Immunotoxicology

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Immunotoxicology (sometimes abbreviated as ITOX) is the study of the toxicity of foreign substances called xenobiotics and their effects on the immune system. [1] Some toxic agents that are known to alter the immune system include: industrial chemicals, heavy metals, agrochemicals, pharmaceuticals, drugs, ultraviolet radiation, air pollutants and some biological materials. [2] [1] [3] The effects of these immunotoxic substances have been shown to alter both the innate and adaptive parts of the immune system. Consequences of xenobiotics affect the organ initially in contact (often the lungs or skin). [4] Some commonly seen problems that arise as a result of contact with immunotoxic substances are: immunosuppression, hypersensitivity, and autoimmunity. [1] The toxin-induced immune dysfunction may also increase susceptibility to cancer. [2]

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The study of immunotoxicology began in the 1970s. [3] However, the idea that some substances have a negative effect on the immune system was not a novel concept as people have observed immune system alterations as a result of contact toxins since ancient Egypt. [3] Immunotoxicology has become increasingly important when considering the safety and effectiveness of commercially sold products. In recent years, guidelines and laws have been created in the effort to regulate and minimize the use of immunotoxic substances in the production of agricultural products, drugs, and consumer products. [3] One example of these regulations are FDA guidelines mandate that all drugs must be tested for toxicity to avoid negative interactions with the immune system, and in-depth investigations are required whenever a drug shows signs of affecting the immune system. [1] Scientists use both in vivo and in vitro techniques when determining the immunotoxic effects of a substance. [5]

Immunotoxic agents can damage the immune system by destroying immune cells and changing signaling pathways. [5] This has wide-reaching consequences in both the innate and adaptive immune systems. [1] Changes in the adaptive immune system can be observed by measuring levels of cytokine production, modification of surface markers, activation, and cell differentiation. [4] There are also changes in macrophages and monocyte activity indicating changes in the innate immune system. [5]

Immunosuppression

Some common agents that have been shown to cause immunosuppression are corticosteroids, radiation, heavy metals, halogenated aromatic hydrocarbons, drugs, air pollutants and immunosuppressive drugs. [4] [3] These chemicals can result in mutations found in regulatory genes of the immune system, which alter the amount of critical cytokines produced and can cause insufficient immune responses when antigens are encountered. [4] These agents have also been known to kill or damage immune cells and cells in the bone marrow, resulting in difficulty recognizing antigens and creating novel immune responses. This can be measured by decreased IgM and IgG antibody levels which are an indicator of immune suppression. [1] T regulatory cells, which are critical to maintaining the correct level of response in the immune system, also appear to be altered by some agents. [5] In the presence of certain immunotoxic substances, granulocytes of the innate immune system have also been observed to be damaged causing the rare disease agranulocytosis. [5] Vaccine effectiveness can also be decreased when the immune system is suppressed by immunotoxic substances. [5] In vitro T-lymphocyte activation assays have been useful when determining which substances have immunosuppressive properties. [4]

Hypersensitivity

Hypersensitive or allergic reactions, such as asthma, are commonly associated with immunotoxic agents and the number of people exhibiting these symptoms is increasing in industrial countries. This partially due to the increasing number of immunotoxic agents. [1] [5] Nanomaterials are commonly absorbed through the skin or inhaled and are known for causing hypersensitive responses by recruiting immune cells. [6] These nanomaterials are often encountered when a person is in contact with chemicals in an occupational, consumer, or environmental setting. [1] Agents that are known for creating a hypersensitive response include poison ivy, fragrances, cosmetics, metals, preservatives, and pesticides. [1] These molecules that are so small, they act as haptens and bind to larger molecules to induce an immune response. [6] An allergic response is induced when T lymphocytes recognize these haptens and recruit professional antigen-presenting cells. [4] IgE antibodies are important when looking at hypersensitive reactions but cannot be used to definitively determine the effects of an immunotoxic agents. [1] Because of this, in vivo testing is the most effective way to determine the potential toxicity of nanomaterials and other agents that are believed to cause hypersensitivity. [6]

Autoimmunity

Immunotoxic agents can increase the occurrence of immune system attacks on self molecules. [1] Although autoimmunity mostly occurs as a result of genetic factors, immunotoxic agents such as asbestos, sulfadiazine, silica, paraffin and silicone can also increase the chance of an autoimmune attack. [1] [5] These agents are known for causing disturbances to the carefully regulated immune system and increasing the development of autoimmunity. [4] Changes in the circulating regulatory and responder T cells are good indicators of an autoimmune response induced by an immunotoxic agent. [3] The effects of autoimmunity have been examined primarily through studies with animal models. Currently, there is not a screen to determine how agents affect human autoimmunity, because of this much of the current knowledge about autoimmunity in response to immunotoxic agents comes from the observations of individuals who have been exposed to suspected immunotoxic agents. [1] [3]

See also

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Immune system Biological system protecting an organism against disease

The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.

