HLA Flashcards
What is MHC?
the cluster of genes that encode the molecules involved in antigen presentation
What are the different types of HLA molecules?
> Class I = HLA-A, HLA-B, HLA-C
> Class II = HLA-DP, HLA-DQ and HLA-DR
What is the function of HLA Class I?
Endogenous antigen is presented to CD8+ T cells (T killer cells)
What is the function of HLA Class II?
Exogenous antigen is presented to CD4+ (helper) T cells (helps production of antibodies by B cells)
What is meant by ‘linkage disequilibrium’?
the occurrence in members of a population of combinations of linked genes in non-random proportion
Describe clonal deletion of B lymphocytes
- If the B cell is immature in the bone marrow (only express IgM, not IgD as well) when exposed to an antigen it will die
- When B cells are undergoing expansion and mutation (clonal expansion) in the bone marrow and fail to get help from CD4 (helper) T cells, then then they will die
Describe clonal deletion of T lymphocytes
- Central tolerance – as T cells develop in the thymus (and B cells in the bone marrow) their receptors are tested for reactivity to self-antigens. If there reactivity is too strong, the lymphocytes are killed.
- Peripheral tolerance – self-reactive lymphocytes that escape deletion during development can be controlled in the periphery by T regulatory cells.
What is an ‘autograft’?
graft of tissue given back to the same person
What is an ‘isograft’?
graft between two identical siblings
What is an ‘allograft’?
graft between two members of the same species
What is a ‘heterograft/xenograft’?
graft between two different species
What is hyperacute rejection?
Immediate rejection due to presence of pre-formed antibodies. Presents with thrombosis and occlusion of graft vessels
What is acute rejection?
Takes weeks to months and involved T-cell mediated response against the foreign HLA
What is chronic rejection?
Takes months to years. Involves T cell responses and antibodies to non-self antigen
How can you prevent rejection in organ transplantation?
Match donor and recipient HLA, use anti-rejection therapy, be aware of previous exposure to forei
Describe type 1 hypersensitivity
IgE mediated release of histamine from mast cells/basophils e.g. asthma, hay fever, anaphylactic shock
Describe type 2 hypersensitivity
IgG and IgM-mediated destruction by complement and/or phagocytosis
Describe type 3 hypersensitivity
Immune complexes causing pathology where they are formed or where they are deposited
Describe type 4 hypersensitivity
Mediated by activated T cells with or without granulomas
Describe type 5 hypersensitivity
mediated by antibodies that stimulate rather than destroy their target
Give examples of type 1 hypersensitivity
hayfever, asthma, anaphylactic shock
Give examples of type 2 hypersensitivity
antibody-mediated haemolytic anaemia, thrombocytopenia, myasthenia gravis, Goodpastures, pemphigus and pemphigoid
Give examples of type 3 hypersensitivity
Where they are formed = extrinsic allergic alveolitis etc.
Where they are deposited = vasculitis, glomerulonephritis, arthritis etc.
Give examples of type 4 hypersensitivity
TB, hepatitis B, coeliac
Give examples of type 5 hypersensitivity
Graves’ disease (autoimmune)
What is HLA B27 associated with?
ankylosing spondylitis, reactive arthritis, colitic arthritis, psoriatic arthritis
What are HLA DQ2 and DQ8 associated with?
Coeliac disease and T1DM
What is Cw6 associated with?
Psoriasis
What is HLA DQ6 associated with?
MS
What is HLA DR4 associated with?
Rheumatoid arthritis
What is HLA DR3 associated with?
Graves’ disease, myasthenis gravis
What is myasthenia gravis?
Autoantibody against ACh receptor muscle weakness, diplopia, respiratory paralysis
What is Eaton-Lambert syndrome?
autoantbody to presynaptic Ca2+ channels at the NMJ muscle weakness
What cancer does Eaton-Lambert syndrome increase the risk of ?
Small cell carcinoma of the lung
What is pemphigus?
skin disease with autoantibodies to desmosomes bullae form within the epidermis and form sores on the skin and mouth ulcers
What is pemphigoid?
skin disease with autoantibodies to hemidesmosomes stable bullae form which are less likely to break down that in pemphigus
What is Goodpasture’s syndrome?
autoantibodies to type IV collagen in basement membranes glomerulonephritis
What is Hashimoto’s thyroiditis?
Hypothyroidism; autoantibodies to TPO and anti-thyroglobulin but most damage is done by T cells
What is pernicious anaemia?
Autoantibodies against parietal cells or anti-intrinsic factor anitbodies present no absorption of B12 and achlorhydria increases risk of gastric cancer
What cancer does pernicious anaemia increase your risk of developing?
Gastric cancer
Describe chronic autoimmune hepatitis
Affects young women, autoantibodies can include ANA, anti-SMA
What autoantibodies may be present in primary biliary sclerosis?
Anti-ANA may be positive as well as anti-mitochondrial antibodies
What autoantibodies may be present in primary sclerosing cholangitis?
Associated with UC, usually ANCA positive
