Hypersensitivity Flashcards
What is Type I Hypersensitivity?
Mediated by IgE and results from actions of mediators secreted by mast cells. Leads to allergies (atopy).
What is Type II Hypersensitivity?
Mediated by Abs that bind tissue Ags and cause complement-dependent tissue injury and disease.
What is Type III Hypersensitivity?
Mediated by circulating Ag-Ab complexes which deposit in vessels and cause complement-dependent injury in the vessel wall (vasculitis).
What is Type IV Hypersensitivity?
Mediated by T cells and results from inflammation caused by cytokines produced by CD4+ Th1 and Th17 cells, macrophages, neutrophils, and/or killing of host cells by CD8+ CTLs.
In Type I Hypersensitivity, what T cells and interleukins play a key role in initiating the response?
Th2 cells and IL-4
Describe the primary exposure and secondary exposure of Type I Hypersensitivity.
Primary: Th2 activated, leading to production of IgE. IgE binds to Fcε receptors on mast cells (without allergen bound).
Secondary: Allergen cross-links with membrane bound IgE, causing activation of mast cells.
What is the difference between the immediate and late phases of Type I Hypersensitivity?
Immediate: Vascular and smooth muscle reactions within minutes of allergen contact.
Late: Inflammatory infiltrate rich in eosinophils, neutrophils, and T cells develops 2-24 hours later.
What causes asthmatic reactions?
Local release of inflammatory mediators from mast cells following encounter with allergen, constricting the airway (Type I Hypersensitivity). Can also be stimulated by cold and exercise.
What mediators secreted by mast cells cause vascular dilation and smooth muscle contraction?
Prostaglandins cause vascular dilation. Leukotrienes cause smooth muscle contraction.
Describe the mechanism of anaphylaxis.
Food allergen may cause massive release of vasoactive amines and cytokines causing contraction of smooth muscle in vasculature (bronchi especially) and vasodilation of capillary endothelium. Leads to blood pressure drop, vascular shock, and difficulty breathing.
How does Allergen-Specific Immunotherapy (Allergen-SIT) work?
Performed by administration of increasing doses of allergen in order to induce peripheral T cell tolerance to allergens (less Th2, more Th1), increase thresholds for mast cell/basophil activation, and decreased IgE-mediated histamine release. Generation of FOXP3+CD4+CD25+ Treg cells is key to Allergen-SIT.
What are the two main effector mechanisms for Type II Hypersensitivity?
Antibody binds to surface, triggering complement-mediated cytotoxicity. Antibody binds to surface, localizing NK cells or macrophages and triggering Ab-dependent cellular cytotoxicity (ADCC).
How can hypersensitivity cause Graves’ Diseases?
In type II, antibodies can bind to thyroid-stimulating hormone receptors. This causes continual release of thyroid hormones without ligand, leading to hyperthyroidism.
How can hypersensitivity cause Myasthenia Gravis?
In type II, antibodies can bind to acetylcholine receptor, preventing binding of acetylcholine. This leads to muscle weakness and fatigue.
Describe Hemolytic Disease of Newborn (HDN). How is it treated?
In type II, during first pregnancy, Rh antigens cross from Rh+ fetus to Rh- mother. Mother makes anit-Rh antibodies. During second pregnancy, anti-Rh antibodies cross placenta and attack fetal blood cells. Can be prevented with immunotherapy of anti-(anti-Rh) at around week 28 of pregnancy.
