What is the main subset of APC
Dendritic cells
|”What do dendritic cells do?
Exist in tissues where they do surveillance. They acquire antigen and then move to lymph nodes where they mature and present the antigen on MHC. This is detected by T cells and then stimulated to proliferate into effector cells and migrates to source of infection.
Both T cells and Dendritic cells are circulating
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What is the 3 signal model that licenses a response?
- Antigen recognition
- Costimulation
- Cytokine release
IF NOT ALL 3, T cell WONT BE ACTIVATED
What do CD8 cells (CTL) do?
Destroy target cells (e.g. viral infected cells/tumours)
ALL CELLS PRESENT SELF ANTIGEN ON MHC 1. But then how are viral antigens recognised by cd8?
As well as displaying self antigen, some viral antigen is also displayed. CD8 recognises this and destroys the cell.
What happens when cytotoxic effectors recognise their target cell?
- Polarisation of cell containing cytoxic vesicles
- Granule release by cytotoxic t cells
- Inducing apoptosis
Explain how perforin and granzyme works
- CD8+ injects perforin into target cell membrane
- Creates pore in membrane and allows granzyme to work.
- Granzyme binds to Caspase enzyme - triggers cascade which induces apoptosis.
Explain the fas pathway of apoptosis.
- CD8 cell has fas ligand (fasL)
- Target cell has fas receptor
- Once fas has bound, it releases caspases - triggers apoptosis.
What does CD8 drive?
Viral evolution
What are the effector functions of CD4 cells?
- Macrophage activation
- Delayed type hypersensitivity response
- B cell activation
- Regulation
MAJOR ROLE IS TO PRODUCE CYTOKINES FOR DOWNSTREAM RESPONSES
What are the 5 subsets of T helper cells.
- Th1 - pro-inflammatory (boosts cellular response by activating gamma IF and macrophages)
- Th2 - boosts anti-multicellular organism response
- produce IL 4 / IL 5 / IL 13 - Follicular T helper cells
- essential for antibody production
- produce IL 21, reside in B cell follicles - Th17 cells - drive antibacterial response
- T regulatory (Treg) -
DENDRITIC CELLS PRODUCE CYTOKINES WHICH TELL THE CD4 CELL WHAT TYPE OF HELPER CELL IT WILL BE
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What defines a T helper cell?
The cytokines they produce and the TFs they use
What is Delayed Type Hypersensitivity?
Reaction to an antigen.
Mainly defence against intracellular pathogens by eradicating them.
However, if antigen not eradicated, chronic stimulation can occur (or granuloma formation)
If the antigen is not a microbe, DTH can cause tissue injury without protection
What do activated macrophages express?
Increased levels of CD40 and TNF- a receptors.
They secrete more TNF - a.
T cells and macrophages cross talk via cytokines
Allergy is driven by?
CD4 th2 cells - eosinophil activation
What are the 2 phases of a DTH reaction?
- Sensitisation
2. Effector
What are differences between T cell memory and B cell memory?
- T cells do not undergo isotope switching or affinity maturation unlike B cells (which allows B cell responses to improve over time)
Differences between naive T cell and memory T cell?
Memory T cell has different cytokine receptor
Memory T cells proliferate faster
What are the different subsets of memory T cells?
Effector memory - local to site of infection
Central memory - go back to spleen/lymph nodes
What is T cell exhaustion?
Over time, especially in chronic infections, the CD8 pool contracts.
CD8 Cells start to exhibit PD1 on their cell which makes them harder to activate.
What are the good and bad things T cells have?
+ pathogen cleared
- autoimmunity
- rejection