hypersensitivity Flashcards
Classification of hypersensitivity
Type I, II, III, IV
Type I
-IgE mediated
-immediate (EEEmediate)
-antigen is freely moving (pollen, peanut proteins)
-antigen enters body, picked up by B cell which releases (excessive) IgE antibodies
-antibody will stick to Mast cells
-Upon second exposure, antigen attaches to antibodies already on mast cells and histamine is released causing inflammation (vasodilation, increased permeability, swelling) and bronchoconstriction
What is Anaphylaxis?
The most serious and potentially life threatening manifestation of mast cell and basophil mediator release
Increased vascular permeability (swelling) and airway constriction in severe cases with exposure to a large load of allergens can prevent blood flow to vital organs (vasodilation causes pooling in periphery), causing anaphylactic shock
clinical necessity–> a likely allergen exposure followed by 2 or more of the following: skin or mucosal tissue involvement, respiratory compromise, hypotension (SBP <90mmHg), persistent GI symptoms
IgE-dependent anaphylaxis occurs after 1st or 2nd exposure to allergen?
second, after IgE antibodies are already circulating from first
Anaphylaxis & Systemic allergic reactions cannot occur on first-time exposure to allergens like drugs, insect venoms, latex, and foods
anaphylaxis signs and symptoms
30 mins to several hours after exposure
include in order of frequency:
-skin–> flushing, blotchy rashes, pruritus (itchy skin)
-respiratory distress, wheezing (lungs, ex/inspiratory), stridor (trachea, inspiratory)
-GI cramping, emesis (vomit), diarrhea
-Hypotension (lightheadedness, dizziness, syncope (fainting)) (caused by exaggerated vasodilation)
Treatment for anaphylaxis (IgE)
Intramuscular epinephrine aka epi pen!!!
antihistamines and corticosteroids have limited value in reversing anaphylactic syndromes (although normally they help reverse allergic reactions)
Type I examples
Atopy
Asthma (bronchoconstriction)
Anaphylaxis
(Atopy: disorders characterized by an exaggerated IgE-mediated immune response)
Type II hypersensitivity
Cytotoxic hypersensitivity
-(called this because it involved antibody-mediated destruction of healthy cells, not talking about CD8 cell involvement)
antigen on external surface of cell in body (fixed)
IgG and IgM involved
Binds and causes activation of complement system, macrophages and NK cells causing damage to tissues
Big picture: (Autommune diseases occur when self-reactive B or T cells escape the regulation process early on. In type II hyper, these cells release excessive IgG and IgM in response to either intrinsic or extrinsic antigens. These antibodies bind to normal host cells/specific tissues, creating an AB-AG complex, and activating the complement cascade which, naturally, kills the targeted cell)
Intrinsic antigen vs extrinsic antigen
made by host vs attaches to host cell
examples of Type II
-drug induced + autoimmune hemolytic anemia
-thrombocytopenia
-neutropenia
-mismatched blood transfusions
-second pregnancy with Rh factor
-Good pasture syndrome (antibodies bind intrinsic antigens on collagen in glomeruli or alveoli)
(Context: blood cells that can be attacked by the complement system after binding of IgG or IgM)
Type II Hypersensitivity process
IgG (sometimes IgM) molecules will bind to the antigen on the cell surface causing an antigen-antibody complex
-complement system activated and cell is eventually killed
non-toxic type II examples:
AB binds to AG and gets in the way, interrupting normal function:
-Myasthenia gravis: AB bind to Ach receptor (self) and prevents Ach from binding
-disease characterized by muscle weakness
-Grave’s disease: AB bind to TSH stimulating receptors causing over activation
-disease characterized by hyperthyroidism
type II key points:
antibody mediated
tissue specific (Type III more systemic)
generally lead to cytotoxicity
Type III
SOLUBLE ANTIGEN binds with antibody IgG, forming small immune complexes that don’t get phagocytized as easily, allowing them to stay in the system longer and then deposit in blood vessel walls (and other tissues) and activate the complement system
“immune complexes” technically only form with soluble, free-floating antigens [hence systemic effect], a strong distinction from type II in which antibodies bind cell surface antigens [hence tissue specific]
A distinction between type II and type III is that type II uses complement proteins in smaller amounts whereas type III uses them RAPIDLY in large amounts
Neutrophils degranulate and cause inflammation of the blood vessels (vasculitis) and cause more destruction of cells and more release of self-antigen
So destruction occurs at site of the tissue deposit of the immune complex (aka systemic), rather than where they are made (as in type II)
(again, for clarification, we are talking about the self reacting cells that should’ve been killed earlier in their development getting activated by T cells and releasing massive amounts of antibodies against their own tissue)
Type III examples
lupus, arthritis (autoimmune), glomerulonephritis (kidneys because they filter blood), serum sickness
