What are dendritic cells and where do they exist and explain their cycle?
MAIN subset of APCs for initiation of a T cell response
- DC exist in tissues and acquire antigen. and then move to lymph nodes (need activation by PAMP/PRR)
- in lymph nodes, DC mature and then present antigen on MHC
Why are T cell mediated immunity required
- Some pathogens are intracellular and hide in the cell
- some organisms evolve to avoid antigen recognition
What do MHC I and MHC II present to?
MHC I- presents intracellular antigen to CD8+ T cells
MHC II- presents extracellular derived antigen to CD4+ T cells
When do T cells migrate and where to?
Once they have encountered the DC bearing the antigen- they can go back into the circulation.
There is a system:
-Chemokine gradient: 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
Summarise the relationship of DC and T cell?
- DC recognises the antigen
- Moves to the lymph node
- Meets the T cell
- T cell migrates to the source of infection
Describe the stages of T cells?
Start as Naive cells: mature recirculating t cells that have not yet encountered antigen
Then become activated
- effector T cells: encountered antigen, proliferated and differentiated into cells that participate in the host defence.
They fulfil their roles and become memory T cells: ready to respond to future infections
What is the difference between necrosis and apoptosis
Necrosis: inflammatory cell death ( classic danger signal)
Apoptosis: programmed cell death ( collapses in on itself)
Broadly speaking, how do Cytotoxic T Lymphocytes kill infected cells?
Inducing apoptosis
What are the two mechanisms for cell mediated cytotoxicity?
1.CD8+ effector T cells kill target cells that present peptides of cytosolic pathogens (viruses) in context with MHC class I molecules on their cell surface. Effector CTLs secrete granules.
2.Cytotoxic T cells (CTL):
Granzyme + perforin – perforin makes a pore in the cell membrane through which granzyme can enter and trigger apoptosis
Fas ligand on CD8 cell binds to Fas receptor on infected cell
When Fas has been engaged – it releases CASPASES
Both pathways upregulate CASPASES which drives apoptosis
What are the effector functions a CD4+ cell can have?
- Macrophage Activation
- B cell Activation
- Delayed Type Hypersensitivity response
- Regulation
What do macrophage activation do?
- get activated by CD4 T cells which enable them to engulf and kill pathogens better
- Activated macrophages express increased levels of CD40 and TNF-receptors
- secrete TNF-α which synergises with IFN-γ in the induction of antimicrobial effector mechanisms
- T cells and macrophages cross talk via cytokines
What is the MAIN function of delayed type hypersensitivity?
what happens if the antigen isn’t eradicated?
what happens if the antigen is not a microbe?
MAIN ROLE: defence against intracellular pathogens
If antigen isnt eradicated: you get CHRONIC STIMULATION and granuloma ( clumping of macrophages) formed
Not a microbe: delayed type hypersensitivity produces tissue injury without protection = HYPERSENSITIVITY
What are the two phases involved in Delayed Type Hypersensitivity and what causes it?
1.Sensitisation – initial exposure to the antigen
You have to be exposed to the antigen first before becoming allergic to it.
2.Effector – on 2nd exposure you can trigger a severe response
- T helper cells due to release of cytokines, these cytokines act as inflammatory mediators and also activate macrophages to secrete their mediators.
- It is independent of antibodies.
What causes immediate hypersensitivity?
Caused by mast cell degranulation
What are the five T helper cell subsets?
Th1 – macrophages activation, Delayed type hypersensitivity reaction, Help for CD8 cells and down regulation of Th2 responses Th2 – MHC class II restricted and help B cells to differentiate into antibody secreting plasma cells. B cell proliferation, B cell differentiation and immunoglobin class switch and downregulation of Th1 responses. Th17 – Protective against some bacterial infections, produce a particular set of inflammatory cytokines and mediate pathogenic responses in autoimmune diseases. Follicular T helper cells – essential for generation of isotype-switched antibodies Treg (Regulatory T cells) – some T cells may differentiate into regulatory cells in the thymus or in peripheral tissue, regulatory T cells inhibit the activation of naive and effector T cells by contact-dependant mechanisms or by secreted cytokines.
What is the main difference between T cell memory and B cell memory?
T cell memory doesn’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 naive T cells- as a memory cell they change the type of cytokine receptor they have on the cell.
What happens during T cell exhaustion?
- chronic infections, CD8 pool contracts
- cells start to exhibit PD1 (programmed cell death) which makes it harder to activate T cells
Which cells are involved in effector memory cells and central memory cells?
CCR7-CD45RA : EFFECTOR ( memory is local to the site of infection)
CCR7+CD45RA: CENTRAL ( go back to the spleen or lymph nodes - longer lasting but take longer to activate)
What is the difference/similiarities between B cells and Dendiritic cell activation?
- B cells only take up antigen that they recognise and DC take up a large variety of antigens.
- The antigen presents by both DC and B cell will 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 naive to the effector state- it will recognise the antigen-MHC complex on the B cell and activate it.
Describe the full process of T-B collaboration
Immunoglobulin (Ig)+ B cells bind specific antigen. The Ig-antigen complex is internalised, processed and antigenic peptides are presented on the B cell surface in context with MHC class II molecules. T helper cells with specific TcR recognise antigenMHC complex on the cell surface. The T-B interactions trigger expression of CD40 ligand (CD40L) on T cells. CD40 L will interact with CD 40 expressed by B cells; T cells secrete cytokines and B cells express cytokine receptors. The activated B cell will differentiate into immunoglobulin (antibody) secreting plasma cells.
