Immunology

Last updated
Immunology
MRSA, Ingestion by Neutrophil.jpg
MRSA (yellow) enguled by neutrophil (purple) Photo Source: National Institute of Allergy and Infectious Diseases
System Immune
Subdivisions Genetic (Immunogenetics)
Significant diseases Rheumatoid arthritis Inflammation
Significant tests
Specialist Immunologist

Immunology is a branch of biology and medicine [1] that covers the study of immune systems [2] in all organisms.

Contents

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 (such as autoimmune diseases, hypersensitivities, [3] immune deficiency, [4] and transplant rejection [5] ); and the physical, chemical, and physiological characteristics of the components of the immune system in vitro , [6] in situ , and in vivo . [7] Immunology has applications in numerous disciplines of medicine, particularly in the fields of organ transplantation, oncology, rheumatology, virology, bacteriology, parasitology, psychiatry, and dermatology.

The term was coined by Russian biologist Ilya Ilyich Mechnikov, [8] who advanced studies on immunology and received the Nobel Prize for his work in 1908 with Paul Ehrlich "in recognition of their work on immunity". He pinned small thorns into starfish larvae and noticed unusual cells surrounding the thorns. This was the active response of the body trying to maintain its integrity. It was Mechnikov who first observed the phenomenon of phagocytosis, [9] in which the body defends itself against a foreign body. Ehrlich accustomed mice to the poisons ricin and abrin. After feeding them with small but increasing dosages of ricin he ascertained that they had become "ricin-proof". Ehrlich interpreted this as immunization and observed that it was abruptly initiated after a few days and was still in existence after several months.

Prior to the designation of immunity, [10] from the etymological root immunis, which is Latin for 'exempt', early physicians characterized organs that would later be proven as essential components of the immune system. The important lymphoid organs of the immune system are the thymus, [11] bone marrow, and chief lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and liver. However, many components of the immune system are cellular in nature, and not associated with specific organs, but rather embedded or circulating in various tissues located throughout the body.

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. [12] 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, in vertebrates, an acquired or adaptive immune system. The latter is further divided into humoral (or antibody) and cell-mediated components.[ citation needed ]

The immune system has the capability of self and non-self-recognition. [13] An antigen is a substance that ignites the immune response. The cells involved in recognizing the antigen are Lymphocytes. Once they recognize, they secrete antibodies. Antibodies are proteins that neutralize the disease-causing microorganisms. Antibodies do not directly kill pathogens, but instead, identify antigens as targets for destruction by other immune cells such as phagocytes or NK cells.

The (antibody) response is defined as the interaction between antibodies and antigens. [14] Antibodies are specific proteins released from a certain class of immune cells known as B lymphocytes, while antigens are defined as anything that elicits the generation of antibodies (antibody generators). Immunology rests on an understanding of the properties of these two biological entities and the cellular response to both.

It is now getting clear that the immune responses contribute to the development of many common disorders not traditionally viewed as immunologic, [15] including metabolic, cardiovascular, cancer, and neurodegenerative conditions like Alzheimer's disease. Besides, there are direct implications of the immune system in the infectious diseases (tuberculosis, malaria, hepatitis, pneumonia, dysentery, and helminth infestations) as well. Hence, research in the field of immunology is of prime importance for the advancements in the fields of modern medicine, biomedical research, and biotechnology.

Immunological research continues to become more specialized, pursuing non-classical models of immunity and functions of cells, organs and systems not previously associated with the immune system (Yemeserach 2010).

