15: B cell activation and Ab 2 Flashcards
how are u heavy chain made
alternative processing of primary RNA Tc for mRNA
what are the two forms of u heavy chain
membrane and secreted form
what for of u protein is made by activated B cells ag dependent
secreted form
what makes membrane u mRNA
resting B cells
what are TP, TM, and Cy for u mRNA
tail piece, transmembrane and cytoplasmic segments
exons of Cu gene
Cu1, Cu2, Cu3, Cu4
how many CH regions of IgG, A, D
3
how many CH regions for IgE and IgM
4
what causes class switching
Heavy chain switching in TD response
what are the different classes of heavy chains
y,a and E
where does isotype switching usually occur and what causes it
GC and is driven by TFH cells
isotype switching that might occur in extrafollicular foci
driven by Th cells
what part of heavy chain leads to class switching
constant regions
what determines Ab specificity
variable regions
what doesn’t change in isotype switching
Abs specificity because determine by variable and not constant regions
what does the ability of B cells to produce many Abs cause
plasticity in humoral immune response
why need various classes of Abs
distinct effector fxns and defense against all different types of pathogens
what causes class switching
B cells activated by TFH cells with CD40L and cytokine signals
IgM fxn
complement activation
IgG is for
opsonization, phagocytosis, complement, neonatal immunity
of does IgG do neonatal immunity
placental transfer
IgE fxn
helminths, mast cell degradatioin
what does mast cell degranulation cause by IgE
immediate hypersensitivity
what works with IgE
IgG4
what cytokine activates IgE and IgG4
IL4
what is IgA for
mucosal immunity
what activates IgA
TGF-B, April, BAFF
how are TH1 cells related to Class switching
when activated, produces IFNy that induces TFH to produce more IFNy that causes IgG
how does TH2 cause class switching
IL-4 causes IgE class switching
what Ig is used for intracellular pathogens
IgG Abs
what does IgG do
block entry microbes, activate complement and cause phagocytosis by macrophages
what does IgE do for helminths elimination
eosinophil and mast cell activation
what controls class switching
location of B cells and controlled by local cytokines
mucosal B cells cause
IgA
what cytokines induce IgA
TGF-B and BAFF
where does TGF-B come from
T reg, macrophages
BAFF is produced from
DCs and Macrophages
what family does BAFF belong to
TNF
how does CD 40 contribute to isotype switching
works with cytokines
what is the enzyme used for isotype switching and affinity maturation
activation-inducing deaminase (AID)
what induces AID
CD40 engagement
what happens when CD40 is deficient
Ag is dominated by IgM for limited switching
what change in IgM mRNA for IgG1
loop out deletion of Cu, C delta and Cy3 for only Cy1
what controls how Ig mRNA gets rearranged
switching sequence before C genes
where does class switching recombination occur and how
activated B cells by changing Cu gene to CH genes
what does CSR precede
Germline Tcs
what initiates Germline Tc
intronic promoters
how do germline Tc work
open chromatin of S region to make more accessible to recombinase
how does CSR make a looped-out deletion
goes between two switch regions with repetitive sequences for loop
what regulates CSR
cytokines
how do all immunoglobin isotypes relate
similar Ag specificity with different biological properties
how does AID work
deaminates cytosines in ssDNA to convert C to U
what happens after AID creates U
Uracil N Glycosylase removes U for apurinic/ apyrimidinic endonuclease (APE1) to create nicks
what does the nick by APE1 lead to
ds breaks
what does affinity maturation cause
increased affinity of Abs for Ag
where is the only place that affinity maturation occurs
TD Ags
what causes mutation of IgV genes
TFH with CD40/CD40L interactions
GC reaction needed because
make B cells with high affinity Ag receptors to produce Abs with highest affinity for Ag
B cells survive by
high affinity Ig that binds FDC presenting Ags
how much is affinity increased by changing an AA
10 fold
how does Ig V gene get mutated
point mutations at high rate
how many pt mutations of IgV genes
1 in 10^3
how much higher is mutation rate for V genes than others
1000x higher
how many VH and VL genes are in each B cell
700
how many mutations in V region
one per cell division
due to B cell clones having V mutations, how different are IgGs from each other
5% germline for 10aa substitiution
where do most V mutations occur and why
V regions at Ag binding region to increase affinity
which Ig has more mutations
IgG
what does a B cell to APC FDC result in
rescue B cells from apoptosis
B cells to TFH result in
B cell survival for CD 40 dependent
why is GC a B cell graveyard
somatic mutation produce B cells without high affinity as well for apoptosis
where do B cells go after somatic mutation
FDC light zone
how does Ag recognition lead to B cell survival
induces expression of BCl-2
how is B cell survival promoted when when B cell binds Ag
once presents Ag for TFH and bind CD40L, signals survival
what do B cells inhibit to promote life
activate endogenous inhibitors of Fas by BCR to Ag recognition
where does FasL come form and what does it induce
TFH expresses FasL and it causes apoptosis
how do B lymphomas develop
B cells in germinal centers
what causes B lymphomas
chromosomal translocation of various oncogenes in Ig gene
what causes the incorporation of oncogenes into Ig genes
DNA breaks by hypermutation and isotype switching
what diseases do GC contribute to
autoimmunity and B cell lymphomas
why are GC centers related to Autoimmunity
Somatic mutations may produce self-reactive B cell clones
what are plasma cells for
Ab production
what activates plasma cells
signals from BCR, CD40, TLR and other cytokine receptors
what makes Short lived plasma cells
extrafollicular compartment in TI response as well as early TD response by extrafollicular B cell foci
where are short lived plasma cells found
secondary lymphoid organs and peripheral of non-lymphoid tissue
when are Long lived plasma cells made
TD response to proteins Ags in Germinal centers
what makes Long lived plasma cells
BCR and IL21
what is the precursor of long lived plasma cells
plasmablasts
how do plasmablast become long lived plasma cells
generated in GC then home to bone marrow for long lived plasma
how do immunizations work
use a T cell dependent Ag so that 2 to 3 weeks later, Bone marrow produces many Abs
what maintains plasma cells and ow
BAFF
how long can plasma cells secrete Abs
months or years after Ag is no longer present
what do Abs provide to body
immediate protection if Ags encountered later
how many Abs in blood are made from long lived plasma cells
50%
can memory cells become plasma cells
yes
pathways of B cells
pre B to Naive to MZ or follicular B
