Allergy and Hypersensitivity Flashcards
what is hypersensitivity
immune disorder caused by an inappropriate response to antigens that are not necessarily pathogens.
how are the 4 classes of hypersensitivity differentiated
- differ by the immune molecules and cells which cause them
- by the way they induce damage
what is allgery
a damaging immune response by the body to a substance (allergen) to which it has become hypersensitive.
what does allergy trigger
unnecessary increases in vascular permeability and inflammation that lead to tissue damage with little benefit.
what are local allergic responses
the symptoms are restricted to the site where the antigen interacts with the body
what kind of response is anaphylaxis
system wide
when does anaphylaxis occur
if the same antigens are more widely disseminated
can Anaphylactic shock can be fatal
yes
what is a description of type I hypersensitivity
allergy and atopy/ immediate hypersensitivity
what is an overview of the mechanism of type I hypersensitivity
IgE driven, involves degranulation of mast cells and basophils
what are clinical examples of type I hypersensitivity
asthma
hay fever
anaphylaxis
what is a description of type II hypersensitivity
antibody mediated
what is the overall mechanism for type II hypersensitivity
IgG driven, involved the complement system and cytotoxic cells
what are clinical examples of type II hypersensitivity
blood transfusion reactions
hemolytic anemia
what is a description of type III hypersensitivity
immune complex-mediated
what is the overall mechanism for type III hypersensitivity
antigen-antibody complexes complement system, neutrophils/inflammation
what are clinical examples of type III hypersensitivity
rheumatoid arthritis
systemic lupus
what is a description of type IV hypersensitivity
cell-mediated delayed-type hypersensitivity
what is an overall mechanism of type IV hypersensitivity
sensitised t cells, cytokines, activated machrophages
what are clincial examples of type IV hypersensitivity
contact dermatitis
what is atopy
predisposition to an immune response against diverse antigens and allergens leading overproduction of immunoglobulin E (IgE).
what can atopy lead to
an increased likelihood of developing a hypersensitivityreaction.
what is an allergen
An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body
How do IgE antibodies recognise an antigen
- via their variable region.
- IgE antibodies bind to one of two types of Fc receptors (FcR) via their constant regions.
what immune cells express the FcεRI receptor and what does it do
Mast cells, basophils, and eosinophils
main mediators of allergy symptoms
what does the cross-linking of FcεRI receptors by allergen/IgE complexes initiate
signalling cascades that resemble those initiated by antigen receptors
what does the signalling cascade initiated by the cross-linking of FcεRI receptors result in
mast cell/basophil degranulation with the release of inflammatory mediators.
what is mediated by IgE antibodies
Allergy is a type I hypersensitivity reaction that is mediated by IgE antibodies.
when do individuals without allergies generally produce IgE antibodies
in response to parasitic infections
for the cross-linking of FcεRI, what Is a requirement of the allergen
The allergen needs to be multivalent (have multiple epitopes) in order to cause cross-linking
what happens during the first exposure of an allergen in type I hypersensitivity
triggers a standard immune response with the production of IgE.
what happens during re-exposure of an allergen in type I hypersensitivity
triggers mast cell degranulation with the associated inflammatory responses.
what is degranulation
a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells
what happens when vasoactive amines are released
vascular dilation
smooth muscle contraction
what happens when proteases are released
tissue damage
what happens when lipid mediators act on prostaglandins
vascular dilation
what happens when leukotrienes are secreted
smooth muscle contraction
what happens when cytokines are released
inflammation
what are the 3 things that can get released through IgE binding in type I hypersensitivity
granule exocytosis
- vasoactive amines
-proteases
lipid mediators secretion
-prostaglandins
-leukotrienes
cytokine secretion
what is the initial contraction of the bronchial and tracheal smooth muscle mediated by
histamines
when is histamines released in the initial contraction of bronchial and tracheal smooth muscle
minutes of release as a result of mast cell degranulation
what happens when histamines bind to the H1 receptor
induces increased vascular permeability and mucous secretion
what do phospholipase released by degranulation initiate
enzymatic breakdown of phospholipids in the plasma membrane leading eventually to the release of leukotrienes and prostaglandins
what do cytokines released by mast cells do
increase the expression of adhesion molecules on endothelial cells, and this facilitates the influx of neutrophils, eosinophils and helper T cells
what does type II hypersensitivity reactions involve
antibody-mediated destruction of cells by antibody classes other than IgE (IgG or IgM).
what are the 3 mechanisms of type II hypersensitivity
- Activation of the complement cascade.
- Antibody-dependent cell-mediated cytotoxicity (ADCC).
- Antibody bound to the target cell attracts and activates phagocytic cells that kill by the process known as opsonization.
how does type II hypersensitivity transfusion reactions manifest
antigens on transfused blood cells generate antibodies in people with a different blood group lacking those antigens resulting in intravascular haemolysis
how does type II hypersensitivity haemolytic disease of the newborn manifest
maternal IgG specific for fetal Rhesus (Rh) antigens cross the placenta and destroy fetal red blood cells if mother is Rh- and father is Rh+
how does type II hypersensitivity malaria manifest
red blood cells pick up antigens from the parasite and antibodies trigger haemolysis
how does type II hypersensitivity drug-induced haemolytic anaemia manifest
red blood cells that have bound drug molecules trigger antibody responses
what do uncleared immune complexes induce
degranulation of mast cells and inflammation triggered by complement activation and attraction and activation of neutrophils at the site of the immune complex.
where can immune complexes be deposited
in tissues and capillary beds where they induce more innate immune activity, blood vessel inflammation (vasculitis) and tissue damage.
what can deposition of immune complexes in the kidney lead to
glomerulonephritis, and in the joints to arthritis.
what does type IV hypersensitivity response require
It requires T cells to be sensitized to antigen (Sensitization phase), and subsequent re-exposure results in cytokine production, inflammation and recruitment of macrophages (Effector phase).
what happens in the sensitisation stage of type IV hypersensitivity
nitial contact with antigen presented by an antigen presenting cell triggers the activation, clonal expansion and differentiation of T helper cells bearing appropriately shaped T cell receptors.
what happens during the effector phase of type IV hypersensitivity
- On re-exposure to antigen, the sensitized T cell produces a variety of cytokines and chemokines.
- These in turn attract and activate macrophages and other non-specific inflammatory cells.
- Activated macrophages are very good antigen presenting cells, so this perpetuates the immune response.
what are red flag symptoms
Red flags are signs and symptoms found in the patient history and clinical evaluation that may tie a disorder to a serious pathology, and therefore require further investigation.
what is the antigen form of type I hypersensitivity
soluble antigen
what is the antigen form of type II hypersensitivity
cell bound antigen
what is the antigen form of type III hypersensitivity
soluble antigen
what is the antigen form of type IV hypersensitivity
soluble or cell bound antigen
