T Cell Activation Flashcards
what are the three signals required for T cell activation?
- TCR signalling
- co-stimulatory interaction
- cytokine signalling
what is the co-stimulator on T cells?
CD28
what happens during co-stimulatory signal engagement?
clonal activation results from the binding between CD-80/86 and CD28 molecule for T cell activation
what happens if CD-80/86 (APC) and CD28 molecule (T cells) do not bind?
no response
what are the co-inhibitors on T cells?
CTLA-4 and PD-1
what do the co-inhibitors CTLA-4 and PD-1 bind to which leads to inactivation or no response?
CTLA-4 engages CD-80/86 on APC = no response
PD-1 engages PDL1/2 on APC = inactivation (anergy)
what is the definition of anergy?
induction of non-responsiveness to further stimuli aka functional inactivation of cells
B7 is another name for what molecule?
CD80/86
the binding of B7 (APC) and CD28 is necessary for what? what happens if B7 binds with CTLA-4?
activation
anergy
What is ICOS-L expressed by and what is its activity?
- expressed by B cells, some APCs, and T cells
- maintenance of activity of differentiated T cells
what is the role of cytokines?
signaling molecules released by APCs or the surrounding environment, act as instructions that guide the T cell to differentiate into a specific subset.
what cytokines activate T helper 1, what is its role and what cytokines does it release?
- IL-12, IFN-g, IL-18
- macrophage activation and IgG production for defense against intracellular microbes associated with autoimmune disease/chronic infection
- IFN-gamma, TNF
what cytokine activates T helper 2 , what is its role and what does it release?
- IL-4
- mast cell and eosinophil activation, IgE production and alternative macrophage activation against helminthic parasites involved with allergic diseases
- IL-4, IL-5, IL-13
what cytokines activate T helper 17 , what is its role and what does it release?
- IL-6, IL-23, TGF-B
- organ-specific autoimmunity by neutrophilic and monocytic inflammation against extracellular bacteria and fungi
- IL-17A, IL-17F, IL-22
what cytokines activate T follicular helper , what is its role and what does it release?
- IL-6, IL-21
- regulates affinity maturation of germinal center B cells
-IL-4, IL-21
what cytokines activate T regulatory cell , what is its role and what does it release?
- IL-2, TGF-B
- suppresses immune response
- IL-10, TGF-beta
what is polarization of response?
each T cell subset produces cytokines that amplify itself but inhibits the others so the response becomes increasingly polarized
explain the steps of activation of macrophages through T helper 1 cells?
- APC produces IL-12
- transcription factor T-bet is activated
- T-bet induces naive T cells to differentiate into TH1 cells
- TH1 cells produce interferon-g which activates macrophages
what do T helper 1 cells stimulate on APCs?
expreession of MHC molecules and CD-80/86 co-stimulatory molecules
IFN-gamma stimulates macrophages to do what?
ingest microbes
what happens when a macrophage is activated by IFN-gamma released by TH1 cells?
- increased expression of MHC and co-stimulators
- secretion of cytokines (TNF, IL-1, IL12, chemokines)
- killing of phagocytosed bacteria
what do T helper 1 cells and IFN-gamma mediate through B cells ?
antibody class switching and the production of IgG which binds to Fc receptors on phagocytes to enhance phagocytosis
which transcription factor is activated when IL-4 binds to receptors on naïve T cells?
GATA3
what does GATA3 do?
induce naive T cells to differentiate into TH2 cells, which are effective against worms
TH2 cells produce both IL-4 and IL-13 that act together to activate and induce what?
- mucus secretion
- alternative activated macrophages (M2)
TH2 cells mediate antibody class switching to ?
IgE (mast cell degranulation) and IgG
TH2 cells also produce which cytokine that activates eosinophils ?
IL-5
what do alternatively activated macrophages (M2) secrete, promote and inhibit?
- secrete IL-10 and TGFB
- promotes tissue repair
- inhibits inflammation and microbicidal activity of classically activated macrophages (M1)
which transcription factor induces naive T cells to differentiate into TH-17 cells?
ROR-gamma-t
what does T helper 17 cell induce and produce?
- induces inflammation
- produces IL-17, IL-22, and pro inflammatory cytokines (TNF, IL-1, IL-6)
what do T helper 17 cells recruit ?
neutrophils and some monocytes
what do T helper 17 cells help to increae?
- barrier function like in the GI tract
-production of anti-microbial peptides for fungal and bacterial infections
T regulatory cells contain CD4, CD25 and T suppressor cells that inhibits or turns down what?
T cell response
what is the transcription factor of a regulator T cell?
FOXP3
what activates FoxP3?
TGFB and antigen specific T cell receptors
T reg expresses which inhibitory molecule? what does it do?
CTLA-4, inhibits proliferation and activation of CD4 and CD8 cells
which T helper cells engage with cytotoxic T lymphocytes and how?
- T helper 1
- by CD40/40L to provide interleukin-2 for proliferation
after targets are eliminatedm, most B/T cells die but a small portion survive and become what?
memory cell populations that have IL-7 receptors and protein CD27
in the absence of antigen but presence of what cytokines cause effectors cells to become memory cells?
- IL-7 and IL-15
maintanence of memory cells is dependent on what? but does not require what?
- cytokines
- antigen recognition
what are superantigens and what do they bind?
- microbial products that non-antigen specifically stimulate the T lymphocytes in an uncontrolled manner when present in low concentrations, resulting in fever, shock, and death
- MCH class II and T cell receptors
