The immune system is a system of biological structures and processes within an organism that protects against disease



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Overview of Immune System:

The immune system is a system of biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. In many species, the immune system can be classified into subsystems, such as the innate immune system versus the adaptive immune system, or humoral immunity versus cell-mediated immunity.


Pathogens can rapidly evolve and adapt, and thereby avoid detection and neutralization by the immune system; however, multiple defense mechanisms have also evolved to recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria possess a rudimentary immune system, in the form of enzymes that protect against bacteriophage infections. Other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants and insects. These mechanisms include phagocytosis, antimicrobial peptides called defensins, and the complement system. Jawed vertebrates, including humans, have even more sophisticated defense mechanisms, including the ability to adapt over time to recognize specific pathogens more efficiently. Adaptive (or acquired) immunity creates immunological memory after an initial response to a specific pathogen, leading to an enhanced response to subsequent encounters with that same pathogen. This process of acquired immunity is the basis of vaccination.


Disorders of the immune system can result in autoimmune diseases, inflammatory diseases and cancer. Immunodeficiency occurs when the immune system is less active than normal, resulting in recurring and life-threatening infections. In humans, immunodeficiency can either be the result of a genetic disease such as severe combined immunodeficiency, acquired conditions such as HIV/AIDS, or the use of immunosuppressive medication. In contrast, autoimmunity results from a hyperactive immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include Hashimoto's thyroiditis, rheumatoid arthritis, diabetes mellitus type 1, and systemic lupus erythematosus. Immunology covers the study of all aspects of the immune system.


This chapter will be discussed in following headings:


1.1 Timeline of Immunology.


1.2 Earlier theories.


1.3 Innate and adaptive systems.


1.4 Immune disorder.


1.5 Branches of Immunology.




Time Line of Immunology

1718 – Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolation on the native population and had the technique performed on her own children.


1796 – First demonstration of vaccination smallpox vaccination (Edward Jenner)


1837 – First description of the role of microbes in putrefaction and fermentation (Theodore Schwann)


1838 – Confirmation of the role of yeast in fermentation of sugar to alcohol (Charles Cagniard-Latour)


1840 – First "modern" proposal of the germ theory of disease (Jakob Henle)


1850 – Demonstration of the contagious nature of puerperal fever (childbed fever) (Ignaz Semmelweis)


1857-1870 – Confirmation of the role of microbes in fermentation (Louis Pasteur)


1862 – phagocytosis (Ernst Haeckel)


1867 – First aseptic practice in surgery using carbolic acid (Joseph Lister)


1876 – First demonstration that microbes can cause disease-anthrax (Robert Koch)


1877 – Mast cells (Paul Ehrlich)


1878 – Confirmation and popularization of the germ theory of disease (Louis Pasteur)


1880 – 1881 -Theory that bacterial virulence could be attenuated by culture in vitro and used as vaccines. Proposed that live attenuated microbes produced immunity by depleting host of vital trace nutrients. Used to make chicken cholera and anthrax "vaccines" (Louis Pasteur)


1883 – 1905 – Cellular theory of immunity via phagocytosis by macrophages and microphages (polymorhonuclear leukocytes) (Elie Metchnikoff)


1885 – Introduction of concept of a "therapeutic vaccination". First report of a live "attenuated" vaccine for rabies (Louis Pasteur).


