Immunologie-P1 Flashcards
T cells monitor _____ compartments (intracellular/extracellular) for antigens derived from pathogens.
intracellular
What are the 2 major subsets of T cells, based on cell surface expression of __ and ___ co-receptors?
CD4+ = helper T cells CD8+ = cytotoxic T lymphocytes
Do T cells recognize native antigen?
NO.
They must first see peptide Ag presented by MHC molecules on APC cells.
What are the professional APCs?
- Dendritic cells
- Macrophages
- B cells
What is the TCR (T cell receptor) composed of?
1 alpha chain
1 beta chain
How do T cells only recognize foreign antigens?
Thymus deletes T cells that respond to self-antigens, so this results in having mature T cells that are specific for FOREIGN antigens.
Which parts of the TCR interact directly w/both MHC molecules and peptide antigens presented by MHC molecules?
Hypervariable regions of TCR (alpha and beta chains)
How is TCR generated randomly through DNA rearrangement?
You select “Cassetes” (different snippets of different alleles) on each gene (A and B). Recombination occurs and the DNA is rearranged. It undergoes transcription, splicing, and translation.
Process of recombination occurs with recombinase gene. (deficiency in recombinase = no T Cell receptors)
Once it is recombined, then you have copies of that TCR. Set. Then clonal expansion.
How does the TCR engage peptide:MHC complexes presented by APC?
- hypervariable region (part of alpha and beta chains) interact directly with peptide:MHC complex. The alpha and beta chains recognize the antigen in the context of the MHC molecule. So alpha and beta chains recognize the POLYMORPHIC regions of the MHC molecules.
- Once the TCR binds the peptide:MHC complex, CD8 and CD4 co-receptors engage the NONpolymorphic regions of MHC I and MHC II, respectively.
- There is also a complex of proteins associated with the TCR, called a complex w/CD3 and zeta chain proteins. These, along with the TCR, form the TCR COMPLEX.
When the TCR binds to MHC:peptide complex, it induces T cell signaling through CD3 and zeta chain proteins. These form Signal 1. - crucial for T cell priming.
What is Signal 1?
Induced T cell signaling through CD3 and zeta chain. This occurs once…
(1) the TCR binds the peptide:MHC complex through the alpha and beta chains recognizing the polymorphic regions of the MHC molecule.
(2) the CD4 and CD8 co-receptors engage with the NONpolymorphic regions of MHCI and II.
Then (3) you have induced T cell signaling. Signal 1.
remember this is a respective process (CD4 T cell vs. CD8 T cell).
What is the involvement of CD4 and CD8 co-receptors in antigen recognition by T cells?
- CD4 and CD8 are NOT co-stimulators. They are co-receptors that stabilize binding.
- CD3: important for signaling
What is Signal 2?
- Signal 2 = costimulation.
- It is produced by interaction between B7 (on the APC) and CD28 (on the T-cell).
- B7 is only expressed by professional APCs that have recently been activated/matured.
What happens if a T cell encounters a peptide:MHC on a cell that is not a professional APC?
- They receive Signal 1, but not Signal 2.
- Leads to anergy (T cell inactivation).
- This prevents T cells that may recognize self-antigens from attacking uninfected tissues.
How does a Th cell (CD4) get activated?
- Foreign body gets phagocytosed and is presented on MHC Class II molecule.
- It is recognized by TCR on Th cell (Signal 1)
- Costimulatory signal given by interaction of B7 (on APC) and CD28 (on Th) [Signal 2].
- Th cell is activated to produce cytokines.
How does a CTL (CD8 cell) get activated?
- Endogenously synthesized (viral or self) proteins presented on MHC I and recognized by TCR on CTL.
- IL-2 from Th cell activates the CTL to kill the virally-infected cell.
What are examples of other costimulatory molecules?
- B7-1 : CD28 *Note - B7-1 is also called CD80
- B7:2 : CD28 *Note - B7-2 is also called CD86
- B7-1 / B7-2 : CTLA-4 –> this is a suppressor. Competes against CD28.
- ICAM-1 : LFA-1 (adhesion)
B7-1 is also called…
CD80
B7-2 is also called…
CD86
What is the purpose of inducing anergy?
Anergy = T-cell inactivation
Purpose: to make sure that the T-cell won’t respond to self-antigens (prevent T-cells that may recognize a self-antigen from attacking uninfected tissues).