Diagnostic immunology

The specificity of the bond between antibody and antigen has made the antibody an excellent tool for the detection of substances by a variety of diagnostic techniques. Antibodies specific for a desired antigen can be conjugated with an isotopic (radio) or fluorescent label or with a color-forming enzyme in order to detect it. However, the similarity between some antigens can lead to false positives and other errors in such tests by antibodies cross-reacting with antigens that are not exact matches. [16]

Immunotherapy

The use of immune system components or antigens to treat a disease or disorder is known as immunotherapy. Immunotherapy is most commonly used to treat allergies, autoimmune disorders such as Crohn's disease, Hashimoto's thyroiditis and rheumatoid arthritis, and certain cancers. Immunotherapy is also often used for patients who are immunosuppressed (such as those with HIV) and people with other immune deficiencies. This includes regulating factors such as IL-2, IL-10, GM-CSF B, IFN-α.

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:

Other immune system disorders include various hypersensitivities (such as in asthma and other allergies) that respond inappropriately to otherwise harmless compounds.

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

Clinical immunologists also study ways to prevent the immune system's attempts to destroy allografts (transplant rejection). [17]

Clinical immunology and allergy is usually a subspecialty of internal medicine or pediatrics. Fellows in Clinical Immunology are typically exposed to many of the different aspects of the specialty and treat allergic conditions, primary immunodeficiencies and systemic autoimmune and autoinflammatory conditions. As part of their training fellows may do additional rotations in rheumatology, pulmonology, otorhinolaryngology, dermatology and the immunologic lab. [18]

Clinical and pathology immunology

When health conditions worsen to emergency status, portions of immune system organs, including the thymus, spleen, bone marrow, lymph nodes, and other lymphatic tissues, can be surgically excised for examination while patients are still alive.

Theoretical immunology

Immunology is strongly experimental in everyday practice but is also characterized by an ongoing theoretical attitude. Many theories have been suggested in immunology from the end of the nineteenth century up to the present time. The end of the 19th century and the beginning of the 20th century saw a battle between "cellular" and "humoral" theories of immunity. According to the cellular theory of immunity, represented in particular by Elie Metchnikoff, it was cells – more precisely, phagocytes – that were responsible for immune responses. In contrast, the humoral theory of immunity, held by Robert Koch [19] and Emil von Behring, [20] among others, stated that the active immune agents were soluble components (molecules) found in the organism's "humors" rather than its cells. [21] [22] [23]

In the mid-1950s, Macfarlane Burnet, inspired by a suggestion made by Niels Jerne, [24] formulated the clonal selection theory (CST) of immunity. [25] On the basis of CST, Burnet developed a theory of how an immune response is triggered according to the self/nonself distinction: "self" constituents (constituents of the body) do not trigger destructive immune responses, while "nonself" entities (e.g., pathogens, an allograft) trigger a destructive immune response. [26] The theory was later modified to reflect new discoveries regarding histocompatibility or the complex "two-signal" activation of T cells. [27] The self/nonself theory of immunity and the self/nonself vocabulary have been criticized, [23] [28] [29] but remain very influential. [30] [31]

More recently, several theoretical frameworks have been suggested in immunology, including "autopoietic" views, [32] "cognitive immune" views, [33] the "danger model" (or "danger theory"), [28] and the "discontinuity" theory. [34] [35] The danger model, suggested by Polly Matzinger and colleagues, has been very influential, arousing many comments and discussions. [36] [37] [38] [39]

Developmental immunology

The body's capability to react to antigens depends on a person's age, antigen type, maternal factors and the area where the antigen is presented. [40] Neonates are said to be in a state of physiological immunodeficiency, because both their innate and adaptive immunological responses are greatly suppressed. Once born, a child's immune system responds favorably to protein antigens while not as well to glycoproteins and polysaccharides. In fact, many of the infections acquired by neonates are caused by low virulence organisms like Staphylococcus and Pseudomonas . In neonates, opsonic activity and the ability to activate the complement cascade is very limited. For example, the mean level of C3 in a newborn is approximately 65% of that found in the adult. Phagocytic activity is also greatly impaired in newborns. This is due to lower opsonic activity, as well as diminished up-regulation of integrin and selectin receptors, which limit the ability of neutrophils to interact with adhesion molecules in the endothelium. Their monocytes are slow and have a reduced ATP production, which also limits the newborn's phagocytic activity. Although, the number of total lymphocytes is significantly higher than in adults, the cellular and humoral immunity is also impaired. Antigen-presenting cells in newborns have a reduced capability to activate T cells. Also, T cells of a newborn proliferate poorly and produce very small amounts of cytokines like IL-2, IL-4, IL-5, IL-12, and IFN-g which limits their capacity to activate the humoral response as well as the phagocitic activity of macrophage. B cells develop early during gestation but are not fully active. [41]