1888 – Identification of bacterial toxins (diphtheria bacillus) (Pierre Roux and Alexandre Yersin)


1888 – Bactericidal action of blood (George Nuttall)


1890 – Demonstration of antibody activity against diphtheria and tetanus toxins. Beginning of humoral theory of immunity. (Emil von Behring) and (Kitasato Shibasaburō)


1891 – Demonstration of cutaneous (delayed type) hypersensitivity (Robert Koch)


1893 – Use of live bacteria and bacterial lysates to treat tumors-"Coley's Toxins" (William B. Coley)


1894 – Bacteriolysis (Richard Pfeiffer)


1896 – An antibacterial, heat-labile serum component (complement) is described (Jules Bordet)


1900 – Antibody formation theory (Paul Ehrlich)


1901 – blood groups (Karl Landsteiner)


1902 – Immediate hypersensitivity anaphylaxis (Paul Portier) and (Charles Richet)


1903 – Intermediate hypersensitivity, the "Arthus reaction" (Maurice Arthus)


1903 – Opsonization


1905 – "Serum sickness" allergy (Clemens von Pirquet and (Bela Schick)


1909 – Paul Ehrlich proposes "immune surveillance" hypothesis of tumor recognition and eradication


1911 – 2nd demonstration of filterable agent that caused tumors (Peyton Rous)


1917 – hapten (Karl Landsteiner)


1921 – Cutaneous allergic reactions (Otto Prausnitz and Heinz Küstner)


1924 – Reticuloendothelial system


1938 – Antigen-Antibody binding hypothesis (John Marrack)


1940 – Identification of the Rh antigens (Karl Landsteiner and Alexander Weiner)


1942 – Anaphylaxis (Karl Landsteiner and Merill Chase)


1942 – Adjuvants (Jules Freund and Katherine McDermott)


1944 – hypothesis of allograft rejection


1945 – Coombs Test aka antiglobulin test (AGT)


1946 – identification of mouse MHC (H2) by George Snell and Peter A. Gorer


1948 – antibody production in plasma B cells


1949 – growth of polio virus in tissue culture, neutralization with immune sera, and demonstration of attenuation of neurovirulence with repetitive passage (John Enders) and (Thomas Weller) and (Frederick Robbins)


1949 – immunological tolerance hypothesis


1951 – vaccine against yellow fever


1953 – Graft-versus-host disease


1953 – immunological tolerance hypothesis


1957 – Clonal selection theory (Frank Macfarlane Burnet)


1957 – Discovery of interferon by Alick Isaacs and Jean Lindenmann


1958–1962 – Discovery of human leukocyte antigens (Jean Dausset and others)


1959–1962 – Discovery of antibody structure (independently elucidated by Gerald Edelman and Rodney Porter)


1959 – Discovery of lymphocyte circulation (James Gowans)


1960 – Discovery of lymphocyte "blastogenic transformation" and proliferation in response to mitogenic lectins-phytohemagglutinin (PHA) (Peter Nowell)


1961-1962 Discovery of thymus involvement in cellular immunity (Jacques Miller)


1961- Demonstration that glucocorticoids inhibit PHA-induced lymphocyte proliferation (Peter Nowell)


1963 – Development of the plaque assay for the enumeration of antibody-forming cells in vitro by Niels Jerne and Albert Nordin


1963 Gell and Coombs classification of hypersensitivity


1964-1968 T and B cell cooperation in immune response


1965 – Discovery of the first lymphocyte mitogenic activity, "blastogenic factor" (Shinpei Kamakura) and (Louis Lowenstein) (J. Gordon) and (L.D. MacLean)


1965 – Discovery of "immune interferon" (gamma interferon) (E.F. Wheelock)


1965 – Secretory immunoglobulins


1967 – Identification of IgE as the reaginic antibody (Kimishige Ishizaka)


1968 – Passenger leukocytes identified as significant immunogens in allograft rejection (William L. Elkins and Ronald D. Guttmann)


1969 – The lymphocyte cytolysis Cr51 release assay (Theodore Brunner) and (Jean-Charles Cerottini)


1971 – Peter Perlmann and Eva Engvall at Stockholm University invented ELISA


1972 – Structure of the antibody molecule


1973 – Dendritic Cells first described by Ralph M. Steinman


1974 - Immune Network Hypothesis (Niels Jerne)


1974 – T-cell restriction to MHC (Rolf Zinkernagel and (Peter C. Doherty)


