1
Q
IgG delivery to tissues
A
-endothelial cells of blood vessels perform pinocytosis and take up plasma proteins for degradation in lysosomes. However, they do NOT take up IgG because associates with a FcRn that diverts the IgG away from the lysosomes and takes it to the basolateral surface of the cell and ejects it
2
Q
poly-Ig receptor
- specificity
- function and how it helps muscousal epithelium
A
- specificity for IgA dimers and IgM pentamers
- taken into the cell by receptor-mediated endocytosis, complex carried to apical surface in endocytic vesicles and is protease cleaves the poly-Ig receptor at sites between the membrane-anchoring region and the Ig-binding site, released from the membrane still bound to a small fragment of the receptor (secretory component), and secretory component keeps Ig held at the mucosal surface which prevent microbial attachment to and colonization of the mucosal epithelium
3
Q
infants and IgG/IgA
- how babies get IgG and why necessary
- how babies get IgA and why necessary
- why does it diminish as they get older
- when do they have lowest levels?
A
- pregnancy, IgG from the maternal circulation is transported across the placenta by FcRn and is delivered directly into the fetal bloodstream so that babies have high level of IgG when born
- baby has protection at birth against pathogens that provoke an IgG response
- infants obtain dimeric IgA in their mother’s milk through digestion in their gut, which contains antibodies against the microorganisms to which the mother has mounted an IgA response
- As the maternally derived IgG is catabolized and the consumption of breast milk diminishes, the antibody level gradually decreases until about 6 months of age, when the infant’s own immune system starts to produce substantial antibody
- IgG levels are lowest in infants aged 3–12 month
4
Q
Mast Cells
- what Ig us characterized with this?
- what do they release? how activated?
- what is the affect?
A
- each cell that expresses FcεRI carries a variety of IgE molecules
- cytoplasm of the resting mast cell is filled with large granules containing histamine and other inflammatory mediators which become activated to release their granules when antigen binds to the IgE molecules bound to FcεRI on the mast-cell surface and cross links them
- increase the permeability of the local blood vessels, enabling other cells and molecules of the immune system to move out of the bloodstream and into tissues which causes a local accumulation of fluid, and the swelling, reddening, and pain that characterize inflammation.
5
Q
Effects of mediators released from IgE crosslinking
A
- cause violent reactions such as sneezing, coughing, vomiting, and diarrhea that forcibly eject pathogens
6
Q
Mast cells and individulas in developed countries
A
- human populations in developed countries, where parasite infections are rare, the mast cell’s response is most frequently seen as a detriment, because its actions are the cause of allergy and asthma.
- make IgE in response to relatively innocuous substances,
- subsequent encounter with the allergen leads to massive mast-cell degranulation and a damaging response that is quite inappropriate to the threat posed by the antigen or its source
7
Q
Neutralizing Antibodies
-what are they
-in relation to flu
in relation to bacteria
A
- High-affinity antibodies that bind to the microbial ligand and prevent the microbe’s attachment to human epithelium stop the infection before it starts
- virus binds to oligosaccharides on cell surfaces through hemagglutinin but antibodies coat the virus, inhibit its attachment to human cells, and prevent infection
- bacteria attach to epi in GI system with bacterial adhesins, S. pyo- protein F, Secreted IgA antibodies specific for protein F limit the growth of the resident population of S. pyogenes and prevent them from causing disease
8
Q
Antibodies and neutralization
- microbial toxins
- animal venoms
A
- bacteria secrete protein toxins that cause disease and must bind to receptor to get into cell and cause effect but antibodies that bind to the receptor-binding polypeptide can be sufficient to neutralize a toxin
- preferred therapy for someone who has been bitten and exposed to venom is to infuse them with antibodies specific for the venom, which bind the toxic polypeptide and prevent it from binding to its receptor and getting into the cell
9
Q
Ab activating complement
- which pathway and what Ig?
- how do the two Ig’s bind complement?
A
- classical pathway also occurs when antibodies of IgM and IgG3 bind to pathogen surfaces
-IgM: conformation of IgM changes to ‘staple’
form when bound to pathogen which allows binding site for C1q on the Fc part of each IgM monomer to accessible - IgG molecule has a single binding
site for C1q in its Fc region and C1q must cross-link
two or more IgG molecules bound to antigen in order to activate C1; depends more on the amount and density of antibodies bound to the
pathogen surface
10
Q
Erythrocytes and complement
A
-Erythrocytes express CR1 and can bind C3b fragments from immune complexes and then take them to liver/spleen for tissue macrophages to remove and degrade the complexes of complement, antibody, and antigen from the erythrocyte surface while leaving the erythrocyte unscathed
11
Q
Fc receptors and IgG
A
- FcγRI, FcγRII and FcγRIII
- difference in binding strengths is the presence of three Ig-like domains in FcγRI and only two in FcγRII and FcγRIII
- FcγRII or FcγRIII will only form stable interactions with two or more IgG molecules that have been cross-linked with antigen
12
Q
FcγRI
- major function
- how?
- regulation
A
- facilitate the uptake and degradation of pathogens by phagocytes and professional antigen-presenting cells
- antibodies made against surface antigens will coat the pathogen with their Fc regions pointing outward and free to bind to the FcγRI expressed on myeloid cell surfaces
- necessity for antigen cross-linking of the bound IgG before a signal can be produced
13
Q
FcαRI
A
- Cells of the myeloid lineage also express an Fc receptor that binds to the monomeric form of IgA present in blood and lymph
- facilitates the phagocytosis of pathogens coated with IgA
