adenoiods, appendix, Peyer's patch- collect antigen from epithelial surface of GI tract
Pathogen collected by specialized epithelial cells called M cells, interspersed b/w enterocytes and take up antigen from gut lumen by endocytosis
Antigens released beneath M cells taken up by DC
GALT organized into B cell/T cell areas, follicles and germinal centers
Naive lymphocytes enter via blood and scan antigen on APC and return to blood via lymphatics
Activated lymphocytes are trapped in GALT to proliferate and differentiate and tend to stay in mucosal system |
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Term
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Definition
Small proteins produced by various cells as result of pathogen recognition or immune invasions by binding to specific receptors , can alter behavior of distant cells (endocrine)
Autocrine: TNF-a on macrophages, IL-2 on T cells
Paracrine: IFNg released by NK cells stimulate macrophages and T cells
Endocrine: GM-CSF released by macrophages and T cells stimulate growth and differentiation of myelomonocytic cells in BM |
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Term
| What is the classification of cytokines? |
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Definition
Hematopoeitin family- includes cytokines functioning as growth factors as well as involved in innate/adaptive immunity, erthropoeitin, IL-3, GM-CSF
NF family- TMF-a/b, LT-b, CD40L, FasL
Cytokines structurally distinct- IL-1, IL-10, IL-12, IFNs |
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Term
| What are chemokines? What are the different classes? |
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Definition
Family of small, inducible, secreted, proinflammatory cytokines involved in immune response- act primarily as chemoattractants/activatiors of specific types of leukocytes
4 classes- based on arrangement of first 4 observed cysteine (C) residues at amino terminus
1. CXC: 1 AA residure separating first 2 conserverd C residues; chemotactic for neutrophil, ELR lacking ones are chemotactic for lymphocytes
2. CC: C residues are adjacent, chemotactic for monocytes, T lymphocytes, B lymphocytes, DC, NK, eosinophils, basophils, but not neutrophils
3. C: lack 2 (first and third) of 4 conserved C residues, chemotactic for lymphocytes
4. CX3C: 3 intervening AA residures b/w first 2 conserved residues, trigger adhesion of T cells and monocytes |
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Term
| What is complement? What is the function? |
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Definition
Group of serum proteins that circulate in an inactive pro enzyme state, can be activated by specific/nonspecific immunologic mechanisms that convert the inactive pro-enzymes into active
Activated complement participate in controlled enzymatic cascade that results in membrane-damaging reactions which destroy pathogenic organisms by formation of membrane attack complex (MAC)
Components: C1q, C1r, C1s, C2-C9 |
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Term
| Where does B cell development occur? What is the order/signals for development? What is the importance of IL-7? |
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Definition
Mainly in bone marrow
Progenitors giver rise to Pro-B cells: resulting from direct interaction w/stromal cells: VCAM-1 adhesion molecule on stromal w/ VLA-4 adhesion molecules on pro-B
Once contact made b/w adhesion molecules C-Kit (R on Pro-B) interacts w/ stem cell factor (SCF) on stromal surface
Pro-B divide/differentiate into Pre-B w/ R for IL-7 (produce by stromal cells to drive maturation)
Adhesion molecules of pre-B downregulated to detach from stromal cells
IL-7 required for continued growth/maturation to immature/mature B cell stages |
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Term
| What are stromal cells? What are the 2 primary functions? |
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Definition
Nonlymphoid cells located in bone marrow, provide microenvironments for B cell maturation
Functions: interact directly w/ Pro-B/Pre-B; secretion of cytokines including IL-7 |
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Term
| What are immunoglobulin genes? What must happen for them to be functional and when does this occur? |
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Definition
Multiple gene segments in germ line DNA
Must be rearranged into functional genes
Occurs during B cell maturation process |
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Term
| When does chain rearrangement occur in Pro-B? What is is called when rearrangement is complete? |
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Definition
Heavy chain Dh to Jh- Early pro-B
Vh to DhJh- Late pro-B
Upon completion of heavy chain rearrangement the cell is pre-B and beings to express microchain |
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Term
| What does the large pre-B cell express? What is it associated with? |
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Definition
Pre-B receptor: membrane micro cahin associated w/ surrogate light chain molcule and Igalpha and Igbeta polypeptides
Surrogate light chains not true immunoglobulins, expressed only in primitive B cell precursors |
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Term
| What happens in small pre-B cells when micro chain/surrogate light chains reach the cell surface? |
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Definition
Signal transmitted back to cell indicating functional heavy chain protein is present- cell halts rearrangement of heavy chain genes, begins arrangement of light chain genes
Production of surrogate light chains ceases and pre-B receptor disappears from surface and micro chain is trapped in ER |
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Term
| What is required for a Pre-B cell to become an immature B cell? What does completion of this process do for the immature B cell and how is it determined? What is expressed on the surface of immature B cells |
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Definition
Light chain rearrangement, only 1 light chain isotype is expressed on membrane of B cells- Kappa or lambda
Ig gene rearrangements- complemention of light chain rearrangements commits immature B cell to particular antigenic specificity- determined by heavy chain VDJ sequence and light chain VJ sequence
Immature B cells express IgM on surface |
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Term
| What must occur for immature B cells to develop into mature B cells? What do early mature B cells express? |
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Definition
Coexpression of IgD and IgM- involves production of 2 mRNAs (one encodes micro chain, other encodes delta chain)
Early mature B cells express low levels of IgD- cells are exported from bone marrow to lymphoid organs where IgD expression increases |
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Term
| What is negative selection of B cells? |
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Definition
| When immature B cells react to self antigens, crosslinking of membrane autoantibodies occurs leading to apoptosis |
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Term
| What are the B cells that arise during embryonic development? What do they precede? What do they lack on their surface? |
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Definition
B1 cells- characterized by expression of CD5 on cell surface- cell surface glycoprotein usually considered a T cell marker
Precedes development of B2 cells which are major subset of B cells
Have little/no IgD on cell surface |
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Term
| Where do B1 cells arise from? What is different about their heavy chain genes? What do they contribute to? |
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Definition
Arise from stem cell that is active during prenatal development
Rearranged heavy chain genes are less diverse than B2- therefore antibodies produced by B1 are low affinity and bind to many different antigens (polyspecificity)
Contribute to production of antibodies that are against common bacterial polysaccharides, not against protein antigens |
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Term
