ross hypersensitivity type III Flashcards
what locations may the immune complexes in type III hypersensitivity deposit?
On endothelial cells, in glomerular, in joints (reactive arthritis) and lymphadenopathy.
what factors can affect the function of immune complexes?
whether mono or polyvalent Ab
ratio of ab to antigens
affinity and ability to activate complement
ability of host to remove complexes.
What are two examples of type III hypersensitivity reactions?
serum sickness and Arthus reaction?
What antigen is targeted by antibodies in the arthus reaction?
Often against animal albumin. Occurs when large amount is injected in, where there is an excess of antigen- small complexes and deposition.
What biologic hase been reported to trigger type III hypersensitivity serum sickness against?
Against rituximab, high Agn to ab ratio.
How does pathogenesis of Arthus reaction work?
local reaction eg. upon vaccines (espeically booter)
Lots of locally administered e.g. peptides, excess ag to ab but in a local area.
Complement activation and mast cell binding and activation.
What autoimmune disease is a good example of type III hypersensitivity? What ab are against?
SLE, characterised by anti-nuclear antibodies.
e.g. anti dsDNA, sm/RO, RNP antibodies.
What areas are polymorphisms associated with immune dysregulation in SLE seen?
complement, BCR adn TCR signalling, IFN-a (driver for B cell antibody production) and apoptotic aphtways.
Monogenic causes of SLE?
C1q, C4, C2 C1r/s. Important for generating C3b/ 3d and C1q importnat for clearnace of apoptotic cells.
What three autoimmune diseases not explained by type III hypersensitivity?
antiphospholipid syndrome (seen in SLE patients)
RA
IgG4 associated diseases.
What is target antibodies in anti-phospholipid syndrome and what clinical problems?
B2 glycoproteins which are cofactors for phosphlipid proteins.
Causes spordaic thrombi- strokes, deep venous thrombosis, pulmonary embolism.
Why isn’t antiphospholipid syndrome a type III hypersensitivity?
Because no immune complexes seen, and Ab seen all the time even when symptoms aren’t present.
(May be triggered by LPS).
Why is RA not a type III hypersensitivity reaction?
a lot of people have antibodies against rheumatic factors, by no disease.
Infliximab (anti TNFa is effective in these patients too).
T cells and macrophages are implicated.
What do RA patients die of?
cardiovascular disease due to prolonged systemic infection, and even more susceptible to infections ot due to immunosuppression.
What disease is IgG4 associated with?
pancreatitis (where there is no cancer)