Immunology Branch of medicine studying the immune system

Immunology is a branch of biology and Medicine that covers the study of immune systems in all organisms. Immunology charts, measures, and contextualizes the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; and the physical, chemical, and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo. Immunology has applications in numerous disciplines of medicine, particularly in the fields of organ transplantation, oncology, rheumatology, virology, bacteriology, parasitology, psychiatry, and dermatology.

Autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other body normal constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, post-infectious IBS, diabetes mellitus type 1, Henloch Scholein Pupura (HSP) sarcoidosis, systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM) and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

T helper cell Type of immune cell

The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. As their name suggests, they "help" the activity of other immune cells by releasing cytokines, small protein mediators that alter the behavior of target cells that express receptors for those cytokines. These cells help to polarize the immune response into the appropriate kind depending on the nature of the immunological insult (virus vs. extracellular bacterium vs. intracellular bacterium vs. helminth vs. fungus vs. protist). They are generally considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils.

Immunosuppressive drug

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.

In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens irrespective of their antigenic make-up. Other components of the immune system adapt themselves to each new disease encountered and can generate pathogen-specific immunity.

Hypersensitivity Medical condition

Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune system and these reactions may be damaging and uncomfortable. This is an immunologic term and is not to be confused with the psychiatric term of being hypersensitive which implies to an individual who may be overly sensitive to physical and/or emotional stimuli. Although there is a relation between the two - studies have shown that those individuals that have ADHD are more likely to have hypersensitivity reactions such as allergies, asthma, eczema than those who do not have ADHD.

Haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein; the carrier may be one that also does not elicit an immune response by itself . Once the body has generated antibodies to a hapten-carrier adduct, the small-molecule hapten may also be able to bind to the antibody, but it will usually not initiate an immune response; usually only the hapten-carrier adduct can do this. Sometimes the small-molecule hapten can even block immune response to the hapten-carrier adduct by preventing the adduct from binding to the antibody, a process called hapten inhibition.

Superantigen

Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically it causes non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where 0.0001-0.001% of the body's T-cells are activated, these SAgs are capable of activating up to 20% of the body's T-cells. Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens.

Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body. They are a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope.

Adaptive immune system Subsystem of the immune system that is composed of specialized, systemic cells and processes

The adaptive immune system, also referred as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.

Immunopathology is a branch of medicine that deals with immune responses associated with disease. It includes the study of the pathology of an organism, organ system, or disease with respect to the immune system, immunity, and immune responses. In biology, it refers to damage caused to an organism by its own immune response, as a result of an infection. It could be due to mismatch between pathogen and host species, and often occurs when an animal pathogen infects a human.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

Immune complex

An immune complex, sometimes called an antigen-antibody complex or antigen-bound antibody, is a molecule formed from the binding of multiple antigens to antibodies. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases. Red blood cells carrying CR1-receptors on their surface may bind C3b-coated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return to the general circulation.

Immune dysregulation is any proposed or confirmed breakdown or maladaptive change in molecular control of immune system processes. For example, dysregulation is a component in the pathogenesis of autoimmune diseases and some cancers. Immune system dysfunction, as seen in IPEX syndrome leads to immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX). IPEX typically presents during the first few months of life with diabetes mellitus, intractable diarrhea, failure to thrive, eczema, and hemolytic anemia. unrestrained or unregulated immune response.

In immunology, an adjuvant is a substance that increases or modulates the immune response to a vaccine. The word "adjuvant" comes from the Latin word adiuvare, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."

A drug allergy is an allergy to a drug, most commonly a medication, and is a form of adverse drug reaction. Medical attention should be sought immediately if an allergic reaction is suspected.

Autoimmune disease Abnormal immune response to a normal body part

An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.

Severe cutaneous adverse reactions are a group of potentially lethal adverse drug reactions that involve the skin and mucous membranes of various body openings such as the eyes, ears, and inside the nose, mouth, and lips. In more severe cases, SCARs also involves serious damage to internal organs. SCARs includes five syndromes: Drug reaction with eosinophilia and systemic symptoms ; Stevens–Johnson syndrome (SJS); Toxic epidermal necrolysis (TEN), Stevens-Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN); and Acute generalized exanthematous pustulosis (AGEP). The five disorders have similar pathophysiologies, i.e. disease-causing mechanisms, for which new strategies are in use or development to identify individuals predisposed to develop the SCARs-inducing effects of specific drugs and thereby avoid treatment with them. Maculopapular rash (MPR) is a less-well defined and benign form of drug-induced adverse skin reactions; while not classified in the SCARs group, it shares with SCARS a similar pathophysiology and is caused by some of the same drugs which cause SCARs.

The p-i concept refers to “pharmacological interaction of drugs with immune receptors”. It explains a form of drug hypersensitivity (DH), namely T cell stimulations by drugs, which can lead to various acute inflammatory manifestations and late complications in the absence of the eliciting drug.

References

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