Immune Complex Disease Flashcards
The rate of IC formation is a balance between what?
- intensity of the exposure
- rate of IC formation Ag/Ab binding (avidity)
- disposal by neutrophil catabolism and transport to distant disposal sites
What does the vigor of the B cell response vary with?
Gender, TLF, MHC
-women have more vigorous antibody response–>women have problem with immune diseases based on b-cell responses
When an immune complex is formed the biologic sites on the heavy chain are exposed, what 2 responses bind the heavy chain and induce inflammatory amplifying systems? What do these systems generate?
- FcR cross link and activation
- Complement via classic or direct pathway
-interleukins, chemokines, and prostaglandin and kinin cascades that mobilize NEUTROPHILS to the site of IC formation
How do IC promote beneficial immune responses and inflammation?
enhance phagocytosis of encapsulated organisms
-these capsules sometimes have charge –>now instead of macrophages directly binding them they can bind the heavy chain of the antibody that is bound to the antigen
- binding them to C3b receptors on neutrophils and macrophages
- crosslinking FcR on macrophages and promoting uptake and cell activation
- aggregation of immunoglobulin on bacterial surface allows cross-linking of Fc-R and activates macrophages–>phagocytosis
What happens if the rate of neutrophil/mac disposal is exceeded by formation?
free IC binds to CR1 RBC receptors via C3b(complement activation)
-inactivates the complex to iC3b and transports it to the liver and spleen
How does the IC get removed from the CR1?
Liver-lined with Fc receptors and C3b receptors
Fixed macrophage system in hepatic sinusoids strips off the complex and degrades it
When these IC are brought to the spleen what happens to them?
-used for antigen
What does free IC do?
endothelial layer of all peripheral vessels is loaded with Fc receptors and C3b receptors once free IC get out there they will bind to those receptors and activate multiple inflammatory amplifying system
When formation exceeds disposal, the net result is inflammation with its consequences locally and systemically, what is it called when its consequences are system, what is it mediated by?
Systemic immune complex disease
“TYPE 3 HYPERSENSITIVITY”
-complexes binding to vascular C3b and Fc receptors
What happens when FcR crosslinking or C3b binds to a tissue or vasculature ?
Activates endothelium to produce IL 8
IL8 recruits neutrophils
Neutrophils release enzymes and break down vascular architecture and tissue damage
What is an arthus reaction?
- Antibody to the antigen already present from past vaccination
- Vaccine Ag deposited by injection
- Massive antigen antibody complex at site of injection-Immediately over-whelmed
- Massive neutrophils activation by complexes
- Massive Inflammation-where you inject it
What happens in serum sickness?
Given antibodies to foreign serum proteins causes antigen antibody complexes
can lead to vasculitis, nephritis, arthritis, arthus reaction, farmer’s lung, rash
- C3b receptors are extremely common at the dermal epidermal junction –>rash
- kidney glomeruli loaded with Fc receptors and C3b receptors
WHat type of disease is lupus?
systemic immune complex disease
- immune complexes bind to Fc and C3b receptors on glomerular basement membrane
- detected by direct immunofluorescence using isotype specific antisera
How do you diagnose IC disease?
Detection/quantification of circulating complexes does not predict disease
- quantification complement components-complement levels should be decreased because the immune complexes are cleaving all these things and consuming complement
- in most cases not helpful - newer assays measure activated C3 which may be useful
How do you treat IC disease?
- eliminate the antigen-drainage of an abscess, antibiotics
- inhibit antibody formation-can be dangerous
suppress inflammation-can also be dangerous
