Human immunity is a complex multi-stage system for protecting the body from harmful external influences (viruses, bacteria, allergens, fungi). There is no single organ responsible for immune defense. This function is assigned to different systems: from the intestine to the microscopic protein substances - immunoglobulins.
General characteristics of immunoglobulins
Immunoglobulins (Ig), also known as antibodies, are glycoprotein molecules (specific protein compounds found in blood plasma). They are an important part of the immune system, the task of which is to protect the body from infections and other foreign substances. In our body, as in vertebrate animals, immunoglobulins are found in the blood and in some secretory fluids. Antibodies help the body identify and destroy extraneous harmful elements. Typically, immunoglobulins are produced as a response to contact with antigens, such as bacteria or viruses. Sometimes immunoglobulins are produced after contact with the body's own tissues, called autoantigens.
Deficiency or excess of antibodies can be a sign of various pathologies, therefore, determining their amount in the blood is an important part in the diagnosis of many diseases. In addition, modern advances in biomedicine allow the use of synthetic antibodies in the treatment of certain diseases.
Immunoglobulins are symmetrical Y-shaped molecules consisting of two heavy long chains (H) and two short lungs (L). The chains are connected to each other either by disulfide (SS) or hydrogen bonds. Each immunoglobulin can be conditionally divided into two parts: constant (C) and variable (V). While the C-part determines the activity of the antibody, the V-region is necessary for binding to specific antigens (that is, specific proteins that signal the presence of a specific bacterium, virus or other foreign object in the body).
The structure and role of the C-part is identical for all types of antibodies. This site can be figuratively called the brain center of immunoglobulin. It is he who controls how effectively the antibody performs its function. The V region of different types of antibodies is different. Due to this variability, antibodies can recognize and bind to different types of foreign bodies in the body. That is, for each type of "alien" there is its own immunoglobulin with a specific structure of the V region.
In other words, each antibody approaches the antigen on the principle of a key and a lock, and in combination with each other form the so-called immune complexes. But also antibodies are able to show flexibility in combination with "strangers", making it easy to adapt to various antigens. However, this ability of immunoglobulins sometimes provokes cross-allergic reactions in humans - when a person with an allergy cannot distinguish between allergens. For example, a person who is allergic to pollen due to malfunctioning immunoglobulins may also respond to raw fruits and vegetables.
Types of immunoglobulins
In the human body, immunoglobulins are presented in two forms:
- soluble (produced by plasma cells);
- associated with the outer membrane of B-lymphocytes, they are also receptor antibodies.
In addition, there are different classes and subclasses (isotopes) of immunoglobulins. They differ in their biological characteristics, structure and focus on the "target". Based on differences in the structure of heavy chains, several classes of antibodies were isolated. Each of them is distinguished by its functions and responses.
In placental mammals, including humans, 5 main classes of antibodies were identified: IgA, IgD, IgE, IgG and IgM. In human blood, only three of them are contained - IgA, IgG and IgM. But the rest, according to experts, are no less useful for maintaining the immune system. All of them differ in the type of heavy chain. For example, gamma chains are characteristic of IgG molecules, IgM have mu chains, IgA have alpha chains, IgE are distinguished by the presence of epsilon chains, and IgD have delta chains. These differences allow immunoglobulins to participate in different types and at different stages of the immune response.
In addition to the main classes of immunoglobulins, there are several subclasses. The difference between them is based on slight differences in the type of heavy chains of each class. In the human body there are 4 subclasses of antibodies. The numbering corresponds to the order of decreasing their concentration in serum. Thus, IgG and IgA antibodies are further grouped into subclasses of IgG1, IgG2, IgG3, IgG4, as well as IgA1 and IgA2.
Most antibodies (IgG, IgD, IgE) in the body are in the form of a monomer (single molecule). An exception is an antibody of class A, which also occurs in the form of a dimer, and IgM, which forms the shape of a snowflake (pentamer).
Characterization of different classes of immunoglobulins
About 15% of the antibodies contained in the body of a healthy person are IgA type immunoglobulins. Two subclasses of IgA may be present in our bodies - IgA1 and IgA2. They differ in the molecular weight of the heavy chains and the concentration in serum. By the way, in serum, IgA is represented mainly as a monomer (consists of one molecule). In secretory fluids, immunoglobulin is present as a dimer bound to a peptide. Most IgA in the body is dimers. They are present in most secretory fluids, including the mucous membranes of the respiratory and urogenital tract, gastrointestinal tract, as well as saliva, tears, colostrum and milk in women. Since IgA is present on the mucous membranes of the digestive system, where it can be exposed to enzymes, this antibody contains a special component that protects the molecule from premature destruction.
Class A immunoglobulins, as a rule, are not specific in terms of "adjusting" to a certain type of foreign body. Typically, antibodies from this group are present in vulnerable areas of the body or in areas where microbes can easily enter. Class A immunoglobulins provide local humoral immunity. This is due to its properties to prevent the penetration of pathogens through epithelial surfaces. Due to the abundance of IgA in the secret of the mucous membranes (saliva, tears), it protects the body from some local infections.
