Where are T cells developed? - Answers Thymus is the place where T cells developed
What is a naive T Cell? - Answers A naive T cell is mature but has not met up with its specific
antigen. It will travel through circulation and lymphatics searching for its antigen.
T cell activation: - Answers T cells require antigen presentation as a first signal. Other molecular
interactions can provide the second required activation signal. Once activated, T cells
differentiate into their effector MHC forms such as CD8+ and CD4+. T cells go on to become
killer T cells( CD8+-MHC I) or T cells differentiate into several different subsets (CD4+-MHC II)
First T cell activation signal: - Answers TCR/MHC-peptide complexes and coreceptors are
reforced and centralize and activates the Central supramolecular activating complex, cSMAC.
Adhesion molecules/bound ligands peripherally localize the signal and activate Peripheral
supramolecular activating complex, pSMAC.
Second T cell activation signal: - Answers Costimulatory ligands interaction and exchange
antigen.
Third T cell activation signal: - Answers Cytokines direct T-cell differentiation into distinct
effector cell types (paracrine or autocrine).
IL-2 is an example of an autocrine type of cytokine response system.
IL-12 is an example of a paracrine type of cytokine response system.
What are positive costimulatory receptors? - Answers They facilitate activation:
-CD28: homodimer expressed on majority of T cells and enhances TCR-induced proliferation
and survival. It binds to B7-1(CD80) and B7-2 (CD86) expressed by APCs
-ICOS: binds to ICOS-ligand on activated APCs. Expressed on memory and effector T cells that
may help maintain activity of already differentiated cells.
What are negative costimulatory receptors: - Answers Help turn activation off:
-CTLA-4(CD152): Induced within 24 hours after activation, peaks 2-3 days post-stimulation. It
binds to B7-1/B7-2 with higher affinity than CD28, but shuts down signaling pathways.
-PD-1 (program death-1, CD279) and BTLA (B- and T-lymphocyte attenuator): PD-1 may help to
mediate T-cell tolerance in nonlymphoid tissues. BTLA may down-regulate inflammatory and
autoimmune responses.
, What are superantigens? - Answers Produced by pathogenic Viral/bacterial proteins that bind to
specific Vβ regions of TCRs and α chain of class II MHC molecules and act as a defense
mechanism against immune system. This non-specifically activates T cells that secrete a
massive amount of cytokines.
What is the difference between exogenous and endogenous superantigens? - Answers
Exogenous superantigens are soluble proteins secreted by bacteria. Endogenous superantigens
are cell membrane proteins generated by viral genes integrated into mammalian genomes.
T cell differentiation signals(1-3) - Answers -(1-2 days) signals 1 and 2 induce upregulation of
prosurvival genes( induces the cell cycle), activates transcription of IL-2 and IL-2R genes, and
leads to proliferation (Production of memory and effector clonal cell populations occur between
4-5 days).
-Signal 3(Cytokine signaling): APCs bind PAMPS via PRRs, inducing cytokine secretion. Different
PRRs engaged (via different antigens) = different cytokines produced. (Ex. Viruses stimulate IL-
12 to induce TH1 subsets, Worms stimulate IL-4 to induce TH2 subsets)
T cell differentiation: Helper T cells - Answers Helper T cells can be divided into five distinct
subsets (TH1, TH2, TH17, TREG, TFH). Each produces a distinct cytokine profile and regulates
distinct activities within the body
Th1 cell differentiation - Answers Naive CD4+ T cell are induced by IL-12, IL-18, and IFN-γ which
facilitate induction of T-bet master regulator in positive feedback loop. Characterized by strong
IFN-γ and TNF cytokine production, which:
-Leads to class switching to IgG classes that support phagocytosis and complement fixation
-Supports differentiation of antiviral CD8+ killer T cells(DC's).
(INTRACELLULAR PATHOGENS)
Th2 cell differentiation: - Answers Naive CD4+ T cell is induced by IL-4 that triggers master
regulator GATA3 to produce Th2 cells. Th2 cells upregulate IL-4, IL-5, and IL-13 production. IL-4
acts to promote activities of eosinophils against helminths by inducing IgE receptors on
eosinophils and induces class switching to IgE in B-cells.
(EXTRACELLULAR PATHOGENS)
Th1 and Th2 cells cross regulation: - Answers Cytokines can achieve cross-regulation:
-IFN-γ from TH1 responses inhibits IgG1/IgE class switching (a common TH2-induced response)
- IL-4 from TH2 responses inhibits production of IgG2a (a common TH1-induced response)