Hypersensitivity Reactions 9/9 Flashcards
1
Q
Type I Hypersensitivity = Immediate Hypersensitivity = Atopic
A
- Pathologic Immune Mechanisms: Th2 cells, IgE antibody, mast cells, eosinophils
- mechanisms of injury:
- mast cell-derived mediators (vasoactive amines, lipid mediators, cytokines)
- cytokine-mediated inflammation through activation of eosinophils and neutrophils
2
Q
Type II = Ab mediated diseases
A
- IgM, IgG antibodies against self cell surface or extracellular matrix antigens
- Mechanisms of tissue injury/disease:
- complement and Fc receptor-mediated recruitment and activation of leukocytes (neutrophils and macrophages)
- opsonization and phagocytosis of self cells
- abnormalities in cellular function (i.e. hormone receptor signalling)
3
Q
Type III = Immune complex - mediated diseases
A
- Immune complexes of circulating Ags and IgM or IgG Abs are deposited in vascular basement membrane
Mechanisms of injury:
- complement and Fc receptor mediated recruitment and activation of leukocytes
4
Q
Type IV: T cell mediated diseases
A
- CD4+ T cells (cytokine-mediated inflammation)
* results in macrophage activation and cytokine-mediated inflammation - CD8+ CTLS (T-cell mediated cytolysis)
* results in direct target cell lysis, and cytokine-mediated inflammation
5
Q
Properties of IgE
A
- has ability to bind both high and low affinity to mast cells
- once bound to cell receptors, the IgE 1/2 life is substantially increased
- from two days to ten days
- control of the switch from IgG to IgE is dependent upon T cells
- part of the adaptive immune response
- Mast cells and basophils have high affinity Fc receptors for IgE
- these are the only cells that contain histamine
- B cells have only low affinity receptors for IgE which is used for Ag presentation
6
Q
Cytokines resulting in Type I hypersensitity
A
- IgE production is T cell-dependent (adaptive immune response)
- requires IL-4/IL-13 to class switch
- IL-5
- IL-10
- Th1 is suppressive
- IFNgamma (macrophages)
- IL-12 (Th1)
7
Q
Allergens
A
Allergen = Ag that gives rise to immediate hypersensitivity
- most are proteins
Classical Allergens:
- Inhaled at small does
- eaten at “large” dose
8
Q
Type I reaction
A
- Upon first exposure to the allergen B cells bind via IgM receptors and activate TH2 cells.
- Acviation of TH2 cells results in IgE class switching in B cells and production of IgE Abs
- IgE Abs bind the FcR on mast cells (immunological priming)
- Upon repeated exposure to an allergen the mast cell is already primed and releases mediators:
- immediate hypersensitivity: releases histamine, heparin, tyrptase, arachidonic acid, LD4, PD2
- Late phase reaction: IL4, TNFalpha
9
Q
Results of activation of mast cells (basophils) and eosinophils
A
Activation of Mast cell/ basophil
- (Biogenic amines) histamines, PAF, PGD2 = vascular leakage, broncho-constriction, intestinal hypermotility
- (cytokines) TNF: inflamation
- (enzymes) tryptase: tissue damage
Activation of eosinophil:
- (cationic granule proteins) : killing of parasites and host cells
- Enzymes (eosinophil peroxidase): tissue damage
10
Q
wheal and flare reaction
A
- way to diagnose what people are allergic to
- wheal = extravasation of sera
- flare = axon reflex
11
Q
Clinical syndromes of Type I hypersensitivity
A
- Allergic Rhinitis Sinusitis (Hay Fever)
* increased mucus secretion, inflammation of upper airways and sinuses - Food Allergies:
* Increased peristalsis due to contractiion of intestinal muscles - Bronchial Asthma:
* Airway obstruction caused by bronchial smooth muscle hyperactivity: inflammation and tissue injury caused by late-phase reaction - Anaphylaxis (drugs, bee sting, food):
* fall in blood pressure (shock) caused by vascular dilation; airway obstruction due to laryngeal edema
12
Q
Late phase reaciton
A
- occurs 4-6 hours after initial type I reaction and persists for 1-2 days
- due to infiltration of PMNs (granulocytes), eosinophils, macrophages, lymphocytes and mast cells
- mast cells produce TNFalpha and IL-1 leading to increased expression of cell-adhesion molecules on venular endothelial cells
- IL-8 (neutrophil chemotactic factor)
- on-site release of IL-3, IL-5, IL-8 and GMCSF
13
Q
Hypersensitivity Type II: Antibody mediated binding to “surfaces”
A
- initiating antigen is a surface: Ab binds to surface, and results in damage of target cells
- in general the Ags are “fixed” and damage is localized to Ag binding cell
- Abs directed against cell surface Ags are usually pathogenic - Abs directed against internal Ags are usually not pathogenic
- it is initiated by IgG/IgM/FcR/C’ - results in damage of target cells bearing the Ag through three mechanisms:
- Abs are bound to cell surfaces/tissues and interact with Fc receptors on cells such as neutrophils, eosinophils and macrophages
- on fixed surface the macrophage goes through frustrated phagocytosis, releases all of its NOS into intravascular space and tissue is degraded
- Abs bound to cell surfaces can also cause the binding of C1 to IgG or IgM resulting in activation of the C’ cascade
- C3 receptor mediated damage to target cell via binding of C3b on target cell and and C3 receptor on neutrophils, eosinophils and macrophages
14
Q
Hemolytic Disease of Newborn
A
- Type II Hypersensitivity
- Mother is Rh(-) and baby is Rh(+): mom is primed for babies RBC - makes IgM against the Rh, and developes anti Rh memory cells.
- In next birth, mothers IgG anti-Rh Ab crosses the placenta via Rn receptor and attacks fetal RBC’s causing ertythroblastosis fetalis
- Rhogan = anti-D IgG: (RhD) binds blood cell markers and prevents IgG from binding the babies RBC’s
15
Q
Transfusion reaction
A
- when use whole blood, you are giving someones serum to another person
- Abs (usually IgM) cause agglutination, C’ activation and intravascular hemolysis
- fever, hypotension, nausea/vomiting, back/chest pain
