IgE Flashcards
What type of hypersensitivity disease:
ANTIBODY DIRECTED AGAINST TISSUE ANTIGENS - mediated by IgG.
TYPE II - ANTIBODY DIRECTED AGAINST TISSUE ANTIGENS - mediated by IgG
Which type of hypersensitivity is mediated by T cells?
TYPE IV - DELAYED HYPERSENSIVITY-mediated by T Cells
Which type of hypersensitivity reaction is commonly seen in clinic - diffuse rash all over body?
IV- reactive to drug reactions (in clinic mostly type IV- diffuse rash all over the body)
TYPE IV - DELAYED HYPERSENSIVITY-mediated by T Cells
Hypersensitivity reaction: anaphylaxis to a drug. What type? Immune reactant? What is the effector mechanism?
Type I
soluble antigen, mast cell activation
Hypersensitivity reaction: drug allergy to penicillin.
What type? Immune reactant? What is the effector mechanism?
Type II
IgG - cell or matrix associated antigen
effector mechanism- complement FcR cells (phagocytes, NK cells)
Hypersensitivity reaction: Atopic eczema. What type? Immune reactant? What is the effector mechanism?
Type I
soluble antigen, mast cell activation
Hypersensitivity reaction:
allergic contact dermatitis, tuberculin reaction
Type IV
Th1 cells
soluble antigen
macrophage activation
Hypersensitivity reaction:
chronic asthma, chronic allergic rhinitis
vs
allergic asthma
Chronic asthma:
soluble antigen
Th2 cells, soluble antigen
IgE production, eosinophil activation, mastocytosis
Allergic asthma:
Type I, IgE, soluble antigen, mast cell activation
Hypersensitivity reaction:
graft rejection, allergic contact dermatitis to poison ivy
CTL Type IV, cell associated antigen
effector mechanism: cytotoxicity
What is a genetic predisposition to develop IgE antibodies upon exposure to environmental allergens?
atopy
if both parents are atopic (then 50% chance of developing the allergy)
What denotes the ability to transfer reactivity to allergens by means of serum (the transfer agent formerly called was reagin and is now known as IgE.)?
atopy
Which cells express HIGH affinity FcεR?
Where are these cells expressed? Which circulate? Which are in tissues?
Mast cells and Basophils
Both contain histamine, TNF-α and leukotrienes in cytoplasm
Mast cells - tissue bound, compartmentalized as mucosal or connective tissue, contain potent vasoactive compounds and cytokines
Basophils- circulating
Degranulation releases the mediators
What are the two types of mast cells? Where expressed?
Tryptase staining identifies all mast cells and is the primary method for identifying tissue mast cells
Mast cells - tissue bound, compartmentalized as mucosal or connective tissue, contain potent vasoactive compounds and cytokines
2 Types of Mast Cells
MC -Tryptase (prominent mast cell type within the mucosa of the respiratory and gastrointestinal tracts and increase with mucosal inflammation)
MC- Tryptase and Chymase (cells are localized within connective tissues, such as the dermis, submucosa of the gastrointestinal tract, heart, conjunctivae, and perivascular tissues…skin)
How are these allergens presented? (What MHC class?)
Describe the sequence of an allergic response.
The immunodominant peptides of these allergens are usually preferentially presented in selected (Class II) D MHC loci by dendritic cells. The D genes, in concert with other non-MHC genes, promote IgE production over IgG responses by influencing the type of TLR activated, type of T-helper cell and cytokine milieu present during allergen presentation by APC.
Contact with an allergen is usually mucosal (respiratory or gastrointestinal), but can be cutaneous or systemic.
Uptake of allergen by antigen presenting cells (DC) via “allergic” TLR that induces the DC to produce IL-4 instead of IL-12
Presentation of the allergen as an immunodominant peptide in a Class II MHC groove. The nature of the peptide and possibly its unique presentation dictate a dominant IgE response.
Allergic responses are dependent on Th-2 activation.
- Presentation of this antigen by a DC in the absence of Th1-TLR binding or by an “allergic” TLR
- Ensuing absence of the Th1 initiator cytokine IL-12 or presence of IL-4 then leads to presentation to a Th2 by default.
- Early release of IL-4 from mast cells or basophils- commonly caused by innate immune responses of these cells to parasites
- ANY situation where IL-4 is the dominant cytokine at the time of antigen appearance.
E. Th-2 cell then provides the critical IL-4 signal to an allergen specific B-cell.
F. The accelerated production of Th-2 cytokines, especially IL-4 and IL-13, dominate the cytokine profile.
G. Promotion of IgE class switching occurs by up regulation of CD-23 (FcεRII receptor) on mast cells and basophils that increase their production of IL-4 and IL-13. This is strongly influenced by gene influenced polymorphisms.
H. IL-4 from Th-2, Basophils and mast cells activate ε germ-line transcription in B-cells and results in IgE synthesis.
What might decreased early exposure to infections in the genetically predisposed individual be associated with?
Timing is important: decreased early exposure to infections in the genetically predisposed individual is associated with insufficient T regulator control of IgE