Artist's impression of monocytes Monocyte.png
Artist's impression of monocytes

Maternal factors also play a role in the body's immune response. At birth, most of the immunoglobulin present is maternal IgG. These antibodies are transferred from the placenta to the fetus using the FcRn (neonatal Fc receptor). [42] Because IgM, IgD, IgE and IgA do not cross the placenta, they are almost undetectable at birth. Some IgA is provided by breast milk. These passively-acquired antibodies can protect the newborn for up to 18 months, but their response is usually short-lived and of low affinity. [41] These antibodies can also produce a negative response. If a child is exposed to the antibody for a particular antigen before being exposed to the antigen itself then the child will produce a dampened response. Passively acquired maternal antibodies can suppress the antibody response to active immunization. Similarly, the response of T-cells to vaccination differs in children compared to adults, and vaccines that induce Th1 responses in adults do not readily elicit these same responses in neonates. [41] Between six and nine months after birth, a child's immune system begins to respond more strongly to glycoproteins, but there is usually no marked improvement in their response to polysaccharides until they are at least one year old. This can be the reason for distinct time frames found in vaccination schedules. [43] [44]

During adolescence, the human body undergoes various physical, physiological and immunological changes triggered and mediated by hormones, of which the most significant in females is 17-β-estradiol (an estrogen) and, in males, is testosterone. Estradiol usually begins to act around the age of 10 and testosterone some months later. [45] There is evidence that these steroids not only act directly on the primary and secondary sexual characteristics but also have an effect on the development and regulation of the immune system, [46] including an increased risk in developing pubescent and post-pubescent autoimmunity. [47] There is also some evidence that cell surface receptors on B cells and macrophages may detect sex hormones in the system. [48]

The female sex hormone 17-β-estradiol has been shown to regulate the level of immunological response, [49] while some male androgens such as testosterone seem to suppress the stress response to infection. Other androgens, however, such as DHEA, increase immune response. [50] As in females, the male sex hormones seem to have more control of the immune system during puberty and post-puberty than during the rest of a male's adult life.

Physical changes during puberty such as thymic involution also affect immunological response. [51]

Ecoimmunology and behavioural immunity

Ecoimmunology, or ecological immunology, explores the relationship between the immune system of an organism and its social, biotic and abiotic environment.

More recent ecoimmunological research has focused on host pathogen defences traditionally considered "non-immunological", such as pathogen avoidance, self-medication, symbiont-mediated defenses, and fecundity trade-offs. [52] Behavioural immunity, a phrase coined by Mark Schaller, specifically refers to psychological pathogen avoidance drivers, such as disgust aroused by stimuli encountered around pathogen-infected individuals, such as the smell of vomit. [53] More broadly, "behavioural" ecological immunity has been demonstrated in multiple species. For example, the Monarch butterfly often lays its eggs on certain toxic milkweed species when infected with parasites. These toxins reduce parasite growth in the offspring of the infected Monarch. However, when uninfected Monarch butterflies are forced to feed only on these toxic plants, they suffer a fitness cost as reduced lifespan relative to other uninfected Monarch butterflies. [54] This indicates that laying eggs on toxic plants is a costly behaviour in Monarchs which has probably evolved to reduce the severity of parasite infection. [52]

Symbiont-mediated defenses are also heritable across host generations, despite a non-genetic direct basis for the transmission. Aphids, for example, rely on several different symbionts for defense from key parasites, and can vertically transmit their symbionts from parent to offspring. [55] Therefore, a symbiont that successfully confers protection from a parasite is more likely to be passed to the host offspring, allowing coevolution with parasites attacking the host in a way similar to traditional immunity.

