Hypersensitivity and Autoimmunity

Question 1

What is hypersensitivity?

Answer 1

A group of disorders in which the normally beneficial components of the immune response act in an exaggerated or inappropriate fashion to environmental antigens which do not normally cause tissue damage.

Question 2

What types of hypersensitivity are mediated via antibodies?

Answer 2

types I, II, III

Question 3

What is type IV caused by?

Answer 3

the inappropriate actions of Th1 cells.

Question 4

How does type I arise?

Answer 4

through the inappropriate synthesis of IgE by the immune system which is directed against environmental antigens

Question 5

How can the body interact with allergens?

Answer 5

• airborne
• ingested
• injected
• skin contact

Question 6

What is atopy?

Answer 6

a state of sub-clinical immune sensitisation

Question 7

What is the pathogenesis of allergy?

Answer 7

• allergen exposure
• mast cell+ allergen specific IgE
• release of inflammatory mediators
• mucosal oedema, capillary leakage, secretions, smooth muscle contraction, vasodilation

Question 8

What is type II mediated via?

Answer 8

IgG or IgM which are directed against antigens found on the surface of cells or fixed with certain tissues

Question 9

Why can the distinction in type II be blurred between hypersensitivity and autoimmune?

Answer 9

The antigens can be exogenous (external) or they can be derived from self

Question 10

Once the antibody has bound to the relevant antigen, damage to the tissue arises through…

Answer 10

• complement activation
• Fc binding of immunoglobulin and stimulation of phagocytes
• antibody dependent cellular cytotoxicity (ADCC)
• effects on target cell function (inhibits/stimulates)

Question 11

How do the clinical conditions arise in type III?

Answer 11

as a result of abnormal deposition of formed antigen/ antibody complexes in tissues

Question 12

In what way are type II and type III reactions similar?

Answer 12

-Both may arise as a result of an antibody reaction occurring against an exogenous or self-antigen

Question 13

What usually happen to immune complexes?

Answer 13

-once formed they usually gain acces to the bloodstream and are kept soluble in the blood and transported attached to RBC to the liver and spleen where fixed phagocytes such as Kupffer cells take up and destroy complexes.

Question 14

Immune complexes can be…

Answer 14

• physiological

- pathological

Question 15

Why do clinical signs occur in pathological immune complex formation?

Answer 15

as a result of predisposing factors in either the antigen involved or in the immune response to that antigen

Question 16

What is the end result of abnormal immune complex formation?

Answer 16

• the complexes precipitate out into tissues and cause inflammation.
• the inflammation can lead to serum sickness or arthus reaction

Question 17

What cytokine products are involved in type IV?

Answer 17

interleukin-2 and y-interferon

Question 18

Why do these inappropriate responses occur?

Answer 18

in response to contact with inert environmental substance or as a reaction to infection with certain micro-organisms

Question 19

What must non-infections environmental agents do to cause a type IV response?

Answer 19

-bind to a host proteins to produce an antigenic stimulus of sufficient size to incite a response

Question 20

What is a low molecular weight agent termed?

Answer 20

hapten

Question 21

Why is type IV frequently called delayed type hypersensitivity?

Answer 21

It can take between 48-72 hours for a response to occur

Question 22

What is the pathogenesis of type IV reactions?

Answer 22

• hapten and carrier or micro-organism cause antigen uptake and presentation
• Th1 antigen recognition/cytokine production
• inflammation

Question 23

Autoimmune disease

Answer 23

A group of clinical disorders characterised by tissue or organ damage mediated through abhorrent cellular and or humoral immunological mechanisms which are directed against autoantigens.

Question 24

Tolerance

Answer 24

The process whereby the immune system avoids producing damaging reactions against self antigens.

Question 25

How does tolerance arise?

Answer 25

through deletions of autoreactive T and B cells during cell mutation or by inhibiting the activity of autoreactive cells which escape the central tolerance process

Question 26

What is the aetiology of autoimmunity?

Answer 26

• genetic factors
• immune regulatory factors
• hormonal factors
• environmental factors
• other factors

Question 27

What are the effector mechanisms involved in autoimmunity?

Answer 27

• cellular (T cells) or antibody (B cell) activity
• autoantibody activation of complement-mediated inflammation
• immune complex formation
• recruitment of innate immune components

Question 28

What are important contributants to autoimmunity?

Answer 28

environmental factors and inheritance of particular HLA alleles