| Where are B1 cells found in adults? What are they often the source of? |
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Definition
In adults B1 cells are maintained through cell replication in peripheral circulation, self renewal dependent upon IL-10
Due to ability to self renew, often source of B cell tumors- chronic lymphocytic leukemia (CLL) |
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Term
| Where do B cells go after development is complete? |
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Definition
| Recirculates b/w blood and secondary lymphoid tissue (lymph nodes, spleen, mucosa-associated lymphoid tissue, lymph)- provide sites where mature naive B cells encounter antigen |
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Term
| Who activates mature naive B cells? When do activated B cells proliferate/differentiate into antibody secreting plasma cells? |
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Definition
Antigen specific B cells held in T cell area- activated by antigen-specific CD4 T helper cells
In lymph nodes/spleen- activated B cells proliferate/differentiate into antibody secreting plasma cells- change in processing of heavy chain mRNA which leads to synthesis of secreted form of immunoglobulin instead of membrane bound form |
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Term
| What do plasma cells do? What cellular organelles are highly developed in plasma cells? Can they divide? |
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Definition
Specialized in constitutive synthesis and secretion of antibody
Cellular organelles responsible for protein synthesis highly developed
Terminally differentiated, cease to divide- don't express cell surface Ig or MHCII molecules therefore cannot respond to antigen or interact w/T cells
Life span 4 weeks |
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Term
| What is the primary lymphoid organ for T cells? What are the two lineages? |
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Definition
Thymus- lymphocytes destined to become T cells migrate from BM to thymus (originate from BM stem cells)
Lineages- alpha:beta, gamma:delta
Thymocytes will develop cell surface proteins related to effector function |
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Term
| What cells secrete chemotactic factor to attract progenitor T cells to thymus? What do immunocompetent T precursor cells lack? |
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Definition
Thymic epithelial cells
Lack antigen receptors- CD3, CD4, CD8 molecules on cell surface |
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Term
| Is the T cell development process similar to B cell maturation? |
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Definition
Yes, assembly of functional gene required for each T cell receptor chain
Each productive T cell receptor gene is expressed as soon as its made- assembled into receptor complex, either pre T-cell (TCR) receptor of final TCR |
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Term
| What are the characteristics of the TCR? |
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Definition
Membrane bound glycoprotein, resembles single antigen-binding arm of Ig molecule
Composed of 2 different polypeptide chains- variable and constant regions
1 antigen binding site- gene rearrangements produce differences in V region of TCR
Once T cell is stimulated w/ antigen no further changes occur in antigen binding site or class switching of constant regions |
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Term
| What do the progenitor cells interact with the signal proliferation? What adhesion molecule do they express? What do the "double negatives" not express? What do they first express? |
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Definition
Stromal cells signal proliferation
Express T cell specific adhesion molecule CD2
Double negatives- no expression of CD4/8; first express CD44 then CD25 |
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Term
| How is the T cell lineage determined? |
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Definition
Race for TCR gene rearrangements of receptor loci
If gamma/delta chain rearrangement completed before productive beta-chain rearrangement then gamma:delta TCR
if productive beta-chain rearrangement occurs before gamma/delta rearrangements are complete- alpha:beta TCR |
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Term
| What is a beta chain assembled with? |
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Definition
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Term
| What do beta, delta, and gamma loci signal? |
|
Definition
halt gene rearrangement, cell begin to proliferate; gene recombination is reactivate- alpha, gamma, delta gene loci
Chain achieves productive rearrangement first- leads to alpha:beta TCR; if gamma/delta gene loci achieve rearrangement first T cell is committed to gamma:delta lineage |
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Term
| What if thymocytes fail to achieve productive rearrangements? |
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Definition
| die by apoptosis, phagocytosed by thymic macrophages |
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Term
| What do the pre-T cell receptors induce development of? |
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Definition
| precursor T cells to double positive phase- when T cells express both CD4/CD8 |
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Term
| What are the 2 processes that double positive cells undergo? What is the purpose of these processes? |
|
Definition
Those bearing antigen receptors for self antigen are destroyed by apoptosis, those that don't react well with MHC antigen are also destroyed
Processes select for T cells that don't react to self and react well to self MHC- required for effective immune response by T cells |
|
|
Term
| What is the difference between positive and negative selection in thymocytes? |
|
Definition
Positive selection- survival of thymocytes whose TCRs recognize antigens bound to self MHC molecules
Negative selection- deletion of thymocytes whose TCRs recognize self antigens |
|
|
Term
| What is a single positive thymocyte? How does this occur? |
|
Definition
positive selection determining whether double positive becomes CD4 or CD8 positive
Interact through alpha:beta receptor with peptide:MHC complex
MHCI- CD8 recruited, CD4 excluded
MHCII- CD4 recruited, CD8 excluded |
|
|
Term
| What is an immunoglobulin? |
|
Definition
Ig, antibody, Ab, B cell receptor glycoprotein complex consisting of 2 heavy chains and 2 light chain polypeptides
Cna be membrane bound on B lymphocyte or soluble component of serum in blood |
|
|
Term
| What are the structures of the chains of the Ig? |
|
Definition
| heavy chain/light chain have variable region and constant region, antigen binding site formed by variable regions of L/H chains- unstructured portion in middle called flexible hinge region held together by disulfide bonds |
|
|
Term
|
Definition
Classification of different Ig molecules based on AA sequence
Exist for both L/H chains of Ig, differences best defined by constant regions |
|
|
Term
|
Definition
| Identifiable allelic variations in constant regions of H/L chains |
|
|
Term
|
Definition
| Refers to unique features of antigen binding site (comprising both H/L chain variable regions)that determine the antigen specificity of a given Ig molecule |
|
|
Term
| What is the most common antibody isotype in the body? |
|
Definition
|
|
Term
| What are the three major functions of Ig? What are the definitions of these actions? |
|
Definition
Neutralization- when Ab binds to bacterial, viral, or protein in such a way as to inactivate them and prevent their causing harm
Opsonization- process of coating surface of pathogen or other particle with particular molecule that makes it more readily ingestible by phagocytes
Complement activation- group of serum proteins that when activated participate in a controlled enzymatic cascade which destroy pathogenic organisms by formation of a membrane attack complex (MAC) |
|
|
Term
| What Ig are best at neutralization? Which are best at opsonization? Which sensitize mast cells? Which activate complement best? Which transport across epithelium? |
|
Definition
Neutralization- IgG1,G2, G3, G4, A