The preserved immune tissues of extinct species, such as the thylacine (Thylacine cynocephalus), can also provide insights into their biology. [56]

Cancer immunology

The study of the interaction of the immune system with cancer cells can lead to diagnostic tests and therapies with which to find and fight cancer. The immunology concerned with physiological reaction characteristic of the immune state.

Reproductive immunology

This area of the immunology is devoted to the study of immunological aspects of the reproductive process including fetus acceptance. The term has also been used by fertility clinics to address fertility problems, recurrent miscarriages, premature deliveries and dangerous complications such as pre-eclampsia.

See also

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab) is the secreted form of a B cell receptor; the term immunoglobulin can refer to either the membrane-bound form or the secreted form of the B cell receptor, but they are, broadly speaking, the same protein, and so the terms are often treated as synonymous. Antibodies are large, Y-shaped proteins belonging to the immunoglobulin superfamily which are used by the immune system to identify and neutralize foreign objects such as bacteria and viruses, including those that cause disease. Antibodies, however, can be generated to recognize virtually any molecule in existence. Each antibody recognizes one or more specific antigens. This term literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

The immune system is a network of biological systems 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.

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP), 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.

An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellular bacteria, protozoa, helminths, and fungi which could cause serious problems to the health of the host organism if not cleared from the body.

In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization.

<span class="mw-page-title-main">Complement system</span> Part of the immune system that enhances the ability of antibodies and phagocytic cells

The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. It is part of the innate immune system, which is not adaptable and does not change during an individual's lifetime. The complement system can, however, be recruited and brought into action by antibodies generated by the adaptive immune system.

<span class="mw-page-title-main">Memory B cell</span> Cell of the adaptive immune system

In immunology, a memory B cell (MBC) is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Memory B cells circulate in the blood stream in a quiescent state, sometimes for decades. Their function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. Memory B cells have B cell receptors (BCRs) on their cell membrane, identical to the one on their parent cell, that allow them to recognize antigen and mount a specific antibody response.

<span class="mw-page-title-main">Adaptive immune system</span> Subsystem of the immune system

The adaptive immune system, also known as the acquired immune system, or specific 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.

<span class="mw-page-title-main">Fc receptor</span> Surface protein important to the immune system

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

<span class="mw-page-title-main">Antibody-dependent cellular cytotoxicity</span> Cell-mediated killing of other cells mediated by antibodies

Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system kills a target cell, whose membrane-surface antigens have been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection.

Immune tolerance, or immunological tolerance, or immunotolerance, is a state of unresponsiveness of the immune system to substances or tissues that would otherwise have the capacity to elicit an immune response in a given organism. It is induced by prior exposure to that specific antigen and contrasts with conventional immune-mediated elimination of foreign antigens. Tolerance is classified into central tolerance or peripheral tolerance depending on where the state is originally induced—in the thymus and bone marrow (central) or in other tissues and lymph nodes (peripheral). The mechanisms by which these forms of tolerance are established are distinct, but the resulting effect is similar.

Molecular mimicry is the theoretical possibility that sequence similarities between foreign and self-peptides are enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of several peptide sequences which can be both foreign and self in nature, just a few crucial residues can activate a single antibody or TCR. This highlights the importance of structural homology in the theory of molecular mimicry. Upon activation, these "peptide mimic" specific T or B cells can cross-react with self-epitopes, thus leading to tissue pathology (autoimmunity). Molecular mimicry is one of several ways in which autoimmunity can be evoked. A molecular mimicking event is more than an epiphenomenon despite its low probability, and these events have serious implications in the onset of many human autoimmune disorders.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a primary immunodeficiency (PID), the immune deficiency must be inborn, not caused by secondary factors such as other disease, drug treatment, or environmental exposure to toxins. Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 430 recognized inborn errors of immunity (IEIs) as of 2019, the vast majority of which are PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, auto-inflammatory disorders, tumors, and disorders of various organs. There are currently limited treatments available for these conditions; most are specific to a particular type of PID. Research is currently evaluating the use of stem cell transplants (HSCT) and experimental gene therapies as avenues for treatment in limited subsets of PIDs.

