Chapter 7 b) SHM, isotypes, GC Flashcards
what are the parts of the GC
the light zone - FDC and ag-specific B cells
the dark zone - Ag specfic B cells
where does B cell activation occur
GC
describe cell movement in the GC
the dark zone and the light zone approach eavh other so that FDC carrying Ag are able to combine with Ag-specific B cells
are GC homogenous or heterogenous?
heterogenous
explain the Somatic hypermutation (SHM) process, it’s purpose, where it occurs, etc
so somatic hypermutauion / affinity selction occurs in the GC
it produces point mutauions in the Ig heavy and light chain rearragamnets
- based on these points mutations selection is done for increased affinity for Ag over time
The point mutaions are done by the presence of activation -induced cytosine demainase (AID)
- this is able to create point mutauions by replacing cysteidine with urancil, whihc is recognized as incorrect thus we try to fix this mistake and in doin so we create mutations, of whihc the one with higher affinity will be selcted for
explain the movement of B cells in the GC
in the T cell zone
- naive B cells are fully activated with T helper cells and Ig memory cells are created as well as the primary focus
TD antigen activation B cell enter the GC and proliferation and SHM occur
from here those that interact with self die by apaoptosis
cells that don’t interact with T helper cells or interact with FDC die of neglect
cells that recive co-stimulatory signals from T helper cells undergo proliferation, CSr and SHM and differentiate into memory cells or plasmablasts (these scret Ab and proliferate)
what is CSR?
class-switch recombination (CSR), is a biological mechanism that changes a B cell’s production of immunoglobulin from one type to another
what is affinity vs avidity
affinity is the stregth of one binding sight between the 1 Fab region and the antigen
- undergoes affinity maturation to increase the binding interaction
- affintiy of IgG>IgM
- only bi-valent
avidity is the total binding affinity of 1 ab
- IgM is a pentamer so it increases it’s avidity becasue there are more binding sites
- does not undergo affinty maturation
what is afiiinty maturation?
Ab affinity increases as response continues: CDRs undergo SHM
B cells with low affinity are excluded from interaction with T helper cells in GC
what are CDR’s?
Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding.
where does SHM occur?
dark zone
what is class switch recombination? whos it regulated by? what’s it do? how does it affect antigen binding? what directs it?
regulated by T cells
causes a change in the isotype produces by B cell
antigen binding specificity does not change
cytokines direct the switch
for isotypes is the light chain or heavy chain reponsible for the isotype?
the heavy chain changing is what determines the isotype
for istopes how do sub-classes exist/
sub class exist based on how the heavy chain pairs with either the kappa or lamba light chains
talk about the IgM
pentamer
Location:
blood (serum)
first Ig produced in immune response
Function:
most efficient in activating the complement system
Ag agglutination
natural antibodies
talk about IgG
location:
bloods, lymph also tissues
longest half life
Function:
four subclasses in mice and humans
precipitaion of antigen (agglutination)
- neutrlaizes toxins
- immobilizes bacteria
- neutrlaizes viruses
opsonization
ADCC
actiavtes complemnt
- only one that cross placenta
-produced in memory response
talk about IgA
dimer
Location:
secreions - dimer
in serum is a monmer
fucntion:
primary defence against local respiratory or gastro-intestinal infections
has a secretiry compoentn
talk about IgE
location:
in the serum, lowest concentration and half-life
Function:
binds with high affinity to mast cells and basophils
hypersenitivity reaction(allergy)
play a role in protection against parasites
talk about IgD
location:
serum in low amounts
secretions in upper respiratory tract
Fucntion;
co-expression with IgM on surface of B mature, naive B cells (IgD>IgM)
binds to mast cells and basophils upson Ag binding increase release of antimicrobial peptides and cytokines
Explain how IgE binds to cells
IgE binds to the Fc receptors of mast cells, with the allergen attached to the cell
this causes degranukation and the release of granule contencts such as histamine and other substances
can CSR occur outside the GC
yes
what aids in CSR?
the AID - activation induced deaminase replaces the RAG
and we need switch pitns
what should be noted about expressing IgD and IgM?
No swithc after C delta so different RNA processing making it possible to have both IgM and IgD not possible for any other isotype
this occurs in the spleen
differences between naive b cells and memory B cells
naive
IgM IgD
low complemnt recpetor
location - speleen, LN, circulation
lower averge receptor affinity
needs co-stimulation
memory
IgM IgG IgA IaE
high complemnt recptors
location - circulation
high average receptor affinity
doesn;t need t cell stimulation
