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phase 1 b cell dev
developing bc acwuire funcitonal bcr thru ordered arrangement of ig genes
phase 2 b cell dev
b cells whse ig receptor binds to self are elimnatede - neg sel
phase 3 - b cell dev
remaining b cells w functional receptor leave bone marrow and move into secondary lymphoid tiss - pos selection
phase 4 - b cell dev
search for infection — non self specific antigen
phase 5 b cell
contact w antigen, ativation nad clonal expansion
phase 6 - b cell dev
attack infection by diff into antibody secreting plasma cells, and memory b cells
how many epitopes does a b cell respond to
one
clonal selection theory
multiple lymph w diff speciaitlies - clonal deletion (deleltion of self reactive clones) - clonal selection - clonal expansion (prolif)
forms of ig that bind to infectious agent
surface and secreted
surface ig
emedded in b cell mem, acts as antigen receptor
secreted ig
secreted by activated plasma b cells -antibodies
ig structure
2 identical heavy chains and 2 identical light chians with constaint and vairbale regions
fc vs fab region
fc at stalk of y — composed of only constant, and top of y is fab w constant and avriable region
hinge in antibody allows
flexibiliy and non-rigidity - look for epitopes via moving and floating
ig variable region - heavy chain encoded by
variable, diversity and joining
ig variable region - light chain encoded by
variabel adn joining region
other methods of diveristy in ig
random deletions and insertions in joinig of heavy and light chain - junctional diversity
what determines class of ig
heavy chain constant region gene segment
effector funciton of antibody derived from
constant (fc) region
igm
first made, naive b cells - pentamter linked by j chain, activate complement and neutralise pathogen
igg
cross placenta (fc), activate complement, small enough to diff into tissue, major ig
iga
dimer by j chain, prominent in mucosal secretions to protect in airways, gut, bm
ige
respond to parasites via degran (fc) mediate allergic reactions
igd
expressed on naive b cells - not usually secreted
effector func of antibodies
precpitation, complement fixation, agglunation, opsonisation, neutralisation
fab
neutralise path/toxins (igg, igg), musocosal immun. (iga)
fc - opsonisation
igg - fc region binds to fc receptor on phag
fc - classical pathway
igm, igg, triggers cascade
fc - antibody mediated cell cytotoxicity
igg - ofnk cells
t cell dev - step 1
hematoopooiietic stem cells in bone marrow migrate to thymys
t cell dev - step 2
t cells undergo thymic education in the thymys
t cell dev - step 3
mature naive t cells translocate to peripheral lymphoid tissue
t cell dev - step 4
actiavted, naive t cells become effector t cells that can mount immune responses
t cell education - pos selection
if the tcr has no capacity to bind self mhc molecules, t cell dies
t cell education - neg selection
if tcr binds host mhc/peptide complexes present in thymus too tighly, t cell dies (remove autoreactive)
chains t cell receptor
heterodimer of alpha and beta chain
tcr alpha domain gene segements
v,j - one c
tcr beta domain gene segments
v, d, j - one c
what do tcr recognise
protein antigens that have been degraded or processed into short peptidse - requires proteolysis
mhc class i cellls
almost all nucleated - recog by cd8
mhc class ii cells
only expressed on macrophages, b cells and dc (apcs) - reocg by cd4
mhc i presentation
peptdes largely derived from endogenous, peptides via proteolysis in cyto, enter er via tap load into mhc1 in lumen of er, go to surface
mhc ii presentation
peptides derived from exogenous, via endosomal network, to endosome, fuse and release contents in mhc-ii enriched compartment, where meets mhc ii from er, and travels to surface
dc activation leads to
increased surface expression of mhci/ii, secretion of cytokines, and expression of costim
activation of dc in secondary lymph
dc pick up antigen and move to draining lymph vessel, settle in t cell area in lymph node
activated dc to naive t cells- signal one
display pathogen peptides on MHC
actiavted dc to naive t cells - signal two
express co stim (cd80, cd86)
activated dc to naive t cells - signal three
secrete selected cytokines