Hypersensitivities 1 Flashcards
Hypersensitivities
Abnormal immune reactions- inappropriately directed immune responses to inherently harmless environmental antigens (food, pollen, etc.)
Types of hypersensitivities
- Type I (IgE mediated)
- Type II (IgG mediated)
- Type III (immune complex mediated)
- Type IV (T cell mediated) – delayed hypersensitivity
Type I hypersensitivity
- Immediate hypersensitivity
- Mediated by IgE antibodies
- Effector cells: mast cells, basophils, eosinophils
- Includes both anaphylaxis and allergy
Anaphylaxis
Systemic and severe (life threatening)
Allergy
Localized and not usually immediately life threatening
Type I hypersensitivity antigen binding
IgE antibody will bind to Fc-receptor (Fc epsilon RI) on mast cells, basophils triggers cells degranulation
What causes the pathogenesis of tissue damage?
- Due to the effects of the released granules
- Results in vasodilation, pruritus, and bronchoconstriction
IgE structure
- 2 heavy chains and 2 light chains
- Similar to IgG
Where are IgE found?
- Predominantly at body surfaces (skin, intestine, and lung)
- Also found bound to mast cells and basophils
- Most individuals produce very low levels if IgE (but will increase with parasite load)
IgE half life
11-12 days
What induces IgE?
parasites
What antibody causes Allergies ?
A result of IgE production to an antigen
Atopy
Condition in which IgE is produced at abnormally high levels to many antigens
IgE Receptors
- Fc(epsilon)RI
- Fc(epsilon)RII
Fc(epsilon)RI
- receptors with very high affinity binding for IgE
- found on mast cells and basophils and sometimes found on eosinophils
- Also found on dendritic cells and monocytes of atopic patients
Fc(epsilon)RII
- Receptor with much lower affinity for IgE
- Found on NK cells, macrophages, dendritic cells, eosinophils, platelets, and some B cells
What does binding of antigen or IgE to dendritic cells and monocytes on atopic patients result in?
Binding to these cells results in increased cytokines and drives further IgE production
Mast cell response to encountering antigen
- Cytokine synthesis and secretion
- Granule exocytosis
- Prostaglandin and leukotriene synthesis
OVERALL: acute inflammatory response
Mast cell response speed
- Almost immediate response and release of immune mediators
- Already visible at 5 seconds, and then very large, obvious release by 60 secs
Granule Exocytosis(seconds to minutes)
- Histamine
- Serotonin
- Tryptase
- Kallikreins
- Proteases
- Proteoglycans
Eicosanoid synthesis and secretion (mins)
- Leukotrienes
- Prostaglandins
- Platelet activating factor
Effect of histidine
Smooth muscle contraction (bronchoconstriction), exocrine secretions (mucus, tears, saliva)
Cytokine synthesis and secretion (hours)
- IL-4
- IL-5
- IL-6
- IL-13
- TNF-alpha
- MIP-1alpha
Effect of serotonin
Vasodilation (edema)
Effect of proteases
- Trypsin
- Chymotrypsin