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The relationship between immunoglobulin and diseases

Posted on: September 29, 2020, by Jason
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immunoglobulin-and-diseases

What is immunoglobulin?

Immunoglobulin (Ig) refers to a globulin that has antibody (Ab) activity or chemical structure and is similar to antibody molecules. Immunoglobulin is a tetrapeptide chain structure composed of two identical light chains and two identical heavy chains connected by interchain disulfide bonds.

What are the 5 immunoglobulins? Immunoglobulins are divided into five categories, namely immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin D (IgD) and immunoglobulin E (IgE).

The immune system is composed of immune tissues, organs, immune cells and immune active molecules. Immunoglobulin is a class of immunologically active molecules which include immune cell membrane molecules, such as antigen recognition receptors, differentiation antigens, major histocompatibility molecules, and some other receptor molecules. It also includes molecules synthesized and secreted by immune and non-immune cells, such as immunoglobulin molecules, complement molecules, and cytokines. Immunoglobulin is a concept in chemical structure. The chemical basis of all antibodies is immunoglobulin, but not all immunoglobulins have antibody activity.

Immunoglobulin Structure

Immunoglobulins can be divided into antibodies and membrane immunoglobulins. Antibodies are mainly found in serum, but also in other body fluids and exocrine fluids. Their main function is to specifically bind antigen.

Membrane immunoglobulin is an antigen receptor on the membrane of B cells, which can specifically recognize antigen molecules. In the body, antibodies and antigens can directly exert effects after binding. For example, antitoxins can neutralize exotoxins, virus-neutralizing antibodies can prevent viruses from infecting target cells, and secreted IgA can inhibit bacterial adhesion to host cells.

In vitro, agglutination and precipitation may occur after the antibody binds to the antigen. Immunoglobulin can activate complement, binding to the Fc receptor on the cell surface, (Fc is a crystalline fragment. Hydrolyze IgG molecules with papain can obtain two Fab and one Fc fragment. This fragment can interact with effector molecules and effector cells, but can’t bind to antigens.) so exhibiting different biological effects, such as opsonization, antibody-dependent cell-mediated cytotoxicity, and mediating type I hypersensitivity.

Through the placenta and mucosa, IgG is the only type of Ig that can pass through humans’ placenta. The transfer of maternal IgG to the fetus through the placenta is an important natural passive immunity, which is of great significance for neonatal anti-infection. Secreted IgA can pass through the mucosa of the digestive tract and respiratory tract, which is the main factor of the body's mucosal local immunity. In addition, antibodies have positive and negative regulatory effects on the immune response.

Immunoglobulin and diseases

1. Immunoglobulin and diabetes

China is now facing a whole new problem: the largest diabetes epidemic in the world. According to a recent study, one in ten adults in China has diabetes, and another 16% are on the verge of developing diabetes. According to the latest findings, the incidence of diabetes in China is almost close to 11% in the United States, surpassing most western countries such as Germany and Canada.

At present, many research data on the epidemiology, pathology, serology of diabetes shows that the onset of diabetes is closely related to autoimmunity, especially insulin dependence. Because the molecular structure of some substances (antigens) on the insulin-secreting B cells in the pancreatic islets is similar to the viral antigens, when the self-immunity is low, the autoantibodies will mistake it for an "invader", thus generating immunity against its own islet cells reaction. They attack on B cells and cause "fights between their own people". As a result, almost all pancreatic islet B cells are "dead", and the function of secreting insulin is severely reduced or even failed. Once the body lacks this blood sugar lowering hormone, there will be a series of manifestations of high blood sugar.

Infusion of intravenous C can help reduce the immune system's attack on insulin, help the recovery of insulin cells, and make insulin secrete normally.

2. Immunoglobulin and cancer

Normal human immunity has the effect of resisting cancer, because cancer cells are very different from normal human cells and belong to "heterogeneous substances." Specifically, immunity against cancer means that the body uses immune cells or immunologically active substances (such as antibodies) to recognize mutations or cancerous cells in the body in time, and then eliminate them. This effect is also called "immune surveillance", which is equivalent to the human body's warning system against cancer. Therefore, when the body is invaded by cancer cells, its onset depends on the body's immunity.

3. Immunoglobulin and rheumatic diseases

According to statistics from the World Health Organization, the incidence of rheumatism in the world’s population of nearly 6 billion is as high as 5%. Nearly 300 million people suffer from rheumatoid arthritis and other rheumatoid diseases. Patients often have kidneys, heart, lungs, liver, blood and immune system diseases and functional abnormalities, which is most common in the elderly.

