B-Cell Mediated Immunity Flashcards
effector B cells
plasma cells and memory cells
memory cell
a clonally expanded population of daughter B cells that occupy secondary lymphoid tissues of the body for long periods of time
1st signal of B cell activation
cross linking of the BCR when the immunoglobulin component binds the antigen. for signal to occur you just have significant cross-linking
Ig alpha/Ig beta complex
Ig alpha/Ig beta complex transmits signals to the nucleus so that the cell knows antigen has bound-component of the 1st signal of B cell activation
CR2
has affinity for C3b complement component, when it binds additional signals are transmitted as part of the 1st signal of activation. tells the immune system that an immune response is needed
CD19
important component of the signaling apparatus
pan marker of B cells, allows you to measure B cells in pt
T/F T helper signal is typically needed to drive B cell response
True
T/F Some non-protein antigen can activate B cells
true
B cell activation with non-protein antigen and lack of T cell
the antigen crosslinks multiple BCRs on the surface of the cell, in addition to PRRs binding to PAMPS. The combination of BCR and PRR engagement is sufficient to partially activate the B cell
T/F B cells activated by T-independent antigens are unable to induce germinal center production and memory cell production
T
TI-1 antigens (mitogens)
antigen has PAMPs, and can crosslink BCRs, and therefore has an intrinsic ability to initiate partial activation of B cells
can activate B cells in a non-specific fashion in very high concentrations-not good because you’d have non-specific antibodies that could attack self determinants
At low concentrations elicit IgM antibody response with programmed class switching to IgG Ex)LPS, pokeweed mitogen
TI-2 antigens
cause B cell activation by heavily crosslinking BCRs on the surface of the B cell
ex) cell wall polysaccharide
No response in infants
B1B cells
innate immunity
subset of B cells that have a restricted BCR repertoire that account for most of the immune response to cell wall polysaccharides
not available to 5 years of age-why we have to have vaccinations esp of capsulated bacteria before 5
Antibody response in the absence of cognate T cells or in the absence of a thymus (no T cells)
T independent only
Antibody response in infants
T dependent and TI-1
Activates T cells
T dependent only (t cells only bind to peptides)
Induction of immunological memory
T dependent only
Activation of B cell in an antigen-independent fashion
TI-1/mitogens only
Requires repeated epitopes (capsular polysaccharide)
TI-2 only
germinal center
form in the lymphoid follicles within the B cell zone of secondary lymphoid tissues
The reaction is formed by the daughter cells of rapidly dividing B cells and T cells
second signal of B cell activation
occurs in the T cell zone of secondary lymphoid tissues if effector CD4 T cell recognizes its cognate antigen on MHC class II of a B cell it will activate it and both will rapidly proliferate At least one pair of the daughter B and T cells will eventually migrate into the lyphoid follicle of the B cell zone and continue proliferating. This will become a germinal center
follicular dendritic cells
NOT THE SAME DENDRITIC CELLS WE'VE ALREADY DISCUSSED express a high density of Fc receptors and complement receptors on their surface. They use these receptors to trap immune complexes, antigens that have been bound by C3b, antibody, or both-developing B cells compete for binding and those that receive survival signals process the antigen and present it to CD4 T cells which then instigate class switching via cytokine production
4 things that occur during creation of a germinal center
- B and helper T cell proliferation
- somatic hypermutation and affinity maturation
- isotype switching
- B cell differentiation into plasma and memory cells
IL-4
class switching to IgE and weak opsonizes like IgG2/4
IL-5
class switching to Ig5
IFN-gamma
macrophage activation, class switching to strong opsonizes IgG1/3
TGF-beta
class switching to weak opsonizes BUT CONSIDER ITS ATNTI-INFLAMMATORY ACTION MORE
single purpose of plasma cell
to produce antibodies
DOES NOTHING ELSE!!! HAS HUGE ER/GOLGI FOR THAT PURPOSE
Naive B cell vs plasma cell
Naive B cell- has Ig on surface, has surface MHC molecules, and undergoes growth, somatic hypermutation, and isotope switching
Plasma cells do none of those things-only high-rate Ig secretion
IgG found in
circulation and extravascular/extracellular spaces
IgM found in
only in circulation
IgA found
primarily in lumen of the gut and respiratory tract, in the secretions, and even in the circulation
IgE found
the epithelium underlying the skin and in the linings of the gut and respiratory tracts. Almost all IgE that is produced very rapidly binds to the high affinity IgE receptors that are expressed on the surface of mast cells as well as eosinophils. This is why there is so little IgE found in the serum, despite the fact that relatively large quantities are produced.
