T Cell and B Cell Activation and Signaling Flashcards
To activate naive T cells
- TCR
- Costimulatory
- Cytokine signaling
CD4+ T helper cells antigen interaction
Via TCR with antigen peptide complexed with class II MHC on antigen presenting cell
CD8+ T cytotoxic cells antigen interaction
TCR interaction with antigenic peptide bound to class I MHC on target cell
CD4+ T helper cell activation
Essential for development of cell-mediated immunity and optimal humeral immunity
TCR receptor signaling
Engagement by peptide/MHC initiates multiple pathways
Regulated by activation/inhibition of protein kinases/phosphatases and amplified by cascades
Costimulatory signaling
CD28 interacting with B7 family members (CD80/CD86) on antigen presenting cells
Acts synergistically with TCR signaling to enhance gene transcription and stabilize cytokine mRNA
Cytokine signaling
Antigen presenting cell makes cytokines or autocrine signaling (to provoke making of transcription factors)
Immediate gene expression
Within 30 min of TCR signaling
ie. TF
Early gene expression
1-6h of TCR signaling
ie. Cytokines
Late gene expression
More than 2 days after TCR signaling
ie. Adhesion molecules
IL-2
T cell growth factor
Allows autocrine growth, cell cycle progression and differentiation into memory and effector cells
GM-CSF
Neutrophil production
First line of defence against bacteria
Major events of TCR signaling
Phospholipase Cgamma activation Increase in intracellular Ca concentrations Protein kinase C activation Nuclear translocation of NFkappaB Activation of Ras/MAPK pathway
Receptors/AP involved in TCR signaling
TCR/CD3 complex, CD4, CD8 coreceptors
Accessory molecules CD2, CD28, CD45
CD45
(T cell signaling)
Cell surface phosphatase that catalyzes the dephosphorylation of inhibitory tyrosine residue on p56lck
Causes activation and phosphorylation of CD3 ITAMs and phospholipase Cgamma
Calcium release
Ca released with 1 TCR
Max release with 10+ TCR
p56lck
(T cell signaling)
CD4/CD8 associated protein tyrosine kinase
Sequestered into lipid rafts (that exclude TCR/CD3) in resting T cell
TCR engangement recruits TCR/CD3 complex into lipid rafts and CD4/CD8 coreceptors that interact with invariant regions of the MHC molecule form clusters
Phosphorylates the ITAMs located on 4 chains of CD3 complex
SMAC
Central and peripheral
Immunological synapse formed by sequestering TCR/CD3 into lipid raft
TCR/CD3 complex molecules on the inside and adhesion molecules on the outside
pSMAC
CD2 on T cell interacting with LFA-3
LFA-1 on T cell interacting with ICAM-1
cSMAC
TCR/CD3 interacting with MHC
p56lck
CD4/CD8 interacting with MHC
ITAMs (T cell)
Located on zeta, gamma, delta and epsilon chains of the CD3 complex
zeta Chain of CD3
(T cell signaling)
Phosphorylated by p56lck
Homodimer forms docking sites for protein tyrosine kinase ZAP70, which memes activated