B AND T CELLS
i) which arm of the immune system are they important in
ii) what is expressed by B cells and T cells that can be identified by immunophenotyping? what two further things can be expressed on T cells
iii) where are both cells created? whaere does each mature?
iv) what is positive and negative selection?
ii) B cells express CD19 and CD20
T cells express CD3 and either CD4 or CD8
iii) both cells created in the bone marrow
B cells mature in BM but T cells migrate to the thymus
iv) pos selection identifies cells that can bind antighen ( T cells that bind MHC bound peptide)
neg selection inolves binding of self antigen to B or T cell receptor and then deletion by apoptosis
GENERATING AN IMMUNE RESPONSE
i) what do B cells recognise? give an example
ii) what do T cells recognise? what must they be presented on? what do CD4 and CD8 recognise?
iii) what type of binding do B cells take up antigen through? what then happens to the receptor?
i) B cells recognise native antigen eg micro-organisms
ii) T cells need antigen to be processed into peptides and presented on MHC molecules
CD4 > MHCII
CD8 > MHC I
iii) B cells take up antigen through specific binding to the B cell receptor
- then the bound receptor is internalised through endocytosis
ANTIGEN UPTAKE IN CELLS
i) what happens to the antigen bound receptor once it is internalised to a B cell? what do they bind? what does this cause?
ii) which MHC are molecules complexed with? what cells will recognise this? once recognised what does this lead to?
i) internalised > bind to lysosyme to create an acidic environement > proteodegradation
ii) peptides complexed with MHC II to be recog by CD4 T cells
- recog by CD4 will cause full activation of both the presenting B cell and T cell
T CELL HELP
i) what do most B cells need when they recognise antigen to generate an immune response?
ii) name an antigen that can trigger B cell receptor cross linking and production of antibodies? which type of antibody usually is it? what is this known as?
iii) what do T dependent responses require? what second signal is required for activation?
i) need T cell help
ii) bacterial polysaccharides can cross link BCR > antibodies
- usually non class switched IgM
- known as T independent response
iii) T dependent response requires antigen presentation in the context of MHC and T cell receptor recognition
- second signal > binding of CD40L to CD40 on B cells
i) what does CD40L on T cells bind on B cells?
ii) name two other co-stim molecule binding on B and T cells? what does this provide
iii) what provides the third activation signal to B cells? which cell is this secreted from?
iv) what does antigenic challenge of the adpative immune system result in? what type of response does this allow on repeat exposure?
i) CD40L binds CD40 on B cells
ii) B cells CD80/86 to T cell CD28 > second signal for activation
iii) third activation signal is when T cells secrete cytokines eg IL-4
iv) antigenic challenge < immunological memory
- repeat exposure = faster and more effective response
GENERATING IMMUNE CELL DIVERSITY
i) what is the primary mechanism for generating diversity? which two cell types does this occur in?
ii) what are the key enzymes that regulate this process (2)
iii) what does somatic hypermutation allow? what is this critical enzyme involved? what type of mutations are introduced
iv) what is the last step in a B cells response to antigen?
i) primary mech is VDJ recombination
- genetic recomb of variable region with a diveristy and joining region
- occurs in B cells (Ig gene) and T cells ( TCR genes)
ii) VDJ recomb is regulated by RAG1 and RAG2
iii) somatic hypermut allows further refinement of the B cell receptor recognition of antigen
- critical enzyme is activation induced cytidine deaminase (AID)
- involves introduction of point mutations into the rearranged VDJ gene segments encoding the variable region
iv) last step in B cell response to antigen is antibody class switching
ANTIBODY CLASS SWITCH
i) does it affect the affinity of the B cell receptor for antigen?
ii) what does it replace? what does this allow?
iii) what is the process of class switching mediated by? (2)
iv) which two isotype of Ig do naive B cells express? are these Ig's produced by class switch recomb?
v) what process are IgM and IgD produced by? what is this due to?
ii) replaces the constant region of the antibody so that it can interact with different effector molecules
iii) mediated by DNA breakage and recombination
iv) naive B cells express IgM and IgD - not prod by class switch because they havent encountered antigen yet
v) IgM and IgD are produced by alternative mRNA splicing due to clos proximity of the mu and delta constant regions in the Ig gene structure
i) what are the two alternative pathways for antigen processing?
ii) how are exogenous antigens taken into cells? what then happens to them? which MHC are they coupled to? which T cells recognise them
iii) where are endogenous antigens broken down in the cell? which proteins allow their transport to the ER?
iv) which MHC are endogenous antigens complexed to? which organelle does this happen in? which T cells recognise these when presented on cell surface?
i) endogenous and exogenous
ii) exogenous are taken into cells by endocytosis and broken down into peptides in the phagolysosome
- couplied to MHC II > cell surface for recog by CD4 T cells
iii) endogenous antigens broken down in the proteosome
- then transported via TAP proteins to the ER
iv) complexed with MHC I > recog by CD8 cells