Hypersensitivity Flashcards
What is hypersensitivity?
An immune response that results in bystander damage to the self
What are the 2 phases of hypersensitivity?
Sensitisation phase - first contact to stimulus
Pathological phase - further contact causing disease
How many hypersensitivity classes are there in Gel and Coomb’s classification?
5
Type I,IIa,IIb,III,IV
What is type I hypersensitivity?
An allergic immune response causing atopic dermatitis, food allergies and allergic asthma
What was the allergic immune response initially formed to destroy?
Parasitic infection
What cells are found in a type I hypersensitivity response?
Mast cells
B-cells
Th2 cells
Eosinophils
IgE antibodies
What occurs during the sensitisation stage of a type I hypersensitivity reaction?
Allergen stimulates dendritic cells
Dendritic cells stimulate Th2 cell formation
Dendritic cells stimulate Tfh cell formation
Allergen + Tfh cells stimulate B cell formation
Th2 cells produce IL-5 to bone marrow
Th2 cells produce IL-4 and IL-13
IL-5 causes eosinophilia
IL-4 and IL-13 stimulate IgE B cells which release IgE
Basophils and mast cells take up excess IgE antibodies as receptors
What is eosinophilia?
An abnormally high level of eosinophils
What occurs during the pathological stage of a type I hypersensitivity reaction?
2nd allergen contact
Allergen binds to IgE receptors on mast cells and basophils
Degranulation releases histamine and tryptase (vasoactive mediators)
Degranulation releases pro-inflammatory cytokines and leukotrienes
What is the effect of histamine and heparin?
Increased vascular permeability and smooth muscle contraction
What is the effect of ECF-A (Eosinophil Chemotactic Factor)?
Eosinophil chemotaxis (Attraction)
What is the effect of NCF-A (Neutrophil Chemotactic Factor)?
Neutrophil chemotaxis (Attraction)
What is the effect of proteases such as tryptase and chymase in a hypersensitivity reaction?
Bronchial mucus secretion
Degradation of blood vessel basement membrane
What is the effect of platelet-activating factor?
Platelet aggregation and degranulation
Contraction of pulmonary smooth muscle
What is the effect of leukotrienes (Slow reactive substance of anaphylaxis (SRS-A))?
Increased vascular permeability
Contraction of pulmonary smooth muscle
What is the effect of prostaglandins?
Vasodilation
Contraction of pulmonary smooth muscles
Platelet aggregation
What is the effect of bradykinin?
Increased vascular permeability
Smooth muscle contraction
What are some of the effects of cytokines?
Systemic anaphylaxis
Increased expression of adhesion molecules
Increased IgE production
What are some common features of a type I hypersensitivity reaction?
Asthma
Urticaria - hives (Itchy red rash)
Angioedema - swelling under the skin
Allergic rhinitis - hay fever
Allergic conjunctivitis
Diarrhoea
Vomiting
Anaphylaxis
How does sodium cromoglicate treat a type I hypersensitivity reaction?
It prevents mast cell degranulation
How does montelukast treat a type I hypersensitivity reaction?
It is a leukotriene receptor antagonist so prevents leukotriene induced symptoms such as airway constriction
How does prednisolone treat a type I hypersensitivity reaction?
It is a steroid
It decreases the immune sresponse and inflammation
e.g. reduced Th2 cells
What treatments are used for a type I hypersensitivity reaction?
Steroids
Adrenaline
Immunotherapy
Anti-inflammatory agents
Anti-histamines
Leukotriene receptor antagonists
Allergen avoidance
What is a Type IIa hypersensitivity reaction?
A reaction in which IgM/IgG antibodies are directed towards antigens present on cell surfaces or the ECM, causing the destruction of antigen-positive cells
What is a Type IIb hypersensitivity reaction?
A reaction in which IgM/IgG antibodies are directed towards antigens present on cell surfaces or the ECM, causing the stimulation of the antigen-positive cells
What are examples of type IIb hypersensitivity reactions?
Grave’s disease - hyperthyroidism due to stimulation of TSH (Thyroid Stimulating Hormone) receptors
Myasthenia gravis - loss in muscle function due to blocking of acetylcholine receptors in neuromuscular junctions
What is a type III hypersensitivity reaction?
A large scale inflammation reaction, caused by the trapping of soluble immune complexes (Antibodies + antigens) on the surrounding basement membrane, leading to neutrophils causing tissue damage. It can lead to tissue death and haemorrhage
What is an example of a type III hypersensitivity reaction?
Acute hypersensitivity pneumonitis
Immune complexes deposited in alveolar and bronchiole walls
What is a type IV hypersensitivity reaction?
AKA Delayed Type Hypersensitivity reactions (DTH)
CD4+ T-cells activated by antigen
Form effector Th1 cells
Macrophage recruitment
Reactivation of Th1 cells by macrophages
Reactivation of macrophages by Th1 cells
Tissue damage due to inflammation
What is dyspnoea?
laboured breathing
