In which arm of the immune response do most hypersensitivity reactions develop?
Adaptive immune response, involving B-cells (humoral antibodies) or T-cells (cell-mediated immunity).
What are the pathologic immune mechanisms of each type of hypersensitivity reaction?
Type I) Immediate IgE antibody from B-cells. Type II) IgM or IgG from B-cells against cell surface antigens. Type III) Immune complexes of IgM or IgG from B-cells with antigen. Type IV) CD4 T-cell delayed hypersensitivity or CD8 T-cell cytolysis.
How do hypersensitivity reactions mimic the portals of entry used by other pathogens?
Inhaled, injected, ingested and contacted materials can all induce an immune response.
Pathogenesis of hay fever?
It is a type I hypersensitivity reaction: 1st pollen exposure -> APC MHC II presents to CD4 T-cell -> CD4 proliferate and differentiate into Th2 cells -> Th2 release of IL-4 and IL-5, B-cells class switch and produce IgG and IgE -> Pollen-specific IgE binds to mast cells. 2nd pollen exposure -> IgE on mast cells cross link -> mast cells degranulate and cause allergic rhinitis.
What is responsible for the clinical signs of type I hypersensitivity?
Memory response: Antigen exposure -> memory cell IgE release -> IgE binds FcRepsilon on mast cell -> IgE cross-link w/antigen -> mast cells and basophils degranulate
2 phases of a type I hypersensitivity reaction
Degranulation of the mast cell is responsible for both immediate and late phases. Immediate within minutes after exposure (vasoactive amines and lipid mediators cause the vascular and smooth muscle response) and late phase 2-4 hours after exposure (cytokine release)
Reaction that you are looking for when testing for allergens in a patient?
Wheal and flare as a result of early release of histamine and vasoactive amines in response to antigen and mast cell degranulation.
Pathogenesis of erythroblastosis fetalis?
It is a type II hypersensitivity: Anti-Rh IgG binds directly to the RBC and activates complement and opsonizes the RBCs for phagocytosis.
Why is allograft rejection not a problem with RBC transfusion?
They do not express MHC molecules, which are the basis of allograft rejection.
What is responsible for the development of anti-B antibodies in a person who is type A blood?
Cross-reactivity with commensal organisms in the gut.
2 types of type III hypersensitivity reactions?
Generalized: immune complexes formed in blood and deposited in tissue. Localized: immune complexes deposited near site of antigen entry (like what happens w/mosquito bites = Localized Arthus Reaction shown below).
Why did people have joint, kidney and vascular lesions after receiving anti-tetanus serum?
Type III hypersensitivity reaction. Since the anti-serum was from a horse, the immune system generated antibodies against horse antigens. These antigen-antibody complexes then deposit in the kidney, joints and blood vessels and cause damage.
How does glomerulonephritis occur as a result of type III hypersensitivity reaction?
Antigen contacts B cells -> B-cells produce antibody that forms a complex with the antigen and deposits in glomerular capillary walls -> antigen-antibody complex is seen as foreign by immune system -> PMN infiltration, cytokine release and lysosomal enzyme release -> necrosis and destruction of capillary wall
What is the mediator of tissue damage in type III hypersensitivity reactions?
Complement and Fc receptor-mediated recruitment of PMNs.
Pathogenesis of tuberculin reaction in someone who was previously infected with Tb?
This is a delayed type IV hypersensitivity reaction: Tb antigen phagocytized by dendritic cell -> migrates to regional lymph node -> dendritic cell matures and presents antigen to naive T cells -> Activated T-cells return to site of infection -> diapedese into area of exposure -> memory T-cells hang out at site of contact, activated Th2 cells secrete IFN-gamma that activates macrophages, activated Th17 cells secrete IL-17 and recruit PMNs and CD8 cells go to work killing other cells.