Chapter 11 Flashcards
Type I (Immediate) Hypersensitivity
Release of mediators from the mast cells
Type II Hypersensitivity
Mediated by antibodies
Type III Hypersensitivity
Mediated by immune complexes
Type IV Hypersensitivity
Mediated by T cells
Immediate Hypersensitivity / AKA (Allergy or Atopy)
Reaction to certain antigens that is mediated by IgE antibody and mast cells
Common types of these reactions
Hay fever, food allergies, bronchial asthma, & anaphylaxis
- Sequence of events in immediate hypersensitivity
Activation of TH2 cells and production of IgE antibodies
Antigens that elicit immediate hypersensitivity (allergic) reactions are called
Allergens
What does TH2 cells secrete
cytokines IL-4 and IL-13 and stimulate B lymphocytes specific for the foreign antigens to switch to IgE-producing plasma cells
Individuals produce large amounts of IgE antibody in response to antigens that do not elicit IgE responses in other people.
Atopic
Strong familial predisposition for Type 1 hypersensitivity reactions; this predisposition is genetically determined.
Atopy
- Sequence of events in immediate hypersensitivity
Activation of mast cells.
Process of coating mast cells with IgE
Sensitization
Coating with IgE specific for an antigen makes mast cells sensitive to activation by a subsequent encounter with that antigen*
Where are mast cells present?
In all connective tissues (esp. under epithelia), and these cells are usually located adjacent to blood vessels
Route of allergen entry determines which mast cells are activated by cross-linking of allergen-specific IgE.
(i) inhaled allergens activate mast cells in submucosal tissues of bronchus; (ii) ingested allergens activate mast cells in wall of intestine.
- Sequence of events in immediate hypersensitivity
FcεRI, high-affinity receptor for IgE, consists of 3 polypeptides.
Where does the one polypeptide bind?
Fc portion of ε heavy chain very strongly
What are the other two chains of the receptor?
Signaling proteins.
Mast cells are always?
Coated with IgE bound to FcεRI
- Sequence of events in immediate hypersensitivity
When mast cells sensitized by IgE are exposed to allergen, the cells are activated to secrete mediators.
Signals lead to three types of responses in the mast cell
(i) rapid release of granule contents (degranulation), (ii) synthesis and secretion of lipid mediators, and (iii) synthesis and secretion of cytokines.
Most important mediators produced by mast cells
vasoactive amines and proteases stored in and released from granules; secreted products of arachidonic acid metabolism; and cytokines
causes dilation of small blood vessels; increases vascular permeability; stimulates transient contraction of smooth muscles.
Preformed vasoamines (e.g., histamine)
damage local tissues.
Preformed proteases
prostaglandins (cause vascular dilation) and leukotrienes (stimulate prolonged smooth muscle contraction).
Arachidonic acid metabolites
induce local inflammation.
Cytokines
produced by mast cells stimulate recruitment of leukocytes (cause late-phase reaction) – principal leukocytes involved are eosinophils, neutrophils, and TH2 cells
Cytokines
liberate proteases that cause tissue damage
Eosinophils and neutrophils
exacerbate reaction by producing more cytokines
TH2 cells
infiltration of tissues with eosinophils, neutrophils, basophils, monocytes, and CD4+ T cells as well as tissue destruction, typically in the form of mucosal epithelial cell damage.
Histology
Preformed mediators in secretory granules
Histamine & Lysosomal enzymes
increase vascular permeability, smooth muscle contraction
Histamine
breakdown extracellular matrix proteins; tissue damage
Lysosomal enzymes (chymotryptase, tryptase, and other proteases)
Newly synthesized
Arachidonic acid metabolites, lipid mediators (leukotrienes & prostaglandins) & Cytokines
IL-4 & IL-13 (promote TH2 differentiation and IgE production); TNF-α (promotes tissue inflammation)
Cytokines
increase vascular permeability; cause smooth muscle contraction; stimulates mucus secretion; chemoattractants for T cells, eosinophils, mast cells, and basophils.
Arachidonic acid metabolites, lipid mediators (leukotrienes & prostaglandins)
