Effector Mechanisms of T cell Immunity Flashcards
What is the major difference between effector T cells and resting naive T cells?
An effector T cell is able to respond to specific Ag w/o need for co-stimulation via B7-CD28 interaction.
What would cause a T cell to undergo anergy?
If no costimulatory signal is felt by the T cell.
What occurs to cell surface proteins on T cells as it migrates out of the lymph nodes and into circulation?
They downregulate the expression of CD69 and upregulate the expression of S1PR, which binds and follows the S1P concentration in the blood
What is the first step in migration on effector T cells from circulation into peripheral tissue?
E- or P-selectin ligands on the T cell bind to the E- or P-selectin molecules on the endothelium causing the effector T cell to start rolling.
What is the responsibility of CXCR3 on the surface of effector T cells during effector T cell migration into peripheral tissue
It binds to CXCL10 on the endothelial cells which causes activation of integrins (they are going from low affinity to high affinity)
What is the last step in migration of T cells from circulation into peripheral tissue?
Integrins on the effector T cell (LFA-1 or VLA-4) bind to their respective ligands (ICAM-1 or VCAM-1, respectively) which causes stable arrest on cytokine-activated endothelium at peripheral site of infection
What are the five ways Th2 cells function to combat helminths?
- Mast cell activation
- Mucus production
- Peristalsis
- IgA production
- Eosinophil activation
Explain how Th1 and Th2 cells stimulate macrophages to do different things
Th1 secretes IFN-γ which causes a monocyte to differentiate into an M1 macrophage responsible for inflammation and phagocytosis
Th2 secretes IL-4 and IL-13, which causes a monocyte to differentiate into an M2 macrophage which has anti-inflammatory effects and aids in wound repair
What would trigger the need for Th1 cells?
What cytokines stimulate differentiation of T helper cells into Th1??
What are the internal STAT and TF molecules they effect?
What does the cell produce as a result?
Remember, the responsibilities of Th1 include: differentiating monocytes into M1 macrophages to kill intracellular pathogens, stimulate IgG secreting plasma cells, stimulate complement binding to activate the classical pathway (via increased IgG serum levels which allows C1 to bind), and increase MHC II and B7 expression on APCs
Intracellular pathogens
IFN-γ and IL-12
IFN-γ: STAT4 → T-bet → enters nucleus
IL-12: STAT1 → enters nucleus
Produces IFN-γ and IL-2
What would trigger the need for Th2 cells?
What cytokines stimulate differentiation of T helper cells into Th2??
What are the internal STAT and TF molecules they directly effect?
What does the cell produce as a result?
Remember, the responsibilities of Th2 include stimulation of IgE producing plasma cells, stimulation of mast cells and eosinophils leading to inflammation, and differentiation of monocytes into M2 macrophages
Helminths or allergens
IL-4 (which comes from mast cells)
IL-4: STAT6 → enters nucleus.
Additionally, GATA-3 is the novel transcription factor which is stimulated by the TCR
Produces IL-4, 5, and 13
What would trigger the need for Th17 cells?
What cytokines stimulate differentiation of T helper cells into Th17??
What are the internal STAT and TF molecules they directly effect?
What does the cell produce as a result?
Remember, the responsibilities of Th17 include destruction of extracellular bacteria or fungi via inducing neutrophilic inflammation, and maintaining barrier structure @ the mucosal surface. It also is the cause of many pro-inflammatory diseases such as MS, IBD, and RA
Extracellular bacteria or fungi
IL-1 and 6 along with TGF-β
IL-6: STAT3 → enters nucleus
TGF-β: RORγT → enters nucleus
Produces IL-17 and 22
What would trigger the need for Treg cells?
What cytokines stimulate differentiation of T helper cells into Treg??
What are the internal STAT and TF molecules they directly effect?
What does the cell produce as a result?
Remember, the responsibilities of Treg include suppression of responses from other Th cell subsets, APCs, and B cells
Interaction with harmless foreign or self-ag
TGF-β
TGF-β: Foxp3 → enters nucleus
Produces IL-10 and TGF-β
Explain the migration of activated Th cells in the lymph nodes
- Activation of Th cell by APC in the medullary region.
- CD4+ T cells decrease expression of the chemokine receptor CCR7, and increase the expression of the chemokine receptor CXCR5.
- Migrate to the edge of the follicular zone.
- Activated Th is now presented w/ Ag from B cell
How do Th1 cells enhance proliferation, differentiation, and cloning of activated CD8+ T cells?
They secrete IL-2 (CD8+ T cell growth factor)
Additionally, IFNs increase MHC expression
How does an activated CD8+ T cell trigger apoptosis of a cell?
CD8+ T cells have stored lytic granules that contain cytotoxins. These cytotoxins include granzymes and perforins.
Granzymes enter target cell via receptor-mediated endocytosis and enter the cytoplasm via perforin-dependent mechanisms. Granzymes then activate caspases triggering apoptosis.
Additionally, activated CD8+ cells express Fas ligand which binds to the death receptor, Fas, which is expressed on many cell types. This also results in the activation of caspases triggering apoptosis.