The neonatal fragment crystallizable (Fc) receptor is a protein that in humans is encoded by the FCGRT gene. It is an IgG Fc receptor which is similar in structure to the MHC class I molecule and also associates with beta-2-microglobulin. In rodents, FcRn was originally identified as the receptor that transports maternal immunoglobulin G (IgG) from mother to neonatal offspring via mother's milk, leading to its name as the neonatal Fc receptor. In humans, FcRn is present in the placenta where it transports mother's IgG to the growing fetus. FcRn has also been shown to play a role in regulating IgG and serum albumin turnover. Neonatal Fc receptor expression is up-regulated by the proinflammatory cytokine, TNF, and down-regulated by IFN-γ.

<span class="mw-page-title-main">Microbial symbiosis and immunity</span>

Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.

<span class="mw-page-title-main">Mucosal immunology</span> Field of study

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucosal immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and benign environmental substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.

Thymic involution is the shrinking (involution) of the thymus with age, resulting in changes in the architecture of the thymus and a decrease in tissue mass. Thymus involution is one of the major characteristics of vertebrate immunology, and occurs in almost all vertebrates, from birds, teleosts, amphibians to reptiles, though the thymi of a few species of sharks are known not to involute. This process is genetically regulated, with the nucleic material responsible being an example of a conserved sequence — one maintained through natural selection since it arose in a common ancestor of all species now exhibiting it, via a phenomenon known to bioinformaticists as an orthologic sequence homology.

<span class="mw-page-title-main">Danger model</span>

The danger model of the immune system proposes that it differentiates between components that are capable of causing damage, rather that distinguishing between self and non-self.

Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, they are secondary, tertiary and other subsequent immune responses to the same antigen. The adaptive immune system and antigen-specific receptor generation are responsible for adaptive immune memory.

