Serology is the scientific study of serum and other body fluids . In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given microorganism ), against other foreign proteins (in response, for example, to a mismatched blood transfusion ), or to one's own proteins (in instances of autoimmune disease ). In either case, the procedure is simple.
49-706: Serological tests are diagnostic methods that are used to identify antibodies and antigens in a patient's sample. Serological tests may be performed to diagnose infections and autoimmune illnesses , to check if a person has immunity to certain diseases, and in many other situations, such as determining an individual's blood type . Serological tests may also be used in forensic serology to investigate crime scene evidence. Several methods can be used to detect antibodies and antigens, including ELISA , agglutination , precipitation , complement-fixation , and fluorescent antibodies and more recently chemiluminescence . In microbiology , serologic tests are used to determine if
98-474: A World Serology Bank (or serum bank) and foresaw "associated major methodological developments in serological testing, study design , and quantitative analysis , which could drive a step change in our understanding and optimum control of infectious diseases ." In a helpful reply entitled "Opportunities and challenges of a World Serum Bank", de Lusignan and Correa observed that the principal ethical and logistical challenges that need to be overcome are
147-433: A foreign protein or substance within the body. Initially, one B cell produces one specific kind of antibody. In either case, the B cell is allowed to proliferate or is killed off through a process called clonal deletion . Normally, the immune system is able to recognize and ignore the body's own healthy proteins, cells, and tissues, and to not overreact to non-threatening substances in the environment, such as foods. Sometimes,
196-409: A high predicted MHC binding affinity. Minor histocompatibility antigens, a conceptually similar antigen class are also correctly identified by MHC binding algorithms. Another potential filter examines whether the mutation is expected to improve MHC binding. The nature of the central TCR-exposed residues of MHC-bound peptides is associated with peptide immunogenicity. A native antigen is an antigen that
245-457: A hormonal component as many of the autoimmune conditions are much more prevalent in women of childbearing age. While the initial event that leads to the production of autoantibodies is still unknown, there is a body of evidence that autoantibodies may have the capacity to maintain their production. The type of autoimmune disorder or disease that occurs and the amount of destruction done to the body depends on which systems or organs are targeted by
294-413: A person by analyzing the antibodies in body fluids. A unique, individual set of antibodies, called individual specific autoantibodies (ISA), is found in blood, serum, saliva, urine, semen, perspiration, tears, and body tissues, and the antibodies are not affected by illness, medication, or food/drug intake. An unskilled technician using inexpensive equipment can complete a test in a couple of hours. Note:
343-564: A person has antibodies against a specific pathogen , or to detect antigens associated with a pathogen in a person's sample. Serologic tests are especially useful for organisms that are difficult to culture by routine laboratory methods, like Treponema pallidum (the causative agent of syphilis ), or viruses . The presence of antibodies against a pathogen in a person's blood indicates that they have been exposed to that pathogen. Most serologic tests measure one of two types of antibodies: immunoglobulin M (IgM) and immunoglobulin G (IgG). IgM
392-405: A person is currently or recently infected, while a positive result for IgG and negative result for IgM suggests that the person may have been infected or immunized in the past. Antibody testing for infectious diseases is often done in two phases: during the initial illness (acute phase) and after recovery (convalescent phase). The amount of antibody in each specimen ( antibody titer ) is compared, and
441-434: A person's own tissues ( autoantibodies ). All people have different immunology graphs. A 2016 research paper by Metcalf et al., amongst whom were Neil Ferguson and Jeremy Farrar , stated that serological surveys are often used by epidemiologists to determine the prevalence of a disease in a population. Such surveys are sometimes performed by random, anonymous sampling from samples taken for other medical tests or to assess
490-415: A person's red blood cells, which determine their blood type , are identified using reagents that contain antibodies, called antisera . When the antibodies bind to red blood cells that express the corresponding antigen, they cause red blood cells to clump together (agglutinate), which can be identified visually. The person's blood group antibodies can also be identified by adding plasma to cells that express
539-468: A positive double strand anti-double stranded DNA (anti-dsDNA) autoantibody test, but only about 25–30% will have a positive RNP. Some individuals who do have an autoimmune disorder will have negative autoantibody test results, but at a later date – as the disorder progresses - the autoantibodies may develop. Systemic autoantibody tests are used to: Antibody profiling is used for identifying persons from forensic samples. The technology can uniquely identify
SECTION 10
#1732793325877588-421: A significantly higher amount of IgG in the convalescent specimen suggests infection as opposed to previous exposure. False negative results for antibody testing can occur in people who are immunosuppressed , as they produce lower amounts of antibodies, and in people who receive antimicrobial drugs early in the course of the infection. Blood typing is typically performed using serologic methods. The antigens on
