4. T cells Flashcards
importance of T cells
aid the clearance of intracellular microbes in macrophages (cell mediated immunity)
help B cells produce different Ig isotypes and high affinity antibodies
recognise virally infected cells and kill them
t cell development process
- peptide antigen recognition via APCs
- clonal expansion
- differentiation
- activation
- antigen elimination
- apoptosis
- surviving memory cells
central tolerance
negative selection and apoptosis of t cells that recognise self cells to prevent autoimmunity
occurs in the thymus
naive cells
have not been stimulated by antigen
effector cells
specialised functions incl. cytokine secretion and cytotoxic activity
memory cells
had antigen presented to them and remain in immune system to be subsequently reactivated if needed
migration of naive, effector and memory t cells
lymph nodes
inflamed tissues
both
frequency of cells for specific antigens (naive, effector, memory)
very low
high (clonal expansion)
low (mostly apoptosed)
which mhc class types do helper cells and cytotoxic cells recognise
helper - 2 (exogenous)
cytotoxic - 1 (endogenous)
t cell activation
requires two signals - from antigen and co-stimulatory molecules
then able to undergo clonal expansion
which cytokine is produced by the second signal
IL-2 to induce proliferation by autocrine action
examples of co-stimulators
CD80/86 or B7 on DCs to bind to CD28 receptors on t cell
what is the most potent stimulator of naive t cells
dendritic cells - express the highest levels of co-stimulators
immature vs mature DCs
immature - Ag uptake mode, non-motile, MHC low, highly phagocytic, B7 low
mature - Ag presentation mode, motile, MHC high, poorly phagocytic, B7 high
t cell activation vs anergy
activation: APC increased expression of co-stimulators and cytokine production
anergy: APC in resying state, no co-stimulator expression
peripheral tolerance
t cell anergy if self-antigen recognition by engagement of inhibitory CTLA4 receptors
t cell assistance in peripheral tolerance
Tregs provide CTLA4 which engages B7 instead of CD28 to stop activation
different types of t cell
helper (1, 2, 17, regs, follicular)
cytotoxic
invariant NKT
gamma/delta
functions of t cells
help b cells - class switching and affinity maturation kill infected cells secrete cytokines tolerance to prevent autoimmunity activate macrophages and neutrophils
how many signals needed for t cell differentiation
3 - same two as activation and proliferation as well as a third (cytokines) for differentiation
which cytokines are produced by apcs for t cell differentiation
IL4, 6, 12, 23
t cell polarisation
cytokines produced by apcs induce t cell differentiation into a specific helper subtype
th1 vs th2
1: cell mediated; bacteria, virus, fungi; IL-12; STAT4; T-bet
2: humoral; parasites, worms; IL-4; STAT6; GATA-3
cytotoxic t cell activation
also requires 2 signals but needs more co-stimulation provided by Th1 or 17 which produce CD40L and IL-2
CD40L
binds to CD40 on APC to make more CD80/86
cross presentation
presentation of exogenous antigen to MHC1 (usually for endogenous) by being loaded with MHC1 proteins
Th1
inflammatory, produce TNFa, activate macrophages, NKs and Tc, intracellular pathogens, increase IgG3&2a for opsonisation
Th2
mast cell, eosinophil, b cell activation for neutralisation of toxins, IgE, worms, allergies, parasites, suppress macrophages
Treg
anti inflammatory, homeostasis, peripheral tolerance, suppresses immune responses, provide CTLA4 for anergy, endocytose CD80/86
Th17
pro-inflammatory, mucosal immunity, bacteria and fungi, recruit neutrophils and monocytes, maintain epithelial barrier
Tfh
antibody production, in lymph node follicles, class switching and affinity maturation, eradicate most pathogen classes
how do t cell migrate around the body
adhere to endothelial cells in blood vessels and roll along, attracted by chemokines and cytokines, enter by extravasation/diapedesis
aka cell homing
selectins vs integrins
rolling effect
adhesion effect
mechanisms of Tc killing
granzymes/perforins
fas-fas ligands (on Tc and target)
both induce apoptosis by caspase activation
