L4 - Adaptive Immune System 1 Flashcards
RECOGNITION OF LYMPHOCYTE SUBSETS
i) how can lymphocyte subtypes be recognised?
ii) which protein do all B cells apart from plasma cells express?
iii) which protein do all T cells express?
iv) which protein do cytotoxic T cells express? which proteins do T helper cells express?
v) what are all lymphocytes derived from? what are the three fates?
i) by proteins on their cell surface
ii) B cells express CD-19
iii) all T cells express CD-3
iv) cytotoxic T cells express CD8
- T helper express CD4
v) all lymphocytes are derived from lymphoid progenitors
- 3 fates = B cell, T cell, NK cell
B AND T CELL DEVELOPMENT
i) which cells guide development of both B and T cells?
ii) cells in which specific location aid development of B cells?
iii) how is development of T cells organised? which organ does this happen in?
iv) how do both cells undergo cell death?
v) why do adults have a lower capacity to produce T cells after puberty? give three ways that they continue to be produced?
vi) how are diverse repertoires of receptors developed on both cells?
i) stromal cells
ii) stromal cells in the bone marrow
iii) T cell development takes place in specific compartments
- happens in the the cortex/medulla of the thymus
iv) cell death by apoptosis
v) the thymus involves after puberty (site of produc) therefore less T cells are produced
- thymus still has some residual corticomedullary tissue
- new T cells can be gen at extra thymic sites eg liver/intestine
- long lived peripheral T cell pool
vi) diverse receptors produced via gene rearrangement
STAGES OF LYMPHOCYTE DEVELOPMENT - B CELLS
i) what is the life span of a naiive B cell?
ii) what do all B cells originate from?
iii) which two gene segments then undergo rearrangement to make a pro B cell?
iv) which receptor does a small pre B cell express?
v) what happens to an immature B cell that is positively selected? what happens if it is negatively selected?
vi) which two Igs may a mature B cell express?
i) 5 days
ii) common lymphoid precursor
iii) rearrangement of D and J gene segments to make a pro B cell
iv) small pre B cell expresses B cell receptor on cell
v) immature B cell pos selec > blood
neg selec > death
vi) mature B cell = IgD and IgM
STAGES OF DEVELOPMENT - T CELLS
i) which organ do precursors migrate to?
ii) what does double negative mean? how many stages of double negative differentiation are there?
iii) what receptor does a DN4 cell express?
iv) what do the cells express in the immature single positive phase? what do they express in the double positive phase?
v) what happens if the cell is positively selected? what if it is negatively selected?
i) migrate to the thymus
ii) double negative = dont express either CD4 or CD8
- four stages of DN differentiation
iii) DN4 expresses a pre T cell receptpr
iv) immature single positive phase > express pre TCR and CD8
- double positive phase > TCR, Cd4, CD8
v) pos selection > released as Cd4 or Cd8 T cell (and alpha beta T cell receptor)
neg selection > cell death
COMMON STAGES OF B AND T CELL DEVELOPMENT
i) what is generated in the first phase? rearrangement of which gene sections aids this?
ii) what is refined in the second phase? which cells are positively selected here? which cells are negatively selected?
iii) what are cells stimulated by in the third phase? what does this result in? what does this lead to?
iv) where does the third phase take place?
i) generation of antigen receptor through rearrangement of V and J gene segments
ii) refinement of antigen receptor repertoire
- challenge receptor with self cells
- positive selec > those that recognise self antigen
- negative selec > those that bind self antigen too strongly
iii) stimulate cells with foreign antigen > results in clonal selec
- clonal selection of lymphocytes results in generation of effector and memory lymphocytes
iv) third phase takes place in secondary lymphoid tissues eg liver or spleen
B CELL ANTIGENS
i) do they need T cells to produce a response?
ii) what do thymus dependent antigens depend on for antigen production? what are most of these antigens?
iii) do thymus dependent antigens cross link spontaneously on B cell surface? why?
iv) name three thymus independent antigens? what do these have on their surface? what does this allow?
i) some do but some dont (most do)
ii) thymus dep depend on T cells to induce antibody production
- most of these are proteins
iii) thymus dep do not cross link on B cell surface as they dont contain repeating motifs
iv) polysaccarides, lipids and nuc acids are all thymus indep antigens > have repeating motifs on surface so allow B cell receptor to be spontaneously cross linked
T CELL INDEPENDENT RESPONSES
i) name two characteristics of this response? what type of antigens does it utilise?
ii) what immunoglobulin predominates in these responses? does the cell have ability to class switch?
iii) what are B cells activated by? what do they also require in addition to this? what can this happen via?