The main function of immunoglobulins of this class is not to destroy antigens, but to prevent the penetration of foreign substances into the circulatory system. IgA itself is rather weak and unable to destroy bacteria on its own. Therefore, they always work together with lysozymes - enzymes that are also present in secretory fluids and can destroy bacteria.
If the concentration of IgA class immunoglobulins in the body is violated, a person often suffers from respiratory infections and kidney diseases, including nephropathy. People whose organisms lack IgA are more prone to autoimmune disorders such as rheumatoid arthritis, lupus, allergies, and asthma.
Various diseases can lead to a decrease in the amount of IgA. One of these is gonorrhea. Gonorrhea-producing bacteria produce an enzyme that breaks down an IgA antibody into two parts: Fc and Fab. Interestingly, Fab can still find bacteria harmful to the body, but without interaction with Fc, it is not able to withstand them.
Class D immunoglobulins in the human body are represented in very small quantities and comprise approximately 0.2% of all antibodies. IgD is known to attach to the surface of certain B lymphocytes as a B cell receptor. Nevertheless, its functions in the human body are still not fully understood. It is believed that IgD is the cause of penicillin allergy. Also, sometimes it can be activated after contact with harmless blood proteins, thereby causing autoimmune reactions in the body.
IgE immunoglobulin, like IgD, is found in serum in much smaller quantities than other classes of antibodies. IgE protects against the penetration of parasites, and is also responsible for allergic reactions.
IgE is found in blood plasma. Of all serum antibodies, only 0.002% is accounted for. But this does not prevent him from fulfilling a vital role for man. Immunoglobulins of this group bind to the surface of basophils and mast cells. Further, an antigen joins them, which in turn leads to the release of substances-moderators of the inflammatory reaction into the bloodstream. That is, IgE controls allergic reactions.
When antigens such as pollen, poisonous substances, fungal spores, dust mites or pet dander bind to IgE, substances such as heparin, histamine, proteolytic enzymes, leukotrienes and cytokines are released in the body. This leads to vasodilation and increase their permeability. As a result of this, hazardous substances can penetrate into the capillaries, and then into nearby tissues, as a result of which symptoms characteristic of an allergic reaction appear. By the way, most of the typical allergic reactions in the form of sneezing, coughing, lacrimation and increased secretion of mucus contribute to removing the remaining allergens from the body.
Studies have shown that disorders such as asthma, rhinitis, eczema, urticaria and dermatitis cause an increase in IgE levels. E-type antibodies are also actively produced in response to the presence in the body of parasitic worms (helminths), persistent infections (herpes viruses, atypical microorganisms) and some arthropods (for example, lice). In addition, IgE plays an indirect role in the immune response, stimulating other immune components to action. It can also protect the surfaces of mucous membranes, causing, in case of danger, inflammatory reactions.
A pathologically low level of antibodies of the IgE class can occur against the background of a rare genetic disease, accompanied by impaired muscle coordination (ataxia telangiectasia).
Class G immunoglobulins are dominant in the human body. They account for 75% of all antibodies. This is partially due to a long half-life: from 7 to 23 days (depending on the subclass). In addition, they can persist in the blood for several decades after contact with the antigen.
There are 4 subclasses of IgG:
- IgG1 accounts for 60 to 65% of the total amount of immunoglobulin in this class. Its deficiency is usually a sign of hypogammaglobulinemia (plasma cell deficiency).
- IgG2 is the second most common isotope, accounting for 20-25% of the total amount of IgG. “Adult” antibody concentrations usually appear by 6–7 years of age. IgG2 deficiency has been associated with recurrent respiratory tract infections.
- IgG3 accounts for 5 to 10% of total IgG. It plays a major role in immune responses against protein or polypeptide antigens.
- IgG4 accounts for up to 4% of the total IgG. Previously, IgG4 was only associated with food allergies, but recent studies have shown that increased serum IgG4 occurs in patients with sclerosing pancreatitis, cholangitis and interstitial pneumonia. However, the exact role of IgG4 is still unknown.
IgG plays a key role in the humoral immune response. This is the main immunoglobulin found in the blood, as well as in lymphatic, cerebrospinal and abdominal fluids. The ability to remain in the body for a long time makes it the most useful antibody for passive immunization. This is the only antibody that can penetrate the placenta of the mother and enter the blood circulation of the fetus, providing postpartum protection for the newborn during the first months of his life.
The main functions of IgG:
- increased phagocytosis in macrophages and neutrophils;
- neutralization of toxins;
- inactivation of viruses;
- destruction of bacteria.
IgM is the most important member of the family of human immunoglobulins, although it has a very short half-life of about 5 days.
Approximately 10–13% of immunoglobulins of the IgM class in the total proportion of serum antibodies in the human body are allocated. They participate in primary immune responses and are the most important of antibodies.
IgM is predominantly found in lymphatic fluid and blood. It is the main neutralizing agent in the early stages of the disease. IgM is the first line of defense of the human body from uninvited guests, so to speak. During the immune response, they are produced first, and then replaced by antibodies G. It is interesting that in children, starting from 9 months of age, the same amount of IgM antibodies is produced in the body as in adults.