References

  1. Fossen C. "What is Biology?". www.ntnu.edu. Retrieved 2018-07-25.
  2. Villani AC, Sarkizova S, Hacohen N (April 2018). "Systems Immunology: Learning the Rules of the Immune System". Annual Review of Immunology. 36 (1): 813–42. doi:10.1146/annurev-immunol-042617-053035. PMC   6597491 . PMID   29677477.
  3. "Hypersensitivities | Microbiology". courses.lumenlearning.com. Retrieved 2018-07-25.
  4. "Specific Disease Types | Immune Deficiency Foundation". primaryimmune.org. Retrieved 2018-07-25.
  5. "Transplant rejection: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 2018-07-25.
  6. Pierce CW, Solliday SM, Asofsky R (March 1972). "Immune responses in vitro. IV. Suppression of primary M, G, and A plaque-forming cell responses in mouse spleen cell cultures by class-specific antibody to mouse immunoglobulins". The Journal of Experimental Medicine. 135 (3): 675–97. doi:10.1084/jem.135.3.675. PMC   2139142 . PMID   4536706.
  7. Miyahara S, Yokomuro K, Takahashi H, Kimura Y (November 1983). "Regeneration and the immune system. I. In vitro and in vivo activation of lymphocytes by liver regeneration and the role of Kupffer cells in stimulation". European Journal of Immunology. 13 (11): 878–83. doi:10.1002/eji.1830131104. PMID   6227489. S2CID   22400759.
  8. "Ilya Ilyich Mechnikov (Elie Metchnikoff) (1845–1916)". The Embryo Project. Arizona State University.
  9. "Phagocytosis: Definition, Process, & Examples". Encyclopedia Britannica. Retrieved 2018-07-25.
  10. "Definition of immunity in English". Oxford Dictionaries. Archived from the original on July 25, 2018.
  11. Lee DK, Hakim FT, Gress RE (October 2010). "The thymus and the immune system: layered levels of control". Journal of Thoracic Oncology. 5 (10 Suppl 4): S273–76. doi:10.1097/JTO.0b013e3181f20474. PMC   2951290 . PMID   20859118.
  12. Gherardi, E (2007-01-02). "The Concept of Immunity. History and Applications". Immunology Course Medical School, University of Pavia. Archived from the original on 2007-01-02. Retrieved 2018-07-27.
  13. Rich, Robert R.; Chaplin, David D. (2019). "The Human Immune Response". Clinical Immunology. Principles and Practice (5th ed.). pp. 3–17.e1. doi:10.1016/B978-0-7020-6896-6.00001-6. ISBN   9780702068966. S2CID   88829315.
  14. Janeway CA, Travers P, Walport M, Shlomchik MJ (2001). "Chapter 9: The Humoral Immune Response". Immunobiology the immune system health & disease (5th ed.). New York: Garland. ISBN   978-0-8153-3642-6.
  15. "What is immunology? | British Society for Immunology". www.immunology.org. Archived from the original on 2018-07-21. Retrieved 2018-07-21.
  16. Miller JJ, Valdes R (February 1991). "Approaches to minimizing interference by cross-reacting molecules in immunoassays". Clinical Chemistry. 37 (2): 144–53. doi: 10.1093/clinchem/37.2.144 . PMID   1993317.
  17. "Transplant rejection: T-helper cell paradigm | British Society for Immunology". www.immunology.org. Archived from the original on April 23, 2019. Retrieved 2019-04-23.
  18. "Clinical Immunology and Allergy Competencies" (PDF). The Royal College of Physicians and Surgeons of Canada. Archived from the original (PDF) on 2021-09-26. Retrieved 2021-09-26.
  19. "Robert Koch | German bacteriologist". Encyclopedia Britannica. Retrieved 2018-07-25.
  20. "Emil von Behring: The Founder of Serum Therapy". www.nobelprize.org. Retrieved 2018-07-25.
  21. Silverstein AM (1989). A history of immunology. San Diego: Academic Press. ISBN   978-0-12-643770-6. OCLC   909269335.
  22. Tauber AI, Chernyak L (1991). Metchnikoff and the Origins of Immunology. New York: Oxford University Press. ISBN   978-0-19-506447-6. OCLC   22906314.
