Hypersensitivity Flashcards
Hypersensitivity
Adaptive immune response in an exaggerated or inappropriate form. Harmful immune responses/ inflammatory reactions within the humoral or cell-mediated branches of the immune system that cause tissue injury and may cause serious disease.
Type I, II, and III hypersensitivity reactions are mediated by what?
Antibody mediated (and are distinguished by the different types of antigens recognized and different classes of antibody involved).
Type I hypersensitivity mediated by what? How fast do they begin? Why? What are the antigens that cause type I called?
IgE induced mast cell activation. Begin within minutes due to mast cell activation and release of preformed mediators.An inflamm component ensues characterized by accumulation of neutrophils, eosinophils, macrophages, and CD4+TH2 cells. Most allergic response occur on mucous membrane surfaces or skin.
Antigens that cause type I are called allergens. (pollens, dust mite faces, fleas, venom, drugs, etc.)
Type II responses are directed against what?
Cell-surface antigens and lead to cell-specific tissue damage e.g. transfusion reaction, drug allergies
Type III responses are directed against what?
Soluble antigens are are mediated by the formation of immune complexes and the ensuing activation of complement
Type IV hypersensitivity reactions are mediated by what? AKA?
Delayed type hypersensitivity reactions are T-cell mediated responses that can be subdivided into 2 classes: TH1 cells activate macrophages and cause tissue damage by activation of an inflammatory response and damage caused directly by cytotoxic CD8+
Atopy
Genetic predisposition toward the development of immediate hypersensitivity reactions against common environmental antigens.
Atopic individuals have higher levels of IgE measured in circulation and higher eosinophil levels than normal counterparts. And more IgE specific Fc receptors per mast cell. IgE synthesis is induced by exposure to antigen and TH2 cytokines, particularly IL-4.
How does a type I hypersens. get triggered?
Triggered by antigens cross-linking preformed IgE antibody that is bound to mast cells, basophils, and activated eosinophils.
FCERI receptor
On IgE molecules. When bound by an antigen- activates mast cells (or basophils if they have entered via blood) to degranulate and release mediators. Key mediators: histamine, TNF, chemotactic mediators (i.e. LTB4- leukotriene and PGD2), chemokines (i.e. IL-8). These lead to vasodilation, inc. vasc. perm., inc. mucus production, and within the lungs bronchoconstriction.
What are the clinical signs of FCERI receptor binding and type I hypersensitivity reaction?
- Dilation of blood vessels- erythema (locally)- if dilation is widespread, can contribute to decreased vascular resistance, a drop in blood pressure, and shock.
- Inc. cap. perm.- swelling and oedema (local). If widespread, decreased vascular resistance, drop in blood pressure, and shock
- Constriction of bronchial airways. Wheezing and difficulty breathing.
- Stimulation of mucous secretion. Congestion of airways.
- Stimulation of nerve endings. Itching and pain in skin.
Anaphylotoxins
Complement zymogens, C3 & C5 cleaved into fragments, a and b, C3a and C5a are the two main anaphylotoxins. Primary roles are to increase local vascular permeability and to attract phagocytes, neutrophils in particular. Thus infections in skin, an organ or in a vascularized tissue often elicit inflammatory reactions whereby released C3a and C5a promote a vascular leakiness- thus additional antibodies, complement, lymphocytes, and phagocytes gain access to the infecting focus. These molecules if administered can cause a condition called anaphylaxis which can be fatal.
** mast cells and basophisl can be triggered to degranulate via anaphylatoxins. Mast cells express a GPLR for C3a and C5a and when occupied, they degranulate. So even in the absence of attached IgE Abs these cells play a role in local inflammation. At the site where infections occur it is important to flush the infecting focus with antibodies and complement proteins and to recruit phagocytes. Histamines released by mast cells alter vascular perm: blood components leak into the tissue results in a red painful weal or boil.
Bee sting
Bee venom contains antigens, which elicit memory B cells and antibodies. IgE Abs attached to FCERI receptors on mast cells. Some individuals, once sensitized, it can be fatal. Can be systemic- where antigens are released into the blood stream- mast cells globally triggered = systemic hypotension, pulmonary hypertension (due to pulmonary vein closure), and smooth muscle contraction of bronchi.
What makes an antigen (allergen) induce a type I hypersensitivity reaction?
Antigen must selectively evoke TH2 cells that drive an IgE response. TH2 cells arise when naive T cells first encounter antigen in the presence of IL-4. There effector TH2 cells interact with antigen specific B cells and stimulate switching of antibody isotype IgE by secreting IL-4 and expressing CD40L. Transmucosal presentation of very low doses of allergen in particularly efficient at inducing TH2 driving IgE responses.
How do you treat an allergy?
Inhibition of the effector pathways activated by antigen cross-linking of surface IgE or by inhibiting IgE production. The most desirable approach is to shift the Ab response from IgE to IgG. Hypo-sensitization in which increasing doses of Ag are given alters the TH response from TH2 to TH1 with down regulation of IgE.
What are two examples of localized anaphylaxis?
Allergic rhinitis (hay fever)- airborne allergies reacting with sensitized mast cells in the conjunctivae and nasal mucosa. Asthma- mast cell degranulation in the lower respiratory tract leads to contraction of smooth muscles and bronchoconstriction.