1975 – Generation of the first monoclonal antibodies (Georges Köhler) and (César Milstein)


1975 - First paper on an Immune Network Theory (Geoffrey W. Hoffmann)


1975 - Discovery of Natural Killer cells (Rolf Kiessling, Eva Klein, Hans Wigzell)


1976 – Identification of somatic recombination of immunoglobulin genes (Susumu Tonegawa)


1979 – Generation of the first monoclonal T cells (Kendall A. Smith)


1980-1983 – Discovery and characterization of the first interleukins, 1 and 2 IL-1 IL-2 (Kendall A. Smith)


1981 – Discovery of the IL-2 receptor IL2R (Kendall A. Smith)


1983 – Discovery of the T cell antigen receptor TCR (Ellis Reinherz) (Philippa Marrack) and (John Kappler)[2] (James Allison)


1983 – Discovery of HIV (Luc Montagnier)


1984 – The first single cell analysis of lymphocyte proliferation (Doreen Cantrell) and (Kendall A. Smith)


1985-1987 – Identification of genes for the T cell receptor


1986 – Hepatitis B vaccine produced by genetic engineering


1986 – Th1 vs Th2 model of T helper cell function (Timothy Mosmann)


1988 – Discovery of biochemical initiators of T-cell activation: CD4- and CD8-p56lck complexes (Christopher E. Rudd)


1990 – Gene therapy for SCID


1991 – Role of peptide for MHC Class II structure (Scheherazade Sadegh-Nasseri & Ronald N. Germain)


1992- Discovery of transitional B cells (David Allman & Michael Cancro)


1994 – 'Danger' model of immunological tolerance (Polly Matzinger)


1995 – Regulatory T cells (Shimon Sakaguchi)


1995 – First dendritic cell vaccine trial reported by Mukherji et al.


1996-1998 – Identification of Toll-like receptors


2001 – Discovery of FOXP3 – the gene directing regulatory T cell development


2005 – Development of human papillomavirus vaccine (Ian Frazer)




Earlier Theories

The concept of immunity has intrigued mankind for thousands of years. The prehistoric view of disease was that it was caused by supernatural forces, and that illness was a form of theurgic punishment for “bad deeds” or “evil thoughts” visited upon the soul by the gods or by one’s enemies. Between the time of Hippocrates and the 19th century, when the foundations of the scientific methods were laid, diseases were attributed to an alteration or imbalance in one of the four humors (blood, phlegm, yellow bile or black bile). Also popular during this time was the miasma theory, which held that diseases such as cholera or the Black Plague were caused by a miasma, a noxious form of "bad air". If someone were exposed to the miasma, they could get the disease.


The modern word “immunity” derives from the Latin immunis, meaning exemption from military service, tax payments or other public services. The first written descriptions of the concept of immunity may have been made by the Athenian Thucydides who, in 430 BC, described that when the plague hit Athens “the sick and the dying were tended by the pitying care of those who had recovered, because they knew the course of the disease and were themselves free from apprehensions. For no one was ever attacked a second time, or not with a fatal result. The term “immunes”, is also found in the epic poem “Pharsalia” written around 60 B.C. by the poet Marcus Annaeus Lucanus to describe a North African tribe’s resistance to snake venom.


The first clinical description of immunity which arose from a specific disease causing organism is probably Kitab fi al-jadari wa-al-hasbah (A Treatise on Smallpox and Measles, translated 1848) written by the Islamic physician Al-Razi in the 9th century. In the treatise, Al Razi describes the clinical presentation of smallpox and measles and goes on to indicate that that exposure to these specific agents confers lasting immunity (although he does not use this term).


The first scientist who developed full theory of immunity was Ilya Mechnikov after he revealed phagocytosis in 1882. With Louis Pasteur’s germ theory of disease, the fledgling science ofimmunology began to explain how bacteria caused disease, and how, following infection, the human body gained the ability to resist further infections.

