Allergy Flashcards
allergy
Immediate hypersensitivity (Type I) = the combined immediate and late-phase reactions
=Immediate ->Begins rapidly (min)
-Has Hypersensitivity (pathology consequences)
-Also includes, late-phase reaction (more slowly developing inflammatory component characterized by the accumulation of neutrophils, eosinophils and macrophages
allergens
the antigens that elicit immediate hypersensitivity. most them are common environmental proteins, animal products, and chemicals that can modify self proteins
common features shared between all allergic reactions
production of IgE antibody, dependent on activation of IL-4 T helper cells (strong IL-4-producing helper T cells responses and produce IgE on exposure to these allergens)
-Requires a priming of the immune response (allergies require sensitization= Previous T cell-dependent allergen-specific IgE production by B cells and binding of IgE to mast cells) mast cells are now sensitive to the antigen and ready to be activated on antigen encounter
-TH2 mediated disease (pathologic features triggered by TH2 cytokines)
-IL-4, IL-5, IL-13 secreted by Th2, TFH, type 2 ILCs and other cells (DTH is type I)
allergic reaction Manifests in different way depending on tissues affected
what is the typical sequence of events in immediate hyper-sensitivity
- exposure to an antigen
- activation of lymphocytes (TH2 cells, IL-4 producing follicular helper T cells and B cells) specific for the antigen
- production of IgE antibody
- binding of antibody to Fc receptors on mast cells (sensitization)
- triggering mast cells by re-exposure to the antigen
- results in the release of mediators (vasoactive amines, lipid mediators and cytokines) from mast cells and the subsequent pathologic reaction/late phase reaction
Different mediators initiated by IgE-mediated mast cell activation cause:
Vascualr and smooth muscle reactions (immediate)
Recruitment of leukocytes (delayed late-phase)
The amount of IgE produced is directly related to
an individuals ability to generate allergen-specific Tfh cels because these cells produce cytokines IL-4 and IL-13 which stimulate B cell class switching to IgE
importance of IgE antibody is that it is the isotype that contains the
epsilon heavy chain which binds to specific Fc receptors on mast cells
two important characteristics or allergens (proteins or chemicals bound to proteins)
- individuals are exposed to them repeatedly
- unlike microbes, they do not generally stimulate the innate immune response associated with macrophage and DC secretion of TH1- and TH17-inducing cytokines
The development of allergic disease begins with
the differentiation of IL-4–, IL-5–, and IL-13–producing CD4+ helper T cells in lymphoid tissues. (but the development of these cells is not completely known)
the result of the differentiation of IL-4–, IL-5–, and IL-13–producing CD4+ helper T cells in lymphoid tissues is:
- Secretion of IL-25, IL-33 and thymic stromal lymphopoietin
- Causes DCs to migrate to lymph nodes
- Drives naïve T cells toward IL-4, IL-5 and IL-13-producing Th2 and Tfh cells
Effector cells of Allergy:
Mast cells
Bsaophils: blood granulocytes that have structural and functional similarities to mast cells
Eosinophils
* each have cytoplasmic granules that contain preformed amines and enzymes
*all three produce lipid mediators and cytokines that induce inflammation
how are mast cells activated ?
activated by cross-linking of FcεRI molecules
-occurs by binding of multivalent antigens to the IgE molecules that are attached to the Fc receptors on mast cells
Activation of mast cells cells results in 3 types of biological responses:
- secretion of preformed granule contents by exocytosis (degranulation):
=activated PKC phosphorylates the myosin light chain component of actin-myosin complexes located beneath the plasma membrane, leading to disassembly of the complex. exocytosis process mediated by members of SNARE protein family - synthesis and secretion of lipid mediators (vascular/smooth muscle response/ immediate reaction)
- controlled by enzyme PLA2 - synthesis and secretion of cytokines (leads to inflammation/late phase reaction)
mediators(molecules released from the activated cells) derived Mast Cells and Eosinophils: two types
- Performed mediators
A) Vasoactive amines-histamine (act on blood vessels and smooth muscle) *can cause vasodilation/vascular leak
B) Granule macromolecules-neutral serine proteases (tryptase/chymase) *contribute to tissue damage and immediate hypersensitivity reactions - Newly synthesized
A) Lipid mediators (prostaglandin D2)
B) Cytokines-many
Immediate Reaction
demonstrated by the wheal and flare reaction to the intradermal injection of an allergen
-reaction is dependent on IgE and Mast cells (their cytoplasmic granules have been discharged)
wheal= vasodilation and congestion (middle)
flare= leakage of plasma fluid and protein (edema)
