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Viruses Bacteria Fungi Parasites |
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Distinguishing self from altered self |
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Born with it Non-specific Starts immediately (near entry points) Sees whole pathogen Non-clonal Monocytes, NK Cells, granulocytes Complement, cytokines, antimicrobial peptides |
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Describe adaptive immunity |
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Acquired Specific Takes a while to start up (most effective) Induced Clonal B Cells and T Cells (memory) Antibodies Have surface receptors for antigens |
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1798 - Smallpox vaccine "Founder of immunology" |
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1879: Attenuated vaccine for chicken cholera |
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1901: A, B, O blood groups |
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1959-1962: Antibody structure |
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Rolf Zinkernagel and Peter Doherty |
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1974: MHC restriction discovery |
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Tsutsumu Tonegawa and Leroy Hood |
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1985: Immunoglobulin gene discovery |
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1987: T cell receptor genes identified |
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1989: Dendritic cells present antigen to T cells |
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Nomura and Charles Janeway |
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Definition
1994 - 1998: Toll-like receptor discovery |
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3 components of the immune system |
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Definition
Soluble: released by cells, affect differentiation and activities of immune cells. Cellular: Innate and adaptive responses Tissues: Primary and secondary organs |
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Life cycle of immune cells |
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Definition
Originate in bone marrow Migrate through blood and lymph Mature and function in peripheral tissues |
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What cells drive differentiation of immune cells? |
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Paths of hematopoietic stem cells |
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Definition
1: lymphoid progenitor --> B-Cells, T-Cells, NK-Cells
2: Myeloid progenitor --> Granulocytes (neutrophil, eosinophil, basophil, mast cell, monocyte) or erythrocytes --> megakaryocytes
Monocytes / mast cells --> macrophage / mast cells
3: Erythroblast --> erythrocytes |
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Most concentrated leukocyte in the blood? |
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Definition
Neutrophils (4400/ml). Can be quickly distributed in response to an inflammatory stimulus |
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AKA: White blood cells Originate in bone marrow from hematopoietic stem cells First produced in liver/yolk sac in young fetus |
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Most numerous leukocyte Phagocytosis/digestion of bacteria/particles Multi-lobed nuclei Short life span Travel to site of inflammation |
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Eosinophils: Parasites Basophils: Cytokines Mast cells: Release histamine |
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MOST IMPORTANT phagocytic cell Role in killing bacteria Secrete pro-inflammatory cytokines Long-lived
(can present processed antigens to T cells, and regulate wound healing/homeostasis) |
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MOST IMPORTANT antigen presenting cells Link between innate and adaptive immunity Take the epitope to the lymph Found in low numbers in tissues |
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Leave bone marrow only partially mature B Cells differentiate in bone (mature in lymph nodes) T Cells differentiate in thymus Cannot be differentiated visually Mediate adaptive immunity |
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Natural Killer (NK) Cells |
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Definition
Lymphocytic lineage (NOT T-CELLS) Kill tumor cells and virally-infected cells Possess Fc receptor Secrete interferons |
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Autoimmunity Graft rejection Hypersensitivity (can't distinguish self form non-self) |
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Where leukocytes are differentiated and produced (not yet committed) Bone marrow Thymus Bursa of Fabricius Peyer's patches |
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Site where B and T cells are induced to function. (develop and respond) Lymph nodes Spleen Bone marrow Peyer's patches |
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Mature in the spleen, then go to tissues Phagocytosis and killing of parasites Fc receptors on surface Bi-lobed nuclei Promotes inflammation Mostly deal with large pathogens |
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Low numbers Multi-lobed nucleus Contain inflammatory molecules Small role in killing parasites Fc receptors |
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Multi-lobed nuclei Different morphologies in different tissue Fc receptors (for parasites) Secretes histamine & serotonin Vasodilator |
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Bone Marrow / Bursa of Fabricius |
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Definition
