T-Cell activation, differentiation + memory Flashcards
How is the adaptive immune repose initiated?
by interaction between naïve T-cell and antigen presenting cell (APC)
How are APCs activated?
~ by pattern recognition receptors @ infection site
~ the processed antigen is presented as peptides on APC PM in the groove of MHC class I and II mol.
~ APC migrate from tissue to lymph nodes + spleen
Activation of T-cells
Antigen recognition:
1) interaction of TCR-CD3 complex w/ MHC peptide
2) co-stimulation signal via CD28 + co-stimulatory ligands on dendritic cells
3) soluble cytokines
Name the types of co-stimulation.
~ positive
~ negative
~ absent
Positive co-stimulation
CD28 + ICOS receptors = t-cell activation
Negative co-stimulation
CTLA-4 + PPI + BTLA receptors = t-cell deactivation
Absent co-stimulation
= anergy/unresponsiveness, which causes:
1) APCs prevented from up regulating CD80/86
2) anergic T-cells fail to respond even when co-stimulated
3) blockage of CD28 = more anergy
IOCS
maintains activity of differentiated T-cells + their responses
CTLA-4
down regulation of T-cell responses
How can cytokines be influenced by an infection?
~ some exotoxins (gram -ve bacteria) behave as super antigens and activate release of cytokines in macrophages and T-cells
~ causes polyclonal T-cell activation of all specificities
~ done as a diversion away from exotoxin-producing pathogen
Superantigen
can simultaneously bind to Vbeta of TCR + alpha chains of MHC class II which allows it to bypass the normal TCR antigen specificity rules
What causes T-cell proliferation?
~ activation of naïve T-cell increase secretion of IL-2 + its receptor (autocrine signalling)
~ this causes the cell to divide multiple times creating a population of effector and memory cells
Name the stages of T Helper differentiation.
1) PRR binding by pathogen antigens stimulates secretion of cytokines
2) cytokines bind to receptors on CD4+ T-cells + influence differentiation (under control on master regulator)
3) different pathogens stimulate different T(H) subsets
T(H)1
~ cell mediated immunity
~macrophage activation
~ inflammation
~ IL-12 + IL-18
T(H)2
~ humoral immunity
~ allergic + anti-helminth responses
~ IL-4