Immunology - Type III Hypersensitivity

Question 1

What does having a hypersensitivity mean?

Answer 1

someone’s immune system has reacted to something in a way that ends up damaging them as opposed to protecting them

Question 2

Definition

Answer 2

happens when antigen-antibody complexes deposit in blood vessel walls causing inflammation and tissue damage

Question 3

Immune complexes

Answer 3

mediate type III hypersensitivity, aka antigen-antibody complexes, made of antigen and antibody

Question 4

Antibodies

Answer 4

recognize specific molecules (antigens the second part of immune complexes (formed when antibodies bind to antigens), can also target antigens on cell surfaces (not considered immune complexes)), sometimes called immunoglobulins, produced by plasma cells (fully matured and differentiated B cells), initially IgM is made which can be secreted or bound to the plasma cell surface where it acts as a B cell receptor
- B cell undergoes cross-linking of two surface bound IgMs -> takes up the antigen and presents a piece of it to T helper cells via t cell receptor to the MHC-class II molecule presenting the piece of antigen along with costimulatory molecule CD4 -> the B cell’s CD40 binds to the T cell’s CD40 ligand -> T cell releases cytokines -> B cell activation and class switching (isotype switching, changes the type of antibodies it makes, in type III hypersensitivity reactions typically B cells will switch from IgM to IgG)

Question 5

Antigens

Answer 5

some unbound and soluble, some bound to cell surfaces, immune complexes formed when antibodies bind to soluble antigens

Question 6

In type III hypersensitivity reactions, antibodies bind to ______ antigens

Answer 6

soluble

Question 7

Drug-induced _____ is a type III hypersensitivity that manifests as purpura, fever, lymphadenopathy

Answer 7

vasculitis

Question 8

In type III hypersensitivity, reactions, B-cells produce ___ antibodies rather than IgM

Answer 8

IgG

Question 9

Complement proteins are ______ in type III hypersensitivity reactions

Answer 9

decreased

Question 10

The mainstay of management of drug-induced vasculitis is ______ __ ______ ____

Answer 10

stopping the causative drug

Question 11

Type III hypersensitivity has a _____ onset of manifestations than type I hypersensitivity

Answer 11

slower

Question 12

Pathology

Answer 12

Hypersensitivity reactions mediated by immune complexes (IgG antibodies binding to soluble antigens, antigens not bound to cell surfaces), formation of immune comlexes -> complement activation (especially C3a + C4a + C5a, anaphylatoxins increase vascular permeability = edema, chemokins = recruitment of phagocytes + neutrophils + mast cells = degranulation of lysosomal enzymes = reactive oxygen species = inflammation + tissue necrosis (fibrinoid necrosis), may also elicit systemic inflammation)

Question 13

Common sites of immune complex accumulation

Answer 13

blood vessel walls = vasculitis, kidneys = glomerulonephritis, joints = arthritis

Question 14

If triggered by single exposure to antigen…

Answer 14

resolves after catabolism of immune complexes (acute serum sickness)

Question 15

If repeated/prolonged exposure…

Answer 15

chronic serum sickness (systemic lupus erythematosus (SLE), polyarteritis nodosa, poststreptococcal glomerulonephritis, reactive arthritis)

Question 16

Common type III hypersensitivity reactions

Answer 16

Henoch-Schönlein purpura, hypersensitivity vasculitis, reactive arthritis, Farmer’s lung, post-streptococcal glomerulonephritis, serum sickness, arthus reaction, systemic lupus erythematosus, subacute bacterial endocarditis, rheumatoid arthritis

Question 17

Signs and symptoms

Answer 17

fever, fatigue, weight loss, rash, urticaria, proteinuria (kidney), arthralgias (joints), ulcers (mucosa), pleuritis + pericarditis (serosa)

Question 18

Diagnosis

Answer 18

antibody testing, histopathology to observe fibrinoid necrosis (necrosis of vessel wall with infiltration of neutrophils + eosinophils + complement + plasma proteins, staining oattern reminiscent of fibrin)

Question 19

3 major differences between type II and type III hypersensitivities

Answer 19

• type II hypersensitivity reactions involve antibodies binding to antigens on cell surfaces and type III hypersensitivity reactions involve immune complexes with soluble antigens
• type II hypersensitivities = complement activated in relatively small amounts, type III hypersensitivities = complement proteins are rapidly consumed in large amounts (specifically C3 and C4) so complement levels in the blood can be used to track disease progression over time
• type II hypersensitivity = clinical symptoms correspond to the tissue where antibodies attach to and destroy cells, type III hypersensitivity = clinical symptoms correspond to the tissue where immune complexes are deposited not where the immune complexes are made