The birth of active immunotherapy may have begun with Mithridates VI of Pontus. To induce active immunity for snake venom, he recommended using a method similar to modern toxoid serum therapy, by drinking the blood of animals which fed on venomous snakes. According to Jean de Maleissye, Mithridates assumed that animals feeding on venomous snakes acquired some detoxifying property in their bodies, and their blood must contain attenuated or transformed components of the snake venom. The action of those components might be strengthening the body to resist against the venom instead of exerting toxic effect. Mithridates reasoned that, by drinking the blood of these animals, he could acquire the similar resistance to the snake venom as the animals feeding on the snakes. Similarly, he sought to harden himself against poison, and took daily sub-lethal to build tolerance. Mithridates is also said to have fashioned a 'universal antidote' to protect him from all earthly poisons. For nearly 2000 years, poisons were thought to be the proximate cause of disease, and a complicated mixture of ingredients, calledMithridate, was used to cure poisoning during the Renaissance. An updated version of this cure, Theriacum Andromachi, was used well into the 19th century. In 1888 Emile Roux and Alexandre Yersin isolated diphtheria toxin, and following the 1890 discovery by Behring and Kitasato of antitoxin based immunity to diphtheria and tetanus, the antitoxin became the first major success of modern therapeutic Immunology.


In Europe, the induction of active immunity emerged in an attempt to contain smallpox. Immunization, however, had existed in various forms for at least a thousand years. The earliest use of immunization is unknown, however, around 1000 A.D. the Chinese began practicing a form of immunization by drying and inhaling powders derived from the crusts of smallpox lesions. Around the fifteenth century in India, the Ottoman Empire, and east Africa, the practice of inoculation (poking the skin with powdered material derived from smallpox crusts) became quite common.  This practice was first introduced into the west in 1721 by Lady Mary Wortley Montagu.  In 1798, Edward Jenner introduced the far safer method of deliberate infection with cowpox virus, (smallpox vaccine), which caused a mild infection that also induced immunity to smallpox. By 1800 the procedure was referred to as vaccination. To avoid confusion, smallpox inoculation was increasingly referred to as variolation, and it became common practice to use this term without regard for chronology. The success and general acceptance of Jenner's procedure would later drive the general nature of vaccination developed by Pasteur and others towards the end of the 19th century. In 1891, Pasteur widened the definition of vaccine in honour of Jenner and it then became essential to qualify the term, by referring to polio vaccine, measles vaccine etc.




Innate Immune System

Microorganisms or toxins that successfully enter an organism encounter the cells and mechanisms of the innate immune system. The innate response is usually triggered when microbes are identified by pattern recognition receptors, which recognize components that are conserved among broad groups of microorganisms, or when damaged, injured or stressed cells send out alarm signals, many of which (but not all) are recognized by the same receptors as those that recognize pathogens. Innate immune defenses are non-specific, meaning these systems respond to pathogens in a generic way. This system does not confer long-lasting immunity against a pathogen. The innate immune system is the dominant system of host defense in most organisms.


The innate immune system is an evolutionarily older defense strategy, and is the dominant immune system found in plants, fungi, insects, and primitive multicellular organisms.




Adaptive immune system

The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by a signature antigen. The adaptive immune response is antigen-specific and requires the recognition of specific "non-self" antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.


The system is highly adaptable because of somatic hypermutation (a process of accelerated somatic mutations), and V(D)J recombination (an irreversible genetic recombination of antigen receptor gene segments). This mechanism allows a small number of genes to generate a vast number of different antigen receptors, which are then uniquely expressed on each individual lymphocyte. Because the gene rearrangement leads to an irreversible change in the DNA of each cell, all of the progeny (offspring) of that cell will then inherit genes encoding the same receptor specificity, including the Memory B cells and Memory T cells that are the keys to long-lived specific immunity.


A detailed description of innate and adaptive immunity can be looked up in chapter 3.




