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List the four major classes of cells of the immune system |
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Lymphocytes Antigen Presenting cells Dendritic cells Effector cells |
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Express clonally distributed receptors for antigens Only cells with specific receptors for antigens therefore are key mediators of adaptive immunity CD – cluster of differentiation Small Large |
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Bursa of fabricus Bone marrow derived The only Ab-producing cells mediate humoral immunity Ag specific Increase in number as a second response Proliferates quickly |
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Regulate ONLY to protein antigens bound to MHC Mature in Thymus Increase in number Cell mediated immunity Ag receptors on surface Secrete cytokines Either activate phagocytes to destroy microbes or kill the host cell with the infection Helper T cells – help B cells produce antibodies and phagocytes to destroy cells Cytotolic or cytotoxic kill cells harboring intracellular microbes |
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natural killers nonT, nonB markers part of innate eliminate tumor cells/virus infected cells antibody dependent cell cytoxicity (ADCC) |
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Antigen Presenting Cells/Accessory Cells |
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Mononuclear cells phagocytes in IS bone marrow derived release cytokines monocytes 10-15 micrometers Bean shaped nucleus Circulating macrophages fixed in tissues (Kupffer cells in liver) |
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Accessory cells Trap protein antigens 0-- lymph nodes Interdigitating DC -- skin, every tissue and organ Follicular DC -- germinal centers of lymphoid tissue |
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effect clearance of antigen Granulocytes – cytoplasmic granules NOT accessory cells neutrophils, eosinophils, basophils, granulocytes |
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phagocytic multiple loved nucleus (3) predominant cell type in acute inflammation |
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receptor for IgE allergic reactions (killing helminthes) |
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IgE receptors immediate hypersensitivities i.e. anaphylactic shock |
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cytoplasmic granules NOT accessory cells |
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Seconday Lympoid Tissue Find T, B , Follicular, and marcophages Bean-shaped Lie along lymphatics Neck, axillae, groin, aorta Sample lymph for protein antigens Lymphatic vessels drain fluid from tissues phagocytic filter/phagocytize particulate matter APC B/T activate lymphocytes |
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Cortex/germinal centers/follicles – Bcells Germinal center means the B-cell has recently responded to an antigen Produce antibodies Follicles contain FDCs involved in activation B cells Paracortex – T cells Medulla – macrophages |
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Secondary Lymphoid Tissue Pharyngeal tonsils and Peyer’s patches Samples blood for blood borne antigens B/T cell activation Filter blood – senescent/abnormal rbc’s destroyed Store iron Phagocytosis of bacteriam – opsonized bacteria – coated with antibody White pulp – follicles/germinal centers- B Periarteriolar – t cells lymphocytes Red pulp – RBC’s macrophages, DC |
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Primary Lymphoid Tissue hematopoiesis B cell Maturation (not T Cell) |
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Primary Lymphoid Tissue cortex/medulla T cell maturation/"education" |
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Secondary Tonsils, adenoids, peyer’s patches, appendix |
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Secondary Urogenital, lung, some in gut |
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Block entry of microbes Elimnate microbes that enter host tissues |
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Block infections Eliminate extracellular microbes Activate macrophages to kill phagocytosed microbes Kill infected cells Eliminate reservoirs of infection |
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Mechanical/flushing Chemical/Biochemical Cells |
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skin – outer layer, dead cells keratinized layer Mucus – epithelial cells mucin prevent bacteria from adhering traps bacteria – cilia flush it, sneeze cough Fluids – saliva – contains enzymes/ Abs Tears – lysozyme Perspiration Urine Vomiting Diarrhea |
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a. pH- stomach (2), urine, vagina – helicobacter pylori b. organic acids – sebaceous glands c. lactoferrin – binds Fe d. HCl- denatures proteins e. Bile salts – membranefunction of bacteria f. Spermine – polyamines found in sperm/seminal fluid (inhibit Gm+) |
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Epithelial Barriers Gamma Delta T-Cell B-1 Lymphocyte |
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Epithelial barriers Peptide antibiotic Phagocytes – ingest/kill microbes neutrophils PMN’s most abundant WBC 4,000-10,000/mL blood 20,000 in an infection 50-70% of differential Leukocytosis = too many = infection 1st responders especially bacteria and fungi Production stimulated by column stimulating factors (CSF) m-CSF, g-CSF, bone marrow 6 hour life Granules Enzymes, defensins monocytes/macrophages 500-1000 cells/ cm2 Persist longer – months Found in connective tissue and every organ in the body T cell Primitive T Cell Serve as sentinels Limited repertoire of antigen receptore <5% T cells B-1 lymphocytes Intraperiotneally IgM recognize CHO agns |
