Immunotoxicity

Question 1

Which categories are chemical-induced immunotoxicity divided into?

Answer 1

1) Immunosuppression
2) Immunostimulation
3) Hypersensitivity
4) Autoimmunity

Question 2

What is immunosuppression?

Answer 2

Suppression of maturation and development of immune cells leading to lower levels of immune cells.

Question 3

How can intended immunosuppression be induced?

Answer 3

Via medicines such as cyclophosphamide and cyclosporin

Question 4

How can unintended immunosuppression be induced?

Answer 4

By toxic substances such as benzene, dioxin (PCDD) and PBS

Question 5

Which drugs are immune enhancers?

Answer 5

• Levamisole (anti-helminthic)
• Interferon (IFN-alfa)
• Interleukiner (IL-2)
• Monoclonal antibodies

Question 6

Why is immunoenhancement/immunostimulation dangerous?

Answer 6

It can lead to multiorgan failure due to cytokine release syndrome

Question 7

What types of immune responses are there?

Answer 7

A – allergy, atopy, anaphylaxis (Type I)
Asthma, rhinitis, urticaria

B – antibody (Type II)
Autoimmune, (blood cells) haemolysis, inflammation

C – immune complex (arthus) (Type III)
Lupus, rheumatoid arthritis, serum sickness glomerulonephritis

D – delayed response (Type IV –> activation of T-cells)
Cell-mediated skin contact hypersensitivity

Question 8

Which two categories can immune responses be divided in from their origin?

Answer 8

1) cell mediated
Involves specifically sensitized thymus-dependent lymphocytes.

2) humoral
Involves the production of antibodies (immunoglobulins) from lymphocytes or plasma cells

Question 9

What are the preconditions to haptene induced immunological reactions?

Answer 9

1) Immunogenformation (APC T-cell receptor mediated interaction)
2) Danger signals from inflammation

Question 10

What is hypersensitivity type 1 reaction?

Answer 10

Anaphylactic reaction

A response to the attachment of the antigen to IgE antibodies, macrophages release mediators such as histamine

Histamine then releases:
–> cytokines
–> leukotrienes
Both mediators cause dilation and increased permeability of blood vessels and constriction of smooth muscles.

Question 11

What is hypersensitivity type 2 reaction?

Answer 11

Cytolytic reaction

IgG or IgM antibodies direct the immune response toward the antigen located on the cell –> Macrophages, NK cells and neutrophils are recruited by the antibodies to the site of the antigen –> destruction of the cell by phagocytosis or lysis.
Complement activiation will also damage the cell.

Question 12

What is hypersensitivity type 3 reaction?

Answer 12

Toxic Precipitin reaction

Freely circulating IgG antibodies form complexes with soluble antigens –> accumulate because they are not removed by the circulation and tissues by phagocytosis –> deposited in e.g. kidney, joints and capillaries where they cause blockage and thrombosis.

Question 13

What is hypersensitivity type 4 reaction?

Answer 13

Cell-mediated hypersensitivity reaction

The response is initiated by sensitized TH1 cells.

TH1 cells are activated by contact with APC –> this stimulates APC to secrete cytokines, which recruit macrophages, neutrophils and eosinophils –> inflammation at the site of exposure.

Question 14

What is immune tolerance?

Answer 14

State of unresponsiveness of the immune system to substances that have the potential to induce an immune response.

Question 15

Which two adverse drug reaction mechanisms are there in immunotoxicity?

Answer 15

Immunological: Hypersensitivity

Non-immunological: Intolerance

Question 16

Which type of immune reaction is seen with penicillin?

Answer 16

All four types of immune reactions are seen

Question 17

Which diseases are induced by a type 1 skin reaction?

Answer 17

Urticaria,
Angiodema,
Exanthematous rashes

Question 18

Which diseases are induced by a type 4 skin reaction?

Answer 18

• DRESS (drug reaction with eosinophilia and systemic symptoms
  Toxic epidermal necrolysis (TEN)
• Steven Johnsons syndrome
• Exanthematous pustulosis

Question 19

How does benzene induce immunotoxicity?

Answer 19

Damages the bone marrow which leads to aplastic anemia due to lower levels of lymphocytes and red blood cells.

Metabolized in the liver to hydroquinone –> in the bone marrow it is converted to the reactive quinone and semiquinone products –> reactive leading to toxicity

Question 20

How does cyclophosphamide induce immunotoxicity?

Answer 20

Inhibits the clonal expansion of T- and B-cells precursors in the bonemarrow –> anemia

Question 21

How does PCB (dioxin (TCDD), dibenzofurans, polychlorinated biphenyls) induce immunotoxicity?

Answer 21

Damages the thymus, which lead to depletion of T cells in the thymus.

Question 22

How does cyclopsporin and rapamycin induce immunotoxicity?

Answer 22

Interferes with the maturation of T and B cells.

Question 23

How does hydralazine induce immunotoxicity

Answer 23

It causes drug-induced systemic lupus erythematosus (SLE).

This is a systemic kind of toxic effect, as there is no particular target organ or tissue. It is an example of immune-mediated toxicity that involves autoimmunity and shows a number of interesting features.