Opsonization- IgG1, G3
Mast cell sensitization- IgE
Activate complement- IgM, IgG1, IgG3
Transport across epithelium- IgA (dimer) |
|
|
Term
| What are the three regions that make up the Antigen Binding Domain? |
|
Definition
Hypervariable region- difference in AA sequence of V domains b/w Ab are concentrated here, H/L hypervariable regions brought together to make antigen binding site
Framework region- flank hypervariable regions, much less variable
Complementarity-determining regions (CDRs)- hypervariable loops, called that b/c they provide a binding surface complementary to that of antigen |
|
|
Term
|
Definition
| small chemical complex (relative to size of macromolecule or cell) that determines specificity of antigen-Ab interaction aka antigenic determinant |
|
|
Term
| What is the germline configuration of heavy and light chains? |
|
Definition
kappa light- chromosome 2, 40 functional Vkappa gene segments, cluster of 5Jk segments, only 1 Ck segment
Lambda- chromosome 22, 30 functional Vl, 4Jl, 4Cl
Heavy chain- chromosome 14, 65 functional VH, 27 DH, 6JH, 1 CH(for IgM) |
|
|
Term
| What is somatic recombination? |
|
Definition
| antibody gene segments of V region rearranged to construct V region sequences |
|
|
Term
| What is the process of Ig H chain gene segment rearrangement? |
|
Definition
Construction of H chain V region joins 3 segments- 1 V, 1D, 1J (diversity, the j/joining, then V segment), difference in D segments and its junction w/ V/J determines sequence variability of 3rd hypervariable region
C region encoded by 1 of the C genes |
|
|
Term
| Is the somatic recombination process the same for TCR and Ig/BCR? |
|
Definition
| Yes, use same enzymes RAG1/2, TdT |
|
|
Term
| What makes up the RSS and what does it stand for? |
|
Definition
Recombination signal sequences
conserved 7 base segment followed by non-conserved spacer and conserved 9 base segment (spaced is 12 or 23 bases in length) |
|
|
Term
|
Definition
| arranged such that segments to be joined (V w/J) will be flanked by different ones, keeps two variable regions from being joined together |
|
|
Term
| What is the Rule of 12/23? What proteins recognize RSS? What happens when proteins are recognized? |
|
Definition
RSS w/ 12 base spacer only joined by RSS w/ 23 base spacer
Main proteins involved in joining that recognize RSS- RAG1, RAG2; interaction of RAG1 w/RAG2 w/ RSS brings ends of segments together, ends are then cleaved in a way to make hairpin loop at each end of segment, hairpins open often asymmetrically and single stranded ends are made double stranded w/ addition of P nucleotides |
|
|
Term
|
Definition
| Adds up to 20 NON-templated nucleotides in b/w segments (N nucleotides) |
|
|
Term
| What is allelic exclusion? |
|
Definition
| Limits expression of Ig genes to only 1 copy |
|
|
Term
| What is the difference between IgM and IgD when it comes to secretion? |
|
Definition
| IgM can be secreted or membrane bound, IgD only found in membrane bound form- different forms created by alternate splicing similar to splicing that gives rise to IgM/D |
|
|
Term
| What is class switching? What cells do it? What process is it similar to? |
|
Definition
Occurs in B cells at time of initial activation w/antigen, proceeds similarly to somatic recombination through different enzymes
Determined by local environment of B cell at activation |
|
|
Term
| What is the same after class switching? What changes? |
|
Definition
| Antigen specificity remains the same, effector function is changed |
|
|
Term
| What is somatic hypermutation? What is the enzyme involved? |
|
Definition
occurs in mature B cells in secondary lymphoid organs, occurs following B cell activation by T-dependent antigen
Enzyme is AID- converts cystidine residues to uracils which can then be changed to thymidines in replications making C to T mutation or they can be excised as errors and replaced w/random nucleotides |
|
|
Term
| Why is mutation of the Ig V regions helpful? |
|
Definition
| Increases antibody affinity for antigen, mutated antibodies as surface Ig are selected for increasing affinity |
|
|
Term
| What is the structure of the TCR? |
|
Definition
Composed of 2 polypeptide chains of equal length which are created by gene segments combined by rearrangement, both chains consist of V domain and C domain and membrane anchoring domain
Alpha chain V region has J segment and B chains V region has both J and D segments
TCR always membrane bound, never secreted |
|
|
Term
| What is the complex needed to transport TCR from ER to cell surface? |
|
Definition
| CD3 complex- CD3g, d, e and zeta |
|
|
Term
| How is the organization of the TCR similar to Ig? |
|
Definition
Alpha chain locus like L chain containing sets of V/J segments
Beta chain locus like Ig H chain containing V/D/J gene segments |
|
|
Term
| Where is the delta chain locus of TCR found? |
|
Definition
| Chromosome 14 w/in alpha chain locus b/w V and J, DNA rearrangement w/in alpha chain locus may result in delta chain locus deletion |
|
|
Term
| How is recombination turned off in B cells and T cells? |
|
Definition
B cells- successfully rearranged H chain binds surrogate L chain and signals end, L chains rearrange until complete receptor is expressed on surface
T cell-successfully rearranged Beta chain binds surrogate Alpha chains signals end of beta, gamma, delta rearrangement as well as inducing alpha chain rearrangement which continues until receptor is made that can be activated |
|
|
Term
| What are the main similarities and differences b/w Ig and TCR genes? |
|
Definition
Similarities in gene rearrangement- similar recombination, both undergo productive/nonproductive rearrangements, both have junctional diversity including P/N nucleotide addition
Difference- TCR loci have fewer V segments, show greater junctional diversity, do not exhibit hypermutations, do not undergo isotype switching, ending of L/alpha chain rearrangements is different |
|
|
Term
|
Definition
| Membrane-associated glycoproteins whose function is to bind peptide antigen and present them to T cells |
|
|
Term
| What is the difference between MHC I and MHC II? |
|
Definition
I- binding/transport of peptide antigens generated in cytosol to cell surface for recognition by CD8 T cells, involved in IgG uptake in gut, regulate Fe metabolism, regulate NK cell function
II- binding and transport of peptide antigens generated in endocytic vesciles to cell surface for recognition by CD4 T cells |
|
|
Term
| What is recognized on the MHC molecule? |
|
Definition
| Displays peptide and T cell receptor recognizing two polymorphic residues of MHC molecule and 1 residue of peptide |
|
|
Term
| What is the basic structure of MHC? |
|
Definition
| alpha 1/2 domains fold to form peptide binding groove, heavy chain, light chain, only 1 transmembrane domain |
|
|
Term
| What is the MHC I molecule consist of? |
|
Definition
Transmembrane heavy chain, alpha chain w/ 3 extracellular domains (a1, 2, 3)
a1/2 farthest from membrane form peptide binding site, MHC I heavy chain encoded by gene on chromosome 6
Covalently complexed invariant polypeptide b2 microglobulin (aka light chain of MHC I) on chromosome 15
Human: HLA-A, B, C |
|
|
Term
| What is the MHC II molecule consist of? |
|
Definition
Two transmembrane chains- 1 alpha 1 beta- both encoded by MHC genes
1 domain from each chain farthest from membrane contributes to form peptide binding site (a1/b1)
Other 2 domains (a2/b2) are supporting domains
Human: HLA-DR, DQ, DP |
|
|
Term
| What are the supporting domains from MHC that interact w/ TC co-receptors? |
|
Definition
alpha 3 domain in MHC I binds to CD8 co-receptor
Beta 2 domain in MHC II bins to CD4 co-receptor |
|
|
Term
| What is the tissue expression of MHC I and II? |
|
Definition
Only activated but not resting T cells express MHC II
Class I expressed in all nucleated cells especially hematopoeitic cells
Class II expressed in limited n umber of cells (prefers to be APC) |
|
|
Term
| What are the isotypes of MHC I and II? |
|
Definition
MHC I- 6 isotypes: HLA-A, B, C highly polymorphic/present Ag to CD8 T cells, also form ligand for receptors on NK cells; HLA-E, G oligomorphic and serve as ligand for NK cell receptor; HLA-F monomorphic, intracellular and function unknown
MHC II- 5 isotypes, HLA-DP, DQ, DR highly polymorphic directly present peptide to CD4; HLA-DM, DO regulates peptide loading of HLA-DP, DQ, and DR |
