Adaptive immune system Flashcards
How long does it take for the adaptive immune system to activate?
Less than 96 hours
What are the 2 main types of cell involved in the adaptive immune system? What do they do?
B lymphocytes - secrete antibodies (immunoglobulins)
T lymphocytes - involves both CD4+ lymphocytes (helper T cells) and CD8+ lymphocytes (cytotoxic T cells)
How does the adaptive immune system recognise pathogens?
- Both B and T lymphocytes have antigen receptors
- B cells have B cell receptors (they are surface transmembrane immunoglobulins)
- T cells have T cell receptors
What is the function of B cell receptors?
B cell receptors interact with antigens
They can then be shed into the blood and tissue fluid as antibodies
Describe the structure of an antibody
- Antibody monomers have 2 heavy and 2 light polypeptide chains
- Heavy chain is roughly 50kDa
- Light chain is roughly 25kDa
- Disulphide bonds link the heavy and the light chains
How are disulphide bridges formed?
Between two adjacent cysteine amino acids
How do antibodies form and achieve high levels of variation?
- Initially, each pre-B cell has the same light chain and heavy chain genes
- There is then gene rearrangement of the V,D and J segments
- DNA is cut by recombinase RAG 1 and RAG 2 and non-selected segments are removed
- Random addition of nucleotides and base deletion is also possible
How do T cell receptors work?
T cell receptors interact with antigenic peptides presented on MHC molecules
Where does this antigenic peptide come from?
- Antigenic peptide is formed from intracellular/ extracellular antigens
- The antigens are chopped up and processed to be presented on an MHC on the cell surface.
What is the difference between MHC class 1 and MHC class 2?
- MHC class 1 is present on all nucleated cells in the body
- Presents intracellular antigens
- MHC class 2 is only found on APCs (macrophages/ dendritic cells/ B cells)
- Presents extracellular antigens
What type of T cells interact with MHC 1?
CD8+ T lymphocytes
What happens when a TCR and an MHC class 1 molecule interact?
- TCR binds to the antigenic peptide on MHC class 1
- CD8 coreceptor helps to stabilise the interaction
- This then causes T cell mediated killing of interacellularly infected cells
What happens when a TCR and an MHC class 3 molecule interact?
- TCR binds to the antigenic peptide on MHC class 2
- CD4 coreceptor helps to stabilise the interaction
- This aids the release of cytokines and helps to activate B cells
Describe the structure of a T cell receptor.
It resembles of fab fragment on a membrane bound antibody
Composed of an alpha and a beta glycoprotein chain
hat is the fab fragment?
Fraction antibody
Where does central tolerance occur? What is it used for?
In the cortex of the thymus
It is used to distinguish and eliminate auto-reactive T cells
What type of cell in the thymus does the T cell originate from?
Thymocyte
What molecules are present on the surface of this thymocyte?
- T cell receptor
- CD4 receptor
- CD8 receptor
Complete the sentence
At this point the thymocyte is described as being….
- TCR +
- CD8 +
- CD4 +
It is double positive
Describe the first stage of central tolerance
Cortical epithelial cells present self-antigen via MHC class I and II to the thymocytes
What happens if there is negative selection at this point?
If there is a high affinity interaction between the TCR and the MHC molecule, apoptosis will occur to kill that thymocyte
What happens with positive selection?
Thymocytes that show low affinity binding to MHC will survive.
What happens during the next stage of central tolerance? (this stage occurs in the cortex still)
- If the TCR on the thymocyte mostly interacts with MC class I, it becomes a CD8+ lymphocyte.
- If the TCR on the thymocyte mostly interacts with MC class II, it becomes a CD4+ lymphocyte
The thymocyte now moves into the medulla, what happens next?
Medullary epithelial cell/ dendritic cells interact with thymocytes.
What happens if there is -ve selection in the medulla?
If there is high affinity binding between teh thymocyte and the medullary epithelial cell, apoptosis of the thymocyte will occur.
What happens if there is +ve selection in the medulla?
Low affinity binding between thymocyte and medullary epithelial cell means the mature T cell can now migrate into the periphery
What are the 4 ways through which antibodies affect pathogens within the innate immune system?
1) Neutralisation
2) Opsonisation
3) Antibody dependent cell mediated cytotoxicity
4) Activation of complement
What are the two different ways through which antibodies can cause neutralisation?
- Neutralisation of pathogen entry
- Neutralisation of bacterial toxins
What happens during neutralisation of pathogen entry?
High affinity neutralising antibodies bind to the surface proteins on the virus and prevent them from binding to host cells
What happens during neutralisation of bacterial toxins?
Neutralising antibodies bind to toxins to stop them binding to cell receptors
What is meant by opsonisation?
The coating of pathogen surfaces to facilitate recognition of pathogens and aid phagocytosis.
What types of molecule are used for coating in opsonisation?
- Complement molecules
- Antibodies
How do antibodies aid opsonisation?
- Macrophges/ neutrophils possess surfave Fc receptors
- Antibodies bind to and coat the surface of the pathogen
- Fc receptors bind to the constant region at the base of the antibodies
What happens during antibody-dependent cell mediated cytotoxicity?
- Antibodies bind to antigens (non-self antigens) on the surface of the host cell
- Fc receptors on NK cells bind to the antibodies
- Cross-linking of Fc receptors signals NK cell to release perforins and kill the host cell
How do NK cells work in the innate immune system?
Work by recognising an abnormality/ absence of MHC class 1
What is the result of activating compliment?
It causes opsonisation, inflammation and formation of membrane attack complexes
How are cytotoxic T cells activated?
They must be activated in lymphoid tissues via MHC class 1 and TCR activations
Cytotoxic T cells then migrate to the infected site
What are the two mechanisms cytotoxic T cells use to destroy infected cells?
1) Perforin/ granzyme killing
2) FAS mediated killing
(lead to death by apoptosis) `
What is the role of a helper T cell?
How does it do this?
- Main role is to activate other cells
- Release cytokines involves in increased antibody production, increased activity of phagocytes and NK cells, increased antigen presentation
What other type of cytokines can CD4 lymphocytes produce?
Anti-inflammatory cytokines
How does the adaptive immune system initially respond to pathogens?
What happens at the end of this immune response?
1) - T and B cells divide
- Cytokine IL 2 is released, IL 2 is expressed
- IL 2 drives cell proliferation
2) A vast majority of T and B cells die but some retain as memory cells, memory B cells and plasma cells (continually secrete antibodies)
What are plasma cells and where are they formed?
- Plasma cells are a differentiated form of B cell
- Found in the medullary cords of lymph nodes, bone marrow and MALT
Where do memory T and B cells reside?
- Some reside in particular tissues
- Some are continually circulating in the blood
What is the benefit of a memory immune response?
- It allows the secondary exposure to be;
1) Faster (easier to activate memory cells)
2) Larger (more antibodies)
3) More efficient (high affinity BCRs + TCRs)
4) More effective (different antibody sub-classes)
