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Immuno Lec 3

Cytokines T cell mediated immunity Inflammation small amounts short range action, systemic effects Pleotropic Redundancy
Pleotropic Different effects on different cells
Redundancy Many cytokines have overlapping functions
Il-1 secreted by Monocytes/Macrophages autocrine Pyrogen B cell proliferation
Il-2 Secreted by CD4+ T Cells Autocrine Proliferation and Differentation of T, B, and NK cells
IL-4 Secreted by CD4+ T Cells B cell proliferation, 2nd signal. Class Switching
IL-7 Secreted by Thymic Cortical Epithelial Cells Bone Marrow Stromal Cells T/B Cell proliferation during development
Interferon alpha and beta Secreted by all Cells (Monos, fibroblasts) Induces antiviral state Activates NK cells
Interferon Gamma Secreted by T Cells, NK cells class switching, Ig2, 3, Mac
Chemokines secreted by many cell types cc -attracts monos and T cells cxc - attracts neutrophils (Il-8)
TNFa Secreted by many cell types Directly kill tumor cells activates monocytes/macs expression of Adhesion molecules
TNFb Secreted by T and B cells directly kill tumor cells activate monocytes/macs Expression of adhesion molecules
Emigration/Extravasion of Naive T cells into 2* Lymphoid Tissue Mediated by adhesion molecules. Four step process, endothelial cells express P-selectin and E-selectin
4 steps of emigration of naive T cells into 2* lymphoid tissue Rolling adhesion - P/E selectins bind to L selectin found on circulating leukocytes Tight binding - further interaction between integrins (LFA-1 and ICAM1) causes it to stop. Diapedesis Migration
Diapedesis Travel across membrane
Migration Travels to site
Antigen Presenting Cells Occurs during migration to T cell areas. Macrophages, B cells, Dendritic Cells
What activates Macrophages on the way to T cell areas Bacterial/Viral cell wall components
CD4+ Cell Activation Two Steps. 1)Ag/MHCII. In 2* lymphoid tissue, macrophage has engulfed extracellular pathogen, TCR reacts with it. 2) Mac comes into contact with Toll Length Receptor on pathogen, then expresses IL-1 and B-7. B-7 engages with CD28 and IL-1 is secreted.
What does the 2 signal requirement for T cell activation ensure peripheral tolerance
What if the T cell only gets signal 1? The T cell becomes anergic. It is not responsive to antigen. It may die. If it contacts self antigen(signal 1), but no infection, signal 2 (B7 and IL1 wont be there).
Superantigen Non-antigen specific stimulation of T cells. not processed Bind MHCII, Vb domain of TCR. Exception to rules. binds externally, it is outside, specificity requirement eliminated. Activates ALOT of T-Cells, massive cytokine release. fever,death,etc.
Naive CD4+ Cell can become what ARMED EFFECTOR CELLS : TH1 and TH2, needs Both Signals Still.
TH1 In Presence of IL-12, IFNy, TGFb. Secretes IL2, IFNy, TNFb. Inflammatory cells, activate CD8, Macro, NK cells. Cell Mediated Immunity. recruit neutrophils. Mediate Delayed Type Hypersensitivity.
TH2 In presence of IL-4 and IL-10. Helper Cells. Humoral immunity(Abs produced). Secrete IL4,5,6,13. Important for activation, differentiation, proliferation of B cells into plasma cells. Provide Signal for Class Switching. Mast/Eos Activation.
Difference between Armed Effector Cells and Naive T Cell Armed effector cells no longer need both signals. They only need the TCR to engage p/MHCII. this reactivates it.
Specific delayed type hypersensitivity specific CD4+ T cells encounter microbes. Requires proper antigen.
Non-specific delayed type hypersensitivity If you have mixed infection, activated macrophages that not specific. will engulf any bystander. produce free radicals and NO, potent Antibacterial activity, damaging to host.
Il-5 Activates eosinophils
CD8+ Activation 2 Signals. Antigen/MHCI B7/IL-1 OR IL-2 activated by langerhan cells. Cd-28 T cell marker.
Langerhan Cells Located below epithelial surface. takes microbes to 2* lymphoid organs. Once effector cells are activated, they go back to site.
CTL Mechanism cytoskeletal reorganization causes granules to concentrate near target cell, exocytosis of granules containing perforin, death by osmotic lysis/apoptosis.
DiGeorge Syndrome Thymic aplasia. no functional thymus. absence of parathyroid gland. no T cell mediated immunity Greatly reduced serum Ig Since you require TH2 to activate B cells, lose those too.
Severe Combined Immunodeficiency SCID. lack of cell mediated and humoral immunity. mutation in gamma chain of IL-2.
Wiscott Aldrich Syndrome Loss of CD43. WASP protein. do not divide properly. do not mature properly. severely impaired cell mediated and humoral immunity.
Mucocutanous Candidiasis defect in T cell immunity infections of skin, nails, mucous membranes.
Human Immunodeficiency Virus Infection AIDS. retrovirus. infects CD4+ cells. gradual decrease in CD4+ cells, breakdown of immune response. Infection with opportunistic organisms.
HIV typical cousse. Three stages. 1*, Latency, AIds. Cd4+ cells drop continuously. anti-Hiv antibody peaks during latency. Virus in blood Peaks in 1*, settles down, then increases during Aids.
Created by: nady