637-423: A single autoantibody, ribonucleic protein (RNP), is the only one present. Those who have more than one autoimmune disorder may have several detectable autoantibodies. Whether a particular autoantibody will be present is both very individual and a matter of statistics. Each will be present in a certain percentage of people who have a particular autoimmune disorder. For instance, up to 80% of those with SLE will have
686-606: 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 . Antigens can be proteins , peptides (amino acid chains), polysaccharides (chains of simple sugars), lipids , or nucleic acids . Antigens exist on normal cells , cancer cells , parasites , viruses , fungi , and bacteria . Antigens are recognized by antigen receptors, including antibodies and T-cell receptors. Diverse antigen receptors are made by cells of
735-465: Is called the antigen-antibody reaction . Antigen can originate either from within the body (" self-protein " or "self antigens") or from the external environment ("non-self"). The immune system identifies and attacks "non-self" external antigens. Antibodies usually do not react with self-antigens due to negative selection of T cells in the thymus and B cells in the bone marrow . The diseases in which antibodies react with self antigens and damage
784-487: Is insufficient to exclude many false positives from the pool of peptides that may be presented by MHC molecules. Instead, algorithms are used to identify the most likely candidates. These algorithms consider factors such as the likelihood of proteasomal processing, transport into the endoplasmic reticulum , affinity for the relevant MHC class I alleles and gene expression or protein translation levels. The majority of human neoantigens identified in unbiased screens display
833-399: Is not diagnostic, but may give clues as to whether a particular disorder is likely or unlikely to be present. Each autoantibody result should be considered individually and as part of the group. Some disorders, such as systemic lupus erythematosus (SLE) may be more likely if several autoantibodies are present, while others, such as mixed connective tissue disease (MCTD) may be more likely if
882-403: Is not yet processed by an APC to smaller parts. T cells cannot bind native antigens, but require that they be processed by APCs, whereas B cells can be activated by native ones. Antigenic specificity is the ability of the host cells to recognize an antigen specifically as a unique molecular entity and distinguish it from another with exquisite precision. Antigen specificity is due primarily to
931-460: Is often ordered first. ANA is a marker of the autoimmune process – it is positive with a variety of different autoimmune diseases but not specific. Consequently, if an ANA test is positive, it is often followed up with other tests associated with arthritis and inflammation , such as a rheumatoid factor (RF), an erythrocyte sedimentation rate (ESR), a c-reactive protein (CRP), and/or complement protein|complement levels. A single autoantibody test
980-496: Is performed to detect if antibodies are bound to red blood cells inside the person's body, which is abnormal and can occur in conditions like autoimmune hemolytic anemia , hemolytic disease of the newborn and transfusion reactions . The indirect antiglobulin test is used to screen for antibodies that could cause transfusion reactions and identify certain blood group antigens. Serologic tests can help to diagnose autoimmune disorders by identifying abnormal antibodies directed against
1029-422: Is produced in high quantities shortly after a person is exposed to the pathogen, and production declines quickly thereafter. IgG is also produced on the first exposure, but not as quickly as IgM. On subsequent exposures, the antibodies produced are primarily IgG, and they remain in circulation for a prolonged period of time. This affects the interpretation of serology results: a positive result for IgM suggests that
SECTION 20
#17327933258771078-465: Is thought that some autoantibody production is due to a genetic predisposition combined with an environmental trigger, such as a viral illness or a prolonged exposure to certain toxic chemicals. There is generally not a direct genetic link however. While families may be susceptible to autoimmune conditions, individual family members may have different autoimmune disorders, or may never develop an autoimmune condition. Researchers believe that there may also be
1127-516: Is usually a self-protein or protein complex (and sometimes DNA or RNA) that is recognized by the immune system of patients with a specific autoimmune disease . Under normal conditions, these self-proteins should not be the target of the immune system, but in autoimmune diseases, their associated T cells are not deleted and instead attack. Neoantigens are those that are entirely absent from the normal human genome. As compared with nonmutated self-proteins, neoantigens are of relevance to tumor control, as
1176-593: The changing patterns of global weather should inform policy measures including where to concentrate vaccination efforts and insect control measures. In April 2020, Justin Trudeau formed the COVID-19 Immunity Task Force , whose mandate is to carry out a serological survey in a scheme hatched in the midst of the COVID-19 pandemic . Antigens In immunology , an antigen ( Ag )