Bursa of Fabricius is in birds B-Cell receptor rearrangement occurs here If excessive blood cell production is demanded, liver and spleen produce lymphocytes. Fewer B-Cells toward center of marrow Site of hematopoiesis Adipose provides energy |
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T-cell maturation (move toward medulla) Variation in size shape in animals Presentation of self antigens ONLY Involutes after sexual maturity |
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Epithelial cells that "tolerize" T-cells Ability to generate immune response Cortex: Dense, immature Medulla: Less dense, mature |
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Structures along GI tract in lamina propria Contain mostly B-cells B-cells central; T-cells surrounding Immune response for ingested antigens M-cells: Site for antigen entry! Take up antigen via immune cells and transport them to lymph nodes |
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Site where B-cells are rapidly dividing |
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Secondary lymphoid organ (largest) Encased in a thick capsule Red pulp: Phagocytes White pulp: Lymphocytes (mostly B-cells) Filters out effected RBC's RBC storage, and backup proliferation Major site of adaptive response to blood-borne pathogens |
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Two components of the White pulp of the spleen |
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Definition
Splenic nodules: B-cells Periarterial Lymphatic Sheaths (PALS): T-cells that line the arteries |
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Points of convergence for blood and lymph Collects lymph for return to blood B-cells: primary lymphoid follicle T-cells: cortical area |
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Bean-shaped Cortex around medulla surrounded by capsule Dendrites and lymphocytes can enter from afferent lymph or from the blood Have germinal centers |
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Definition
Distributed throughout body Collect and sample antigens Only lymphocytes can use HEV's! |
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Flow of lymph through a lymph node |
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Definition
Afferent lymph vessel --> Subcapsular sinus --> Cortical sinus --> Medullary sinus --> Efferent vessel |
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High Endothelial Venules (HEV's) |
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Definition
Found in the lymph nodes Specialized capillaries where lympocytes exchange from blood. Cells LACK tight juncitons! Used a lot by T-cells |
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Small soluble proteins and glycoproteins Regulate and mediate immune responses Large number and variety Homeostatic roles Activate or suppress immune activities NOT antigen-specific! pleiotripic (diff. activities) Highly regulated expression Redundant actions Influence synthesis/action of others Many non-immune functions (wound repair) |
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Growth factors Interleukins Interferons Chemokines |
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Family of cytokine Simulate hematopoiesis Regulate leukocyte growth/differentiation |
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Mediators and regulators of mature lymphocytes and leukocytes (Innate and adaptive immunity) Very diverse group |
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Mediate and regulate antiviral and innate immunity. Inhibit viral replication (block receptors) Regulate developing fetus Accelerate B-cell diferentiation Mostly from: T-cells, macrophages, fibroblasts |
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"Chemoattractants." Regulate directed movement of immune cells Induced by a variety of stimuli Divided into 4 classes |
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HIGHLY specific! Single or multimeric Some share common subunits Receptors can be grouped into families A cell can have receptors for many cytokines |
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Jobs of type I interferons a/B |
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Definition
Induction of "antiviral state" Increase expression of MHC1 on host cells Activate NK cells to kill viral cells |
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Definition
produced by helper T-cells and NK cells ACTIVATES macrophage immune function! Isotype switching to opsonize antibodies Increases MHC expression |
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Colony Stimulating Factors |
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Definition
Promote differentiation of progenitor cells. Different kinds: Granulocyte (GSF): Neutrophils, eosinophils Macrophage (GSF): Monocytes, macrophages GM-CSF: Granulocytes or Macrophages IL-3: Macrophages or granulocytes IL-7: Produced by stromal cells in bone/spleen |
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Regulates host inflammatory response Produced mostly by macrophages and epithelial cells 2 forms: 1a and 1B (overlapping activities) CNS: fever, sleepiness Vascular: adhesion molecules, IFN-y Liver: Acute phase protein production |
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Definition
Produced by: Th1 Causes autocrine proliferation of T-cells Augments Ig synthesis PRIMARY growth factor for T-cells! |
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Definition
Produced by: macrophages and T-cells Liver: Acute phase protein expression Hypothalamus: fever by pyrogen Adipose: Decreased fat storage |
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CRITICAL cytokine Differentiation of T-cells toward Th1 Produced by: Dendrites and macrophages Activate NK cells for IFN-y |
