Immunotoxicity Flashcards
Which categories are chemical-induced immunotoxicity divided into?
1) Immunosuppression
2) Immunostimulation
3) Hypersensitivity
4) Autoimmunity
What is immunosuppression?
Suppression of maturation and development of immune cells leading to lower levels of immune cells.
How can intended immunosuppression be induced?
Via medicines such as cyclophosphamide and cyclosporin
How can unintended immunosuppression be induced?
By toxic substances such as benzene, dioxin (PCDD) and PBS
Which drugs are immune enhancers?
- Levamisole (anti-helminthic)
- Interferon (IFN-alfa)
- Interleukiner (IL-2)
- Monoclonal antibodies
Why is immunoenhancement/immunostimulation dangerous?
It can lead to multiorgan failure due to cytokine release syndrome
What types of immune responses are there?
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
Which two categories can immune responses be divided in from their origin?
1) cell mediated
Involves specifically sensitized thymus-dependent lymphocytes.
2) humoral
Involves the production of antibodies (immunoglobulins) from lymphocytes or plasma cells
What are the preconditions to haptene induced immunological reactions?
1) Immunogenformation (APC T-cell receptor mediated interaction)
2) Danger signals from inflammation
What is hypersensitivity type 1 reaction?
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.
What is hypersensitivity type 2 reaction?
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.
What is hypersensitivity type 3 reaction?
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.
What is hypersensitivity type 4 reaction?
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.
What is immune tolerance?
State of unresponsiveness of the immune system to substances that have the potential to induce an immune response.
Which two adverse drug reaction mechanisms are there in immunotoxicity?
Immunological: Hypersensitivity
Non-immunological: Intolerance
Which type of immune reaction is seen with penicillin?
All four types of immune reactions are seen
Which diseases are induced by a type 1 skin reaction?
Urticaria,
Angiodema,
Exanthematous rashes
Which diseases are induced by a type 4 skin reaction?
- DRESS (drug reaction with eosinophilia and systemic symptoms
Toxic epidermal necrolysis (TEN) - Steven Johnsons syndrome
- Exanthematous pustulosis
How does benzene induce immunotoxicity?
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
How does cyclophosphamide induce immunotoxicity?
Inhibits the clonal expansion of T- and B-cells precursors in the bonemarrow –> anemia
How does PCB (dioxin (TCDD), dibenzofurans, polychlorinated biphenyls) induce immunotoxicity?
Damages the thymus, which lead to depletion of T cells in the thymus.
How does cyclopsporin and rapamycin induce immunotoxicity?
Interferes with the maturation of T and B cells.
How does hydralazine induce immunotoxicity
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.
