Hypersensitivity & 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 is bystander damage?

Answer 2

The exaggerated immune response associated with hypersensitivity is what causes the tissue damage, rather than the antigen

Question 3

What mediates types 1,2 and 3 hypersensitivity?

Answer 3

Antibodies

Question 4

What causes type 4 hypersensitivity?

Answer 4

Inappropriate actions of Th1 cells

Question 5

What is another name for type 1 hypersensitivity?

Answer 5

Allergy

Question 6

How does type 1 hypersensitivity arise?

Answer 6

Through the inappropriate synthesis of IgE by the immune system acting against environmental antigens (allergens)

Question 7

In what ways can environmental antigens/allergens be encountered?

Answer 7

Airborne
Ingested
Injected
Skin contact

Question 8

What other factors give rise to allergic problems?

Answer 8

interacting genetic factors
environmental influences
hormonal and neurological influences
immune regulatory factors.

Question 9

Explain the difference between allergy and atopy?

Answer 9

Allergy = the presence of IgE in association with clinical symptoms

Atopy = the presence of IgE with no related symptoms

Question 10

Explain the pathogenesis of type 1 hypersensitivity

Answer 10

• allergen exposure causes mast cells to release granule contents and plasma cells to produce IgE specific to the allergen
• causes the release of inflammatory mediators (newly formed e.g. prostaglandins and pre-formed e.g. histamine)
• allergic response (mucosal secretion/vasodilation/oedema/capillary leakage/smooth muscle contraction)

Question 11

What is type 2 hypersensitivity?

Answer 11

• Inappropriate production of IgG or IgM antibodies which are directed against antigens found on the surface of cells or fixed within certain tissues
• Antigens can be external or self

Question 12

Describe the mechanism of the tissue damamge that occurs in type 2 hypersensitivity

Answer 12

• antibody binds to the relevant antigen
• complement is activated
• Fc binding of immunoglobulin and stimulation of phagocytes
• ADCC (antibody dependent cellular cytotoxicity)
• inhibition or stimulation of target cell function

Question 13

What is type 3 hypersensitivity?

Answer 13

clinical conditions which arise as a result of abnormal deposition of formed antigen/antibody complexes (immune complexes) in tissues

Question 14

Describe the physiological immune complex process

Answer 14

• once formed they gain access to the bloodstream
• kept soluble in the blood and transported on RBCs to the spleen/liver
• phagocytes take them up and destroy them

Question 15

Describe the pathological immune complex process

Answer 15

• complexes precipitate out into tissues, causing inflammation

Question 16

What forms can the inflammation caused by immune complex precipitation taje?

Answer 16

Systemic illness with deposition in many tissues (serum sickness)

Localised disorder with deposition locally in tissues (arthus reaction)

Question 17

What is type 4 hypersensitivity?

Answer 17

Inappropriate production/action of Th1 cells and cytokine products in response to contact with inert environmental substances or in reaction to infection with certain micro-organisms

Question 18

Why do the reactions associated with type 4 hypersensitivity occur?

Answer 18

the body’s immune system finds it difficult to destroy agents due to their function, structure or ability to evade, confound or counteract immune responses

Question 19

Why is it difficult for non-infectious environmental agents to produce a substantial immune response in themselves?

Answer 19

They are of too low a molecular weight

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

Question 20

What is a hapten?

Answer 20

A non-infectious environmental agent with too low a molecular weight to produce a substantial response in itself

Question 21

What is a carrier in relation to type 4 hypersensitivity?

Answer 21

The host protein that a hapten binds to to produce an antigenic stimulus of sufficient size to incite a response

Question 22

What is another name given to type 4 hypersensitivity and why?

Answer 22

‘Delayed-type hypersensitivity’

There is a delay of 48-72 hours between antigen exposure and any clinical effect

Question 23

Describe the pathogenesis of type 4 hypersensitivity

Answer 23

• hapten and carrier bind
• antigen uptake and presentation
• Th1 antigen recognition and cytokine production (overactivity / dysregulation)
• inflammation

Question 24

What is an autoimmune disease?

Answer 24

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

Question 25

What is tolerance in association with autoimmunity?

Answer 25

The process whereby the immune system avoids producing damaging reactions against self antigens Breakdown is a requirement for the development of autoimmune disease

Question 26

How does tolerance arise?

Answer 26

Through deletion of autoreactive T and B cells during maturation (central tolerance) Through inhibiting activity of of autoreactive cells which escape central tolerance (peripheral tolerance)

Question 27

What factors give rise to autoimmunity?

Answer 27

``` Genetic factors Immune regulatory factors Hormonal factors Environmental factors Other factors (age/trauma/malignant disease) ```

Question 28

Describe the effector mechanisms involved in autoimmune disease?

Answer 28

*Identical to those which operate in normal immune responses: - T/B cell activity - antibody activation of complement-mediated inflammation - immune complex formation - recruitment of innate immune components (phagocytes etc.)

Question 29

What are two major contributors to autoimmunity ?

Answer 29

- environmental factors - inheritance of particular HLA alleles (susceptibility) * lead to a breakdown of tolerance

Question 30

Describe the spectrum of clinical autoimmune disorders

Answer 30

From; organ specific disorders (autoimmune endocrine disorders) to non-organ specific disorders (connective tissue disorders)