Hypersensitivity and Autoimmunity

Question 1

Type I

Answer 1

• Allergy
• Inappropriate genesis of IgE
• IgE is directed against environmental antigens which may be airborne, ingested, injected or encountered through skin contact
• You need symptoms otherwise it’s atopy

Question 2

Reasons we get these allergic reactions

Answer 2

Combination of:

• interacting genetic factors
• environmental influences
• hormonal
• neurological influences

Question 3

Pathogenesis of type I

Answer 3

• Allergen exposure
• Mast cell + allergen specific IgE
• Release of inflammatory mediators (mucosal oedema, capillary leakage, secretions, smooth muscle contraction, vasodilatation)

Question 4

Type II

Answer 4

• Mediated by IgG or IgM antibodies which are directed against antigens found on the surface of cells or fixed within certain tissues
• Antigens can be exogenous or derived from self

Question 5

Mechanisms of type II damage

Answer 5

• Complement-dependent lysis (complement activation)
• Fc receptor-mediated damage: Fc binding of immunoglobulin and stimulation of phagcytes
• Antibody-dependent cellular cytotoxicity (ADCC): actively lysing target cell
• Effect on target cell function: inhibition and stimulation

Question 6

Type III

Answer 6

• Abnormal deposition of formed antigen (Ag)/antibody (Ab) complexes (immune complex formation) in tissues
• Can be exogenous or self

Question 7

Type III - Immune complex formation

Answer 7

• Normal physiological process
• Complex formed to gain access to the blood stream and are kept soluble in the blood and transported to liver and spleen where the complexes are destroyed

Question 8

What are the two ways that immune complexes can be formed?

Answer 8

• Physiological: normal, no symptoms or disease association
• Pathological: antigen factors, host response factors. 2 forms, serum sickness where immune complexes are deposited everywhere and arthus reaction where complexes form locally in tissues

Question 9

Pathogenesis of type III

Answer 9

• Excessive or abnormal immune complex formation -> complement activation + recruitment of inflammatory cells -> tissue damage

Question 10

Type IV

Answer 10

• Mediated by Th1 cells and the cytokine products (mostly interleukin-2 and gamma-interferon)
• Inappropriate response to inert environmental substances
• Reaction to infection with certain micro-organisms
• Usually delayed onset of about 48-72 hours

Question 11

Why is there a type IV reaction from inert environmental substances?

Answer 11

• Too low a molecular weight to produce a substantial immune response
• Agent = HAPTEN and host protein is a CARRIER
• Carrier is necessary to produce antigenic bulk but the immune response is physically directed against the HAPTEN

Question 12

Why is there a type IV reaction from micro-organisms?

Answer 12

• Happens when body finds it hard to destroy these environmental agents
• Micro-organisms such as mycobacteria don’t do any harm but the immune response causes tissue damage.
• It evades, confounds or counteracts the immune response

Question 13

Pathogenesis of type IV reactions

Answer 13

• Hapten + endogenous protein or microorganism

- > antigen uptake & presentation (HLA class II) -> Th1 antigen recognition/cytokine production -> inflammation

Question 14

Mechanisms of immunological tolerance

Answer 14

• Central tolerance

- Peripheral tolerance

Question 15

Central tolerance

Answer 15

• Arises through deletion of autoreactive T&B cells during cell maturation
• AKA positive and negative selection

Question 16

Peripheral tolerance

Answer 16

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

Question 17

Why is recognition of self not always damaging?

Answer 17

• T cells recognise antigen which is complexed with self molecules
• Antibodies can recognise and bind portions of other antibodies which regulates their production and activity

Question 18

What is autoimmune disease?

Answer 18

• Clinical disorders characterised by tissue or organ damage mediated through aberrant cellular and/or humoral immunological mechanisms
• Directed against autoantigens: can be throughout many tissues, or localised in specific organs or tissues

Question 19

Factors involved in autoimmune disease

Answer 19

• Genetic factors
• Immune regulatory factors (defective tolerance induction, defective peripheral tolerance mechanisms)
• Hormonal factors (esp. female hormones)
• Environmental factors (infectious agents, sunlight, drugs, chemicals, nutritional factors)
• Misc (age, trauma, malignant disease)

Question 20

What pathogenic mechanisms are involved in autoimmune disease?

Answer 20

Same as normal immune response:

• Cellular or antibody activity
• (auto)antibody activation of the complement-mediated inflammation
• Immune complex formation (Type III hypersensitivity)
• Recruitment of innate immune components (phagocytes/cytokines/NK cells)

Question 21

Pathogenesis of autoimmune disease

Answer 21

Initiating event (environment) -> genetic factors e.g. particular HLA alleles -> breakdown of self tolerance -> autoreactivity -> humoral =/- cellular -> tissue damage

Question 22

Organ-specific vs non-organ specific

Answer 22

• Organ specific: Hashimoto’s thyroiditis

- Non-organ: Rheumatoid arthritis