  23. 1 2 Tauber AI (1994). "The Immune Self: Theory or Metaphor?". Immunology Today. Cambridge: Cambridge University Press. 15 (3): 134–6. doi:10.1016/0167-5699(94)90157-0. OCLC   4930079483. PMID   8172646.
  24. Jerne NK (November 1955). "The natural-selection theory of antibody selection". Proceedings of the National Academy of Sciences of the United States of America. 41 (11): 849–57. Bibcode:1955PNAS...41..849J. doi: 10.1073/pnas.41.11.849 . PMC   534292 . PMID   16589759.
  25. Burnet FM (1959). The Clonal Selection Theory of Acquired Immunity. Cambridge: Cambridge University Press.
  26. Burnet FM (1969). Cellular Immunology: Self and Notself. Cambridge: Cambridge University Press.
  27. Bretscher P, Cohn M (September 1970). "A theory of self-nonself discrimination". Science. 169 (3950): 1042–49. Bibcode:1970Sci...169.1042B. doi:10.1126/science.169.3950.1042. PMID   4194660. S2CID   26916828.
  28. 1 2 Matzinger P (April 2002). "The danger model: a renewed sense of self" (PDF). Science. 296 (5566): 301–05. Bibcode:2002Sci...296..301M. CiteSeerX   10.1.1.127.558 . doi:10.1126/science.1071059. PMID   11951032. S2CID   13615808.
  29. Pradeu T, Vitanza E (2012). The limits of the self: immunology and biological identity. Oxford: Oxford University Press. ISBN   978-0-19-977528-6. OCLC   793571104.
  30. Langman RE, Cohn M (June 2000). "A minimal model for the self-nonself discrimination: a return to the basics". Seminars in Immunology. 12 (3): 189–95, discussion 257–344. doi:10.1006/smim.2000.0231. PMID   10910739.
  31. Clark WR (2008). In defense of self: how the immune system really works . New York: Oxford University Press. ISBN   978-0-19-533663-4. OCLC   917294223.
  32. Coutinho A, Forni L, Holmberg D, Ivars F, Vaz N (1984). "From an antigen-centered, clonal perspective of immune responses to an organism-centered network perspective of autonomous reactivity of self-referential immune systems". Immunological Reviews. 79: 151–68. doi:10.1111/j.1600-065x.1984.tb00492.x. PMID   6235170. S2CID   46481630.
  33. Irun C (2000). Tending Adam's garden: Evolving the cognitive immune self. San Diego: Academic Press.
  34. Pradeu T, Carosella ED (November 2006). "On the definition of a criterion of immunogenicity". Proceedings of the National Academy of Sciences of the United States of America. 103 (47): 17858–61. Bibcode:2006PNAS..10317858P. doi: 10.1073/pnas.0608683103 . PMC   1693837 . PMID   17101995.
  35. Pradeu T, Jaeger S, Vivier E (October 2013). "The speed of change: towards a discontinuity theory of immunity?" (PDF). Nature Reviews. Immunology. 13 (10): 764–69. doi:10.1038/nri3521. PMID   23995627. S2CID   11366176.
  36. Janeway CA, Goodnow CC, Medzhitov R (May 1996). "Danger – pathogen on the premises! Immunological tolerance". Current Biology. 6 (5): 519–22. doi: 10.1016/S0960-9822(02)00531-6 . PMID   8805259. S2CID   14347980.
  37. Vance RE (2000). "Cutting edge commentary: a Copernican revolution? Doubts about the danger theory". Journal of Immunology. 165 (4): 1725–28. doi: 10.4049/jimmunol.165.4.1725 . PMID   10925247.
  38. Matzinger P (May 2012). "The evolution of the danger theory. Interview by Lauren Constable, Commissioning Editor". Expert Review of Clinical Immunology. 8 (4): 311–17. doi:10.1586/eci.12.21. PMC   4803042 . PMID   22607177.
  39. Pradeu T, Cooper EL (2012). "The danger theory: 20 years later". Frontiers in Immunology. 3: 287. doi: 10.3389/fimmu.2012.00287 . PMC   3443751 . PMID   23060876.
  40. Goldsby RA, Kindt TK (2003). Immunology (5th ed.). San Francisco: W.H. Freeman. ISBN   978-0-7167-4947-9.
  41. 1 2 3 Jaspan HB, Lawn SD, Safrit JT, Bekker LG (February 2006). "The maturing immune system: implications for development and testing HIV-1 vaccines for children and adolescents". AIDS. 20 (4): 483–94. doi: 10.1097/01.aids.0000210602.40267.60 . PMID   16470112. S2CID   20277590.
