T Cells Flashcards
MHC I Features
Intracellular pathogens
expressed on all nucleated cells
alpha chain 45kD in three distinct domains
B2 microglobulin 12kD
MHC II Features
Extracellular pathogens
APCs only
alpha chain 33kD
beta chain 28kD
T Cell Receptor
alpha chain has VJ, beta chain has VDJ and variable region, arranged in some way as immunoglobulins
Factors contributing to TCR/Ig Diversity (5)
- multiple copies of VJD
- D region can be transcribed in different reading frames
- imprecise joining may occur during rearrangements of genes
- nucleotides may be randomly inserted/deleted
- any alpha chain may join with any beta chain
Medawar and Burnet - 1960 Nobel Prize
Demonstrated acquired immune tolerance - non-identical cattle twins happily carried additional set of red blood cells from their sibling - acquired through shared placenta in the wommb - gradual learning process through embryonic life
Th2 production
IL-4 –> STAT6 –> GATA3 –> Th2
Th1 production
IL-12 –> STAT4 –>T-bet –> Th1
Th17 production
IL-6/IL-23–> STAT3 –> Ror gammat T –> Th17
Treg production
TGF-beta –> STAT5 –> Foxp3 –> Treg
Functions of CD4+ (2)
- maturation of B cells into plasma cells and memory B cells
- activation of cytotoxic cells nad macrophages - release of different types of cytokines to facilitate different types of immune responses
Activation of T cell steps (3)
Signal 1: TCR binds to antigen as it is held in the MHC complex on the surface of the APC (stabilised by binding of CD4/8 to MHC)
Signal 2: CD28 (T cell) binds to CD80/86 (B7.1/2) on APC
Signal 3: differentiation controlled by different cytokine release
ALSO PRIMING - cell-cell interactions - transient - hold cells together - LFA-1 on T cell to ICAM-1 on APC
Th 1 cells effector cytokines and functions (3) (generally proinflammatory)
- IFN-gamma - activates macrophages and B cells
- IL-2 - stimulates B cell growth
- TNF-beta - activates macrophages and neutrophils
Th2 cells effector cytokines and functions (3)
- IL-4 - B cell activation, inhibition of macrophage activation
- IL-5 - eosinophil growth and proliferation
- IL-10 - inhibits Th1, inhibits macrophage cytokine release
CD8+ activation(2)
- Simple activation - interaction with proffesional APC
- long lasting memory cell production - CD8 t cells primed in the presence of CD4 cells undergo second round of clonal expansion - occurs via CD40L (T CELL) and CD40 on APC-DC cell (licensing) - then activates CD8 T cell
methods of killing by CTL (2)
Fas/FasL interaction
Cytotoxic proteins inside granules (perforin and granzyme)