1225-579: The adjuvant component of vaccines plays an essential role in the activation of the innate immune system. An immunogen is an antigen substance (or adduct ) that is able to trigger a humoral (innate) or cell-mediated immune response. It first initiates an innate immune response, which then causes the activation of the adaptive immune response. An antigen binds the highly variable immunoreceptor products (B-cell receptor or T-cell receptor) once these have been generated. Immunogens are those antigens, termed immunogenic , capable of inducing an immune response. At
1274-406: The antigens; depending on the antigen and the type of the histocompatibility molecule, different types of T cells will be activated. For T-cell receptor (TCR) recognition, the peptide must be processed into small fragments inside the cell and presented by a major histocompatibility complex (MHC). The antigen cannot elicit the immune response without the help of an immunologic adjuvant . Similarly,
1323-470: The autoantibodies, and how strongly. Disorders caused by organ specific autoantibodies, those that primarily target a single organ, (such as the thyroid in Graves' disease and Hashimoto's thyroiditis ), are often the easiest to diagnose as they frequently present with organ related symptoms. Disorders due to systemic autoantibodies can be much more elusive. Although the associated autoimmune disorders are rare,
1372-451: The body's own cells are called autoimmune diseases . Vaccines are examples of antigens in an immunogenic form, which are intentionally administered to a recipient to induce the memory function of the adaptive immune system towards antigens of the pathogen invading that recipient. The vaccine for seasonal influenza is a common example. Paul Ehrlich coined the term antibody ( German : Antikörper ) in his side-chain theory at
1421-440: The corresponding antigen and observing the agglutination reactions. Other serologic methods used in transfusion medicine include crossmatching and the direct and indirect antiglobulin tests . Crossmatching is performed before a blood transfusion to ensure that the donor blood is compatible. It involves adding the recipient's plasma to the donor blood cells and observing for agglutination reactions. The direct antiglobulin test
1470-424: The destruction of the infected cell. Endogenous antigens are generated within normal cells as a result of normal cell metabolism , or because of viral or intracellular bacterial infection . The fragments are then presented on the cell surface in the complex with MHC class I molecules. If activated cytotoxic CD8 T cells recognize them, the T cells secrete various toxins that cause the lysis or apoptosis of
1519-501: The doctor may request one or more diagnostic studies that will help to identify a specific disease. As a rule, information is required from multiple sources, rather than a single laboratory test to accurately diagnose disorders associated with systemic autoantibodies. Tests may include: Autoantibody tests may be ordered as part of an investigation of chronic progressive arthritis type symptoms and/or unexplained fevers, fatigue, muscle weakness and rashes. The antinuclear antibody (ANA) test
Serology - Misplaced Pages Continue
1568-428: The end of the 19th century. In 1899, Ladislas Deutsch (László Detre) named the hypothetical substances halfway between bacterial constituents and antibodies "antigenic or immunogenic substances" ( French : substances immunogènes ou antigènes ). He originally believed those substances to be precursors of antibodies, just as a zymogen is a precursor of an enzyme . But, by 1903, he understood that an antigen induces
1617-404: The fact that a person may have more than one autoantibody, and thus have more than one autoimmune disorder, and/or have an autoimmune disorder without a detectable level of an autoantibody, complicating making a diagnosis. The diagnosis of disorders associated with systemic autoantibodies starts with a complete medical history and a thorough physical exam. Based on the patient's signs and symptoms,
1666-510: The fragments to T helper cells ( CD4 ) by the use of class II histocompatibility molecules on their surface. Some T cells are specific for the peptide:MHC complex. They become activated and start to secrete cytokines, substances that activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells , macrophages and other particles. Some antigens start out as exogenous and later become endogenous (for example, intracellular viruses). Intracellular antigens can be returned to circulation upon
1715-463: The immune system ceases to recognize one or more of the body's normal constituents as "self", leading to production of pathological autoantibodies. Autoantibodies may also play a nonpathological role; for instance they may help the body to destroy cancers and to eliminate waste products. The role of autoantibodies in normal immune function is also a subject of scientific research. The causes of autoantibody production are varied and not well understood. It
1764-482: The immune system so that each cell has a specificity for a single antigen. Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as clonal selection . In most cases, antibodies are antigen-specific , meaning that an antibody can only react to and bind one specific antigen; in some instances, however, antibodies may cross-react to bind more than one antigen. The reaction between an antigen and an antibody
1813-435: The infected cell. In order to keep the cytotoxic cells from killing cells just for presenting self-proteins , the cytotoxic cells (self-reactive T cells) are deleted as a result of tolerance (negative selection). Endogenous antigens include xenogenic (heterologous), autologous and idiotypic or allogenic (homologous) antigens. Sometimes antigens are part of the host itself in an autoimmune disease . An autoantigen