Immune Disorder

An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:


By the component(s) of the immune system affected


By whether the immune system is overactive or underactive


By whether the condition is congenital or acquired


According to the International Union of Immunological Societies, more than 150 primary immunodeficiency diseases (PIDs) have been characterized. However, the number of acquired immune-deficiencies exceeds the number of PIDs.


It has been suggested that most people have at least one primary immunodeficiency. Due to redundancies in the immune system, though, many of these are never detected.


Primary immune deficiency diseases are those caused by inherited genetic mutations. Secondary or acquired immune deficiencies are caused by something outside the body such as a virus or immune suppressing drugs.


Primary immune diseases are at risk to an increased susceptibility to, and often recurrent ear infections, pneumonia, bronchitis, sinusitis or skin infections. Immunodeficient patients may less frequently develop abscesses of their internal organs, autoimmune or rheumatologic and gastrointestinal problems.


Immunodeficiency thus is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired ("secondary") but some people are born with defects in their immune system, or primary immunodeficiency. Transplant patients take medications to suppress their immune system as an anti-rejection measure, as do some patients suffering from an over-active immune system. A person who has an immunodeficiency of any kind is said to be immunocompromised. An immunocompromised person may be particularly vulnerable to opportunistic infections, in addition to normal infections that could affect everyone.


TYPES:


Following are the types of immune-deficiency


1. By affected component


This includes:




Humoral immune deficiency, with signs or symptoms depending on the cause, but generally include signs of hypogammaglobulinemia (decrease of one or more types of antibodies) with presentations including repeated mild respiratory infections, and/or agammaglobulinemia (lack of all or most antibody production) which results in frequent severe infections and is often fatal. The main pathogens involved include Streptococcus pneumonia, Hemophilus influenza and Pneumocystis jirovecii which affect B-cells, Plasma cells and antibodies.



T cell deficiency, often causes secondary disorders such as acquired immune deficiency syndrome.



Granulocyte deficiency, including decreased numbers of granulocytes (called as granulocytopenia or, if absent, agranulocytosis) such as of neutrophil granulocytes (termed neutropenia). Granulocyte deficiencies also include decreased function of individual granulocytes, such as in chronic granulomatous disease.


Asplenia, where there is no function of the spleen


Complement deficiency is where the function of the complement system is deficient

In reality, immunodeficiency often affects multiple components, with notable examples including severe combined immunodeficiency (which is primary) and acquired immune deficiency syndrome (which is secondary).


2. Primary or secondary


Distinction between primary versus secondary immunodeficiencies are based on, respectively, whether the cause originates in the immune system itself or is, in turn, due to insufficiency of a supporting component of it or an external decreasing factor of it.




Primary immunodeficiency (PID)

A number of rare diseases feature a heightened susceptibility to infections from childhood onward. Primary Immunodeficiency is also known as congenital immunodeficiencies. Many of these disorders are hereditary and are autosomal recessive or X-linked. There are over 80 recognised primary immunodeficiency syndromes; they are generally grouped by the part of the immune system that is malfunctioning, such as lymphocytes or granulocytes.


The treatment of primary immunodeficiencies depends on the nature of the defect, and may involve antibody infusions, long-term antibiotics and (in some cases) stem cell transplantation.




Secondary immunodeficiencies

Secondary immunodeficiencies, also known as acquired immunodeficiencies, can result from various immunosuppressive agents, for example, malnutrition, aging and particular medications (e.g. chemotherapy, disease-modifying antirheumatic drugs, immunosuppressive drugs after organ transplants, glucocorticoids). For medications, the term immunosuppression generally refers to both beneficial and potential adverse effects of decreasing the function of the immune system, while the term immunodeficiency generally refers solely to the adverse effect of increased risk for infection.


Many specific diseases directly or indirectly cause immunosuppression. This includes many types of cancer, particularly those of the bone marrow and blood cells (leukemia, lymphoma, multiple myeloma), and certain chronic infections. Immunodeficiency is also the hallmark of acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV). HIV directly infects a small number of T helper cells, and also impairs other immune system responses indirectly.




