Hypersensitivity and Allergy Flashcards
What are hypersensitivity reactions usually mounted against?
Harmless foreign antigens Autoantigens Alloantigens
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 subsequent 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 (Ab mediated blood cell destruction) e.g. autoimmune haemolytic anaemia, thrombocytopenia, neutropenia
What are the consequences of immune complex formation in type 3 hypersensitivity?
Immune complexes deposit in blood vessels and tissues Activate complement and cause cell recruitment Can also activate other cascades such as clotting This can cause tissue damage and vasculitis
Give some examples of diseases caused by delayed type hypersensitivity.
Chronic graft rejections Graft-versus-host disease Coeliac disease Contact hypersensitivity
Describe the mechanism of delayed type hypersensitivity.
The transient/persistent antigen is presented to TH1 cells by APCs. Th1 then releases IFN-gamma which activates macrophages. Activated macrophages produce TNF-alpha, which is responsible for much of the tissue damage Th1 also releases IL-2 to activate cytotoxic T lymphocytes (CTLs) to release perforin Th1 also release fibroblast growth factor (FGF), stimulating fibroblasts to promote fibrosis and angiogenesis
What are three important cytokines released by Th2?
IL-4 IL-5 IL-13
What is the difference between the antigens involved in type 2 and type 3 hypersensitivity?
Type 2 – insoluble antigens (cell surface or matrix bound antigens) Type 3 – soluble antigens
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.
About 80% of atopics have a family history The genetic component is polygenic but genes of the IL-4 cluster on chromosome 5 and genes for the IgE receptor 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 - more common in small families Infections - early life exposure to infections is protective Animals - more exposure is protective Diet - breast feeding, anti-oxidants, fatty acids protect
What type of hypersensitivity and which antibody is responsible for anaphylaxis, urticaria and angioedema?
Type 1 hypersensitivity - IgE mediated
What type of hypersensitivity and which antibody is responsible for chronic urticaria?
Type 2 hypersensitivity - IgG mediated
What type of hypersensitivity is responsible for asthma, rhinitis and eczema?
Type 1 - IgE mediated and type 4 hypersensitivity
Describe sensitisation in atopic airway disease.
- Dendritic cells capture allergens from the airway and present them to naive CD4+ T cells
- Once the T cells are exposed to the antigen by APCs, they can become: Th1 cells or T regs or Th2 memory cells
- Th1 cells secrete IFN-gamma which inhibts Th2 proliferation
- Treg cells produce IL-10 which inhibits the development of CD4+ T cells into Th2 cells
- Th2 cells lead to the activation of B cells via IL-4 and IL-13
- The B cells produce IgE antibodies
Describe what happens in second exposure to the allergen in the atopic airway.
In second exposure, the allergens are presented by dendritic 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?
0-5%
Describe the appearance of the nucleus of eosinophils.
Bi-lobed
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
