Immune Complex Disease Flashcards
What is an immune complex?
Ag + Ab
What is avidity?
How fast Ab will stick to Ag
What 2 inflammatory activating systems can the immune complex activate?
- FcR crosslinking and activation
- Complement activation via the classical pathway
What is the role of neutrophils in controlling immune complex inflammation?
In a normal inflammatory response, most IC are catabolized by neutrophils and monocytes after binding to their Fc receptors
Outside of neutrophils what is the second mechanism for the disposal of immune complexes?
Free IC bind to CR1 RBC receptors via C3b and are transported to the liver and spleen where the fixed macrophage system in the hepatic sinusoids strips off the complex and degrades it
What blood cells transport more IC per cell?
WBCs have more of the CR1 receptor per cell
What blood cells transport more IC overall?
RBCs transport more overall as they are much more abundant in the blood
What is the CR1 receptor?
It is a receptor for C3b. It will bind C3b and convert it to iC3b, which is inactive
When can ICs cause disease?
When formation of the ICs exceeds the destruction of the ICs the net result will be increased inflammation which can have local and systemic effects.
What are Arthus reactions?
Caused by pre-existing Ab to a certain Ag being stimulated by another injection of Ag that will cause overwhelming IC formation that the RBCs and neutrophils cannot keep up with.
-> Results in pain, redness and swelling
What are the possible treatments of IC disease?
- Inhibit antibody formation
- Suppress inflammation
Both of these can be risky though
How is the FcR involved in immunoregulation?
Fc cross-linking by Antigen-IgG complexes tells the B cell system it has achieved its goal
What is ITAM?
IT Activating Motif
What is the function of ITAM?
IgG-IC targets Ag to FcR on macrophage/monocyte which will lead to activation
What is the function of ITIM?
IT Inhibiting Motif
IgG-IC targets Ag to FcR on B cells which will inhibit B cell proliferation
What is the function of the ITIM for fetal blood cells?
The mother has specific IgG Ab that combines with fetal RBC and that complex binds to a B cell with anti-fetal RBC specificity that, when “dense” enough on B cells, turns them off by crosslinking their FcR and BCr.
The mother’s B cells have been “fooled” into thinking they have made “enough”of the specific antibody.
What is the Rh problem in pregnancy?
An Rh+ male mates with Rh- female and in the 1st pregnancy, anti-Rh+ Ab will develop. These will trigger a response in the 2nd pregnancy that will destroy the 2nd fetus.
How is the Rh problem treated?
Infusion of large amounts of anti-Rh IgG after birth and it
will bind to residual fetal cells which tricks the system into believing that it has already mounted a large response and the B cell system is shut down against Rh.
Memory CD4/B cells are not generated
What is IgM anti-Rh was used to treat the Rh problem instead of IgG into-Rh?
It would not inhibit IgG anti-Rh antibody synthesis and the 2nd response would still occur
