B cell immunity II Flashcards
what are the general steps of the immune response, start to finish?
1) innate immunity and phagocytosis
2) antigen presentation to T cells
3) T cell activation by 3 signals
4) differentiation of CD4 T cells into T helper effector subsets
5) activation of B cells by T follicular helper cells
6) formation of germinal centres by activated B cells
7) improvement in quality of the B cell antibody response by somatic hypermutation and class switching
8) B cell differentiation into plasma cells
9) immunological memory
how are parasites destroyed?
extracellular pathogens can also be recognized (via PAMPs) by the complement proteins which can destroy them or mark them for destruction
what is DC licencing?
occurs during antigen presentation to T cell
dendritic cell licensing: the dendritic cell is also receiving a signal from the T cell, activating it in many ways
dendritic cell presents peptide on its MHC class II molecule to the CD4 T cell’s CD4 protein
dendritic cell takes in exogenous antigens
autocrine signalling of the T cell
describe DC cross-presentation and activation of the CD8 T cell
dendritic cells can take material that comes from the phagocytic pathway (MHC class II) and shuttle the peptides to the class I pathway
dendritic cell presents its peptides on its MHC I to the CD8 T cell’s CD8 protein
there will also be paracrine signalling between the CD4 T cell and the CD8 T cell
how does the CD4 T cell differentiate into a specific type of helper T cell
depending on where the T cell is being activated and what kind of infection is activating it (signals/information is received by the PRRs), APC cells will make polarizing cytokines (paracrine signalling) that tell the T cell what kind of helper T cell to become
another receptor on the T cell will receive the polarizing cytokines and activate the STAT pathway that acts on genes to tell the cell what type of effector cell to become
describe the activation of B cells by follicular helper T cells
when the BCR recognizes it’s antigen, the B cell is stimulated phagocytose the material and then present it on their MHC class II molecule (interacts with CD4 T cells that are mature – only dendritic cells can activate naive T cells)
the mature T cell in the follicle (follicular helper T cell) can activate the B cell that’s presenting a peptide it recognizes
remember, 3 signals are required for activation
—– BCR signalling
—– costimulatory signalling
—– cytokine signalling
this overall recognition is very rare as both B cells and T cells are antigen specific
once the B cell is activated by the follicular helper T cell, the B cell can be instructed to start dividing via clonal expansion/selection
dividing cells are called plasmablast
the B cells/plasmablast can differentiate into 3 types of B cells
—– germinal center B cell
—– plasma cell
—– memory B cell
what is a dividing B cell referred to?
plasmablast
what can a plasmablast differentiate into?
germinal center B cell
plasma cell
memory B cell
what happens if B cells make antibodies with non-peptide antigens (T independent antigens)?
B cells can make antibodies with T independent antigens and without T cells, but the quality of antibodies tends to be lower and not improve over the course of the immune response
describe the formation of germinal centres by activated B cells
naive B cells from the bone marrow enter the lymph node where they’ll encounter T cells and become activated
—- the specific area where they are activated is referred to as the germinal centres
if B cells encounter their antigen, they form a primary focus and start proliferating into a germinal centre
—- the first B cell differentiates into what’s called a germinal centre B cell - focusing point
what are germinal centres?
focus area where T (follicular helper) cells, B cells, and dendritic cells interact with each other
where somatic hypermutation and class switching of antibodies happens
describe the “structure”/organization of germinal centres
the dendritic cells and T cells are mainly found in the light zone
actively dividing B cells move back and forth between light and dark zone
in the light zone, they receive signals from the T cells
——- note: T cells care being activated by the dendritic cells and then they in turn, activate the B cells
in the dark zone, they undergo cell division
what are somatic hypermutations?
in the variable region, random mutations are induced in the DNA (nucleotides get mutated or substituted)
—– small changes so they do not change the specificity but instead alter it
these mutations can reduce or improve affinity of the BCR for its antigen
—— these high affinity BCRs/antibodies will be positively selected because the B cells can now recognize their target with higher affinity
what is class switching? describe it (when will it occur, how does it occur, etc.)
initially, naive B cells always make IgM BCR/antibodies
following an interaction with T follicular helper cells in the germinal center, a class switch can occur
due to genetic recombination; constant region segments are removed (deleted and lost) and replaced by downstream genes
class switch is random - dependent on signals from infection – we don’t know what gene will replace IgM’s but for sure it won’t be IgD for reasons unknown
class switching is irreversible
what is the most common class switch?
from IgM to IgG
maybe because there are 4 types of IgG genes