iv) which Ig do naiive B cells express on their surface? (2) what Igs do they secrete once activated by a T indepedent antigen?
i) short lived and no memory > utilises simple repetitive antigen
ii) IgM is secreted by activated B cell - cant class switch as need T cell help for this
iii) B cells activated by direct B cell receptor cross linking
- also require a second activation signal which can be via TLR
iv) naiive B cells have IgM and IgD on surface
- secrete IgM once activated
ANTIGEN RECOGNITION BY B VS T CELLS
i) what does the BCR consist of? (2) are these membrane bound/secreted/both?
ii) what does the TCR consist of? are these membrane bound/secreted/both?
iii) association with which signalling complex in the membrane allows signalling of a) B cells (2), b) T cells?
iv) what type of antigen do B cells bind? what type of antigen do T cells bind?
v) how many signals does B and T cells need for activation?
i) BCR = 2 heavy and 2 light chains
- both membrane bound and secreted
ii) TCR = alpha and beta heterodimer
- only membrane bound
iii) B cells - association with IgA and IgB (B cell co-R complex)
T cells - assoc with CD3 complex
iv) B cells bind intact antigen in solution
T cells bind processed antigen on an antigen presenting cell on either MHC I or MHC II
v) B cells = 2 signals
T cells = 3 signals
B CELL T CELL INTERACTIONS
i) what has evolved to allow interaction with eachother? what is found on the B cell and the T cell - give two examples?
ii) response to which type of antigens requires both B and T cell interaction? what is the nature of this contact?
iii) what do the B and T cell recognise - in relation to antigen
iv) where does signal 1 come from? where does signal 2 come from?
i) reciprocal receptor expression
- B cell CD40 and T cell CD40 ligand
- B cell CD80/86 and T cell CD28
ii) response to proteins/peptides (complex antigens)
- needs direct B and T cell contact
iii) B and T cells recognise the same antigen but different epitopes on it
iv) signal one from antigen receptor and signal two from co-timulatory signal eg from TLR
T DEPENDENT B CELL RESPONSE
i) what provides the first signal?
ii) where does the antigen then move to? what is it then displayed on?
iii) which type of T cell recognises an antigen MHC complex? which receptor is this via? what does this provide to the T cell
iv) binding of which two elements then provides signal 2 to the T cell? what does this result in? what is upregulated?
v) what do T cells increase production of? what effect does this have on the B cell?
i) antigen binding to BCR provides first signal (signal 1)
ii) antigen then internalised into cell and processed in lysosome > displayed on MHC molecule
iii) T helper (CD4) recognises antigen MHC complex via the T cell receptor > provides signal 1
iv) binding of CD80/CD86 on B cell to CD28 on T cell provides signal 2 to T cell > results in T cell activation and upregulation
of CD40 ligand = signal 2 to B cell
v) T cells increase production of cytokines which activate the B cell = signal 3
B CELL ACTIVATION BY T CELLS
i) activated T cells increase the production of what molecule? what effect does this have on B cells? what signal does this provide?
ii) by what mechanism does the B cell then differentiate? what is the purpose of this?
iii) what are the two fates of a B cell after proliferation and differentiation?
i) activated T cells increase production of cytokines
- cytokines help to activate the B cell > signal 3
ii) B cells differentiate via somatic hypermutation
- to improve affinity of B cell receptor for antigens
iii) B cells > antibody secreting B cell (plasma cell)
or memory B cell
PRIMARY AND SECONDARY ANTIBODY RESPONSES
i) what is the main aim of the adaptive immune system?
ii) what does immunological memory allow?
iii) what % of the population need to be vaccinated/infected and recovered to provide herd immunity?
iv) what is the antibody predominantly secreted in primary response? which Ig does this change to in secondary response?
i) respond in a specific way to lots of antigens
ii) immuno memory allows host to react quickly and effectively to an antigen
iii) 60% of pop need vacc/infec for herd immunity
iv) IgM predom in primary response and IgG predom in secondary response
SUMMARY
i) name three things that T independent antigens may contain?
ii) what happens to the B cell receptor as first signal for activation by T indep antigens? what is also required for full activation?
iii) what structure are T dependent antigens? how many signals does this type of activation require? name each one
i) polysacc, lipid, nucleic acid (simple repeating epitopes)
ii) B cell receptor cross links
- requires second co-stim signal from TLR
iii) T dep antigens are usually proteins/peptides and req 3 sigs
- 1) B cell R engagement
2) binding of CD40 (B cell) and CD40 L (T cell)
3) cytokine stimulation of B cells by T cells
