Immune Complex Disease

Question 1

What is an immune complex?

Answer 1

Ag + Ab

Question 2

What is avidity?

Answer 2

How fast Ab will stick to Ag

Question 3

What 2 inflammatory activating systems can the immune complex activate?

Answer 3

• FcR crosslinking and activation

- Complement activation via the classical pathway

Question 4

What is the role of neutrophils in controlling immune complex inflammation?

Answer 4

In a normal inflammatory response, most IC are catabolized by neutrophils and monocytes after binding to their Fc receptors

Question 5

Outside of neutrophils what is the second mechanism for the disposal of immune complexes?

Answer 5

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

Question 6

What blood cells transport more IC per cell?

Answer 6

WBCs have more of the CR1 receptor per cell

Question 7

What blood cells transport more IC overall?

Answer 7

RBCs transport more overall as they are much more abundant in the blood

Question 8

What is the CR1 receptor?

Answer 8

It is a receptor for C3b. It will bind C3b and convert it to iC3b, which is inactive

Question 9

When can ICs cause disease?

Answer 9

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.

Question 10

What are Arthus reactions?

Answer 10

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

Question 11

What are the possible treatments of IC disease?

Answer 11

• Inhibit antibody formation
• Suppress inflammation

Both of these can be risky though

Question 12

How is the FcR involved in immunoregulation?

Answer 12

Fc cross-linking by Antigen-IgG complexes tells the B cell system it has achieved its goal

Question 13

What is ITAM?

Answer 13

IT Activating Motif

Question 14

What is the function of ITAM?

Answer 14

IgG-IC targets Ag to FcR on macrophage/monocyte which will lead to activation

Question 15

What is the function of ITIM?

Answer 15

IT Inhibiting Motif

IgG-IC targets Ag to FcR on B cells which will inhibit B cell proliferation

Question 16

What is the function of the ITIM for fetal blood cells?

Answer 16

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.

Question 17

What is the Rh problem in pregnancy?

Answer 17

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.

Question 18

How is the Rh problem treated?

Answer 18

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

Question 19

What is IgM anti-Rh was used to treat the Rh problem instead of IgG into-Rh?

Answer 19

It would not inhibit IgG anti-Rh antibody synthesis and the 2nd response would still occur