Lecture 5: Hypersensitivities Flashcards
Hypersensitivity vs immunodeficiency
Hypersensitivity
◦ When one or more element of our immune system is over-active
◦ An acquired condition, to which inherited genes can pre-dispose
◦ Patients suffer from allergies and auto- immune disease
immunodeficiency
◦ When one or more element of our immune system is missing
◦ Due to either inherited or acquired conditions
◦ Patients suffer from recurrent infection
4 types of hypersensitivity
Name, antibody or cell involved, cause and reaction and disease example
Type 1
Allergic
IgE
IgE on mast cells binds to allergen and mast cells release high levels of histamine
Asthma Hayfever Eczema Anaphylaxis Food allergy
Type 2
Auto-immune
IgM, IgG, Complement
T cells fail to recognize self antigens and make antibodies to self
Auto Immune Haemolytic Anaemia Idiopathic thrombocytopenic purpura
Type 3
Immune complex
IgG, complement
Antibody binds to soluble antigens, forming immune complexes. These are not cleared as normal, and lodge in joints and kidney
Rheumatoid arthritis
Systemic lupus erythematosus
Type 4
Delayed cell mediated
T cells
T cells activated by antigen presenting cells at second exposure release too much cytokine, which leads to long lasting inflammation
Dermatitis Multiple sclerosis Coeliac disease
main cause of type 1 and 4
over production of histamine and cytokines, leading to allergies and ongoing inflammation
main cause for type 2 and 3 and difference
Types II and III represent failure of the immune system
In type II, T cells lose their ability to differentiate “self” from “non-self”
In type III, complement fails to adequately clear immune complexes
Role of mast cells
- defend against pathogens, for example parasites
- Dilate blood vessels
- induce inflammation through the release of histamines and heparin
- Recruit macrophages and neutrophils
Type 1(allergic);
Mast cell and IgE involvement and what does this lead to
◦Mast cells have IgE receptors
◦ IgE antibodies bind to specific antigens, for example on parasites
◦ The parasite is then bound to the mast cell, and can be eliminated
Mast cells release histamine, which gives increased vascular permeability to allow cells of the immune system to do their work. Histamine acts on smooth muscle to allow mucus expulsion of parasites (for example from the bowel)
◦In allergies, the IgE that has been made to allergen antigen binds to the mast cell
◦ The mast cell rapidly degranulates, releasing histamine in large quantities
High histamine release=bronchial hyper-activity (wheezing in asthma),sneezing and runny eyes in hayfever
◦ High histamine release = too much increased vascular permeability = swelling and shock (anaphylaxis)
what causes anaphylaxis
Histamine overproduction
How to diagnose food allergies
SKIN PRICK TESTS:
- Provide results in about 20 minutes.
- A liquid containing a tiny amount of the food allergen is placed on the skin of your arm or back.
Your skin is pricked with a small, sterile probe, allowing the liquid to seep under the skin.
The test, is considered positive if a wheal (resembling the bump from a mosquito bite) develops at the site where the suspected allergen was placed.
- As a negative control, you’ll also get a skin prick with a liquid that doesn’t contain the allergen; this should not provoke a reaction, allowing comparison between the two test sites.
- Positive control = histamine
BLOOD TESTS:
- With some tests there is also the potential for severe reactions, including one
that may be life-threatening such as anaphylaxis.
- In these cases, the allergen-specific IgE antibody test may be ordered. It is normally found in very small amounts in the blood.
- This test measures the amount of allergen-specific IgE in the blood in order to detect an allergy to a particular substance.
Why do skin prick tests cause false positives
The test may be detecting proteins that are similar among foods but do not trigger allergic reactions. For example, if you are allergic to peanuts, your tests may show a positive response to other members of the legume family, such as green beans, even if eating green beans has never been a problem for you.
why do some people have allergic reactions
Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissue that have the capacity to elicit an immune response in a given organism
particular polymorphisms in particular genes controlling elements of the immune system seem to pre-dispose us
Type 2: General info and example
If T cells fail to recognise a “self” antigen, and recognise it as foreign, we make auto-antibody.
Auto-antibodies attack our own cells!
An example is auto-antibody haemolytic anaemia, where we start to destroy our own red cells
Destruction may be complement- mediated, or cytotoxic destruction by K cells
Type III: immune complex
General info
◦ Antigen:antibody complexes are soluble (not bound to cells).
◦ The body normally clears these via complement activation, but in auto immune disease, they are deposited in the tissues or joints
◦ Here they attract cells of the immune system, which cause local tissue damage and inflammation
Type IV: Delayed cell mediated general info
◦ “Delayed” because it happens on re- exposure to an antigen (not first exposure)
◦ T cells activated by antigen presenting cells at second exposure release too much cytokine, which leads to long lasting inflammation
Prevention and treatment for hypersensitivity (5)
◦ Antihistamines reduce allergy symptoms and Adrenaline is needed quickly in anaphylaxis
◦ Steroids inhibit the influx of eosinophils, basophils and lymphocytes into the target sites, and inhibit cytokine production
◦ Localised effect steroids include:
◦ Flixotide for asthma prevention
◦ Flixonase for hayfever prevention
◦ Systemic effect steroids include:
◦ Prednisone for more severe conditions like SLE and RA
◦ Monoclonal antibodies block implicated cells of the immune system:
◦ For example, Belimumab for SLE
◦ Immunosuppressive drugs interfere with DNA synthesis and are toxic to B cells and their use is reserved for serious autoimmune conditions
◦ For example, azathioprine for severe SLE
◦ Blood Products; Intragam P is a New Zealand blood product consisting of IgG antibodies from a large pool of NZ blood donors. These antibodies can bind to the auto-antibodies in Type II (for example ITP), and prevent the auto-antibody binding to its target antigen
Examples of Immunodeficiency
Inherited (primary) or acquired (secondary)
Primary; due to gene mutations leading to …
◦ Defects of T cell function
◦ Defects of B cell function
◦ Defects of complement
◦ Defects in production of myeloid cells
◦ Defects in innate system receptors
Secondary; conditions in the environment affect us
◦ Old age; decreased production of antibodies
◦ Malnutrition; defects in antibodies
◦ Drugs; interfere with production
pathways of either cells or antibodies
◦ Infections; production of cells or antibodies becomes overwhelmed
◦ Cancer; tumours interfere with normal cell or antibody production
