Hypersensitivity Lecture Objectives Flashcards
List the Gell and Coomb’s Classification of hypersensitivity
Type I: Immediate hypersensitivity
Type II: antibody mediated hypersensitivity
Type III: Immune Complex mediated hypersensitivity
Type IV: Cell mediated hypersensitivity
What is the sensitization phase for hypersensitivity type I
Occurs when antigen exposure induces B cell activation leading to IgE production with IgE binding to FceR on mast cells and basophils. IgE antibodies bind to high affinity Fc epsilon receptors present on mast cells and basophils awaiting re exposure to the initiating antigen.
What is the effector phase for hypersensitivity type I?
Early phase -> triggered by products of mast cell degranulation (result of histamine release)
Late phase – > sustained inflammation and involves Th2 cells, eosinophils and basophils.
Th2 secretes IL-5 which leads to mobilization of eosinophils
Describe the clinical manifestations of hypersensitivity reaction rhinitis
refers to inflammation of the nasal mucous membranes, sneezing, nasal congestion and watery discharge from the eyes following antigen exposure.
Describe the clinical manifestations of hypersensitivity reaction asthma?
inflammatory processes stimulate repair mechanisms that lead to structural changes in the bronchial tree (airway remodeling).
The bronchial wall thicken, and the airway narrows.
wheezing occurs if there is bronchoconstriciton
Describe the clinical manifestations of anaphylaxis
systemic, potentially fatal, reaction that affects both the cardiovascular and respiratory systems, leading to cardiac arrhythmia and hypotension
Prophylactic pharmacological interventions include anti-histamines or sodium cromoglycate. What is the rationale for prophylactic intervention for these drugs
Anti-histamines are H1 histamine receptor antagonists that competitively inhibit binding to H1-binding sites. (no effect on bronchoconstriction)
Sodium Cromoglycate stabilizes the mast cell and basophil membranes, decreasing the release of inflammatory mediators following crosslinking of cell bound IgE by antigen.
Epinephrine and steroids are NOT prophylactic. Explain the rationale for administering each
Epinephrine –> important antidote following exposure to agents triggering severe, life threatening immediate type hypersensitivity reactions. Provides transient protection
Steroids–> control the persistent/recurrent symptoms over the four to eight hours post exposure. block late phase reactions after early phase anaphylaxis
What is the mechanism underlying desensitization (allergy shots)
immunization with antigen that stimulates the production of IgG antibodies instead of IgE, following promotion of naive CD4+ T cells to differentiate to Th1 phenotype.
IgG antibodies should neutralize the antigen before it reacts with the cell bound IgE.
What is the limitation of the skin test ?
used to determine sensitivity to different allergens but the problem with that could be anaphylaxis during the test so an in vitro antigen specific radioallergosorbent (RAST) test is used.
what is the limitation of the RAST test?
RAST measures quantitatively the allergen specific IgE antibodies present in the serum. The limitation of this test is that IgE bound to mast cells are not estimated, potentially leading to false negative results. Also IgG antibodies specific for the antigen may competitively bind the antigen, preventing detection of IgE.
People with allergies to nuts and shellfish, or insect stings should carry three things. List these and when each should be used
- An epi-pen (to deliver immediate epinephrine in the event of exposure)
- Benadryl (to be taken after #1,en route to the hospital)
- A medic-alert bracelet (in case they can not communicate their significant medial history)
Type II (antibody mediated) sensitization phase
marked by production of IgG and IgM antibodies specific for a cell surface antigen
antigen either constitutive of the cell or exogenous antigens that have bound to the cell surface
any cell may be target
Type II (antibody mediated) effector phase
No re-exposure needed –> antigen has not been eliminated upon primary exposure
destruction of cells via ADCC by NK cells (perforin and granzyme)
classical pathway (due to IgM and IgG production)
opsonin mediated phagocytosis due to deposition C3b on target cells
opsonin mediated phagocytosis with IgG and FcgammaR
Type III (immune complex mediated) sensitization phase
IgM and IgG antibodies bind with soluble antigens to form immune complexes
in autoimmune diseases: immune complexes formed in excess - over capacity of the reticuloendothelial system (normal immune clearance mechanism)
Type III (immune complex mediated) effector phase
- C5a –> chemotactic for neutrophils
immune complexes formed in excess –> deposit capillary wall –> stimulate complement activation –> generates anaphylotoxins (c5a) and C3b opsonin
C5a bind mast cells/basophils –> increases vascular permeability - Neutrophils activation by FcgammaR
activated neutrophils secrete inflammatory mediators –> ROIs, proteolytic enzymes, elastase and collegenase
damaged endothelium exposing subendothelium this activates intrinsic coagulation pathway –> bradykinin and kallikrein are made
frustrated phagocyte –> can no phagocytized
Is a transfusion reaction type II or III and why?
type II
IgM antibodies, isohaemagglutinins, bind to these glycoproteins on red cells, and activate complement leading to lysis or opsonin mediated (C3b) phagocytosis
Is hemolytic disease of the newborn (Erythroblastosis fetalis), primarily due to Rh incompatibility type II or III?
type II
negativeRh mom with positiveRH progeny –> Mom exposed after any placental transfer, can be prior to current pregnancy –> IgG or C3b phagocytosis
Are autoimmune reactions to cellular antigen or tissues and hyperacute rejection of transplanted tissue, type II or III?
Type II
What autoimmune diseases are associated with type II hypersensitivity?
- Goodpasteur’s syndrome –> glomerular and pulmonary basement membranes are a site of immune mediated damage due to the formation of antibodies to basement membrane antigens (Common to both kidney and lungs)
- Chronic Idiopathic uticaria –> form antigen to Fc part of IgE antibody or Fcepislon portion on mast cell –> only cutanous mast cell – >itchy and annoying
what autoimmune diseases are associated with type III hypersensitivity?
- Systemic Lupus Erythematosus (SLE) –> kidney glomeruli causes glomerulonephritis
- RA –> complexes deposited on joints
- Farmer’s Lung –> complexes deposited in lungs
- Arthus Reaction –> localized after subQ or intradermal injection of same antigen (prior to exposure to antigen)
- Serum Sickness –> Tetanus vaccine given less than 5 years apart
Type IV hypersensitivity reaction sensitization phase ?
naïve CD4+ T cells (Thp), are activated and differentiate to Th1/Th2 cells secreting cytokines
Th cells clonally expand, with some becoming memory cells, providing immunosurveillance as they circulate via blood and lymph
Type IV hypersensitivity reaction effector phase ?
Re-exposure to antigen –> activate Th1 memory cells –> Antigen re-introduced topically or intradermally
Persistent intracellular existence of microbe –> tissue damage via inflammatory mediators and cytokines secreted by activate neutrophils and tissues MO after phagocytosis
What is an example of a chronic type IV hypersensitive reaction
Granulomatous inflammation: granuloma formation
CD4+
