Hypersensitivity and Autoimmunity

Question 1

Hypersensitivity

Answer 1

A group of disorders where the normally beneficial components of the immune response act in and exaggerated/inappropriate fashion to environmental allergens which do not normally cause tissue damage. The response is responsible for the tissue damage.

Question 2

Type 1 hypersensitivity

Answer 2

Most allergic reactions. IgE mediated producing an immediate response. There is often a genetic predisposition. Sensitisation occurs upon first exposure which primes the mast cells for action. It is upon second exposure at which a reaction occurs.

Question 3

Atopy

Answer 3

A genetic to produce IgE to normally innocuous allergens. A state of sub-clinical immune sensitisation.

Question 4

Allergy

Answer 4

A clinical expression of the atopic tendency

Question 5

Allergen

Answer 5

An antigen that produces an abnormally vigorous immune response.

Question 6

IgE

Answer 6

Antibody produced by cells

Question 7

Mast cells

Answer 7

Granulocytes, WBCs with Fce receptors that release histamine.

Question 8

Inflammatory cells

Answer 8

Eosinophils and basophils

Question 9

Mediators

Answer 9

Cause the symptoms; histamine, proteases, eosinophils

Question 10

Cytokines

Answer 10

Communicate; IL-4, 5, 10 and LTB4, LTC4

Question 11

Type 2 hypersensitivity

Answer 11

Cytotoxic hypersensitivity involving the antibody mediated destruction of cells. It is tissue-specific. Involves IgG and IgM. Once the antigen and antigen-antibody complex has bound to the RBC there is activation of the complement system. Complement occurs followed by phagocytosis, antigen-dependent cell-mediated cytotoxicity then finally Non-cytotoxic mechanism; antibody-mediated cellular dysfunction. Symptoms are shown where complexes are made.

Question 12

Type 3 hypersensitivity

Answer 12

The antigen-antibody complex invades blood vessel walls causing inflammation and damage. It is mediated by immune complexes (soluble antigens only) and IgG is produced by B cells. Symptoms are shown where immune complexes are deposited. It can occur against exogeneous or self antigens.

Question 13

Type 4 hypersensitivity

Answer 13

T cell mediated as well as CD8+ (cytotoxic) and CD4+ (helper). It is a delayed response occurring 48-72 hours later to recruit Th1 cells. Responsible for systemic diseases such as rheumatoid arthritis, MS and IBD. These reactions occur because the body’s immune system find it difficult to destroy these environmental antigens.

Question 14

Immunological tolerance

Answer 14

The process in which the immune system avoids producing damaging reactions against self-antigens.

Question 15

Central tolerance

Answer 15

The deletion of autoreactive T and B cells during maturation.

Question 16

Peripheral tolerance

Answer 16

Inhibiting the activity of autoreactive cells which escape the central tolerance process.

Question 17

Autoimmune disease

Answer 17

A large group of clinical disorders which are characterised by tissue or organ damage mediated through abnormal immunological mechanisms which are directed against auto-antigens. The breakdown of one or more of the processes of tolerance is a requirement for the development of autoimmune disease.

Question 18

Aetiology of immune disease

Answer 18

Environmental factors; infectious agents, sunlight, drugs, chemicals, nutritional factors.
Immune regulatory factors; defective peripheral tolerance, defective tolerance induction.
Genetic factors; familial predisposition, inheritance of particular H LAs.
Other; age, malignancy, trauma, hormonal factors.

Question 19

Pathogenic mechanisms involved in autoimmune disease

Answer 19

1. Cel (T) mediated
2. Antibody (B) mediated
3. (Auto)antibody activation of complement mediated inflammation.
4. Immune complex formation (i.e. TII)
5. Recruitment of innate immune components (phagocytes, cytokines, NK cells)

Question 20

Organ specific vs non-organ specific autoimmune disorders

Answer 20

Organ-specific; autoimmune endocrine disorders e.g. thyroid, stomach, adrenal gland, pancreas. Immune response is directed towards antigen in a single organism.
Spectrum
Non-organ specific; connective tissue disorders. E.g. muscle, kidney, skin, joints. Immune system attacks self antigens in several organs.