An increase in IgM can be regarded as a sign of a recent infection or the presence of antigen in the body.
The role of immunoglobulins in the body
Antibodies are part of the humoral immune response and act very specifically, as they are always directed against a specific antigen.
The task of any antibody in the human body is to participate in immune responses. Immunoglobulins have the ability to form immune complexes with antigen molecules, activate the complement system (a complex of proteins contained in the blood, necessary to protect the body from foreign agents) and cause inflammation. All this should neutralize the antigen and safely remove it from the body.
Due to different biochemical properties, different classes of antibodies can perform specialized functions:
- neutralize parasites (IgE);
- neutralize microorganisms (IgM, IgG);
- protect against repeated diseases such as mumps (IgG);
- protect the mucous membranes (IgA);
- participate in the synthesis of lymphocytes (IgD);
- protect the fetus (IgG) and the newborn baby (IgA).
Antibodies and immunological memory
The immune response is divided into primary and secondary. The primary response appears during the first contact with the antigen, after which the body produces mostly IgM class immunoglobulins, which are then replaced by more specific and stable IgG antibodies.
A secondary immune response occurs upon repeated contact with the same antigen. It is more intense than the primary, the concentration of antibodies reaches higher levels than the first time.
This effect is due to immunological memory and the presence of memory in b-lymphocytes. These cells live in the body for years, and when they come into contact with the antigen, they begin to divide very intensively and produce specific antibodies.
How to determine the amount of antibodies
Antibodies make up 12% to 18% of whey proteins. To assess the number of individual protein fractions, in the laboratory, a so-called proteinogram is compiled.
Antibody test, enzyme-linked immunosorbent assay (ELISA), as a rule, is carried out with venous blood (allows you to determine the number of immunoglobulins of the IgM, IgG, IgE, IgA class). In addition, it is possible to determine the amount of an IgA class antibody by biochemical study of human saliva or feces - the method of polymerase chain reaction (PCR). In certain situations, the test may be performed using another material, such as cerebrospinal fluid.
If a critical increase in certain immunoglobulins is diagnosed in the patient’s blood, they speak of hypergammaglobulinemia.Typically, in such patients, antibodies of the IgM class are excessively increased, while the rest remain in short supply.
Against the background of a pathological increase in some antibodies, various diseases can develop, including:
- acute and chronic inflammation;
- parasitic, bacterial, viral or fungal diseases;
- autoimmune diseases;
- cirrhosis of the liver;
A pathologically low amount of antibodies in the serum can occur against the background of:
- congenital genetic disorders;
- taking certain drugs, including antimalarial, cytostatic, glucocorticoid;
- infections, including HIV;
- oncological diseases;
- nephrotic syndrome;
- extensive burns;
- severe diarrhea.
Immunoglobulins and vaccination
Antibodies play a key role in the development of immunity after vaccination. As a result of contact with the antigen contained in the vaccine, the immune system produces antibodies. First, less stable and specific IgM, and then more stable IgG. For example, during vaccination against hepatitis B virus, the vaccine is administered three times with a certain interval between vaccinations. This allows you to create a persistent immunity to the disease. The effectiveness of such vaccination is determined by a change in the amount of IgG antibodies in the body.
Antibodies in medicine
Thanks to the development of biochemistry, molecular biology and medicine, in our time it has become possible to synthesize immunoglobulins in laboratory conditions (usually IgG antibodies). Such antibodies are called monoclonal, since they come from a clone of one cell and work against a specific antigen.
Today monoclonal immunoglobulins are used to treat various diseases. This technique was first applied in 1981 to treat lymphoma. And already in 1984, the inventors of monoclonal antigens - the German biologist Georg Köhler and the British immunologist Cesar Milstein - received the Nobel Prize.
In modern medicine, monoclonal antibodies are used for:
- destruction of cancer cells;
- inhibition of individual cells of the immune system after organ transplantation (to prevent transplant organ rejection);
- suppression of immune responses in autoimmune diseases.
|Molecular weight||320 000||180 000||200 000||150 000||900 000|
|Serum concentration||1-4 mg / ml||0-0.4 mg / ml||10-400 mg / ml||10-16 mg / ml||0.5-2 mg / ml|
|Percentage of total immunoglobulin||15%||0,2%||0,002%||75%||12%|
|Spread||Intravascular and secreting||Lymphocyte surface||Basophils and mast cells in saliva and nasal secretions||Intra- and extravascular||Predominantly intravascular|
|Function||Protect the mucous membranes||Unknown||Parasite protection||Secondary immune response||Primary immune response|
Immunoglobulins are microscopic elements that play a very important role in our organisms. If not for antibodies, even the smallest infection would be deadly for a person.
Specialty: doctor pediatrician, infectious disease specialist, allergist-immunologist.
Total experience: 7 years.
Education: 2010, Siberian State Medical University, pediatric, pediatrics.
Experience as an infectious disease specialist for more than 3 years.
He has a patent on the subject "A method for predicting a high risk of the formation of a chronic pathology of the adeno-tonsillar system in frequently ill children." As well as the author of publications in the journals of the Higher Attestation Commission.