L5 - Adaptive Immunity (sensing Microorganisms) Flashcards
What recognises antigens?
B and T cells
Define antigen, epitope, paratope
- Molecule that is recognised by adaptive immune cells, will bind either a T cell receptor or antibody (B cell receptor)
- Precise part of the antigen recognised by the T or B cell receptor (antigen can have multiple of these)
- Part of the antibody or T cell receptor that binds epitope
What are the cells of the adaptive immune system and what are their functions
- B cells make antibodies
- Helper T cells communicate
- cytotoxic T cells - identify and kioll infected cells or tumour cells
- regulatory T cells - turning off immune response
What are antigen presenting cells (APC)
Macrophage or DC
What is the difference between T and B cells antigen recognition
T cells only recognised Ag presented to them by APC
B cells recognise antigen on its own
Outline key points regarding T cell antigen receptor and B cell antigen receptor
T cell antigen receptor = TCR
- only membrane bound
B cell antigen receptor
- both membrane bound and secreted
- immunoglobulin = membrane form
- B cell secrete receptors = antibodies
- membrane formed called BCR or surface Immunoglobulin
What do TCR and BCR recognise?
- T cells recognise protein only (linear peptide sequences)
- antigen presenting cell breaks down antigen into short peptide sequences so they can be presented to t cells
- can work out permutations = enough diversity to distinguish any microbe using 8-25 aa sequence
- B cells organise anything organic → shape rather than linear sequences
- can recognise discontinuous episose
- they have to bind directly to bacteria
Describe the difference between discontinuous and linear epitope
- antibody binds to surface of molecule
- linear epitope = entire epitope is ina continuous chain (chop up = still will recognise
- discontinuous = 2 loops coming together the in between bit of a loop is internal so antibody cant see it. what the antibody binds to is the bits of the loop, denature → become linear → epitope will be destroyed
Describe the structure of an antibody
- antigen binding region is the 2 arms
- binds through charge/hydrophobicity
- both sites are identical ( can bind 2 identical epitope at teh same time
- heavy chain and light chain held by disulphide bonds
How many chains does TCR have? How many binding sites does it have compared to antibodies
2 chains, 1 binding site compared to Ab
How do you create an almost infinite range of different antigen receptors?
- antigen binding site are very variable, the rest is constant
- both heavy and light is needed to bind → creates variability by combining different v G C segments
- light chain = TCR alpha chain
- heaby = TCR beta chain
How is somatic recombination used to induce variability in antigen receptors
Antigen binding domains are modular. VDJ recombinase allows choice of gene segments by recombination. Allows us to make lots of diff combinations from the few different genes
Where are the recomb signal sequences, what do they do, is the change in DNA permanent?
- recombination signal sequences at either end
- detects where to join the diff segments together
- permanent and irreverible change in the DNA, can only generate antigen receptor once →important because we dont want the specificity of your B/T cells to change
- antigen part of antibody is spliced onto constant region that gives function on the rna level
How is further diversity created using junctional diversity
- Joining of v d and J not always precise (sometimes slips a few bases and changes AA sequence)
- Deletion of bases - P nucleoptide edition means 2 diff segments are joined tight which creates a hairpin that is knicked
- Sequence aligns
- Fill in the gaps - random addition of other nucleotides (N nucleotides) → done by terminal deoxyribose nucleotidal transferase, tru and match 2 ends up, once a complementary somewhere you fill in the gap
Name = complementary determining regions
Describe the productive vs non productive rearrangements
Majority of rearrnagemt will not result in functional protein
- only those that create functional protein will survive, the others die via apoptosis
2x chromosome so 2 sets of VDJ genes so 2x chances to make a productive rearrangement for each chain
Each B cell is specific for one Ag so only one Ab allowed per cell. Successfully arranged chain will block gene rearrangement on the other chromosome (allelic exclusion)
Talking numbers: roughly how many B cells and T cells in body and how many able to respond to any one antigen
3 billion B
300 billion T
Only 30 B cells in human able to respond to any one antigen
Describe colonial expansion, also what cytokine drives this?
- T/B cell sees its Ag and becomes activated and divides
- all daughter cells have identical Ag specificity
- time taken is what makes the adaptive response slow
- IL-2 (cytokine)
How do microbes evade the immune system?
Through antigenic variation
- chnages (even few bases) in the antigen means the T or B cells will not longer recognsie
- new invasion strategy as only small molecule changes will render T or B not abl to recognise
- antigenic shift → takes up gene from animal so theres a drastic change whcib removes memory response
What is adaptive immunity’s Achilles heel?
T and B cells can’t tell what they are recognising (pollen, food, dust, our own cells)
What is central tolerance? Where are these cells removed?
Mechanism by which T and B Cells capable of recognising self antigens are deleted before they are released systemically to fight infections
Self reactive T cells are removed in thymus
Self reactive B cells are removed in bone marrow