Branches of Immunology

There are many branches of Immmunology. Some of them are briefed here:




Classical immunology

Classical immunology ties in with the fields of epidemiology and medicine. It studies the relationship between the body systems, pathogens, and immunity. The earliest written mention of immunity can be traced back to the plague of Athens in 430 BCE. Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. Many other ancient societies have references to this phenomenon, but it was not until the 19th and 20th centuries before the concept developed into scientific theory.


The study of the molecular and cellular components that comprise the immune system, including their function and interaction, is the central science of immunology. The immune system has been divided into a more primitive innate immune system, and acquired or adaptive immune system of vertebrates, the latter of which is further divided into humoral and cellular components.


The humoral (antibody) response is defined as the interaction between antibodies and antigens. Antibodies are specific proteins released from a certain class of immune cells (B lymphocytes). Antigens are defined as anything that elicits generation of antibodies, hence they are Antibody Generators. Immunology itself rests on an understanding of the properties of these two biological entities. However, equally important is the cellular response, which can not only kill infected cells in its own right, but is also crucial in controlling the antibody response. Put simply, both systems are highly interdependent.


In the 21st century, immunology has broadened its horizons with much research being performed in the more specialized niches of immunology. This includes the immunological function of cells, organs and systems not normally associated with the immune system, as well as the function of the immune system outside classical models of immunity (Yemeserach 2010).




Clinical immunology

Clinical immunology is the study of diseases caused by disorders of the immune system (failure, aberrant action, and malignant growth of the cellular elements of the system). It also involves diseases of other systems, where immune reactions play a part in the pathology and clinical features.


The diseases caused by disorders of the immune system fall into two broad categories: immunodeficiency, in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease and primary immune diseases), and autoimmunity, in which the immune system attacks its own host's body (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimoto's disease and myasthenia gravis). Other immune system disorders include different hypersensitivities, in which the system responds inappropriately to harmless compounds (asthma and other allergies) or responds too intensely.


The most well-known disease that affects the immune system itself is AIDS, caused by HIV. AIDS is an immunodeficiency characterized by the lack of CD4+ ("helper") T cells, dendritic cells and macrophages, which are destroyed by HIV.


Clinical immunologists also study ways to prevent transplant rejection, in which the immune system attempts to destroy allografts




Computational immunology

Computational immunology is a branch of bioinformatics and it is based on similar concepts and tools, such as sequence alignment and protein structure prediction tools. Immunomics is a discipline like genomics and proteomics. It is a science, which specifically combines Immunology with computer science, mathematics, chemistry, and biochemistry for large-scale analysis of immune system functions. It aims to study the complex protein–protein interactions and networks and allows a better understanding of immune responses and their role during normal, diseased and reconstitution states. Computational immunology is a part of immunomics, which is focused on analyzing large scale experimental data.




Diagnostic immunology

Immunodiagnostics is a diagnostic methodology that uses an antigen-antibody reaction as their primary means of detection. The concept of using immunology as a diagnostic tool was introduced in 1960 as a test for serum insulin. A second test was developed in 1970 as a test for thyroxine in the 1970s.


It is well-suited for the detection of even the smallest of amounts of (bio)chemical substances. Antibodies specific for a desired antigen can be conjugated with a radiolabel, fluorescent label, or color-forming enzyme and are used as a "probe" to detect it. Well known applications include pregnancy tests, immunoblotting, ELISA and immunohistochemical staining of microscope slides. The speed, accuracy and simplicity of such tests has led to the development of rapid techniques for the diagnosis of disease, microbes and even illegal drugs in vivo (of course tests conducted in a closed environment have a higher degree of accuracy). Such testing is also used to distinguish compatible blood types.


