7 Effector T-Lymphocytes Flashcards
Q: When can antibody responses be insufficient? What is required to deal with this?
A: Some pathogens are intracellular and hide in the cell
(Some organisms evolve to avoid antigen recognition)
To deal with these pathogens, T cell mediated immunity is required
Q: What does an antigen presenting cell do in essence? (3) What is its main subset?
A: chew up a pathogen, put it up onto an MHC and show it to a T cell
Dendritic Cells
Q: Name the two families of MHC molecule and state which types of T cell gets activated by them. What is this important in terms of?
A: MHC I - presents intracellular antigen to CD8+ T cells
MHC II - presents extracellular derived antigen to CD4+ T cells
disease susceptibility
Q: What is the only way that TCR recognises a peptide?
A: in the context of MHC - the antigen must be presented on the MHC molecules
Q: Where do T cells start? Where do they mature? Where do they then move to? What occurs here? What system it used? describe (2).
A: T cells start in the bone marrow, they mature in the thymus and they move to the lymph nodes
Once they have encountered the dendritic cell bearing the antigen that they recognise - they can migrate back into the circulation (go to site of infection)
There is a molecular address system that is used:
- 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
So in summary…DC recognises the antigen - moves to the lymph node - meets the T cell - T cell migrates to the source of infection
Q: What do memory cells start as? When do they become memory cells?
A: start as naïve, you then become activated (effector cells), they fulfil their roles and then they become memory cells
Q: Summarise the effector functions of CD8+ T cells. Alternative name? Main role? How do they function? Result? (3)
A: = 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.
- 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
Q: What is necrosis? What is apoptosis?
A: inflammatory cell death (this is a classic danger signal)
programmed cell death (instead of exploding outwards, it collapses in on itself)
Q: How many cells can CD8 kill? Why is regulation important? What does CD8 drive?
A: CD8 cells don’t just kill one cell. They can induce apoptosis in a target cell then move on and induce apoptosis in the next target cell - it can control an area
Regulation is important to make sure you don’t cause too much damage.
CD8 is important because it drives viral evolution
Q: What are the 2 mechanisms of inducing apoptosis? What do both these pathways do? (2)
A: 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 where the 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
Q: In what process is the function of CD4+ T cells / T helper cells critical? Variation? Functions? (4) Main role? method?
A: Critical in host defence
A naïve T cell can differentiate into different subsets which produce restricted cytokine patterns
They have a range of effector functions: Macrophage activation Delayed Type Hypersensitivity Response B cell activation Regulation
CD4 are helper cells and their role is to turn off or turn on the response of other cells by producing cytokines
Q: How are macrophages activated? What happens as a result? (2) Communication.
A: 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
Q: What is delayed type hypersensitivity associated with? Why is it described as delayed?
A: Tend to be associated with ALLERGY
It is delayed because it takes a couple of days to develop
Q: Describe the function of the delayed type hypersensitivity response. What’s its main role? What happens if the antigen is not a microbe?
A: Seems pathological but it is protective as well
MAIN ROLE: defence against intracellular pathogens
delayed type hypersensitivity produces tissue injury without protection = ‘hypersensitivity’
Q: How many waves does a classic allergic response have?
A: two waves: acute mast cell driven and T cell driven
Q: How many phases are part of the delayed type hypersensitivity response? What are they?
A: 2 phases:
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
Q: What is delayed type hypersensitivity mediated by? (2) Independent of? Due to? (2)
A: mediated by helper T cells and macrophages and it is independent of antibodies.
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.
Q: How are B cells activated?
A: membrane bound BCR recognises antigen -> receptor bound antigen is internalised and degraded into peptides-> peptides associate with ‘self’ molecules (MHC class II) and is expressed at cell surface -> complex= recognised by matched CD4 T helper cell -> B cell is activated
Q: What are the 5 families of T helper cells? Describe.
A: 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
Q: How are T helper cell subsets split? (2)
A: split into subsets based on the types of molecules they produce and they can affect the functions of other cells by producing cytokines
Q: What is immunological memory a consequence of? What are memory responses characterised by? (2) What can it confer?
A: The memory is a consequence of clonal selection.
The memory responses are characterised by a more rapid and heightened immune response - the pathogen should be cleared before you show symptoms
Can confer life-long immunity
Q: What is the difference between T cell memory and B cell memory? (3)
A: 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
Q: What are the 2 subsets of memory T cells? 2 equations.
A: 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
CCR7-CD45RA = EFFECTOR memory cells
CCR7+CD45RA = CENTRAL memory cells
Q: What is CD45RA?
A: expressed on naïve T cells and expression is lost when the naïve T cell becomes mature
Q: What is CCR7?
A: (chemokine receptor) allows a further subdivision to human memory T cells
Q: Explain T cell exhaustion. (2) When is this a particular problem?
A: Over time, especially in chronic infections, the CD8 pool contracts
Cells start to exhibit PD1 (programmed death) receptors which makes it much harder to activate T cells
when the infection isn’t cleared
Q: What are the pathological reactions that can be caused by T cells? (2)
A: Autoimmunity - antigenic peptide derived from self protein
Rejection (transplants) - antigenic peptide derived from self protein of transplant donor
Q: What is the role of regulatory T cells? by?
A: inhibit activity of naive and effector T cells by contact dependent mechanisms/ secreted cytokines
Q: What do Th-17 cells produce? Role? (2)
A: cytokines: IL-17
protective against some bacterial infections and mediate pathogenic responses in autoimmune disease
Q: What’s the role of Th2 cells? What do they secrete? (3)
A: help B cells differentiate into antibody secreting plasma cells
IL-4, IL-5, IL-13
Q: What’s the role of Th1 effector cells? What do they produce? (3)
A: activate infected macrophages and CD8 cells
IFN-y, IL-2, TNF-a