|
|
Term
| How does enhancement of MHC II expression occur? |
|
Definition
IFN-g produced by NK cells during innate immune reactions to microbes or by T cells during adaptive immune reactions, stimulates MHC II expression on APC and thus enhances activation of CD4 T cells
IFN-g has similar effect on expression of MHC I and activation of CD8+ T cells |
|
|
Term
| What does MHC polymorphism depend on? |
|
Definition
MHC I HLA-A, B, C relies on heavy chains (no b2 microglobin)
MHC II depend on variable contribution by a/b chains
alpha/beta chains of HLA-DP/DQ are polymorphic
Polymorphism of HLA-DR is almost entirely by b chain contribution (a chain monomorphic w/ no contribution) |
|
|
Term
| How does natural selection enhance diversity of MHC? Define polymorphism and polygeny. |
|
Definition
Balancing selection- maintain polymorphism
Directional selection- introduce new haplotypes
Polymorphism- presence of multiple alternative forms of gene with the population
Polygeny- refers to existence of multiple similar genes encoding MHC I heavy chains, MHC iI alpha chain and beta chains |
|
|
Term
| What is co-dominant expression of MHC? |
|
Definition
| Refers to 2 different allels at locus responsible for different phenotypes and both affect the phenotype of the heterozygote, products of all alleles found on all expressing cells |
|
|
Term
| How are new MHC alleles generated? |
|
Definition
Interallelic conversion of segmental exchange: small fragment of 1 HLA allele is replaced by homologous section of another allele with the same gene
Gene conversion: when this recombination even involve 2 separate genes |
|
|
Term
| How does the peptide binding motif bid peptide to MHC? |
|
Definition
peptides that can bind to MHC variant have same or very similar AA at 2-3 particular positions along peptide sequence, AA side chains insert into pockets on MHC molecules that are lined by polymorphic AA (anchor residues)
Set of anchor residues determine binding of peptides to particular MHC isoform is called peptide-binding motif (less well characterized in MHC II) |
|
|
Term
| What is degenerate binding specificity of MHC molecules? |
|
Definition
| Ability of peptide binding grooves on MHC I and II to bind peptides along many different AA sequences, unlike TCR or Ig specificity for Ag |
|
|
Term
| What makes up the peptide-MHC complex? |
|
Definition
MHC molecules have binding pockets to accomodate amino terminus, carboxy, terminus, and peptide backbone of peptide that will be presented to T cell
MHC I- bind peptides 8-10 AA long, limitation due to 2 ends of peptide grasped by pockets at end of groove
MHC II do not pin down peptides at ends of groove, rather allow them to extend beyond groove allowing them to accommodate large peptides |
|
|
Term
|
Definition
| T cell responding to given peptide presented by 1 MHC allotype will not respond to same peptide if presented by different MHC allotype |
|
|
Term
| Define autologous, allogenic, and alloreactive. When is alloreactivity a problem? |
|
Definition
A self MHC is autologous (self) and all other MHC isoforms are allogenic (non-self)
T cells that respond to complex of peptide and allogenic MHC molecules are called alloreactive T cells- issue in organ transplantation |
|
|
Term
| What is mixed lymphocyte reaction (MLR)? |
|
Definition
| In vitro experimental reaction where T cells from individual are cultured w/lymphocytes from another individual, second individuals lymphocytes are irradiated to inhibit proliferation, first's proliferate indicating occurence of antigen presentation by allogenic MHC |
|
|
Term
|
Definition
| Antibody raised by 1 member of species against an allotypic protein form another member of same species |
|
|
Term
| What are two ways that alloreactivity can occur? |
|
Definition
| with cross reactive recognition- peptide dominant binding: peptide fits strongly to TCR; MHC dominant binding: allogenic MHC bind strongly to TCR |
|
|
Term
| What are superantigens? How do they cause issues? |
|
Definition
distinct calss of antigen that stimulate primary T cell response after being presented as intact protein molecules (unlike a peptide:MHC complex)by MHC class II
Bacterial: SE, TSST
Viral- Rabies viral antigen, Epstein Barr viral antigen
Superantigens bind to Vbeta region of TCR and outer surface of MHC II
SAg induces polyclonal T cell response resulting in production of large amounts of cytokines (IL-1/2, TNF-a) responsible for inducing systemic shock, also inhibits induction of specific adaptive response which favors pathogenenicity of bacteria |
|
|
Term
| What do the T cells fight in their respect CD4/8? |
|
Definition
CD8- fight intracellular infections, cytotoxic T cells- kill infected cells
CD4- fight extracellular infection, aka helped T cells as they help other cells to respond to extracellular infection
Th1- activate tissue macrophages to phagocytose and kill extracellular pathogens, secrete cytokines/chemokines
Th2- stimulate B cells to make antibodies, which bind to extracellular bacteria and virus particles |
|
|
Term
| What are the cytokines released by Th1, activated macrophages, and Th2? |
|
Definition
Th1- Il2, IFN-g
macrophages- Il6, IL-12, IL-18, TNF-a (needed to produce Th1- 12,18)
Th2- IL-4,IL-5, IL-10, IL-13, IL-6 (4, 5, 6 differentiate B cell into plasma cell) |
|
|
Term
| What does the TCR recognize? |
|
Definition
| fragments of proteins associated w/ MHC molecules |
|
|
Term
| What does Ig receptor (B cell receptor) recognize? |
|
Definition
| Proteins (conformational determinants, denatured, or proteolyzed determinants), nucleic acids, polysaccharides, some lipids, small chemicals (haptens) |
|
|
Term
| Define antigen processing and antigen presentation. |
|
Definition
Antigen processing- TCR can recognize antigen only as peptide in association w/ MHC
Antigen presentation- binding of processed antigen (peptides) by an MHC and its display at cell surface |
|
|
Term
| What are the functions of DC, macrophages, and B cells as APCs? |
|
Definition
DC- native T cell activation, clonal expansion and differentiation into effector T cells
Macrophages- effector T cell activation of macrophages (cell-mediated immunity)
B cell- effector T cell activation, B cell activation and antibody production (humoral immunity) |
|
|
Term
| What APCs capture microbials that enter through skin/GI/respiratory tract? What about microbials in blood? |
|
Definition
Skin/GI- DC
Blood stream- APCs in spleen |
|
|
Term
| What is the role of dendritic cells in antigen capture/presentation? |
|
Definition
| Immature DC in skin capture antigen that enters through epidermic and transport antigens to regional lymph nodes, during migration DCs mature and become efficient APCs |
|
|
Term
| How does the cell insure that MHC II bind the correct peptide? |
|
Definition
| a/b chains translocated to ER after being synthesized in ribosome where they bind invariant chain preventing binding to other peptides in ER; invariant delivers MHC II to endocytic vesicles where they bind peptide, invariant is cleaved inside MHCII to smaller fragments- small fragment of invariant called CLIP binds site of MHC molecules and prevents peptide binding |
|
|
Term
| How is MHC I loaded with cytosolic peptides? |
|
Definition
Intracellular pathogen exploit ribosomes to synthesize viral proteins (present in cytosol), cytosolic proteins are degraded by protesome and peptide fragments are taken to ER by TAP
Newly synthesized MHC I and beta 2 are translocated to ER where they complete folding/load peptide aided by chaperones
On entering ER, MHC I bind membrane protein clanexin (calcium dependent) which stabilizes class I heavy chain until beta 2 microglobulin binds
Clanexin is released from alpha:beta2 microglobulin heterodimer which then binds complex of chaperone protein (calreticulin and Erp57) and binds TAP-1 via tapasin
When bound- folding of MHC I is completed, released from chaperones to leave ER in vesicle, goes through golgi , finally expressed on cell surface to be recognized by CD8 |
|
|
Term
| How does MHC bind peptides derived from extracellular sources? |
|
Definition
| Extracellular particles internalized following attachment to receptor on cell surface, involve generation of vesicles that become acidic by proton pump, degrade vesicle w/ contents to generate peptides, vesicle w/peptide fuse w/vesicles of MHC II, peptide is loaded onto MHC II molecules then peptide:MHC II complexes are carried to cell surface |
