B Cells 8 Flashcards
What are the 6 key functions of Ab?
- neutralization
- opsonization
- complement + MAC –> phagocytosis, lysis
- ADCC on NK cells –> apoptosis of infected cells
- ADCC on granulocytes –> Ab binds pathogen, then degranulation
- transport
what allows Igs to do their roles?
Fc receptors
what are Fc receptors?
transmembrane receptors that bind the Fc portion of Igs
what cells are Fc receptors found on? (7)
- macrophages
- granulocytes
- DCs
- mast cells
- B cells
- epithelial cells
- neutrophils
what is each FcR specific for?
specific for the constant Fc region of one class of Ig
what is important to trigger signaling?
crosslinking FcR
what is crosslinking?
more than 1 FcR binds an Ab that is bound to an Ag –> must occur to have signaling
what are the 4 roles of FcR?
- degranulation
- opsonization
- transport/maintenance of serum Ab levels
- ADCc
how do FcR bridge the gap btwn adaptive and innate?
allows non-specific immune cells to take advantage of antigen-specific antibodies
describe how opsonization works
aggregation of Ag binding will allow crosslinking of FcRs on phagocyte surface –> triggers intracellular signaling for phagocytosis
what Ab are involved in opsonization?
IgG
does free IgG trigger opsonization?
no!! it can bind FcR but without Ag there is no signaling
since opsonization requires aggregation of IgG, what does this mean about the number of epitopes required?
for opsonization, the phagocyte must have multiple epitopes on its surface to allow multiple IgG to bind and aggregate, thus allowing crosslinking
describe IgG subclasses
subclasses have distinct effector capabilities: some are good at complement fixation, some are good at ADCC by NK cells
but ALL bind to FcR and allow opsonization
describe ADCC on NK cells
- IgG binds antigen on surface of target cell
- NK cells have FcRs for IgG –> FcR recognizes IgG
- crosslinking –> signaling
- NK cell releases toxic granules –> apoptosis
describe ADCC vs innate activation of NK cells
ADCC requires IgG, innate requires absent MHC I as activating signal
both release the same toxic granules to kill
when is ADCC required instead of innate activation of NK cells?
normally, our cells present self-protein to show they’re healthy BUT if a virus hijacks this machinery, viral proteins will be presented and act as epitopes, allowing ADCC and the cell can still be killed
what is IgE involved in?
allergy, asthma, helminths, protozoa
is IgE made in large or small quantities?
small quantities, but potent effects
what is the role of IgE?
induce degranulation of eosinophils, basophils, mast cells to damage large pathogens
describe eosinophil and mast cell activation
- TH2 cytokines activate eosinophils and mast cells
- IgE binds FcR on eosinophils and mast cells
- IgE can bind Ag and degranulate
describe mast cells at baseline
they do have IgE bound to FcR at baseline but not crosslinked –> no signaling
what types of things can be neutralized?
- toxins
- viruses –> internalized
- intracellular bacteria
what Ig classes are involved in neutralization? what do they do?
IgG and IgA bind to toxins/pathogens to prevent them from binding their targets
where is IgA found (4)?
- mucous in gut
- milk from mammary glands
- tears
- saliva
describe neutralization of toxins
normally, toxin binds cellular receptors and is endocytosed where it has toxic effects
Ab binds toxin to BLOCK binding to cellular receptor
describe neutralization of bacteria
Ab block colonization of bacteria
describe neutralization of viruses
Ab binds virus, blocking binding to virus receptor and fusion
what is the result of complement activation?
forms MAC, inflammation, and/or opsonization
what complement pathway is involved in complement activation by Ab? how does it work
classical
C1q can bind Ab on pathogen surface, triggering signaling cascade to make C3 convertase and cleave C3 –> C3a + C3b
how can Ab link adaptive to innate?
thru classical pathway of complement
which 2 types of Ig can trigger complement cascade? which is most effective?
IgM and IgG
IgM most effective for complement
why is IgM most effective for complement? (5)
- first Ab produced
- lower affinity –> no SHM
- pentavalent –> 10 binding sites! makes up for lower affinity
- good place for C1q to bind
- forms dense Ab-pathogen complexes that are efficiently engulfed
why are FcRs important for transport?
allow targeting of diff Ig classes to diff parts of the body
where are IgA, IgE, and IgG each located?
IgA –> found in mucosal tissue, breast milk (passive immunity)
IgE –> near epithelial surfaces
IgG –> widely distributed everywhere in serum, in fetus
what Ab do newborns have in circulation?
IgG
how do FcRs allow Ig transport across barriers
ex. Ab bind epithelial surface, endocytosed, then released on the opposite side
where is IgD found?
a minor (0.2%) component of blood but is present in higher levels in secretions of upper respiratory tract
what is the function of IgD?
bind basophils and mast cells so they release AntiMicrobial Peptides (AMPs), cytokines, and chemokines
(not well understood)
