Question | Answer |
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. |