Hypersensitivity and Allergy Flashcards
What are hypersensitivity reactions usually mounted against?
Harmless foreign antigens
Autoantigens
Alloantigens- antigens from other individuals of same species, eg- transfusions
What are the four type of hypersensitivity reaction?
Type 1 – immediate hypersensitivity
Type 2 – antibody-mediated cytotoxicity
Type 3 – immune complex mediated
Type 4 – delayed cell mediated
Describe the mechanism of type 1 hypersensitivity?
On 1st exposure you get sensitisation – IgE is produced, which binds to mast cells and basophils
On second exposure, antigen cross-links the IgE on the mast cells causing degranulation and release of inflammatory mediators
What types of diseases are examples of type 2 hypersensitivity?
Organ specific autoimmune diseases: e.g. myasthenia gravis, glomerulonephritis, pemphigus vulgaris, pernicious anaemia
Autoimmune cytopenias e.g. autoimmune haemolytic anaemia, thrombocytopenia, neutropenia
What are the consequences of immune complex formation in type 3 hypersensitivity?
Formation of antigen-antibody complexes in the blood which deposit in tissues and activate complement and cause cell recruitment
This can cause tissue damage such as vasculitis
Give some examples of diseases caused by delayed type hypersensitivity.
Chronic graft rejections
Graft-versus-host disease
Coeliac disease
Describe the mechanism of delayed type hypersensitivity.
The transient/persistent antigen is presented to T cells, which then activate macrophages and CTLs
Activated macrophages produce TNF-alpha, which is responsible for much of the tissue damage
What is atopy?
A form of allergy in which there is a hereditary or constitutional tendency to develop hypersensitivity reactions in response to allergens
How common is atopy?
Very common – about 50% of young adults in the UK
List some genetic risk factors of atopy.
The genetic component is polygenic but genes of the IL-4 cluster and genes on chromosome 11q have been linked to atopy
Among which age group is atopy most common?
Teens
Describe the gender difference in asthma
Males – asthma in childhood is more common
Females – asthma in adulthood is more common
What other environmental factors affect atopy?
Family size, infections, animals, diet, age
What type of hypersensitivity is responsible for anaphylaxis, urticaria and angioedema?
Type 1 hypersensitivity
What type of hypersensitivity is responsible for chronic urticaria?
Type 2 hypersensitivity
What type of hypersensitivity is responsible for asthma, rhinitis and eczema?
Type 1 and type 4 hypersensitivity
Describe sensitisation in atopic airway disease.
T cells are naïve before they have seen their antigen
Once the T cells are exposed to the antigen by APCs such as dendritic cells, they can become Th1 cells (producing IFN-gamma), T regs or Th2 cells. In hypersensitivity the Th2 route is the more dominant. The Th2 cells lead to the activation of B cells to antibody producing plasma cells by IL-4 and 13 which leads to the production of IgE antibodies.
Describe what happens in second exposure to the allergen.
In second exposure, the allergens are presented by APCs to memory Th2 cells, which then release IL-5, which causes eosinophil degranulation.
Th2 cells also release IL-4 and IL-13, which stimulate production of IgE by plasma cells.
The antigens crosslink the IgE on the surface of mast cells causing degranulation
What percentage of blood leukocytes are eosinophils?
2-5%
Describe the appearance of the nucleus of eosinophils.
Bilobed
What receptors do mast cells have on their cell surface?
IgE receptors
What mediators are released by mast cells?
Preformed: histamines, cytokines, toxic proteins
Newly synthesised: leukotrienes, prostaglandins
What percentage of blood leukocytes are neutrophils?
55-60%
What three processes cause airway narrowing in an acute asthma attack?
Vascular leakage leading to airways wall oedema
Mucus secretion fills up the lumen
Smooth muscle contraction around the bronchi
