Define Hypersensitivity Reactions.
Hypersensitivity is the triggering of an immune response to a harmless antigen or molecule. The inappropriate response leads to tissue damage and sometimes death.
There are 4 main types of Hypersensitivity reactions.
Type I - IgE mediated, allergic response
Type II - Antibody-dependent, cytotoxicity IgM, IgG mediated
Type III - IgG binds to soluble Antigens and forms immune complexes.
Type IV - Delayed-type, cell mediated (Th activated by APC and in the future, T memory cells activate macrophages) antibody-independent
Define Type I Hypersensitivity.
Also known as 'Immediate hypersensitivity', Type I is commonly associated with allergic responses.
Atopy (30-50% UK population) is an inherited tendency to make Type I responses
These responses to 'allergens' are mediated by IgE, Mast cells (Degranulation causes the release of Histamine) and Th2 responses.
Describe the Th2 response that occurs during Type I hypersensitivity reactions.
Allergen is picked up by an APC and presented on MHC class II to naice CD4+ T cells.
In response to IL-4 released by the APC, the naive CD4+ T cell differentiates into a Th2 helper cell.
Th2 cells release IL-4, IL-5 and IL-13 that act on B cells to causes them to differentiate into plasma cells that produce allergen-specfic IgE antibodies
IgE causes Mast cells to degranulate and release histamine.
Give examples of diseases that cause Type I hypersensitivity reactions and their respective treatments.
Asthma - ß2-adrenoceptor agonist
Perennial rhinitis (Hay fever) - Antihistamines
Allergic eczema - Corticosteroids
What is omalizumab and for which type of hypersensitivity reactions is it used?
A monoclonal antibody against IgE for Type I hypersensitivity reactions.
What does the presence of autoantibodies indicate?
Autoimmune disease affecting B cell activity.
What is Grave's thyroiditis?
An autoimmune disease characterised by the production of anti-thyroid autoantibodies that bind to the TSH receptor.
Breakdown of the normal negative feedback loop results in the continuous production of thyroid hormones - 'Hyperthyroidism'
Why is there a risk of baby being born with Grave's tyroiditis if the mother has the disease?
Just prior to birth, maternal IgG is transferred to the foetus.
Which subsets of T helper cells are involved in Type I diabetes?
Th1 and Th17 which recruit monocytes/macrophages and CD8+ T cells.
Define the types of immunodeficiencies.
Primary - Rare - Cellular or molecular defect
Secondary - More common - Arises as a result of cytotoxic or irradiation therapy, or acquired by a disease (HIV, Leukaemia)
An absent thymus causes what disease?
Di George syndrome
Characterised by severely reduced number and function of T cells
A mutation in CD3-gamma chain is likely to have what effect?
Reduced number of T cells and thus reduced T cell responses.
Give an example of a disease where the number of B cells is normal but there is abnormal production of immunoglobulins.
What might cause defective APC/T cell interaction?
IFN-gamma receptor deficiency.
What is the disease characterised by reduced killing activity and migration of Neutrophils?
Chronic granulomatous disease.
What is the disease that is characterised by the failure of cell development of B, T or both cell types?