T-cell 4: T-cell activation Flashcards
T-cell activation - what does it need?
- what cell type?
- what 3 signals from this cell type?
Needs activation from APCs (MHC-antigen complex) to become mature (until this, it is considered a naive cell)
APC delivers 3 signals to activate a T-cell
1) MHC peptide needs to bind to the T-cell receptor (ACTIVATION)
2) B7 molecules on APC need to bind to CD28 (survival)
3) correct cytokine profile (for T-cell differentiation)
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T-cell proliferation requires which cytokine
- resting vs activated T-cells and the cytokine?
- what does the cytokine do?
IL-2
- actually produced by t-cell (autocrine)
- resting t-cells have a moderate affinity IL-2 receptor, and don’t produce much IL-2
- activated T-cells express a high affinity IL-2 receptor, and make more IL-2
- binding of IL-2 to its receptor signals the T-cell to enter the cell cycle to induce proliferation
CD8+ t-cells Activation
- what do CD8+ help with?
- what cell activates CD8+ cells?
- why is this crazyish?
- if CD8+ binds to this cell, what 3 things happen?
- CD8+ help with killing host cells infected with intracellular pathogens (most likely virus)
- APC’s are infected the the virus/endogenous pathogen
- Viral proteins made inside the APC are processed to be presented as smaller peptides on the MHC
- -> in this case APC can present on both MHC class I and MHC class II!!!! OMG APC’s can have both?!?
- if the corresponding CD8+ t-cell encounters the APC, there will be binding
- binding and additional co-stimulation will activate the T cell (B7-CD28)
- activated t-cell now produces IL-2, leading to proliferation of that T-cell clone
- activated t-cell then becomes a cytotoxic T-cell
Cytotoxic t-cells
- what does CTL do to an infected cell (how does it kill)?
What 2 pathways are there for this? explain them
- the cytotoxic t-cell looks for any host cell displaying the same antigen that the activated CTL recognizes will be targeted
- CTL will cause the infected cell to undergo apoptosis
Apoptosis (2-pathways)
1) Fas-pathway
- Fas ligand (Fas-L) on the cytotoxic t-cell will bind to Fas on the target cell –> apoptosis
2) Perforin and Granzyme
- Perforin: molecule that forms pores in the cell membrane of the target cell
- Granzymes are proteases involved in inducing apoptosis. They enter the pores formed by perforin
CD4+ t-cells
- list all the functional CD4+ t-cell types
- explain how HIV causes some of it’s effect in terms of CD4+ absense
There are a number of different functional CD4 t-cells
- Th1: help macrophages and other phagocytes to kill intracellular organisms (HIV: will be prone to pathogens that reside in vesicles - like mycobacteria and pneumocystis)
- Th2: production of antibodies (specifically IgE)
- Th17: recruitment of other inflammatory cells and neutrophils
- Tfh: help B-cells make antibodies (so HIV: not just opportunistic infections - also things that it can’t protect itself against. Don’t have t-cells that help b-cells make antibodies)
- Treg
HIV: significantly diminished CD4+ cell count
- explains why patients with HIV are prone to very specific opportunistic infections
- not just opportunistic infections: also bacterial pneumonia - this is because they don’t make proper antibodies
T-cells activate macrophages
- what type of T-cell? what does it use to activate macrophages?
- what is required?
when a Th1 cell helps a macrophage become more efficient at killing the pathogen, it does it through: Interferon gamma (IFN gamma), which is a macrophage activating factor - this interaction requires CD40 ligand on the TH1 cell binding CD40 on macrophage -->lack of CD40 ligand --> prone to specific infections
Th2 and Tfh help B-cells make antibodies
- what 3 things are required in the binding of B-cells to T-cells for B-cells to make antibodies? What affects the B-cell antibody isotope?
1) MHC/peptide to T-cell receptor
2) CD40 on B-cell to CD40 Ligand on helper t-cell
3) cytokine profile (helps determine antibody isotype)