transcytosis
active transport of Ig into circulation or extravascular spaces. Involves binding of Ab to receptor that is endocytose and then transported from the basolateral t the apical surface of the cell and then release
transcytosis of IgA
IgA (and IgM but poorly) bind to a receptor known as the poly-Ig receptor for transport across the epithelial layers that line the gut and respiratory tracts as well as into secretions such as saliva and breast milk
IgM transport inefficient bc so large
poly Ig receptor found on basolateral surface of epithelial cells of gut/respiratory tract, endocytose and transported to the apical surface where the Ig receptor is cleaved but leaves a small component on the AB called the secretory component-increases half life
T/F most plasma cells that make IgA migrate to the secondary lymphoid tissue of the gut and the respiratory tract (the GALT and the MALT)
true
scretory component
helps to stabilize IgA multimers, increasing their half-life in mucosal secretions
Brambell receptor FcRB (FcRn)
responsible for active transport of IgG across vascular endothelium and into extravascular spaces. It is also responsible for transporting IgG across the placental barrier into the fetal circulation during pregnancy
also probably protects the IgG as it travels through the liver
expressed on vascular epithelial cells/lumen of capillaries
an IgG molecule binds to FcRB, the complex is endocytosed and transported within an acidified vesicle to the other side of the cell. When the complex reaches the basolateral surface, the basic pH of the extravascular fluid causes the IgG molecule to be released
T/F FcRB transports IgG into extravascular spaces as well across the placental barrier during pregnancy, providing passive immunization of the child for the first 6-9 months after birth
true
passive immunization
the transfer of immunity to a non-immune person by introduction of specific antibody, immune serum, or T cells from an immune individual
natural passive immunzation
the transfer of antibodies from a mother to her fetus via placental transfer of IgG (by FcRB), or transfer of IgA antibodies from the mother to her child via colostrum or breast milk.
maternal IgG levels in child
highest when first born, last to about 9 months
child doesn’t start making it’s own until birth
child begins making IgM
during fetal development but increases after birth, peak at 1 year of age
only one to be produced during fetal development
IgG peaks
in adulthood
toxin neutralization
antibody binds toxin and sterically hinders it so that it can’t bind its receptor and get into cell
strong neutralizers
IgG and IgA
viral neutralization
antibodies bind viral envelop proteins and interfere with receptor binding and endocytosis into the host cell
bacterial neutralization
prevent bacterium from attaching to cell
FceRI receptor
the high affinity IgE receptor on mast cells and eosinophils. It is the only Fc receptor that binds to its antibody ligand when that antibody is not bound to its cognate antigen
important because of its role in the function of mast cells and eosinophils
FcgRIII
important because of its role in antibody-dependent cell-mediated cytotoxicity
opsonization of pathogen
encourages uptake and destruction by macrophages or neutrophils
opsonization
antibody binds pathogen
antibody coated bacterium binds Fc receptors on cell surface of macrophage
macrophage membrane surrounds pathogen and phagocytosis occurs
binding of C3b is covalent and permanent T/F
true
antibody binding is reversible T/F
true
Antibody Dependent Cell Mediated Toxicity (ADCC)
intracellualr viral pathogens can recreate proteins onto the cell surface which can be recognized by opsonizes IgG1/3. NK cells then recognize the antibodies and induce apoptosis in the same manner as CTLs.
Recognition is by FcgRIII receptor
true/false Mast cells use their FceRI receptors to essentially “steal” IgE molecules so that they can use them as antigen-specific receptors
true
mast cell degranulation
when IgE molecules on the surface of mass cells become cross-linked the mast cel degranulates and releases inflammatory mediators
Eosinophils
another innate cell type that can be recruited into an acquired response by antibody responses. Like mast cells, eosinophils express the high affinity IgE receptor (FceRI) on their surface and steal IgE as soon as it is secreted by plasma cells. Their most important role in immune responses is to kill multicellular parasites. Parasites for unknown reasons illicit IgE responses
hybridoma
cloned B cell line that has been fused with a tumor cell
monoclonal antibody
produced by a cloned hybridoma cell line and consist of antibodies that all have an identical specificity for antigen and are of the same isotype.
polyclonal antibody
preparation of antibodies that were secreted by B cells of different lineages within the body
has antibodies of all isotypes except IgD