The Enzyme-Linked ImmunoSorbent Assay or ELISA and the Lateral-Flow test, also known as the dipstick or rapid test, currently are the two predominant formats in immunodiagnostics.




Systems immunology

Systems Immunology is a recent research field that, under the larger umbrella of systems biology, aims to study the immune system in the more integrated perspective on how entities and players participate at different system levels to the immune function.


The immune system has been thoroughly analyzed as regards to its components and function by using a very successful "reductionist" approach, but its overall functioning principles cannot easily be predicted by studying the properties of its isolated components because they strongly rely on and arise from the interactions among these numerous constituents. Systems immunology represents a different approach for the integrated comprehension of the immune system structure and function based on complex systems theory, high-throughput techniques, as well as on mathematical and computational tools.




Nutritional immunology

Nutritional immunology research is centered around studying the mechanisms underlying the modulation of immune responses by nutritional, naturally occurring and orally active compounds.


Nutritional immunology researchers have discovered novel mechanisms by which naturally occurring compounds such as conjugated linoleic acid, abscisic acid, n-3 polyunsaturated fatty acids, resveratrol, curcumin, limonin, Vitamin E, Vitamin A, and Vitamin D modulate immune responses. Recent advances in nutritional immunology research include applying systems biology, as well as modelling and simulation approaches to accelerate the identification of novel therapeutic targets, biomarkers and the discovery of novel mechanisms of action. In one embodiment Nutritional Immunology relates to the preventive applications of personalized medicine with particular emphasis on immune modulatory effects of naturally occurring, safe and orally active compounds.


Nutritional immunology is an emerging discipline that evolved with the study of the detrimental effect of malnutrition on the immune system. While malnutrition still remains a worldwide problem, life-stage [neonate or old age] and natural stress are increasingly becoming the major causes of lowered immune status in both humans and animals. Unlike immunodeficiency caused by malnutrition, life-stage and natural stress need a more comprehensive strategy and cannot be addressed simply by correcting nutritional problems. Lowered immune status because of life-stage or natural stress is characterized by a reduced of antigen presenting cells [APC] function, resulting in a less efficient or altered immune response, leading to increased susceptibility to infections disease, increase in autoimmunity and cancers.




Immunotoxicology

Immunotoxicology (sometimes abbreviated as ITOX) is the study of immune dysfunction resulting from exposure of an organism to a xenobiotic. The immune dysfunction may take the form of immunosuppression or alternatively, allergy, autoimmunity or any number of inflammatory-based diseases or pathologies. Because the immune system plays a critical role in host resistance to disease as well as in normal homeostasis of an organism, identificantion of immunotoxic risk is significant in the protection of human, animal and wildlife health.


In the non-adult (embryo, fetus, neonate, juvenile, adolescent) this study is referred to as Developmental Immunotoxicology (commonly abbreviated as DIT). For most toxicants examined to date, the developing immune system exhibits a heightened sensitivity compared with that of an adult. For this reason, DIT screening has applications to human, animal and wildlife health protection.




Cancer immunology/Immunooncology

Cancer immunology is a branch of immunology that studies interactions between the immune system and cancer cells (also called tumors or malignancies). It is a growing field of research that aims to discover innovative cancer immunotherapies to treat and retard progression of the disease. The immune response, including the recognition of cancer-specific antigens, is of particular interest in the field as knowledge gained drives the development of new vaccines, antibody therapies, and tumor marker-based diagnostic tests. For instance in 2007, Ohtani published a paper finding tumour infiltrating lymphocytes to be quite significant in human colorectal cancer. The host was given a better chance at survival if the cancer tissue showed infiltration of inflammatory cells, in particular those prompting lymphocytic reactions. The results yielded suggest some extent of anti-tumour immunity is present in colorectal cancers in humans.




Over the past 10 years there has been notable progress and an accumulation of scientific evidence for the concept of cancer immunosurveillance and immunoediting based on (i) protection against development of spontaneous and chemically-induced tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.


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