Cell Mediated Immunity Flashcards
Helper T cell activation
binding of TCR to MHC 2 peptide complex (antigen binding), costimulatory molecules (B7:CD28), cytokines (IL-1, IL-6, TNF alpha) from APC to T cell
What determines T cell specialization
by antigen presented on MHC class 2
TH 1 cells
intracellular pathogens, promotes cell mediated immunity
IFN gamma (inhibits TH2, activates macrophages), IL-2 (turns CD8 cytotoxic), TNF alpha
TH 2 cells
promotes humoral immunity, extracellular pathogen removal
secretes IL-4, IL-5 (activates B cell, promotes class switching)
antibody dependent cell mediated cytotoxicity (ADCC)
NK cells, macrophages and monocytes, neutrophils, eosinophils
Cytotoxic cells (CTL) kill by
kill by perforins, cytokines (TNF), granzymes (serine proteases)
Fas ligand on CTL can interact with Fas on target cell to cause apoptosis of target cell
interleukin 2 (IL-2)
cytokine produced by activated naive T cells to proliferate
proliferation of T cell
interleukin 7 (IL-7)
secreted by APC to ensure T cells survive
LFA-1:ICAM-1 interactions
how T cells initially binds to APC, not involved in the activation of T cell, induces conformational change in APC that prolongs cell to cell contact
what happens when T cell meets non bacterial protein antigen
without bacteria, non bacterial protein will be taken up by macrophage but no B7 will be expressed (unstimulated macrophage). T cell will still bind to MHC presenting non bacterial protein but without co-stimulation, there will be no T cell proliferation/activation
what happens when T cell meets bacteria and non-bacterial protein
results in proliferation/differentiation of T cells specific for nonbacterial protein
What would violate the two signal model for T cell activation
If you have a strong enough signal (MHC binds tightly to TCR) you may not need CD28:B7 costimulation.
How do you turn off T cell response
elimination of antigen, elimination of stimuli, IL-2/IL-2R signaling to proliferate, kill immunoregulatory cells
TNF alpha (tumor necrosis factor)
activates endothelium to induce macrophase binding and exit from blood vessel at site of infection
CD8 T cells effector molecules
perforin, granzymes, granulysin, fas ligand
First Checkpoint (T cell development)
mediated by pre-TCR, beta selection, between double negative and double positive, determined by beta chain rearrangement
Second Checkpoint (T cell development)
mediated by alpha Beta TCR, between double positive and single positive, positive/negative selection
CTLA-4
master regulator of T cell activation, synthesized by T cell and binds to B7 with greater affinity removing co-stimulation.
Factors in turning off T cell response
elimination of antigen, elimination of other stimuli, IL-2/IL-2R signaling via T regulatory cells, killing by immunoregulatory cells via Fas-Fas ligand
surface cathepsin B
protects CTL from self destruction after degranulation
proteinase inhibitor 9
serpin that inhibits granzyme B, expressed by CTL, dendritic cells, endothelial cells, some tumors
protects CTL from self destruction after degranulation