1862-602: The methods of obtaining specimens, how informed consent is acquired in busy practices, and the filling in of gaps in patient sampling . In another helpful reply on the World Serum Bank, the Australian researcher Karen Coates declared that: Improved serological surveillance would allow governments , aid agencies , and policy writers to direct public health resources to where they are needed most. A better understanding of infection dynamics with respect to
1911-699: The molecular level, an antigen can be characterized by its ability to bind to an antibody's paratopes . Different antibodies have the potential to discriminate among specific epitopes present on the antigen surface. A hapten is a small molecule that can only induce an immune response when attached to a larger carrier molecule, such as a protein . Antigens can be proteins, polysaccharides, lipids , nucleic acids or other biomolecules. This includes parts (coats, capsules, cell walls, flagella, fimbriae, and toxins) of bacteria , viruses , and other microorganisms . Non-microbial non-self antigens can include pollen, egg white, and proteins from transplanted tissues and organs or on
1960-539: The pool of neoantigens. Tumor antigens are those antigens that are presented by MHC class I or MHC class II molecules on the surface of tumor cells . Antigens found only on such cells are called tumor-specific antigens (TSAs) and generally result from a tumor-specific mutation . More common are antigens that are presented by tumor cells and normal cells, called tumor-associated antigens (TAAs). Cytotoxic T lymphocytes that recognize these antigens may be able to destroy tumor cells. Tumor antigens can appear on
2009-464: The prevalence of antibodies of a specific organism or protective titre of antibodies in a population. Serological surveys are usually used to quantify the proportion of people or animals in a population positive for a specific antibody or the titre or concentrations of an antibody. These surveys are potentially the most direct and informative technique available to infer the dynamics of a population's susceptibility and level of immunity. The authors proposed
Serology - Misplaced Pages Continue
2058-465: The production of immune bodies (antibodies) and wrote that the word antigen is a contraction of antisomatogen ( Immunkörperbildner ). The Oxford English Dictionary indicates that the logical construction should be "anti(body)-gen". The term originally referred to a substance that acts as an antibody generator. Antigen-presenting cells present antigens in the form of peptides on histocompatibility molecules . The T cells selectively recognize
2107-476: The protein-coding part of the genome (the exome ) and predict potential neoantigens. In mice models, for all novel protein sequences, potential MHC-binding peptides were predicted. The resulting set of potential neoantigens was used to assess T cell reactivity. Exome–based analyses were exploited in a clinical setting, to assess reactivity in patients treated by either tumor-infiltrating lymphocyte (TIL) cell therapy or checkpoint blockade. Neoantigen identification
2156-436: The quality of the T cell pool that is available for these antigens is not affected by central T cell tolerance. Technology to systematically analyze T cell reactivity against neoantigens became available only recently. Neoantigens can be directly detected and quantified. For virus-associated tumors, such as cervical cancer and a subset of head and neck cancers , epitopes derived from viral open reading frames contribute to
2205-576: The side-chain conformations of the antigen. It is measurable and need not be linear or of a rate-limited step or equation. Both T cells and B cells are cellular components of adaptive immunity . Autoantibodies An autoantibody is an antibody (a type of protein ) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus ) are associated with such antibodies. Antibodies are produced by B cells in two ways: (i) randomly, and (ii) in response to
2254-512: The signs and symptoms they cause are relatively common. Symptoms may include: arthritis -type joint pain, fatigue, fever, rashes, cold or allergy-type symptoms, weight loss, and muscular weakness. Associated conditions include vasculitis which are inflammation of blood vessels and anemia . Even if they are due to a particular systemic autoimmune condition, the symptoms will vary from person to person, vary over time, vary with organ involvement, and they may taper off or flare unexpectedly. Add to this
2303-454: The surface of the tumor in the form of, for example, a mutated receptor, in which case they are recognized by B cells . For human tumors without a viral etiology, novel peptides (neo-epitopes) are created by tumor-specific DNA alterations. A large fraction of human tumor mutations are effectively patient-specific. Therefore, neoantigens may also be based on individual tumor genomes. Deep-sequencing technologies can identify mutations within
2352-460: The surface of transfused blood cells. Antigens can be classified according to their source. Exogenous antigens are antigens that have entered the body from the outside, for example, by inhalation , ingestion or injection . The immune system's response to exogenous antigens is often subclinical. By endocytosis or phagocytosis , exogenous antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present
2401-404: Was successful for multiple experimental model systems and human malignancies. The false-negative rate of cancer exome sequencing is low—i.e.: the majority of neoantigens occur within exonic sequence with sufficient coverage. However, the vast majority of mutations within expressed genes do not produce neoantigens that are recognized by autologous T cells. As of 2015 mass spectrometry resolution
#876123