T-Cell Development, Activation, and Effector Function-Thompkins Flashcards
understand the structure and function of the TCR complex
- TCRs are transmembrane heterodimers composed of either an alpha and a beta chain or a gamma and delta chain
- extracellular variable regions contain the antigen binding region
- 4 transmembrane peptides collectively called CD3 that help transduce signals to activate the T cell
is CD3 of the TCR complex a receptor?
no! it does not bind ligand but is essential for intracellular signaling
understand how T cell diversity, specificity, and tolerance are generated in the thymus
diversity is generated through gene rearrangement; a unique genetic mechanism that only occurs inside B and T cells during development and requires protein complexes including RAG1 and RAG1 (recombination activating genes 1 and 2)
describe T cell rearrangement
- combinatorial diversity: multiple V, D, J, and C segments are rearranged in 2 chains (either alpha + beta or gamma + delta)
- junctional diversity: random nucleotides additions and deletions
understand the 3 signals necessary for T cell activation
- antigen/epitope presented by MHC
- co-stimulation
- cytokines
describe signal 1 in T cell activation; is this signal sufficient for full activation?
signal 1 is TCR/MHC/antigen interaction:
naive T helper and cytotoxic T cells exit the thymus and migrate to lymph nodes, can only be activated by an APC (almost always a dendritic cell) presenting a specific antigen/epitope;
NOT sufficient for full activation!!
describe signal 2 in T cell activation
co-stimulation is signal 2;
CD80/86 molecules on the APC must interact with CD28 molecules on the T cell
describe APC expression of CD80-86
only expressed on APCs and in low levels unless APCs are activated by cytokines, pathogens, or T cells (danger signals)
what happens if a naive T cell encounters signal 1 (antigen) without signal 2 (co-stimulation)? what is the purpose?
this triggers apoptosis (cell death) or anergy (a state of non-responsiveness) of the T cell; this is another check that helps reduce self-reactivity and maintain peripheral tolerance, because APCs don’t only present dangerous things, sometimes they’re just cleanin shit up
describe signal 3 in T cell activation; generally
cytokines in the environment or produced by the APC provide signal 3 and help determine T cell fate by providing context
describe signal 3 in T cell activation; specifically (4)
- naive T cells express a low affinity IL-2 receptor
- after signal 1 and 2, the t cell then expresses a high affinity IL-2 receptor and also secrete IL-2
- when bound to IL-2, the high affinity IL-2 receptor induces T cell proliferation (autocrine and paracrine function)
- the antigen-specific T cell leave the lymph node and go to tissue to fight
understand the differences between naive, effector, and memory T cells
naive: mature, but not interacted with an antigen yet
effector: t helper cells with many functions or cytotoxic t cells
memory: specific for an antigen; remain after contraction following adaptive response, for years or a lifetime to provide long-lasting protection against previously encountered microbes
what are the 5 most common T helper cells?
- Th1
- Th2
- Th17
- Tfh
- Treg
what is the function of Th1 cells? what cytokines do they produce? (2) principle cell target and major immune reaction?
defense against intracellular parasites; produce IFN-y and TNF-a; target macrophages and function in macrophage activation
what is the function of Th2 cells? what cytokines do they produce? (4) principle cell target and major immune reaction?
allergy, asthma, controls parasites and extracellular pathogens;
produce IL-4, IL-5, IL-6, and IL-13; target eosinophils; function in eosinophil and mast cell activation
what is the function of Th17 cells? what cytokines do they produce? (2) principle cell target and major immune response?
defense against pathogens, autoimmunity (important for transplantation rejection and cancer); produce IL-17 and IL-22; target neutrophils and function in neutrophil recruitment and activation
what is the function of Tfh cells? what cytokines do they produce? (3) principle cell target?
help germinal center B cells make antibodies, class-switching and affinity maturation; produce IL-21 and IFN-y or IL-4, target B cells
what is the function of Treg cells?
these are from a subset of self-reactive thymocytes that survive selection; are immunosuppressive T cells that can help prevent autoimmune responses in the periphery, contributing to peripheral tolerance
define peripheral tolerance
a mechanism that takes place outside primary lymphoid organs that prevents immune responses against self or harmless materials like food or commensals
what is the function of cytotoxic T cells? how is this accomplished? (2)
kill pathogens via
1. release of cytotoxic granules: perforin forms a pore for granzyme to enter and induce apoptosis
2. Fas/FasL binding: FasL binds the death receptor Fas; Fas ligation signals activation of caspases leading to target cell apoptosis
understand the difference between alpha-beta and gamma-delta T cells
- gamma-delta T cells are a small fraction of the T cells in most mammals, but are the majority of T cells in ruminants and chickens
- gamma-delta T cells do not express CD4 or CD8; double negative
- do not require MHC/antigen interaction and can instead recognize unprocessed antigen without the help of MHC
- often mucosally associated
- less diverse repertoire because of few V gene segments
- cytotoxic function, similar to CD8+ T cells
