HLA

Question 1

What is MHC?

Answer 1

the cluster of genes that encode the molecules involved in antigen presentation

Question 2

What are the different types of HLA molecules?

Answer 2

> Class I = HLA-A, HLA-B, HLA-C

> Class II = HLA-DP, HLA-DQ and HLA-DR

Question 3

What is the function of HLA Class I?

Answer 3

Endogenous antigen is presented to CD8+ T cells (T killer cells)

Question 4

What is the function of HLA Class II?

Answer 4

Exogenous antigen is presented to CD4+ (helper) T cells (helps production of antibodies by B cells)

Question 5

What is meant by ‘linkage disequilibrium’?

Answer 5

the occurrence in members of a population of combinations of linked genes in non-random proportion

Question 6

Describe clonal deletion of B lymphocytes

Answer 6

• 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

Question 7

Describe clonal deletion of T lymphocytes

Answer 7

• 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.

Question 8

What is an ‘autograft’?

Answer 8

graft of tissue given back to the same person

Question 9

What is an ‘isograft’?

Answer 9

graft between two identical siblings

Question 10

What is an ‘allograft’?

Answer 10

graft between two members of the same species

Question 11

What is a ‘heterograft/xenograft’?

Answer 11

graft between two different species

Question 12

What is hyperacute rejection?

Answer 12

Immediate rejection due to presence of pre-formed antibodies. Presents with thrombosis and occlusion of graft vessels

Question 13

What is acute rejection?

Answer 13

Takes weeks to months and involved T-cell mediated response against the foreign HLA

Question 14

What is chronic rejection?

Answer 14

Takes months to years. Involves T cell responses and antibodies to non-self antigen

Question 15

How can you prevent rejection in organ transplantation?

Answer 15

Match donor and recipient HLA, use anti-rejection therapy, be aware of previous exposure to forei

Question 16

Describe type 1 hypersensitivity

Answer 16

IgE mediated release of histamine from mast cells/basophils e.g. asthma, hay fever, anaphylactic shock

Question 17

Describe type 2 hypersensitivity

Answer 17

IgG and IgM-mediated destruction by complement and/or phagocytosis

Question 18

Describe type 3 hypersensitivity

Answer 18

Immune complexes causing pathology where they are formed or where they are deposited

Question 19

Describe type 4 hypersensitivity

Answer 19

Mediated by activated T cells with or without granulomas

Question 20

Describe type 5 hypersensitivity

Answer 20

mediated by antibodies that stimulate rather than destroy their target

Question 21

Give examples of type 1 hypersensitivity

Answer 21

hayfever, asthma, anaphylactic shock

Question 22

Give examples of type 2 hypersensitivity

Answer 22

antibody-mediated haemolytic anaemia, thrombocytopenia, myasthenia gravis, Goodpastures, pemphigus and pemphigoid

Question 23

Give examples of type 3 hypersensitivity

Answer 23

Where they are formed = extrinsic allergic alveolitis etc.

Where they are deposited = vasculitis, glomerulonephritis, arthritis etc.

Question 24

Give examples of type 4 hypersensitivity

Answer 24

TB, hepatitis B, coeliac

Question 25

Give examples of type 5 hypersensitivity

Answer 25

Graves’ disease (autoimmune)

Question 26

What is HLA B27 associated with?

Answer 26

ankylosing spondylitis, reactive arthritis, colitic arthritis, psoriatic arthritis

Question 27

What are HLA DQ2 and DQ8 associated with?

Answer 27

Coeliac disease and T1DM

Question 28

What is Cw6 associated with?

Answer 28

Psoriasis

Question 29

What is HLA DQ6 associated with?

Answer 29

MS

Question 30

What is HLA DR4 associated with?

Answer 30

Rheumatoid arthritis

Question 31

What is HLA DR3 associated with?

Answer 31

Graves’ disease, myasthenis gravis

Question 32

What is myasthenia gravis?

Answer 32

Autoantibody against ACh receptor muscle weakness, diplopia, respiratory paralysis

Question 33

What is Eaton-Lambert syndrome?

Answer 33

autoantbody to presynaptic Ca2+ channels at the NMJ muscle weakness

Question 34

What cancer does Eaton-Lambert syndrome increase the risk of ?

Answer 34

Small cell carcinoma of the lung

Question 35

What is pemphigus?

Answer 35

skin disease with autoantibodies to desmosomes bullae form within the epidermis and form sores on the skin and mouth ulcers

Question 36

What is pemphigoid?

Answer 36

skin disease with autoantibodies to hemidesmosomes stable bullae form which are less likely to break down that in pemphigus

Question 37

What is Goodpasture’s syndrome?

Answer 37

autoantibodies to type IV collagen in basement membranes glomerulonephritis

Question 38

What is Hashimoto’s thyroiditis?

Answer 38

Hypothyroidism; autoantibodies to TPO and anti-thyroglobulin but most damage is done by T cells

Question 39

What is pernicious anaemia?

Answer 39

Autoantibodies against parietal cells or anti-intrinsic factor anitbodies present no absorption of B12 and achlorhydria increases risk of gastric cancer

Question 40

What cancer does pernicious anaemia increase your risk of developing?

Answer 40

Gastric cancer

Question 41

Describe chronic autoimmune hepatitis

Answer 41

Affects young women, autoantibodies can include ANA, anti-SMA

Question 42

What autoantibodies may be present in primary biliary sclerosis?

Answer 42

Anti-ANA may be positive as well as anti-mitochondrial antibodies

Question 43

What autoantibodies may be present in primary sclerosing cholangitis?

Answer 43

Associated with UC, usually ANCA positive