Allergic Disease Flashcards
What is the definition of an allergic reaction?
An undesirable, damaging, discomfort-producing and sometimes fatal reaction produced by the normal immune system directed against innocuous antigens in a pre-sensitised (immune host)
What is meant by “innocuous antigens” and “pre-sensitised host”?
Innocuous antigens:
- this is an antigen that is not usually harmful
Pre-sensitised host:
- the host has had prior exposure to the innocuous antigen
What are the 4 types of hypersensitivity?
Type I - anaphylactic
Type II - cytotoxic
Type III - immune complex
Type IV - delayed type
Types I, II and III are mediated by antibodies
Type IV is a mediated by cells
What are the characteristics of a type I (anaphylactic) allergic reaction?
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What are the characteristics of a type II (cytotoxic) reaction?
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What are the characteristics of a type III (immune complex) reaction?
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What are the characteristics of a type IV (delayed type) reaction?
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What is the immunopathogenesis of a type II (cytotoxic) reaction?
- It is an IgG/IgM antibody response against combined self/foreign antigen at the cell surface
- the antigens are on the cell surface
- this leads to complement activation/phagocytosis/ADCC
What are the clinical features and common antigens associated with a type II cytotoxic allergic reaction?
Clinical features:
- onset of minutes to hours
- cell lysis and necrosis
Common antigens:
- penicillin
What diseases are associated with a type II hypersensitivity reaction?
- Erythroblastosis fetalis
- goodpasture’s nephritis
How does haemolytic disease of the newborn work?
- IgG molecules produced by the mother pass through the placenta
- Some antibodies attack antigens on the surface of red blood cells in the foetal circulation
- The foetus then develops reticulocytosis and anaemia
- Many erythroblasts are present in the fetal blood
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What is the immunopathology of type III hypersensitivity reactions like?
IgG/IgM antibodies against soluble antigens
this leads to immune complex deposition in the skin, kidneys and joints
What are the clinical features and associated diseases of Type III hypersensitivity reactions?
Clinical features:
- onset of 3 - 8 hours
- vasculitis
Associated diseases:
- the traditional cause is serum sickness
- SLE
What is meant by serum sickness?
A reaction to proteins in antiserum derived from a non-human animal source occurring 5-10 days after exposure
The immune system mistakes the proteins for harmful antigens
the body produces antibodies which combine with the proteins to form immune complexes
What happens to the immune complexes after they have formed?
The complexes precipitate and enter the walls of blood vessels to activate the complement cascade
they initiate an inflammatory response
What are the typical symptoms of serum sickness?
rashes
itching
joint pain (arthralgia), especially finger and toe joints
fever, as high as 40 °C and usually appears before rash
lymphadenopathy (swelling of lymph nodes), particularly near the site of injection, head and neck
malaise
hypotension (decreased blood pressure)
splenomegaly (enlarged spleen)
glomerulonephritis
protein in the urine
blood in the urine
shock
Complete the table with the route of antiserum administration and the site of immune complex deposition
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What is the immunopathology and clinical features of a type IV hypersensitivity reaction?
Immunopathology:
- antigen specific T-cell mediated cytotoxicity
Clinical features:
- delayed onset of 48-72 hours
- erythema and induration
What are the common causes and associated diseases associated with Type IV hypersensitivity?
Common causes:
- metals e.g. nickel
- tuberculin reaction
Associated diseases:
- contact dermatitis
What is the mechanism behind a Type IV hypersensitivity reaction?
- CD4+ Th1 cells recognise foreign antigen in a complex with the MHC class II on the surface of APCs
- The T cells are drivers of pathology that secrete chemokines and cytokines that cause damage
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What cytokines and chemokines are secreted as part of the Type IV delayed response?
- Macrophages secrete IL-12, which stimulates the proliferation of further Th1 cells
- T cells secrete Il-2 and IFN-gamma, which induces further release of other Th1 cytokines
- Activated CD8+ T cells destroy target cells on contact, whilst activated macrophages produce hydrolytic enzymes
What is the end result of the type IV hypersensitivity reaction?
Overreaction of helper T cells and overproduction of cytokines damages tissues, causes inflammation and cell death
Why do people get allergies?
- The components of the immune system involved in allergic responses are primarily involved in responses to parasitic infection
- the immune system has evolved to generate a rapid tissue-based response to reinfection
- the lack of infectious drive is also a contributatory factor
What characteristics of the immune response to parasitic disease is the same in an allergic reaction?
Increased levels of IgE:
- both total and cross-reactive (specific to pathogen)
Tissue inflammation with:
- eosinophils and mast cells
- basophil infiltration
Presence of CD4+ T cells secreting:
- IL4, IL5 and IL13
What is meant by the ‘hygiene hypothesis’?
Immune stimulation by microbes protects against allergies
If the immune system is not fighting against bacteria, it turns to fight against the harmless antigens
A pathogen-free environment leads to increased incidence of disease
What is the mechanism behind the hygiene hypothesis?
- There is deviation from a Th1 response to a Th2 response
- there is lack of antigenic competition from infections, which leads to immune regulation
What is meant by the genetic influences on the allergic immune response?
What is significant about the genetic component?
Only involves polygenic diseases
cytokine gene cluster IL3, 5, 9, 13
IL12R, IL4R
FceRI
IFN-gamma and TNF
These are NOT sufficient for disease, only susceptibility
What are the 4 groups of susceptibility genes for allergic diseases?
- Environment sensing genes
- Atopic immune responses
- Tissue response genes
- Barrier function genes
What is meant by ‘environment setting’ genes?
They encode molecules that directly modulate the effect of environmental risk factors for allergic disease
e.g. Modulate the effect of exposures involving tobacco smoke and air pollution on asthma susceptibility
What is meant by barrier function genes?
They tend to be expressed in the epithelium
they affect epithelial and dermal barrier function, allowing the allergen to enter the body more easily
What is meant by the genes that regulate atopic inflammation?
They regulate Th1/Th2 differentiation and effector function
they regulate atopic sensitisation
What is meant by ‘atopy’?
personal and/or familial tendency to become sensitised and produce IgE antibodies in response to ordinary exposure to allergens, usually proteins