|
|
Term
| How is peptide loading of MHC II faciliated by HLA-DM? |
|
Definition
| endocytic peptides can't bind peptide binding site due to CLIP, HLA-DM binds MHC II and facilitates CLIP release and site can be freely loaded and then carried to cell surface |
|
|
Term
| What is cross presentation of antigens? |
|
Definition
Cells infected w/ intracellular microbes such as viruses are captured by APCs particularly DC and antigens of infectious microbes are broken down and presented in association w/ MHC molecules of APCs, T cell recognize microbial antigens and costimulators expressed on APCS and T cells are activated
Example show CD8+ T cells recognizing MHC I associated antigen, same cross presenting APC may display MHC II antigens from microbe for recognition by CD4 helper cells |
|
|
Term
| What are the 5 different classes of antibodies? |
|
Definition
IgG, IgA, IgM, IgD, IgE
Made up of 4 polypeptide chains- 2 light chains, 2 light chains held together by noncovalent and disulfide bonds |
|
|
Term
| What do the Fab and Fc parts of the antibodies do? |
|
Definition
Fab- binds antigen
Fc- initiates complement activity, binds to cell receptors nonimmunologically |
|
|
Term
| How are B cell activated in humoral immunity? |
|
Definition
Binding to protein/carb epitopes of antigen, surface IgM on B cell are cross linked and drawn to localized area, clustering of B cell receptors signals to interior- communicated by Igalpha/beta which are associated w/ IgM
Also requires additional signals from B cell co-receptor (located close to B cell receptor) or CD4 helper T cell |
|
|
Term
| What are thymus independent antigens? What can immunodeficient patients without a thymus do? |
|
Definition
Bacterial pathogens possess complex polysacchardies, lipopolysaccharides, peptidoglycans- antigenically distinct from mammalian cells, able to activate naive B cells w/out help of helper T cells
Immunodeficient patient- able to make antibodies to extracellular bacterial pathogens |
|
|
Term
| What are thymus-dependent antigens? |
|
Definition
Activates B cell in secondary lymphoid tissue- involves B cell, specific antigen, helper CD4 T cells
Antigens arrive at lymph node through lymphatic system, antigen-specific lymphocytes arrive at lymph node through blood (enter lymph node from blood through HEV), Antigens are processed/presented by APCS (macrophages or DCs)
Antigen-specific CD4 T cells are activated to become effector T helper cells- interact w/ DCs, DCs present specific antigen to MHC II receptors on B cells |
|
|
Term
| What is clonal selection? |
|
Definition
| Only B cells capable of responding to particular antigen will be induced to produce antibody, differentiate into antibody-secreting plasma cell or memory cell capable of antibody response to subsequent exposure |
|
|
Term
| What are B cells initially programmed to produce? |
|
Definition
| IgM antibodies- effector T cells enable B cells to switch to production of a different class of antibody |
|
|
Term
| What is a germinal center? |
|
Definition
B cells activated by helper T form a focus of dividing B lymphoblasts- attached to cognate helper T cells
Rate of division increases
B lymphoblasts become centroblasts
Responsible for characteristic swelling of lymph nodes
Specialized microenviroment for B cell proliferation, somatic hypermutation, selection for antigen binding |
|
|
Term
| What are centroblasts and centrocytes? |
|
Definition
Centroblasts- B cell maturing in germinal centers, somatic hypermutation initiated by T cell cytokines, eventually mature into...
Centrocytes- nondividing, mutated surface immunoglobulin- affinity for its specific antigen can be higher, lower, or same
Population of centrocytes express immunoglobulins with a range of affinities for a specific antigen |
|
|
Term
| What is an additional characteristic of neutralization? |
|
Definition
| Antibody blocks binding to virus receptor, antibodies against adhesins block colonization and uptake |
|
|
Term
| Where can you find Fc receptors and what are these cells functions? |
|
Definition
Macrophages, neutrophils, eosinophils
Phagocytosis |
|
|
Term
|
Definition
| Antibody dependent cell-mediate cytotoxicity |
|
|
Term
|
Definition
| Series of approximately 30 blood proteins- many are inactive enzymes (zymogens), these proteins complement the antibodies in defending against pathogens |
|
|
Term
| What is the similarity between all three pathways of complement activation? |
|
Definition
Lead to cleavage of C3 into C3b and C3a-
C3 binds to pathogen's surface, called complement fixation, aids in opsonization
C3a attracts inflammatory cells |
|
|
Term
| What are the steps of the classic pathway of complement activation? |
|
Definition
Activated C1s cleaves C4 to C4a/b, some C4b binds covalently to microbial surface
Activated C1s cleaves C2 to C2a/b
C2a binds to surface C4b forming classical C3 convertase- C4b2a
C4b2a binds C3 and cleaves it into C3a/b, C3b binds covalently to microbial surface |
|
|
Term
| What initiated the classic pathway? |
|
Definition
| antigen-antibody complexes |
|
|
Term
| What is MAC and what does it do? |
|
Definition
| Membrane Attack Complex- C5b, C6, C7, C8 combine to form a complex which initiates the polymerization of C9 to form a MAC which forms a pore in the membrane causing the lysis of the cell |
|
|
Term
| What are antibody effector functions? |
|
Definition
As B cell response to infection progresses- isotype switching can occur
Isotype switching- diversifies functional properties of antibody Fc region- Fc regions deliver antibody to anatomical sites, link bound antigen to molecules/cells that affect their destruction |
|
|
Term
| What are the antibody classes? |
|
Definition
|
|
Term
| How do individual Ig classes differ? |
|
Definition
| Molecular weight, rate of migration in protein electrophoresis, ability to activate complement, ability to bind to tissue cells, valence-number of antigenic determinants it can bind |
|
|
Term
| What are the characteristics of IgM? |
|
Definition
First antibody produced, present in blood/ECF, able to efficiently bind to microorganisms and particulate antigens, bind/activate complement, secreted as pentamer- allows IgM to bind effectively to microorganisms and particulate antigens, large size inhibit IgM's ability to leave blood/penetrate infected tissues
No receptors for IgM Fc region on phagocytic cells- cannot recruit these cells into immune response |
|
|
Term
| What are the characteristics of IgG? What do circulating IgM/G prevent? |
|
Definition
Second antibody produced, dominant blood-borne antibody, bind/activate complement, able to cross the placental barrier- passive immunity for baby
Circulating IgM/G- prevent septicemia- inhibits spread of microorganisms by neutralizing those microbes that enter the blood |
|
|
Term
| What antibody is highest in secondary response? |
|
Definition
|
|
Term
| What are the characteristics of IgA? |
|
Definition
Monomeric- provides antibody-binding protection in fluids/tissues
Dimeric- protects surfaces of epithelial-epithelial vulnerable to infection; produced in MALT which underlies basement membrane of mucosal epithelium
Provided by mother to baby through breast feeding |
|
|
Term
| What are the IgA dimer functions? |
|
Definition
Protects surface of epithelia in direct contact w/external enviroment- GI, ENT, respiratory, urinary, genital, mammary glands
Made in patches of mucosal associated lymphoid tissues (MALT)- CT that unlies basement membrane of mucosal epithelium
IgA- secreting plasma cells are on one side of epithelial and the target antigens are on the other side |
|
|
Term
| What carries IgG across the epithelium? |
|
Definition
|
|
Term
| What are the characteristics of IgE? |
|
Definition
Binds to Fc receptors of mast cells, basophils, and eosinophils
Mast cells in mucosa of GI/respiratory tracts and dermis of skin- granules contains histamine and other inflammatory molecules, inflammatory mediators increase vascular permeability allowing cells and fluid to accumulate- causes swelling, reddening, pain; causes contraction of smooth muscle that can expel parasites, fluid can flush out parasites |
|
|
Term
| How is the FceRI receptor on mast cells, basophils, and activated eosinophils differ from antigen receptors on B/T cells? |