  42. "Neonatal Immunology | British Society for Immunology". www.immunology.org.
  43. Glezen WP (December 2001). "Maternal vaccines". Primary Care. 28 (4): 791–806, vi–vii. doi:10.1016/S0095-4543(05)70041-5. PMID   11739030.
  44. Holt PG, Macaubas C, Cooper D, Nelson DJ, McWilliam AS (1997). "Th-1/Th-2 Switch Regulation in Immune Responses to Inhaled Antigens". Dendritic Cells in Fundamental and Clinical Immunology. Advances in Experimental Medicine and Biology. Vol. 417. pp. 301–06. doi:10.1007/978-1-4757-9966-8_49. ISBN   978-1-4757-9968-2. PMID   9286377.
  45. Sizonenko PC, Paunier L (November 1975). "Hormonal changes in puberty III: Correlation of plasma dehydroepiandrosterone, testosterone, FSH, and LH with stages of puberty and bone age in normal boys and girls and in patients with Addison's disease or hypogonadism or with premature or late adrenarche". The Journal of Clinical Endocrinology and Metabolism. 41 (5): 894–904. doi:10.1210/jcem-41-5-894. PMID   127002.
  46. Verthelyi D (June 2001). "Sex hormones as immunomodulators in health and disease". International Immunopharmacology. 1 (6): 983–93. doi:10.1016/S1567-5769(01)00044-3. PMID   11407317.
  47. Stimson WH (September 1988). "Oestrogen and human T lymphocytes: presence of specific receptors in the T-suppressor/cytotoxic subset". Scandinavian Journal of Immunology. 28 (3): 345–50. doi:10.1111/j.1365-3083.1988.tb01459.x. PMID   2973658. S2CID   38920551.
  48. Benten WP, Stephan C, Wunderlich F (June 2002). "B cells express intracellular but not surface receptors for testosterone and estradiol". Steroids. 67 (7): 647–54. doi:10.1016/S0039-128X(02)00013-2. PMID   11996938. S2CID   1056135.
  49. Beagley KW, Gockel CM (August 2003). "Regulation of innate and adaptive immunity by the female sex hormones estradiol and progesterone". FEMS Immunology and Medical Microbiology. 38 (1): 13–22. doi: 10.1016/S0928-8244(03)00202-5 . PMID   12900050.
  50. Kanda N, Tamaki K (February 1999). "Estrogen enhances immunoglobulin production by human PBMCs". The Journal of Allergy and Clinical Immunology. 103 (2 Pt 1): 282–88. doi:10.1016/S0091-6749(99)70503-8. PMID   9949320.
  51. McFarland RD, Douek DC, Koup RA, Picker LJ (April 2000). "Identification of a human recent thymic emigrant phenotype". Proceedings of the National Academy of Sciences of the United States of America. 97 (8): 4215–20. Bibcode:2000PNAS...97.4215M. doi: 10.1073/pnas.070061597 . PMC   18202 . PMID   10737767.
  52. 1 2 Parker BJ, Barribeau SM, Laughton AM, de Roode JC, Gerardo NM (May 2011). "Non-immunological defense in an evolutionary framework". Trends in Ecology & Evolution. 26 (5): 242–48. doi:10.1016/j.tree.2011.02.005. PMID   21435735.
  53. "Commentaries on Evolutionary Foundations of Cultural Variation: Evoked Culture and Mate Preferences". Psychological Inquiry. 17 (2): 96–137. 2006. doi:10.1207/s15327965pli1702_2. S2CID   219729311.
  54. Lefèvre T, Oliver L, Hunter MD, De Roode JC (December 2010). "Evidence for trans-generational medication in nature" (PDF). Ecology Letters. 13 (12): 1485–93. doi:10.1111/j.1461-0248.2010.01537.x. hdl: 2027.42/79381 . PMID   21040353.
  55. Koga R, Meng XY, Tsuchida T, Fukatsu T (May 2012). "Cellular mechanism for selective vertical transmission of an obligate insect symbiont at the bacteriocyte-embryo interface". Proceedings of the National Academy of Sciences of the United States of America. 109 (20): E1230–37. doi: 10.1073/pnas.1119212109 . PMC   3356617 . PMID   22517738.
  56. Old J (2015). "Immunological insights into the life and times of the extinct Tasmanian tiger (Thylacinus cynocephalus)". PLOS ONE. 10 (12): e0144091. Bibcode:2015PLoSO..1044091O. doi: 10.1371/journal.pone.0144091 . PMC   4684372 . PMID   26655868.