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steps involved in recruiting leukocytes to local tissues |
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Macrophages recognize microbe and produce cytokines (TNF and IL-1) Cytokines stimulate endothelial cells to express E and P-selectin Circulating neutrophils and monocytes express CHO that bind to selectins Neutrophils become tethered to endothelium, blood disrupts binding, so leukocytes on the endothelial surface As the cells are rolling, tissue macrophages that encountered the microbe respond to TNF and IL-1 and produce chemokines Chemokines stimulate rapid increase in affinity of leukocyte integrins for their ligands on the endothelium Binding of integrins to their ligands stops the rolling, the cytoskeleton of the leukocytes is reorganized and the cells spread out on endothelial surface Chemokines also stimulate motility of leukocytes Leukocytes begin to migrate to site of infection |
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(a, b, c generated in phagolysosome) ROI – H2O2, -O2-, O2, OH• phagocyte oxidase – chronic pyramulomatous disease formed in response to a microbe we can’t kill TB – WBC’s form a wall around TV Tissue necrosis myeloperoxidase +H2O2 hyperchlorite iNOS – inducible nitric oxide synthase arginine NO NF iNOS eNOS regulates Blood pressure |
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Lysosomal proteins Cationic proteins-cathepsim Lactoferrin – Fe binding protein Protection against O2 reactions SOD – superoxidase dismutase Catalase |
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TNF, IL-1/6, Il-12. IFN8 responsible for communications between leukocytes and between leukocytes and other cells hormones of IS leukocytes, lymphocyes, endothelia cells, fibroblasts Pleiotropic – multiple biologic activities principle source is macrophages Act on very specific receptor non-promiscuous overproduction = septic shock =bacteremia – bacteria in blood (too much = sepsis) produced in small amounts shock – low bp septic shockTNF/IL-1, IL-6 cardiovascular metabolic – glucose/lipid metabolism DIC – coagulation pathway poor organ perfusion multiple organ failure You’re Gonna Die blood flow, O2 cells |
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Chemotactic cytokines 8-12 kd 2 internal disulfide bonds 2 classes = C-C & C-X-C IL-8/GRO-1 (polys) MCP – 1, 2, 3 (monocyte) MIP-11B (monocyte) Eotaxin – eosinophils Help tether leukocytes to endothelium Increase affinity of integrins (tethered to endothelium) TNF/IL-1= increase expression of ligans for integrins PECAM-1 (Platelet-endothelial cell adhesion molecule) Gradient of chemokines Immunodefiency diseases leukocyte adhesion deficiency don’t make enough adhesion molecules (E, P, intregrins, ligands) always get infections leukocytes can’t reach local site |
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Plasma mannose-binding lectin (MBL) |
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Recognizes microbial carbohydrates Coat microbes for phagocytosis or activate the complement cascade by the lectin pathway Acute phase response |
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Agns Recognized by B Cells |
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membrane bound agn receptors proteins, PS lipids, NA membrane bound OR soluble agns |
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Agns Recognized by T Cells |
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ONLY PEPTIDE ANGTIGENS ASSOCIATED WITH MHC’S T Cell receptor recognizes some residues of peptide antigen MHC restriction – recognition of MY antigens |
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Events that lead to antigen capture |
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APC – process and present peptides to T-Cells skin, respiratory, cut, blood Langerhan cells = dendritic cells (epithelial) phagocytose or pinocytose agns respond to chemo- and cytokines change confirmation and migrate to lymph go to lymph for high concentration of T-cells microbes enter the body immature dendritic cells express membrane receptors that bind microbes dendritic cells use recepotors to capture and endocytose microbial antigens combination of cytokines and direct TLR signaling activates the dendritic cell, resulting in several changes in phenotype and function activated dendritic cells lose adhesiveness and express surface receptors for chemokines chemokines direct dendritic cells to migrate via lymphatic vessels to lumph nodes |
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Humans Class 1 – HLA-A, HLA-B, HLA-C All codominant Class II – DP, DQ, DR Class III – not surface MHC, code for cytokines (steroid synthesis, TNF, complement proteins)
Mice Class I – K Class II – DM, I-A, I-E Class III – Same as humans |
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Diagram an MHC molecule and show the domains |
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Class I 2 polypeptides chain – in MHC locus microglobulin – (not coded in MHC locus) 3 domains in external portion of chain peptide binding cleft, bind in floor, highly polymorphic 2 – disulfide bonds immunoglobulin domain, invariant, binds to CD8 Transmembrane region – 25-30 aa Class II polypeptides 1 Peptide binding cleft 10-30 size will fit because it doesn’t have to fit inside cleft Extremely polymorphic binds to CD4 on THC Invariant Immunoglobulin doman 2 – invariant, hydrophobic Can’t bind to CD4 3 domains in external portion of chain |
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present peptides to T-cells only 1 peptide at a time per MHC low affinity peptides bind to MHC molecules during assembly MHC – self/non-self |
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