|
Definition
Antigen binding to FceRI receptors results in immediate effector function- cell proliferation, differentiation not required
Individual cells not restricted to single antigenic specificity- bound IgE molecules can be different specificities
Results in strong quick response |
|
|
Term
| What is different about the actions of cytokines? |
|
Definition
| Often redundant and pleiotropic, one cytokine can act with or against another, can act both locally and systemically, act through specific membrane receptors, receptors can be regulated in expression by other cytokines, signaling often has negative feedback loops to limit their effect |
|
|
Term
| What would happen if you were deficient in gamma chains for cytokines? |
|
Definition
| Immunodeficieny- gamma chain shared by multiple cytokines |
|
|
Term
| What are the 2 types of interferons? |
|
Definition
Type I- mediate innate immune responses to viral infections (alpha, beta, epsilon, kappa, omega)
Type II- function to stimulate effector cells of immune system, innate or adaptive (gamma) |
|
|
Term
| What is the common response of cytokines to T cell activation? |
|
Definition
| secrete cytokines that promote generation of more effector cells |
|
|
Term
|
Definition
| Secreted proteins that stimulate leukocyte movement/migration, recruit cells of immune system to site of infection, regulate trafficking of leukocytes in/through peripheral lymphoid tissues, promote angiogenesis/wound healing, roles in development/organogensis |
|
|
Term
| What is the most important T cell co-stimulatory receptors? |
|
Definition
|
|
Term
| What two things do TCRs recognize simultaneously? |
|
Definition
| MHC variant ridge, processed peptide antigen |
|
|
Term
| What are negative and positive selection for TCRs? |
|
Definition
Positive- screens TCR that recognize self MHC
Negative- TCRs that recognize self MHC/self peptide too well |
|
|
Term
| What do CD4/8 both associate? What does it do? |
|
Definition
protein tyrosine kinase Lck
Lck phosphorylates ITAMs when co-receptor binds to MHC ligand, ZAP-70 binds to phosphorylated zeta chain ITAMs and is phosphorylate/activated |
|
|
Term
| What is CD28 used to differentiate? |
|
Definition
| b/w proper antigen presenting cells and any other cell in body, important for activation of naive T cells |
|
|
Term
| What cells are constitutively mature, nophagocytic lymphoid cells? What cells have to be induced by co-stimulator delivery? |
|
Definition
Active- Dendritic cells
Inducible- macrophages and B cells |
|
|
Term
| What do co-stimulatory receptors (CD28) provide to TCR that's recognized antigen? |
|
Definition
| survival signals, completion of signals to transcribe IL-2 mRNA, signals to stabilize IL-2 mRNA, signals to change chromatin structure to allow multiple genes to be transcribed |
|
|
Term
| What is the two signal hypothesis? |
|
Definition
Signal 1- induces some responses- ICR
Signal 2- prevents cell death, allows IL-2 expression (CD28) |
|
|
Term
|
Definition
state of antigen specific non-responsiveness
T cell survives yet no longer responds to TCR stimulation even with proper co-stimulation
Mechanism of peripheral tolerance (prevention of auto-immunity) |
|
|
Term
| What cannot happen without signal 2 to TCR? What can happen without it? |
|
Definition
Maintenance of IL-2 production and proliferation
Without it can have effector functions (killing or helper) |
|
|
Term
| What is cross stimulation? |
|
Definition
| A macrophage able to deliver a co-stimulatory signal to T cells recognizing either a nonbacterial or bacterial antigen and then proliferating/differentiating of T cells specific for bacterial/nonbacterial protein |
|
|
Term
| How does affinity for IL-2 change in activation of T cells? |
|
Definition
| moderate before activation, high affinity after activation, binding of IL-2 signals the T cell to enter cell cycle and induces T cell proliferation |
|
|
Term
| What are the characteristics of adhesion molecules? |
|
Definition
| used to enhance strength of interaction w/ APCs, regulate naive T cell homing to lymph nodes to scan for antigen, regulate activated T cell homing to site of injury/infection |
|
|
Term
| What is the first level of determination for a naive T cell? |
|
Definition
|
|
Term
| What are the differences between a naive T cell and an effector cell? |
|
Definition
naive- long life, homing to lymph tissues, lack effector functions
Effector- short life, homing to site of injury/infection, strong effector activity |
|
|
Term
| What is the difference between effector memory cell vs central memory cell? |
|
Definition
Effector memory- moderate to long life, homing to site of injury/infection, poor proliferative capacity, strong effector activity
Central memory-very long lived, self-renewing, homing ONLY to lymph tissue, excellent proliferative capacity, lack effector functions |
|
|
Term
| What are the determinants for naive T cell fate? |
|
Definition
Strength/duration of TCR interactions
Strength/TYPE of costimulation
Type/abundance of cytokines
APC type (may be related to strength/type) |
|
|
Term
| What do Th1, Th2, Tfh, Th17, Treg, and CTL cells do? |
|
Definition
Th1- produce IFN-g, respond to intracellular microorganisms
Th2- produce IL4, 5, 13 to respond to helminths and other extracellular microorganisms
Tfh- follicular helper cell- regulate maturation of B cell response
Th17- produce IL-17A, IL-17F, IL-22 to respond to extracellular bacteria and fungi at mucosal surfaces
Treg- produce TGFbeta and IL-10 to suppress autoimmunity
CTL- cytolytic to antigen expressing cells, respond to intracellular microorganisms |
|
|
Term
| For Th1, what is the T cell type? What are the main targets? What are the effector interactions? What induces differentiation? What are the mediators of activity? What is the initial antigen recognition cell interaction and where is it located? Where do they go? |
|
Definition
CD4+
Targets-intracellular bacteria/protozoans
Effector- macrophages
Differentiation- IFNg, IL-12
Mediators- IFNgamma!! IL-2, TNFa, FasL
Cell interaction-Dendritic cell in lymph nodes
Go to macrophage to site of infection |
|
|
Term
| What does the macrophage and Th1 cell use to interact? |
|
Definition
|
|
Term
| What does Th1 do based on cytokine used to activate? IFNg/CD40, FasL/TNFb, IL-2, IL-3/GM-CSF, TNFa/b, CCL2? |
|
Definition
IFNg/CD40- activates macrophage to destroy engulfed bacteria
FasL- kills chronically infected cells releasing bacteria to be destroyed by fresh macrophages
IL-2- induces T cell proliferation
IL3- induces macrophage differentiation in bone marrow
TNFa- activate endothelium to induce macrophage binding and exit to blood vessel at site of infection
CCL2- causes macrophages to accumulate at site of infection |
|
|
Term
| For Th2, what is the T cell type? What are the main targets? What are the effector interactions? What induces differentiation? What are the mediators of activity? What is the initial antigen recognition cell interaction and where is it located? Where do they go? |
|
Definition
CD4+
Target- bacteria and some viruses, allergens, parasites
Effector- macrophages, other cells
Differentiation- IL-4
Mediators- IL-4, IL-5, IL-13
Cell- dendritic cell in lymph node
Macrophages to site of infection |
|
|
Term
| For Treg, what is the T cell type? What are the main targets? What are the effector interactions? What induces differentiation? What are the mediators of activity? What is the initial antigen recognition cell interaction and where is it located? Where do they go? |
|
Definition
CD4+
Targets- self derived antigens
Effector- autoreactive T cells
Differentiation- IL-2, TGFb, Retinoic Acid
Mediators- IL-10, TGFb, receptors
Unknown cell in lymph node
T cells/others to any peripheral tissue or LN |
|
|
Term
| What is other CD that Treg express and why is that important? |
|
Definition
| constituitively express CD25 (high affinity IL-2 receptor), inhibit other "self" reactive T cells through secreted cytokines and potentially some cell to cell contact mechanisms |
|
|
Term
| For Tfh, what is the T cell type? What are the main targets? What are the effector interactions? What induces differentiation? What are the mediators of activity? What is the initial antigen recognition cell interaction and where is it located? Where do they go? |
|
Definition
CD4+
Targets- Any?
