T cell activation and generation of effector T cells Flashcards
Signals for Naive T cell activation
To be fully activated and differentiated into effector or
memory T cell, the T cell needs 3 different signals:
. Signal I: Antigen recognition
• Signal 2: Co-stimulation
. Signal 3: Cytokines
1st Signal: Antigen recognition
• Is the signal that initiates the immune response, so that the immune response is antigen- specific
• TCR in T cell recognises the antigen in the context of MHC
–• CD4 TCR recognises MHC Il/peptide complex
–• CD8 TCR recognises MHC I/peptide Inactivation
Where is the co-stimulatory signal?
- Most commonly on dendritic cells
* But may also be provided by macrophages or B cells
2nd Signal: Co-stimulatory molecules
TCR signalling is NOT enough to activate a naive
T cell
co-stimulatory molecules
are also required.
1) B7:CD28
—CD28 is expressed by the T cell
—B7-1 (CD80) and B7-2 (CD86) molecules are expressed by the APC
2nd Signal: Negative co-stimulatory molecules
They inhibit the downstream effector processes initiated by TCR
MHC/peptide interaction
Reduce inflammation after the infection has cleared
Not expressed by naive T cells, there are induced upon activation
For example
CTLA-4 and PD-I, LAG3
• PD-I: Programmed cell death
protein I.
Mainly expressed in T cells in
peripheral tissues.
Cytotoxic T-Lymphocyte Antigen 4: CTLA-4
CTLA-4 is expressed approx 2-3 days post
stimulation
It has high affinity/avidity for CD80 but
opposing effects to CD28.
• It is mostly expressed in T cells in secondary
lymphoid organs.
• Peak levels of expression lower than CD28
but avidity of interaction is much higher
• Therefore, competes favourably with CD28
for ligation to CD80/86
IL-2 Induction of T Cell proliferation
IL-2 is a growth, survival and differentiation factor for T cells and T regs.
Post TCR signalling
Following successful signalling via the TCR, a naïve T cell will:
—Modify the expression of surface molecules
—Upregulate cytokine production
—Undergo active rounds of proliferation
–Upregulate expression of pro-survival genes
–Upregulate expression of IL-2 and IL-2R-a
Differentiate into effector or memory cells
What induces T cell polarisation into the different
subsets?
• The polarising cytokines
• These are generated by the
stimulating APC
• Which cytokines they
produce depends on:
–• The cellular origin of the APC
–• The maturation and activation status of the APC
–• Which pathogens or inflammatory mediators were encountered by the APC
–• In which tissue environment the encounter takes place
THI cells
-These were the first identified subsets
-THI polarisation occurs in response to the presence of intracellular pathogens such as viruses and bacteria
that are ingested by and destroyed by phagocytes.
-Master transcription factor that controls differentiation— T-bet
THI cells: Function
• They produce IFNg
• Help to activate macrophages to ingest and destroy microbes
• Induce antibody class switching to lgG (opsonization).
• All helpful response in eliminating an intracellular
pathogen
TH2 cells: Development
TH2 polarization occurs in response to phagocyte - independent immune responses.
TH2 polarizing cytokine is IL-4
• Dendritic cells do not make IL-4
• Eosinophils, basophils and mast cells produce IL-4. ILCs a so produce L-4
Transcription factors: IL-4 activates STAT6 which promotes expression of GATA3
GATA 3 is a transcriptional activator of IL-4 and IL-13 genes
TH2 cells: Function
TH2 cells produce IL-4, IL-5 and IL-13, effector cytokines that help eliminate extracellular parasitic
infections such as worms
Promote class switching to lgE, which causes inflammatory cytokines to be released by eosinophils and mast cells.
They also increase intestinal movement and mucus production.
lgE also mediates allergy
