4. adaptive immune system 1 Flashcards
features of the innate response
rapid
pattern recognition receptors are germline encoded
increased cytokines, costimualtory molecules - instructive role for adaptive
direct response for host defences (phagocytosis, antimicrobial activity)
features of the adaptive response
slow
recognition - initially low affinity receptors
influence from innate system - gene rearrangement, clonal expansion
response: T and B cells with receptors
has memory
B and T cell development environments
specialised microenvirnoments
B cell - bone marrow, until terminal differentiation
t cell - thymus
what happens to T cells after puberty?
thymus atrophies - only some residual thymocytes
new t cells generated extrathymic sites
long-lived peripheral t cell pool
how and b and t cell developments guided?
stromal cells
t cells - compartmentalised, distinct types cortex and medulla
b cells - in bone marrow
both involve apoptosis
lymphocyte differentiation
b cell - lymphoid stem cell - pro-B lymphocyte - pre-B lymphocyte early B lymphocyte activated B cell or plasma cell
t cell - lymphoid stem cell - early thymocyte - common thymocyte Th lymphocyte or Tc lymphocyte
1st phase development
generation of antigen receptor
V(D)J gene rearrangement = antigen receptor
2nd phase development
refinement of antigen receptor repertoire
antigen receptor tested for antigen recognition
positive and negative selection
occurs in primary lymphoid organs
what happens during positive selection?
antigen receptor that recognises ‘self’ antigen weakly
what happens during negative selection?
antigen receptor that binds strongly to ‘self’ antigens is eliminated via apoptosis
3rd phase development
stimulation by foreign antigen
clonal selection of lymphocytes
generation of effector and memory lymphocytes
occurs in secondary lymphoid organs
thymus dependent antigens
b cells are dependent on helper t cells to induce antibody production
eg proteins
thymus independent antigens
cells do not need t helper cells to induce antibody production
eg polysaccharides, lipids
t cell independent responses
simple repetitive antigens (often carbs)
mostly IgM (+IgD on naïve B cells)
modest affinity
b cells activated by direct b cell receptor cross linking
also can be activated by toll like receptors
t cell/b cell collaboration
required for antibody response to complex antigens
requires direct b-t cell interaction
involves multiple surface receptors on t and b cells
both cells must recognise antigen
both need signal 1 and signal 2
t cell dependent b cell response
antigen binds to b cell receptor = signal 1 to b cell
antigen is internalised, processed and antigenic peptides displayed on MHC
t helper cell recognises antigen-MHC complex via t cell receptor = signal 1 to t cell
cd80/cd86 on b cell binds to cd28 on t cell = signal 2 to t cell
t cell activation leads to up regulation of cd40 ligand
cd40l binds to cd40 on b cell = signal 2 to b cell
cytokine production by t cell helps activate b cell
b cell proliferates and differentiates into antibody secreting b cell (plasma cell)
b cell antigen recognition
form antigen receptor by V(D)J recombination - 2 heavy chains, 2 light chains (membrane and secreted) signal by associating with signalling complex in membrane = Ig-alpha and Ig-beta
can bind to intact protein antigen in solution
t cell antigen recognition
form antigen receptor by V(D)J recombination - alpha-beta heterodimer (membrane only)
signal by associating with signalling complex in the membrane = CD3 complex
binds peptides displayed on surface of antigen presenting cell