Primary effector interactions- B cells
Inducers of differentiation- IL-21
Mediators- IL-4, IFNg, IL-21, inducible costimulator (ICOS), CD154
Usually dendritic cells in lymph nodes
B cell goes to lymphnode/germinal centers for effector functions |
|
|
Term
| What can T helper cells do once activated to resting APCs? |
|
Definition
| can interact with it presenting same antigen and activate them |
|
|
Term
| Where do dendritic cells and naive T/B cells enter the lymph node? |
|
Definition
DC- through afferent vessels from peripheral tissue
Naive T/B- enter through blood vessels (HEV) then separate into different areas |
|
|
Term
| What happens when naive T cells and DCs interact in lymph node? |
|
Definition
| Naive T cells recognize antigen, proliferate, and acquire effector functions, then mature T cells go to border w/ B cell zone where they can scan B cells for antigen and activate resting B cell presenting same antigen at DC |
|
|
Term
| What do B cells do after activation of T cell activated by DC in lymph node? |
|
Definition
| B cells form germinal center and undergo class switching and somatic hypermutation, B cells then selected by antigens expressed on surface of DC before they migrate |
|
|
Term
| For Th17, what is the T cell type? What are the main targets? What are the effector interactions? What induces differentiation? What are the mediators of activity? What is the initial antigen recognition cell interaction and where is it located? Where do they go? |
|
Definition
CD4+
Targets- bacteria/fungi
Effector?
Differentiation- IL-6, TGFb
Mediator- IL-17A, IL17-F, IL-22
Dendritic cell in lymph node
unknown cell on mucosal surfaces |
|
|
Term
| What two T cells are NOT terminal differentiated states? |
|
Definition
|
|
Term
| Which cells are less likely to change phenotype than iTreg and why? |
|
Definition
| nTreg- due to methylation and other epigenetic differences at different loci |
|
|
Term
| For CTL, what is the T cell type? What are the main targets? What are the effector interactions? What induces differentiation? What are the mediators of activity? What is the initial antigen recognition cell interaction and where is it located? Where do they go? |
|
Definition
CD8+
Targets- virus infected, tumor cells
Effector- virus infected cells (dendritic cells)
Mediators- IFNg, IL-2, FasL, granzymes, perforin, granulysin
Dendritic cell in lymph node to any cell as effector at site of infection |
|
|
Term
| What are the primary cytolytic factors and what do they do? |
|
Definition
Perforin- polymerizes to form pore in target membrane
Granzymes- serine proteases, which activate apoptosis once in cytoplasm of target cell
Granulysin- induces apoptosis |
|
|
Term
| What do most cells express and some CD8+ T cells/Th1 cells express that causes apoptosis? |
|
Definition
|
|
Term
| What are the 4 major thymic events for T cells? |
|
Definition
| Thymocyte precursors enter, proliferation/somatic recombination, selection, maturation/egree |
|
|
Term
| What are the markers during selection for T cells? |
|
Definition
Precursors- double negative
Positive selection- double positive-CD3, 4, 8
Negative selection- single positive- CD3 and C4 or CD8 |
|
|
Term
| What is the goal of T cell selection positive and negative? |
|
Definition
Positive- ensure T cell is capable of recognizing antigen
Negative- minimize number of potentially autoreactive T cells in periphery |
|
|
Term
| What is the implication/result of recombination being shut off via Beta chain with a surrogate alpha chain in T cells? |
|
Definition
| 30% of T cells have 2 antigen receptors on surface (beta w/ 2 different alpha chains) hence alloreactivity common |
|
|
Term
| What does positive selection shut off? |
|
Definition
| Transmits signal to shut off expression of either CD4 or CD8 |
|
|
Term
| What happens to T cell that fails to recognize antigen in a lymph node? |
|
Definition
| Leave and go to next lymph node |
|
|
Term
| What are the 4 steps after antigen recognition by T cell? |
|
Definition
Activation of proliferation
Period of proliferation/differentiation to acquire effector functions
Activity as effector T cell w or w/out migration
Cell death or memory |
|
|
Term
| Why do WBCs increase with T cell proliferation? |
|
Definition
| Multiple T cells w/different antigen specificities activated by given pathogen so increase in WBC, many cells have to die to bring WBC count back to normal |
|
|
Term
| Where is CD152/CTLA-4 normally kept in T cell? |
|
Definition
| TGN- endosome like compartment or sent to lysosome for degradation |
|
|
Term
| What does CD152 have high affinity for? When does it go to cell surface |
|
Definition
CD80/86 over CD28
After initial activation |
|
|
Term
| What are two mechanisms for inhibiting T cells? |
|
Definition
binding of phosphatase that remove P groups from ITAMs in TCR/CD3 complex
Competing w/CD28 for binding |
|
|
Term
| What is needed for IL-2 transcription? When does it increase? Can it be produced by other cells than T cells? |
|
Definition
TCR/CD3 and co-stimulator signals needed
Increases 8-12 hours after activation, stops 24-48 hours later
IL-2 not produced by other cell types, but other types can respond to IL-2 |
|
|
Term
| What happens when IL-2 is withdrawn? |
|
Definition
cell death
Effector memory cell (not central memory cells) |
|
|
Term
| What are the two parts of adaptive/acquired immunity? |
|
Definition
cell mediated immunity-mediated by T cells
humoral immunity- mediated by antibody |
|
|
Term
| What are the first, second, and third lines of defense? Definitions |
|
Definition
First-innate- mechanical barriers, chemical barriers, microbiological
Second- innate- inflammation, interferrons, phagocytosis, complements
Third- adaptive- naturally acquired: active (infection) passive (maternal antibody), artificallly acquired: active (vaccination) passive (immune serum)
First- refers to surface protection composed of anatomical/physiological barriers that keep microbes from penetrating sterile body compartments
Second- refers to cellular and chemical system that comes immediately into play if infectious agents make it past that surface defenses
Third-include specific immune response that must be developed uniquely for each microbe through the action of specialized immune effector cells, long term and has memory |
|
|
Term
| What are the mediators of the second line of defense? What cells release IFNs? How is complement activated? |
