4. B cells Flashcards
three basic principles of adaptive immunity
- diverse repertoire of receptors for antigens
- clonal expansion of the complementary type
- memory cells for faster secondary response
TCR vs BCR
alpha/beta or gamma/delta vs heavy and light chain
membrane bound only vs membrane or free antibody
antigen presented peptide recognition vs whole molecule antigen recognition
BCRs can also be different isotypes
what is initial generation of diversity
Gene rearrangement and heterodimer formation. Occurs in bone marrow for B cells or the thymus for t cells - naive cells.
heterodimer formation
the mixing of alpha, beta, gamma and delta chains or heavy and light chains
Fv region
variable region
two binding sites
determines antigen specificity
Fc region
constant region determines the class and function of antibody
gene rearrangement
different combinations of variable, diversity and joining genetic regions form the complementarity determining regions
which enzymes complete gene rearrangement
RAG1/2 (recombination activating genes)
light chain gene rearrangements
VJ and C only either kappa (two thirds) or lambda (one third)
heavy chain gene rearrangements
VDJ and C
beta
mathematics of gene rearrangement
61 HCV regions x 26 HCD regions x 6 HCJ regions x 40 LCV regions x 7 LCJ regions = 4.9x10^6 (but in reality there are more than 5 million)
Junction region diversity
the region where the different segments join together creates more diversity
nucleotides can be accidentally removed or deliberately inserted by TdT (terminal deoxynucleatidyl transferases)
TCR gene rearrangement
VDJ - beta, delta
VJ - alpha, gamma
B cell development
- BCR
- whole antigen recognition
- differentiation into plasma cells that secrete antibodies
- antibody binding to antigen
processes and locations of B cell development
gene rearrangement in bone marrow, clonal expansion in lymph nodes, hypermutation in dark zone of germinal centre, selection in light zone
B cell activation by three types of antigen
T independent 1
T independent 2
T dependent
receptors involved in b cell activation
BCR
PAMPs (innate)
co-stimulatory molecules
cytokines produced by Tfh cells
T independent 1 antigens
polyclonal
non-specific
e.g. PRR
T independent 2 antigens
alone produce IgM
large molecules with a repeating determinant
activates B cells by causing the BCRs to cluster
no memory cells produced
aided by cytokines released by dendritic cells to induce class switching
T dependent antigens
B cell phagocytoses whole antigens and degrades them to be presented to T helper cells which activate the B cell
Forms memory cells
B cell activation via T cells sends signals that include…
proliferation, differentiation, isotype switching, upregulation of surface molecules, development of germinal centre
post-activation B cell development includes…
hypermutation and class switching once antibody has met antigen do not occur in T cell take place in the germinal centre need T helper cells
enzyme involved in affinity maturation and class switching
AID (activation induced cytidine deaminase)
affinity maturation principle
as B cells proliferate, their Ig genes mutate randomly. only the best ones with better binding and higher affinities are kept while the rest die by apoptosis
affinity maturation process in germinal centre
Centroblasts hypermutate in dark zone, enter light zone as centrocytes after co-stimulation and activation by Tfh cells and cytokines, leave as memory or plasma cells.
lack Bcl2 meaning they can be apoptosed if not high affinity. only safe if antigen is presented to it from follicular dendritic cells
hypermutation
deliberate mutation of Ig genes
class switching
changing the Fc region to change the function
but the Fv region is still the same
importance of antibodies
neutralises toxins and viruses
opsonisation to promote phagocytosis by macrophages
activates the complement cascade
agglutination of debris and viruses
antibody dependent cell mediated cytotoxicity through Fc regions
which isotype can form dimers
IgA2
which classes are more likely to be produced before and after switching and why
before: M and D - genes come first
after: G, A and E - genes come later on
IgD
membrane bound
naive B cells
IgM
default
pentamers - immune complexes but too large to cross into tissues or placenta
activate the complement cascade through classical pathway
IgG
main antibody after switching opsonisation important in neonatal immunity - only antibody that can cross the placenta targets for NK cells (ADCC) 4 subclasses
IgA
mucosal
dimerises - protects from enzymatic breakdown but usually as monomer
2 subtypes
IgE
parasites
mast cells - causes the mast cells to degranulate
low concentration but can increase in allergy (immediate hypersensitivity)
