Toxic responses of the
immune system
Dr.Bushra Hassan Marouf
25/04/2017
Lec: 2
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Immune system
• Immunity is a homeostatic process, a series of
delicately balanced, complex, multicellular, and
physiologic mechanisms that allow an individual to
distinguish foreign material from "self" and neutralize
and/or eliminate the foreign matter.
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• Immunotoxicology can be most simply defined as
the study of adverse effects on the immune system
resulting from occupational, inadvertent, or
therapeutic exposure to drugs, environmental
chemicals and biological materials.
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Continuum of immunotoxicity?
(Adverse outcome of immunotoxicity?)
• Decreased immunocompetence (immunosuppression)
may result in repeated, more severe, or prolonged
infections as well as the development of cancer.
• Immunoenhancement may lead to immune-mediated
diseases such as hypersensitivity responses or
autoimmune disease.
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Organs of immune system
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Reflexes such as coughing, sneezing, and
elevation in body temperature are also a
part of innate immunity.
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Antigen
• An antigen is defined functionally as a substance that
can elicit the production of a specific antibody and can
be specifically bound by that antibody.
• Generally antigens are about 10KDa ,Smaller antigens
are termed haptens and must be conjugated with
carrier molecules (larger antigens) to elicit a specific
response.
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Antibody; immunoglobulin
Fragment Antigen Binding
Fragment Crystalizable
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Immunomodulation by Xenobiotics((immune suppression, immune
enhancement, hypersensitivity, and autoimmunity)
• Immunosuppression
Immunosuppression can be produced by numerous natural and
synthetic chemicals
• Halogenated aromatic hydrocarbons : Polychlorinated biphenyls
• Polycyclic aromatic hydrocarbons :
• Nitrosamines
• Pesticides: Organophosphate pesticides
• Metals: Lead, Arsenic, Mercury, Gold, Nickel, Chromium, Cobalt
• Inhaled substances: Tobacco Smoke, Asbestos, Silica, Formaldehyde.
• Oxidant gases: Ozone (O3), Sulfur dioxide (SO2),Nitrogen dioxide (NO2)
• Aromatic hydrocarbons,
• Carbon tetrachloride, Ethylene glycol monomethyl ether
• Mycotoxins : Aflatoxin
• Estrogens ,Androgens ,Glucocorticoids
• Immunosuppressive Drugs: Cyclophosphamide, Azathioprine,
Cyclosporin
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Tobacco Smoke
In humans smokers ,
• The number of alveolar macrophages is increased three- to
fivefold in smokers compared with nonsmokers, and the
macrophages that are present appear to be in an activated
state but have decreased phagocytic and bactericidal activity.
• Decreased serum immunoglobulin levels and decreased NKcell activity have been reported.
• Concentration-dependent leukocytosis (increased numbers of
T and B cells) is well defined in smokers compared with
nonsmokers.
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Recombinant DNA–Derived Proteins
• Biologics (e.g., blood or vaccine products) and recombinant
DNA–derived proteins result in some manner from living
organisms. Any foreign protein may elicit the production of
neutralizing antibodies. The effects of neutralizing
antibodies also may lead to hypersensitivity reactions.
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Ultraviolet Radiation
• Ultraviolet radiation (UVR) suppresses delayed
hypersensitivity responses in both animals and humans and
results in a decreased host resistance to infection.
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Immune-Mediated Disease
• The purpose of the immune system is to protect the individual
from disease states—whether infectious, parasitic, or
cancerous—through both cellular and humoral mechanisms.
However, situations arise in which the individual's immune
system responds in a manner that produces tissue damage,
resulting in a self-induced disease:
• (1) hypersensitivity, or allergy, and
• (2) autoimmunity.
• Hypersensitivity reactions result because the immune system
responds in an exaggerated or inappropriate manner.
• In the case of autoimmunity, mechanisms of self-recognition
break down and immunoglobulins and T-cell receptors react
with self-antigens, resulting in tissue damage and disease.
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Coombs and Gell classification of hypersensitivity
• All four types of hypersensitivity reactions require prior exposure
leading to sensitization to elicit a reaction upon subsequent
challenge.
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Classification of hypersensitivity
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Type I (Immediate Hypersensitivity)
Type II (Antibody-Dependent Cytotoxic Hypersensitivity)
Type III (Immune Complex–Mediated Hypersensitivity)
Type IV cell delayed-type hypersensitivity (DTH) response.
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Type III (Immune Complex–Mediated
Hypersensitivity)
• Type II and III immunopathies include anemia, leukopenia,
thrombocytopenia, pneumonitis, vasculitis, lupus-like
reactions, or glomerulonephritis, and are often
indistinguishable from autoimmune reactions
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Hypersensitivity reactions to xenobiotics
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Metals
Pesticides
Natural Rubber Latex Products
Cosmetics and Personal Hygiene Products
Enzymes: Subtilin and papain
Formaldehyde
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Metals:
• Metals and metallic substances, including metallic
salts, are responsible for producing contact and
pulmonary hypersensitivity reactions. Platinum,
nickel, chromium, beryllium, and cobalt are the most
commonly implicated salts.
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Drugs:
• Hypersensitivity responses to drugs are among the
major types of unpredictable drug reactions.
• Immunologic mechanisms of hypersensitivity
reactions to drugs include types I through IV.
Penicillin is the agent most commonly involved in
drug allergy.
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Pesticides:
• Pesticides have been implicated as causal agents in
both contact and immediate hypersensitivity reactions.
Natural Rubber Latex Products:
• Natural rubber latex is used in the manufacture of over
40,000 products, including examination and surgical
gloves. Dermatologic reactions to latex include irritant
dermatitis and contact dermatitis.
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Cosmetics and Personal Hygiene Products:
• Contact dermatitis and dermatoconjuctivitis may result
from exposure to many cosmetic and personal hygiene
products. These agents contain paraben esters, sorbic
acid, phenolics, organomercurials, quaternary ammonium
compounds, and formaldehyde.
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Enzymes
• Subtilin and papain are enzymes that can elicit type
I hypersensitivity responses.
• Subtilin; is used in laundry detergents. Both
individuals working where the product is made and
those using the product may become sensitized.
Subsequent exposure may produce signs of rhinitis,
conjunctivitis, and asthma.
• Papain; is another enzyme that is known to induce
IgE-mediated disease. It is used most commonly as
a meat tenderizer and a clearing agent in beer
production.
plant enzyme papain as the tenderizing agent
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Formaldehyde
• Formaldehyde exposure occurs in the cosmetics and
textile industries and in the furniture, auto upholstery,
and resins industries. Occupational exposure to
formaldehyde has been associated with the occurrence
of asthma
Even smoothing products that do not list formaldehyde on the
label, or that claim to be "formaldehyde free" or "no
formaldehyde," can still expose workers to formaldehyde.
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When heat is applied in the Brazilian blowout process causes the methylene glycol to
dehydrate, yielding formaldehyde gas and water vapors.
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Autoimmunity
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Induction of Autoimmune Disease :
Genes versus environment
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Autoimmune Reactions to Xenobiotics
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