Humoral Immunity II - Ab Effector Functions Flashcards
what designates Ab isotype
H chain
what leads to B cells with IgM and IgD on the surface
alternative splicing
what is the BCR?
surface IgM
what occurs once a B cell encounters an Ag?
new IgM and IgD are produced in plasma cell and secreted
first Ab secreted in response to any pathogen
IgM
what is CSR
isotype switching, permits DNA recombination of rearranged V region with another H chain gene
what drives IgG production?
IFN gamma
what drives IgA production?
TGF beta
what drives IgE production?
IL-4
what drives IgM production?
IL-2, IL-4, IL-5
when does CSR occur?
when GC B cells engage TFH cells, usually after affinity maturation
what is produced when GC B cells engage TFH cells
cytokines and AID are produced
describe the order of TFH and GC B cells interacting
- TFH activated in interfollicular zone by DC
- DC gives TFH signal 3
- signal 3 triggers gene expression of corresponding cytokines to drive specific Ig isotype production
what triggers cytokine production by TFH?
engagement of TFH with B cell or with FDC by ICOS
what are switch regions
S regions are highly repetitive sequences that mediate recombination
what activates AID
ligation of CD40 on GC B cells
what directs AID to selected S regions?
TFH cytokines
what does AID do
targets cytosines in S regions for deamination to uracil
what happens to uracil that was produced by AID?
uracil dna glycosylase removes it, leaving a gap
what makes a nick in the DNA strand where the gap is ?
APE1 (endonuclease)
what occurs once there are nicks on both sides of the DNA strand
circular DNA is made, which is excised
1st step of successful microbial infection
attachment to host tissues and colonization
what is neutralization?
Ab prevent microbe attachment and therefore the infectious process
where does influenza virus bind?
surface glycoproteins of respiratory epithelia via HA hemagglutinin
what does the flu vaccine generate?
protective Ab (IgG) which are present in mucus of resp tract
how does flu vaccine work?
IgG made are present in mucus of resp tract and bind to flu virus H and prevent attachment, virus is coughed up and swallowed, and destroyed in stomach
how does neutralization of toxins work with vaccines?
vaccine formulates Ab that bind toxin, but don’t prevent attachment and colonization. just prevent toxin
how do Ab perform opsonization
IgA and IgG bind ag on microbe surface, and Fc receptors on the phagocytes bind Ab. this ligation promotes phagocytic uptake of the Ab coated microbe.
what is antibody dependent cell cytotoxicity
- NK cells express Fc gamma receptor that can be used to activate cytotoxic functions of NK
steps of ADCC
- Ab are attached to Ag on cell
- NK cell FCgamma receptor binds to Fc regions of IgG1 or IgG3
- ligation signals NK cells to release granzyme/perforin to induce apoptosis on target cells
when is ACDD used?
parasitic worm killing! IgE binding to Fc epsilon receptor
what cells express Fc alpha receptors for opsinization in mucosa
- macrophage
- neutrophil
- eosinophil
what cells express Fc epsilon receptors for degranualation
- eosinophil
- mast cell
- basophil
what cell expresses Fc gamma receptor for ADCC?
NK cell
what cell expresses Fc gamma receptor for opsinization
macrophage
what is the most common serum Ig
IgG1
what are IgG used for?
- neutralization
- opsonization
- complement activation
- ADCC in NK cells
what IgG can cross placenta
1,3,4
what triggers CSR to IgG
IFN gamma
how does IgG1-3 activate classical pathway of complement
pentameric structure of IgM activates complement
- staple form permits C1 binding to Fc parts of IgM
- C1q binding activates C1r which cleaves C1s, which cleaves C4 and C2.
- C4b fragments covalently bond to pathogen surface
- C2a fragments bind to C4b.
- C4bC2a is classical C3 convertase!
- C3 convertase cleaves C3 to C3b and C3a.
- C3b binds to pathogen surface
- C3bBb generated from fragments and coats surface with C3b
what occurs once pathogen is coated with C3b?
neutrophils and macrophages can phagocytose using CR1
what if phagocytosis is difficult?
membrane attack complex forms after C3b turns into C5 convertase
how does IgG mediate activation of complement?
C1q crosslinks with 2 or more surface bound IgG to activate classical complement
how are soluble Ag removed by IgG?
IgG has higher affinity than IgM, making stable immune complexes with soluble antigen
what can immune complexes do?
activate classical pathway! and also develop during course of immune response
what occurs if IC build up in small blood vessels or glomeruli?
complement activation due to IC can cause glomerulonephritis, increased neutrophil and macrophage recruitment, frustrated phagocytosis where they spew their contents into the environment and cause vasculitis and hemorrhaging
how can RBC capture immune complexes?
IC activates complement, so they are coated with C3b.
RBC express CR1 and capture IC!
how are IC removed from the blood stream?
- RBC captures IC via CR1 attaching to C3b
- blood passes through the spleen and liver
- splenic macrophages use Fc receptor to attract IC
- then produce protease to cleave RBC CR1 and eat it
which IgG cross placenta?
IgG1, IgG3, Ig4
what ab provide main protection for baby up to 1 year
IgG1, IgG3, IgG4.
what Ab does fetus produce before birth
IgM but is not a lot
what Ab is provided through breast milk
IgA to protect mucosal surfaces from infection
what is the main function of IgA1 and IgA2
- neutralization especially on mucosal secretion
structure of IgA
- secretory piece
2. j chain
what does secretory piece do on IgA
it is made by epithelia, translated from basolateral to luminal surface of epithelia, and protects from proteolysis
what does J piece of IgA do
structural stability and aids in translocation
how does secretory piece on IgA protect from proteolysis?
interacts with mucins in mucus and holds IgA in place in mucosa
what does IgM do
- complement activation
2. agglutination of microbes (use in diagnostics)
which is the first BCR expressed on naive mature B cells
IgM (monomer)
which is the first Ig synthesized by B cells
IgM (pentamer)
functions of IgE
- immunity to parasites
2. allergic responses
what occurs in an allergic response?
basically, cell makes Th2 response instead of a Th1 response.
- TFH makes IL-4
- IgE released from Plasma cell
- IgE binds to mast cell and eosinophil where allergen is
- triggers degranulation immediately