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Tumor Necrosis Factor (TNF-a) |
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Definition
MEDIATOR of ENDOTOXIC SHOCK (gram- sepsis) Produced by: Macrophages, NK cells Activities: Cell killing Immunocyte activation Liver: acute phase protein expression Fever Regulates hematopoiesis 2 different receptors (shed during response) |
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Definition
Monocyte Endothelium Brain (hypothalamus) Liver (acute phase...) |
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How does TNF-a work on vascular endothelium? |
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Definition
Macrophages make TNF-a which signals the endothelium to make adhesion molecules which grab the neutrophils in the blood and bring them through the epithelium and into the tissue to act on bacteria |
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Definition
Macrophages make TNF to bring phagocytes and lymphocytes into tissues. Increased platelet adhesion. Phagocytosis of bacteria. Plasma and cells drain into lymph nodes. Removes infection via adaptive immunity. |
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Definition
Liver and spleen make macrophages to make TNF for blood. Causes systemic edema, decreased blood volume, neutropenia. Leads to intravascular coagulation and organ failure. DEATH |
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Definition
Since cytokines work together to impact peripheral immune events, "storms" can lead to tissue injury, shock, death. |
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Overexpression of cytokines Caused by Gram- cell walls (LPS) TNF-a is major cytokine responsible Species vary in sensitivity to LPS-induced shock cat, horse, pig>dogs>mice>>birds |
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Definition
Regulate humoral immune response! "anti-inflammatory" Inhibits macrophage activation IL-4 acts on T-cells: Promotes Th2 Enhanced proliferation Produce Th2 cytokines Inhibit Th2 differentiation |
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Definition
Chemotactic for neutrophils |
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Definition
Chemoattractand for CD8+ T cells and neutrophils |
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Definition
Chemoattractant for memory CD4+ T cells, eosinophils, and monocytes |
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Definition
Chemoattractant for monocytes |
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Definition
Chemoattractant for NK cells and resting T cells |
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Cytokines for communication |
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Definition
B and T cells communicate using cytokines Used for activation of B cells, B cell differentiation into plasma cells, and Ig class switching (isotypes) |
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Definition
Single nucleotide polymorphisms in cytokines that are linked to changes in gene expression.
Can change the nature of the inflammatory response |
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Manipulating immune response |
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Definition
Cyclosporin A: inhibits transplant rejection Corticosteroids: inhibits inflammation Anti-TNF-a therapy: for rheumatoid arthritis |
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Pro-inflammatory cytokines |
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Definition
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Anti-inflammatory cytokines |
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Definition
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Cytokines that inhibit virus replication |
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Definition
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Macrophage activating cytokines |
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Definition
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B-cell activating cytokines |
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Definition
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T cell stimulating cytokines |
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Definition
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Eosinophil/Mast cell activating cytokines |
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Definition
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Substance that induces antibody generation Induces a specific immune response AKA: Immunogens B cells recognize large molecules T cells only recognize epitopes Allergen: antigen causes allergic reaction |
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Definition
Part of large molecule bound by antibody Multivalency: Sometimes repeated many times on a macromolecule Spatial arrangement affects Ab binding |
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Definition
Small molecules, not normally immunogenic, but are antigens when linked to a carrier. Linkage forms a new epitope Ex: Penicillin to albumin |
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3 types of antibodies generated by haptens |
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Definition
1. Against the carrier 2. Against the hapten 3. Against the new epitope by hapten-carrier linkage |
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What makes a good antigen? |
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Definition
1. Foreignness 2. Complexity 3. Size 4. Stability 5. Speed of release
Proteins are best, lipids are worst Host factors affect potential immunogenicity |
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Definition
One epitope is similar enough to trigger response against a different epitope, even on different molecules.
