adaptive immunity L5 Flashcards
antigens
proteins found on surface of cells
have self or non self - pathogens or innocuous which are non harmful found on food etc
recognised by T and B cells
NOT THE SAME AS PAMPS
EPITOPE
precise part of antigen that is recognised by T/B cell receptor, an antigen can have multiple epitopes so many different sites for B or T cells to respond
PARATOPE
part of antibody or T cell receptor that binds to the epitope
BCR structure
2 heavy and 2 light chains, Fab region - variable region - VDJ recombo
Fc - constant region, determines effector functions
2 antigen binding sites
membrane bound to b cell or secreted as antibody/Ig
can recognise linear or discontinuous epitopes
TCR
Alpha (VJ) and beta (VDJ) chains, only one binding site and no Fc region
only membrane bound form, so no Fc region
can only recognise linear epitopes and those presented by MHC and APC cells
linear epitopes
these are where the protein has been broken down and epitome is linear due to being presented by APC after phagocytosis, non native form
discontinuous or conformational epitopes
these are the 3d native proteins
T cell receptor only one because…..
only use receptor for recognition unlike B cells as they have effector roles
how to create almost infinite range of different antigen receptors?
creating variability through recombination of different segments in the antigen binding area - these are modular to allow for variability - uses VDJ recombinase
VDJ somatic recombination
this is on chromosome 14
heavy chain or beta - VDJ - starts first
light chain or alpha - VJ - second
V1 V2 V3
D1 D2
J1 J2
CM CD - constant regions always there - RNA splicing to join VDJ to constant region
junctional diversity
after random rearrangement of VDJ genes, increase diversity even further due to the imprecise joining other V D J segments
- addition of bases via TdT
deletion of based by exonuclease
sequences misaligments/frame shifts
gap filling
allelic exclusion
in one B cell, 2 sets of chromosome 14 so 2 chances to produce a production/functional protein for receptor.
each B cell is specific for one Ag, so only one type of Ab is allowed per B cell, so once one has successfully been rearranged, block the gene rearrangement on the other chromosome to stop process
clonal expansion
this is necessary to increase the T/B cell population for response
- only once T/B cell detects specific antigen and then activates, dividing by mitosis so identical Ag specific
IL-2 cytokine drives T cell clonal expansion
immune evasion via antigen variation
this is where antigen changes so the T/B cells are no longer specific for it, and evades immune response
antigenic drift - small gradual mutations that cause the reinfection to have reduce immunity as slightly different
antigen shift - sudden change/mutation, new strain
influenza evasion example
surface proteins HA and NA
antigen drift - reinfection in epidemics
antigenic shift - severe pandemics
trypanosome and malaria antigenic varaiton
switch between multiple versions of surface proteins
HIV evasion. antigenic variation
high mutation rate so prevents immune effective and difficult for vaccines - occurs in host
central tolerance
T/B cells that recognise self-antigens need to be destroyed, done in thymus or bone marrow. This sometimes misses some, and it doesnt get rid of innocuous ones so allergies can develop
advantages of adaptive
very adaptable and highly diverse due to somatic recombination of VDJ segments and junctional diversity
highly specific
has immune memory
disadvantages
slow and requires time to activate and clonal expand
high speciality means it is easy for microbe to evade reocngitons
receptors cannot tell between pathogens and food antigens
phases of adaptive immune response
day 0-7 - antigen recognitions naive T and B activated as detecting antigen, clonal expansion and differentiation - lymphocyte activation
day 7-14 - antigen elimination via humeral or cell-mediated immunity
day14 + contraction and apoptosis of cells, some remain and these are memory cells