|
Definition
Inflammation mediated by mediators released by tissue damage, recognition of pathogen by cells of innate immune system
Phagocytosis mediated by macrophages, neutrophlis
IFNs released by infected cells, NK cells
Complement activated by alternative patheay |
|
|
Term
| What are examples of direct and indirect mechanisms of tissue damage? |
|
Definition
Direct- exotoxin release, endotoxin release, direct cytopathic effect
Indirect- immune complexes, anti-host antibody, cell mediated immunity |
|
|
Term
| How can pathogens be recognized by macrophages? |
|
Definition
Directly- Pattern Recognition Receptors
Indirectly- by receptors for complement or Fc portion of Ig |
|
|
Term
|
Definition
Lots of cytokine activation
On all gram negative bacteria |
|
|
Term
| Rheumatic fever causes what? |
|
Definition
| Heart and joint issues from cross reactions from antibody to basement membrane |
|
|
Term
| What is a marker for macrophages? |
|
Definition
|
|
Term
| What are the two most important opsins? |
|
Definition
| Complement and antibody- C3b |
|
|
Term
| TLR 2/4 are involved in what? |
|
Definition
LPS induced signaling cascade, expressed on macrophages/DCs, allow cell to produce cytokine
TLR 2- peptidoglycan induce cytokine production on gram + bacterial cells |
|
|
Term
| Which 2 cytokines activate vascular endothelium? |
|
Definition
IL-1b, TNF-a
locally TNF-a allow permeability of cell membrane |
|
|
Term
|
Definition
| Hepatocytes which make CRP which can activate complement |
|
|
Term
| CXCL8 is a what? Function? |
|
Definition
|
|
Term
|
Definition
| Activate NK and differentiation of T helper cells into Th1 |
|
|
Term
| What is the systemic detrimental affect TNF-a basis of? |
|
Definition
Gram negative septic shock
nyceria menigitis
Large amount of TNF and cytokines made which are now in system and thus activates vascular endothelium cell and increase vascular permeability
thus everything in blood vessel can be depleted out, decreased blood pressure, also activate platelet activation factor- so clots start (DIC) and thus bleeding and ischemia to organs |
|
|
Term
| What are the proinflammatory cytokines? |
|
Definition
|
|
Term
| What are the chromosomes associated with Ig chains, TCR chains, and MHC? |
|
Definition
Ig kappa-2, lambda-22, heavy chain-14
TCR alpha-14, beta-7 gamma-14 b/w V/J
MHC alpha-6, beta-15 |
|
|
Term
| What is dendritic cell dependent on for final maturation? |
|
Definition
|
|
Term
|
Definition
Activate complement via lectin pathway and opsonin
Activate C1q which you need antibody to activate in classic pathway but here functioning as if classic pathway in ABSENCE of antibody so it works faster |
|
|
Term
| CRP/MBL levels increase with what? |
|
Definition
| Increase in infection, used in clinical practice |
|
|
Term
|
Definition
| C4 and C2 to initiate complement activation via lectin pathway of complement activation |
|
|
Term
| If endothelium is inflammed what is expressed to attach to neutrophils? Upregulated by what molecules? |
|
Definition
| ICAM-I on surface, upregulated by CXCL8 and go to site of infection |
|
|
Term
| What are the steps of recruitment of neutrophils? |
|
Definition
| Rolling adhesion, tight binding, diapedesis, migration |
|
|
Term
| Microbes are brought in for phagocytose by what complement? |
|
Definition
| C5a then coated by C3b to go into phagosome |
|
|
Term
| IFN a/b released by what cells? What effect does IFNb have? How do they limit viral infection? |
|
Definition
virally infected cells
IFN-b: autocrine or paracrine, which upregulates IRF7 and transcribes/translates IFN-a
Together IFNa/b- make antiviral proteins- chew up viral DNA
And inhibit elongation factor-2 |
|
|
Term
| What are the three type I infereron used for? |
|
Definition
| Hep B/C, MS, certain leukemia/lymphoma |
|
|
Term
| What are the 3 consequences of IFNa/b activation? |
|
Definition
| Induce resistance to viral replication in all cells, increase MHC I expression/AP in all cells, activate NK cells to kill virus-infected cells |
|
|
Term
| What does the NK cell produce to activate macrophages? When cytotoxic T cells take control, what do they secrete to turn off NK cells? |
|
Definition
| IFNg, macrophages produce cytokines to enhance differentiation of effector T cells, cytotoxic cells secrete IL-10 |
|
|
Term
| What are the two sets of receptors for NK cells? |
|
Definition
Inhibitory and activating
Inhibitory- recognize MHC I
Activating- recognize altered MHC I expression |
|
|
Term
| Which pathway is earliest in complement activation? |
|
Definition
|
|
Term
| What is the process for alternative pathway? |
|
Definition
C3 is hydrolyzed to iC3 reacts with B, is cleaved by D to make iC3Bb soluble C3 covertase- breaks down C3 to C3a/b
C3b is cleaved to C3Bb surface bound C3 covertase which is microbial surface to continue cascade and whole thing will be damaged in membrane complex |
|
|
Term
| What are the regulatory proteins of complement system? |
|
Definition
| DAF and MCP on human cell surface that disintegrate complex so no formation of complement pathway |
|
|
Term
| How do T cells leave cell? How do APCs come in? How do naive T cell enter lymph nodes? |
|
Definition
| Efferent, afferent, high endothelial venules |
|
|
Term
| What are M cells? What is different about T cells in GALT system? |
|
Definition
can endocyse antigen directly in GALT and present to underlying dendritic cells which can present to T cells
In GALT T cells tend to stay in mucosal system |
|
|
Term
| What are the bridges between innate and adaptive responses? |
|
Definition
IL-12 from DC/MQ/B cells (critical for Th0-1 differentiation) stimulate NK cells to produce INFg
IFNg and IL-12 activate/differentiate naive CD4 T cells into Th1 cells |
|
|
Term
| What are the cytokines that drive Th1 and Th2? |
|
Definition
Th1- IFNg, IL-2, TNF-b
Th2- IL-4, 5, 10, TGF-b |
|
|
Term
| What dictates that Naive T cells get recruited vs an effector lymphocytes? |
|
Definition
Naive- L selectin and CD34 on resting endothelium
CCL21/CCR7
LFA-1/ICAM-1
Effector T cell- on activated vascular endothelial cell- Lymphocyte VLA-4/LFA1 inflamed VCAM-1/ICAM-1 (no L-selectin)
Absence of selectin and increased expression/expression of others allows effector cells to migrate in to site of infection |
|
|
Term
| Secondary response predominant isotype is? |
|
Definition
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