Results in immunity against unrelated antigens |
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Response toward antigens in tissues |
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Definition
Taken up by dendrites and macrophages Moved to lymph nodes Elicit IgG isotype |
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Response toward antigens in mucosal surfaces |
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Definition
Taken up by M-cells or dendrites Extend through epithelial lining Elicit IgA and IgE isotypes |
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Definition
Degradation of proteins into epitopes to bind MHC for presentation |
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Definition
Displaying antigens as peptide fragments Exogenous (ouside cell): MHC II Endogenous (inside cytosol): MHC I |
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Definition
Normally, immune system cannot recognize self proteins.
Errors cause antibodies and T-cells to be made against self-antigens. "Auto-antigens"
4 Classes Ex: Sperm, mitochondria, insulin... |
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Definition
Some pathogens express proteins that resemble host molecules. T-cells will then also recognize host cells presented by MHC I |
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2 ways to induce autoimmunity |
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Definition
Disruption of cell/tissue barrier Molecular mimicry |
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Definition
Presented on surface of tumor cells MHC I and MHC II Not found on normal cells |
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Exotoxins that highly stimulate T-cells Do not require prior processing Cross-link MHC and T-Cell receptor Over-stimulates T-cells (overproduce cytokines) Drive hyperinflammation |
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3 Functions of antibodies |
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Definition
Opsonization Complement Activation Neutralization |
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How does complement action work? |
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Definition
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Definition
Coating foreign particle with antibodies Helps neutrophils/macrophages become phagocytic |
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Adaptive immunity from antibodies |
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Definition
Antibody production begins 4-7 days after exposure Antibodies are antigen-specific, principle mediators of adaptive immunity Ab's are found in plasma and on mucosal surfaces |
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Definition
Heterodimeric, produced by B-cells Antigen specific Function in many environments Interact w/ Ag's non-covalently! Different constants make diff. isotypes SUBunits are covalently linked Heavy subunit determines isotype Fab contains Ag binding site Digested via Papain |
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Constant region confers functional specificity by: |
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Definition
IgG and IgM activate classical pathway IgE binds to mast cells and basophils IgG binds to receptors on macrophages, neutrophils, NK cells |
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Expression of isotypes in blood vs. mucosal surfaces |
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Definition
IgG>IgM>IgA in blood IgA>>IgM>IgG on mucosal surfaces |
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Definition
Does NOTHING special Antigen receptor on naive follicular B cells |
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Term
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Definition
Mast Cell Activation (and basophils)
Induced by IL-4 |
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Definition
Cross epithelium Neutralization Vascular diffusion
Induced by TGF-B |
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Definition
Complement activity
Inhibited by IL-4, IFN-y, TGF-B |
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Definition
Opsonization Cross placenta Vascular diffusion Complement activity NK Cell activation Neutralization
Induced by IL-4 |
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Definition
Vascular diffusion Cross placenta Neutralization Complement activity
Induced by IFN-y and TGF-B |
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Definition
Rearrangement of DNA only occurs on one chromosome for each light or heavy chain genes. "Chromosomal silencing" |
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Definition
Rearrangement of DNA only occurs on one chromosome for each light or heavy chain genes. "Chromosomal silencing" |
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Term
4 ways to contribute to antibody diversity in bone marrow |
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Definition
Multiple germline genes H and L chain recombinations Imprecise joining of segments Random insertion of bases
Somatic hypermutation: only after encounters an antigen |
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Definition
Recognize conserved sequences flanking each gene segment Cleave out intervening DNA Deficiency in RAG = immunocompromised High rate of mistakes |
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Definition
When a B cell is active and proliferating, an enzyme chemically changes bases to a different base for a new codon.
AID enzyme converts cytidine to thymididine
Impacts the V region segment |
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Definition
If a mutation provides better binding, these B-cells are selected. |
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