Immunology 7- Effector T Lymphocytes Flashcards
Define Naïve T cells:
mature recirculating T cells that have not yet encountered antigen
Effector T cells:
encountered antigen, proliferated and differentiated into cells that participate in the host defense
Memory T cells:
Encountered antigen, contracted, rea [dy to respond to future infections.
Target cells:
Cells on which effector T cells act
How can T cells enable other cells to function better
They are large producers of cytokines and chemokines - they can affect the function of other cells
They can cause better digestion and better killing
What is the role of the Dendritic cells
DC exist in tissues (surveillance) acquire antigen, move to lymph nodes (needs activation by PAMP/ PRR)
What is the role of HLA-B57
it presents a single peptide from one of the HIV proteins - that peptide is key to the function of the viral protein and so the CD8 cells kill any cells with that epitope.
Describe what happens when a dendrite interacts with an infected cell
- Cell infected
DC collects material
Moves to the lymph nodes - MHC:peptide
TCR interaction - Naïve T becomes effector
- Effector cell sees MHC:Peptide on infected cell
Performs function - Effector pool contracts to memory
How do Activated T-cells know where the site of infection is
Chemokine gradient - so if the cells express the right chemokine receptors they can follow these gradients
Adressins and Integrins - allows the cells to move out of the vessels
What are the 3 signals required for a response from T-cells
Antigen Recognition
Co-stimulation
Cytokine Release
Function of CD8+ T cells - Cytotoxic T Lymphocytes
Their main role is to target and kill infected cells
When a virus peptide is presented on the MHC Class I of a cell, the effector CTL identifies the MHC I with a foreign peptide and kills it.
Necrosis - inflammatory cell death (this is a classic danger signal)
Apoptosis - programmed cell death (instead of exploding outwards, it collapses in on itself)
Specific recognition of target cells by cytotoxic effectors causes polarisation of cytotoxic vesicles within the cell.
This causes release of granules by T cells
This induces apoptosis in targets
Cell mediated cytotoxicity
Perforin + Granzyme -
CD8 injects perforin into the membrane of the target cell. This makes a pore in the membrane and allows granzyme to enter the cell.
Fas-fas Ligand
Fas ligand (FasL) = on the CD8 cell
Fas Receptor = on the target cell
When Fas has been engaged - it releases caspases
Both of these pathways upregulate CASPASE within the target cell which drives apoptosis.
range of effector functions of cd4 t cells
Macrophage activation
Delayed Type Hypersensitivity Response
B cell activation
Regulation
What are the 5 families of T helper cells:
Th1 - pro-inflammatory (boosts cellular response, produce IF gamma and activates macrophages)
Th2 - boosts anti-multicellular organism responses
Follicular helper T cells - essential for generation of isotype-switched antibodies
Th17 - important for control of bacteria
Treg - T cells that regulate the activation or effector functions of other T cells
What are t helper cells defined by
the cytokines they produce and the transcription factors they use
Macrophage Activation
They get activated by CD4 T cells which enable them to engulf and kill pathogens better
Once activated, they increase the levels of pro-inflammatory molecules: TNF-a and CD40
T cells and macrophages cross-talk - via cytokines
Function of Delayed Type Hypersensitivity
Seems pathological but it is protective as well
MAIN ROLE: defence against intracellular pathogens
If the antigen isn’t eradicated - you get chronic stimulation and granuloma formation
If the antigen is NOT A MICROBE, delayed type hypersensitivity produces tissue injury without protection = ‘hypersensitivity’
2 Phases of Delayed Type Hypersensitivity
Sensitisation - you have to be exposed to the antigen first before becoming allergic to it. No one is allergic to anything without being exposed to it once.
Effector - on second exposure you can trigger a severe response
How do helper T-cells cause Delayed Type Hypersensitivity
It is due to pronounced secretion of cytokines by helper T cells activated by the antigen in the area. The cytokines act as inflammatory mediators and also activate macrophages to secrete their potent mediators. It takes several days to develop so it is known as delayed type hypersensitivity.
Immediate Hypersensitivity is caused by mast cell degranulation
In general what does a cd4 t helper cell do
their role is to turn off or turn on the response of other cells by producing cytokines
B cell activation
B cells only take up the antigen that they recognise whereas DCs take up a large variety of antigens
The antigen presents by both DC and B cell will be the same so they will both present the same peptide-MHC complex which can be recognised by the T cell
The T cell will go from naïve to the effector state - it will recognise the antigen-MHC complex on the B cell and activate it
Difference between T cell memory and B cell memory
T cells don’t undergo isotype switching or affinity maturation
Once a T cell response has been made, it stays the same. B cell responses improve over the time.
Memory T cells are different from naïve T cells - as a memory cell they change the type of cytokine receptor they have on the cell.
Two subsets of memory T cells
Effector Memory - memory is local to the site of infection - the effector memory cells will live in the lungs if you’ve had lung infection
Central Memory - go back to the spleen or lymph nodes. Longer lasting but slower to activate response.
T cell exhaustion
Over time, especially in chronic infections, the CD8 pool contracts
This is a particular problem when the infection isn’t cleared e.g. HIV, CMV
Cells start to exhibit PD1 (programmed death) receptors which makes it much harder to activate T cells
