lecture 1- antibody effector functions Flashcards
Fc receptor on naive B cells called ___ prevents involvement of naive B cells in secondary responses when there’s a pre-existing antibody response against the pathogen
FcyRIIB1
1- primary response: if naive B cells binds pathogen, this causes…
2- secondary: if naive B cells binds pathogen coated with specific antibody…
3- if memory B cell binds pathogen…
1- naive B cell activated- production of low affinity IgM antibodies
2- negative signal given to naive B cell to prevent activation- no production of low affinity IgM
3- memory B cell activated and becomes antibody-producing plasma cell - production of high affinity IgG
describe what happens with Rh- mothers and Rh+ babies
first pregnancy: incompatibility, primary immune response- IgM and low-affinity IgG, fetal erythrocytes only have minor destruction because initial antibody response is not high affinity and not high affinity IgG
second pregnancy: if mom not treated and has another Rh+ baby, secondary immune response- high-affinity IgG –> massive destruction of erythrocytes –> anemic baby
- if mother is treated and infused with anti-Rh IgG : primary immune response is inhibited by presence of RhD-specific IgG –> fetal erythrocytes not destroyed –> healthy baby
many antibody effector functions depend on specific ___
Fc receptors
name 7 antibody effector functions
1- neutralization
2- complement fixation
3- immune complex formation
4- opsonization
5- triggers physical mechanisms of pathogen elimination
6- triggers allergic responses, mast cell degranulation
7- antibody dependent cellular cytotoxicity (ADCC)
antibody functions sequentially
IgM produced first, pentameric, binds pathogen strongly and activates complement through classical pathway, b/c of large size, stays in bloodstream
- somatic hypermutation, affinity maturation, and isotype switching lead to production of high affinity IgG and monomeric IgA - smaller size of these allows them to leave bloodstream and enter sites of infection
- the receptor FcRN transports IgG from bloodstream to extracellular spaces
which Fc receptor transports IgG from bloodstream to extracellular spaces?
explain
FcRN
- acidic pH of endocytic vesicle causes association of IgG with FcRN, protecting it from proteolysis
infection in blood elicits what antibody responses?
IgM, IgG, monomeric IgA
describe dimeric IgA
- dimeric IgA (held together by J chain) protects mucosal epithelial surfaces
- dimeric IgA made my plasma cells in lamina propria, but needs to be transported across epithelium by Poly Ig receptor (specific for IgA dimers and IgM pentamers because it binds to J chain)
- facilitates transcytosis of IgA
which receptor transports dimeric IgA across epithelium
Poly Ig receptor
name a few functions of dimeric IgA
- can export toxins and pathogens from lamina propria while being secreted
- able to neutralize antigens internalized in endosomes
- binds pathogen on M-cell surface and takes it to lymphoid tissue
locations of dimeric IgA, IgE, IgG
dimeric IgA: respiratory, urinary, digestive, breast milk
IgE: skin and mucosal surfaces
IgG: only one that can cross placenta
what happens to antibody levels in infant’s first year of life
declines in maternally transferred antibodies couples with development of their own IgM, IgG, IgA
- at around 3 months, start making own new antibodies (IgM first)
pathogen/viral neutralization is done by what antibody
dimeric IgA
what is meant by neutralization?
antibody getting in the way/interfering with the interaction between a virus and its preferred receptor on the surface (essential for its ability to infect cell)
toxin neutralization- cholera
cholera toxin prefers to bind to a specific cell-surface protein, if neutralized, antibody binds to the part of toxin that wants to bind to receptor (toxin has been neutralized- cannot perform function)
describe complement fixation
pentameric IgM is perfect ligand for C1q (classical path)
- initiation of class path by IgM binding to antigen on pathogen surface
- in absence of C1, wouldn’t have classical path- immune complex disease
- IgG also capable of fixing complement- binding of at least two molecules of IgG to pathogen is required for complement fixation
describe immune complexes
protein complex formed by binding of antibodies to soluble antigens
- size of immune complex depends on concentration of antibody and antigen
- large complexes also coated with complement and cleared by phagocytes
- smaller complexes tend to accumulate in small vessel walls where they can activate complement and cause damage
. renal podocytes, leads to damage of glomeruli
. patients with deficiencies in early components of complement cascade (C1) cannot coat immune complexes with C4b and C3b and cannot remove them –> kidney damage
most important Fc receptor for opsonization is ___, specific for this antibody, ___
FcyRI
IgG
describe opsonization (antibody and Fc receptor)
phagocyte expressing FcyRI can bind to IgG that is bound to a pathogen –> leads to efficient internalization and destruction by killing of that microbe
Fc receptor for allergic and anti-parasite responses is ___
antibody involved is ___
FcERI
IgE
describe allergic and anti-parasite responses
IgE binds to mast cells through FcERI receptor (FcE) –> high-affinity interaction, when antigen they are specific for binds –> leads to degranulation and release of histamine –> variety of symptoms
- eosinophils
Antibody-dependent cellular cytotoxicity is mediated by ___ cells that express this receptor ___ that can kill cells coated with ___
NK cells
FcyRIII (CD16)
IgG1 or IgG3
the only Fc receptor expressed by NK cells
FcyRIII (CD16)
ADCC mechanisms is purely dependent on…
antibodies coating a target cell and expression of FcyRIII
FcyRI
opsonization- expressed by phagocytes- can bind to IgG
FcyRIII (CD16)
expressed by NK cells - ADCC
FcyRIIB
expressed by naive B cells preventing them from participation in secondary responses (inhibition)
FcRN
expressed on vascular endothelium - moves IgG across endothelial layer - increased Ig half-life
the four subclasses of IgG differ in the structure of the ___
hinge
