Immune Complex Disease Flashcards
Hypersensitivity type I
Allergies and asthma
Hypersensitivity type II
diseases caused by antibodies, i.e. immune throbocytopenia
Hypersensitivity type III
diseases caused by antigen/antibody complexes, i.e. lupus erythematosus
hypersensitivity type IV
diseases associated with “delayed hypersensitivity or TIMMI
formation of an Immune complex depends on
the source and intensity of antigen exposure
The rate of IC formation is the balance between antigen exposure, Ag/Ab binding(avidity, valence), disposal by neutrophil catabolism and transport to distant disposal sites.
the vigor of the B cell response to the antigen-gender variability, TLR and MHC genes
what two inflammatory amplifying systems can an IC activate
FcR crosslinking and activation and
complement via the classic or direct pathway
both mobilize neutrophils to the site of infection
The vigor of IC formation
based on characteristics of antigen and how they interact with host factors such as fender, age and MHC and other “immune” related genetic loci of the host
antigen bound to IgG binds
Fc(gamma)R on monocytes and neutrophils. this is an important interaction that mediates an inflammatory response
ICs can be eliminated by
- effective neutrophil destruction of antigen-reduces the amount of antigen at the inflammation site
- catabolism by neutrophils and monocytes
- Transport via CR1 receptors on erythrocytes to the liver for disposal
CR1
receptor for C3b on all peripheral blood cells except platlets. Binds C3b and converts it to iC3b, transports IC to liver for disposal or sleep for B-cell activation
if IC formation exceeds its disposal
pathologic inflammation either local or systemic can result (
causes of production exceeding disposal of ICs
intensity and duration of the antigenic stimulus and impaired disposal(usually secondary to increased production of complexes)
How do immune complexes cause inflammation
FcR cross-linking
FcR crosslinking results in
activates neutrophils and macrophages
causes release of IL8 and other proinflammatory cytokines that recruit more inflammatory cell to the area
Destroys underlying vascular architecture and tissue damage
Arthus Reaction
large #s of Ab’s already present when the antigen is introduced (usually by revaccination) causes formation of immune complexes so quickly that the system of removal by RBC is immediately overwhelmed. The ICs cause mass neutrophil activation by binding C3bR and FcR which triggers release of IL-8. Causes pain, swelling, and redness at injection site
treatment of IC disease
Eliminate the antigen-drainage of an abcess, antibiotics
Inhibit antibody formation- can be dangerous
Suppress inflammation- also can be dangerous
Function of IC delivered to the spleen and lymphoid tissue
strongly stimulate antibody production (these are NOT disposal sites like the liver)
Crosslinking of FcRs on B-cells
tells the B-cells that there is enough Ab present and to stop producing more Ab (inhibitory signal)
ITAM
Immunoreceptor tyrosise-based activation motif (ITAM)- triggered by the binding of IgG-IC to an Fc(gamma)R on a macrophage, monocyte, neutrophil, or DC. - results in increased phagocytosis. The receptor has high affinity and can therefore be activated by small amounts of IC
ITIM
immunoreceptor based tyroside inhibitory motif (ITIM)- triggered by binding of IgG-IC to a Fc(gamma)R on a B-cell which inhibits B-cell proliferation and Ab formation. The receptor is low affinity and therefore needs a lot of ICs to become bound.
How do we prevent Anti-Rh IgG from causing problems during pregnancy
Give the mother Anti-Rh IgG so that it binds the fetal RBC and the complexes bind B-cells turning off their response so that they do not make anti-Rh IgG (bc they think they already made enough)
what would giving Anti-Rh-IgM do
activating signal- not inhibitory maybe do something with Tregs
