Hypersensitivity Flashcards
1
Q
- hypersensitivity mediated by IgE and results from actions of mediators secreted by mast cells
- immediate
- most often trigger is environmental antigens
- atopy: genetic tendency to develop allergic dz
A
type 1 hypersensitivity
2
Q
- hypersensitivity mediated by antibodies that bind tissue antigens and cause complement-dependent tissue injury and disease
- IgG and IgM antibodies activate complement system by CP, results in prod of C3a and C5a comp byproducts that recruit leukocytes and induce inflammation
- antibodies opsonize cells that leads to phagocytosis of cells through FcRγ or CR1 receptors
- activated in Fc receptor or CR1 dependent manner: neutrophils and macrophages release inflammatory mediators (ROS and lysosomal enzymes that damage adjacent tissues and cause inflammation)
A
type II hypersensitivity
3
Q
- hypersensitivity mediated by circulating antigen-antibody complexes which deposit in vessels and cause complement-dependent injury in the vessel wall (vasculitis)
- IC’s induce vascular inflammation and subsequent ischemic damage to tissues
- major mechanism triggering damage is CP of complement activation and recruitment of leukocytes
A
type III hypersensitivity
4
Q
- hypersensitivity mediated by T cells and results from inflammation caused by cytokines produced by Th1 and Th17 cells, macrophages, or killing of host cells by CTLs
- major triggers are autoimmunity, exaggerated or persistent responses to environmental antigens and some microbial antigens (M. tuberculosis)
- tissue injury results from products of recruited neutrophils and macros: lysosomal enzymes, ROS, nitric oxide, and proinflammatory cytokines
- also called delayed-type hypersensitivity (DTH)
A
type IV hypersensitivity
5
Q
type I hypersensitivity
- pathologic immune mechanisms:
- mechanisms of tissue injury/dz:
A
- Th2 cells (IL4-), IgE antibodies, mast cells, eosinophils
- mast cell-derived mediators (vasoactive amines, lipid mediators, cytokines); cytokine-mediated inflammation (eosinophils, neutrophils)
6
Q
What is the unique property of IgE?
A
IgE enters circulation and is rapidly bound by FcRε (CD23) on mast cells in tissues
7
Q
What are the effects of subsequent allergen encounters in terms of mast cell function?
A
- cross-linking causes mast cell degranulation that releases: vasoactive amines, cytokines/chemokines, lipids
- physiological results: vascular smooth muscle contraction (SM appears on the tunica media of larger venules that drain the post-capillary venules), endothelial vasodilation, leukocyte chemotaxis and activation
8
Q
What are the general steps of type I hypersensitivity? (3)
A
- primary exposure to allergen causes activation of Th2 cells and production of IgE
- binding of IgE to FcεR of mast cells (patient is sensitized)
- secondary exposure: antigen dependent cross-linking of membrane bound IgE causes activation of mast cells that results in release of inflammatory mediators
9
Q
What are the inflammatory mediators in type I hypersensitivity and their effects?
A
- vasoactive amines, lipid mediators: immediate hypersensitivity reaction (minutes after repeat exposure)
- cytokines: late phase reaction (6-24 hours after repeat exposure)
10
Q
What are the important mediator molecules of type I hypersensitivity? (5)
A
- histamines (vasoactive amines): come from the granule of mast cells; causes dilation of small vessels and increases vascular permeability
- proteases: come from the granule of mast cells; causes local tissue damage
- prostaglandins (lipid mediators): come from enzymatic mod of arachidonic acid; cause vascular dilation
- leukotrienes (lipid mediators): come from enzymatic mod of arachidonic acid; stimulate prolonged smooth muscle contraction
- cytokines (e.g. TNF): come from transcriptional activation of cyto genes; induce local inflammation (late phase reaction) by recruiting leukocytes
11
Q
Describe the immediate and late phase reactions in terms of timing and morphology
A
- immediate: develops within minutes after antigenic exposure; vascular and smooth muscle reactions causes vasodilation, congestion, and edema
- late phase: develops within 2-24 hours after antigenic exposure; causes inflammation rich in eosinophils, neutrophils, and T cells
12
Q
Describe asthma in terms of type I hypersensitivities
A
- asthma: reversible airway obstruction, often caused by local release of inflammatory mediators from mast cells
- inflammatory mediators: increased capillary perm (prostaglandins) and spasmodic contraction (leukotrienes) of smooth muscle surrounding bronchi
- causes decrease in size of bronchial lumen = shortness of breath
- non-immunologic stimuli (cold, exercise): stimulate same airway inflammation and bronchospasms
13
Q
Describe anaphylaxis in terms of type I hypersensitivity
A
- exposure to allergen (food) causes massive release of vasoactive amines and cytokines from mast cells/basophils throughout the body
- causes smooth muscle contraction in vasculature and vasodilation of capillary endothelium
- blood pressure drops = vascular shock
- mediators also increase smooth muscle contraction in bronchi and bronchioles, causing difficulty breathing
14
Q
What are allergen tests used for, how are they performed, and what are their results indicative of?
A
- tests assess type I hypersensitivities to various allergens
- often performed on ventral side of arm (adults) and backs (children)
- grid is marked, small quantities of standardized allergens are injected into dermis
- positive reactions are indicated as redness and swelling within 20-30 min after exposure
15
Q
- single curative approach to allergic diseases
- performed by administration of increasing doses of allergen
- aims: increase peripheral T cell tolerance, increase threshold for mast cell/basophil activation, decrease IgE mediated histamine release
- generation of induced regulatory FOXp3, CD4, CD25, and Treg cells is the mechanism of tx
A
allergen-specific immunotherapy (allergen-SIT)