As the main synthetic product of the immune system, immunoglobulin has obvious anti-disease effects. It can regulate the normal operation of the human immune system, stabilize the human immune defense line, resist the invasion of bacteria and viruses in vitro, and prevent fever, fatigue and joints inflammation caused by susceptible factors. So middle-aged and elderly people can enjoy their old age in peace.

Where does immunoglobulin come from?

1. Where does immunoglobulin come from?

IgG is the only immunoglobulin that can be passed to the fetus through the placenta, and breast milk is rich in immunoglobulins. After the baby is born, the immune factors transferred by the mother's placenta and the mother's milk during the lactation period enable the baby to get the initial disease resistance.

2. Synthesis of immune organs in the body

Most of the immunoglobulin required by the human body depends on the synthesis of immune organs. As children grow up to about 15 years old, their immune organs gradually mature and basically reach the level of adults. By the age of 22, the immune organs have the strongest function and the strongest ability to synthesize immune globulin. Later, with the increase of age, the immune organs began to shrink. After the age of 55, some immune organs even completely degenerate, the number of synthetic immunoglobulins decreases, and the immune globulin in the body will sharply decrease.

3. In vitro supplementation

In vitro injection of gamma globulin is a relatively quick and effective way to enhance the body's resistance to prevent infection. It is mainly used for the prevention and treatment of immunodeficiency diseases, infectious hepatitis, measles, chickenpox, mumps, herpes zoster and other viral and bacterial infections. It can also be used for endogenous allergic diseases such as allergic rhinitis, eczema, myasthenia gravis, ITP, systemic erythema lupus and Kawasaki disease.

Significance of immunoglobulin test

Immunoglobulin is a type of protein with antibody activity in human serum and body fluids, also known as gamma globulin. It has antibacterial and antiviral effects, strengthens the phagocytosis of cells, and can kill or dissolve pathogenic microorganisms under the cooperation of complement. It is an important component against diseases.

immunoglobulin structure
immunoglobulin structure

Serum immunoglobulins can be divided into five types, namely IgG, IgM, IgA, IgD, and IgE. The normal value varies due to different subjects, ages, regions, and methods. Various immunoglobulins not only differ in quantity, but also have their own characteristics in function:

1. IgG

Most antibodies with antibacterial, antiviral, and antitoxin effects belong to IgG. It is the only immunoglobulin that can pass through the placenta. Increased IgG is seen in IgG multiple myeloma, systemic lupus erythematosus, rheumatoid arthritis, chronic active hepatitis, tuberculosis, kala-azar and certain infectious diseases. Decrease is seen in nephrotic syndrome, certain tumors, leukemia, heavy chain disease, light chain disease and certain immunodeficiency diseases.

2. IgA

IgA has antibacterial and antiviral effects. It cannot pass through the placenta, and children can only get it from breast milk.  

Reference value: 0.7~3.9 g/L for adults.

There are two types of IgA in human blood, namely serotype and secretory type. The former exists in the form of a monomer, and the latter is composed of a connected dimer and secretory sheet. The place where synthesis and secretion take place are located in the intestine, respiratory tract, breast, salivary glands and lacrimal glands, so they mainly exist in the gastrointestinal tract, bronchial secretions, colostrum, saliva and tears. They are the main antibodies involved in mucosal immunity and play an important role in local anti-infection. It is through colostrum that babies obtain secretory IgA, which achieves the effect of natural passive immunity. 

Elevated IgA is seen in IgA type multiple myelopathy, systemic lupus erythematosus, rheumatoid arthritis, liver cirrhosis, eczema, thrombocytopenia and other diseases. The low iga levels is seen in heavy chain disease, light chain disease, malabsorption syndrome, certain immunodeficiency diseases, repeated respiratory infections, blood transfusion reactions, autoimmune diseases, etc.

3. IgM

IgM is a high-efficiency antibody with strong bactericidal power, especially effective against Gram-negative bacteria such as Escherichia coli. 

Reference value: 0.4~3.5 g/L for adults.

It is the first antibody synthesized and secreted in the process of ontogeny. IgM can be produced in the late stage of fetal development. The content of IgM is minimal in newborns, and it gradually rises at birth, reaching adult levels at 1/2 to 1 years old.

An increase of this antibody in the cord blood indicates that the fetus has an intrauterine infection (such as rubella virus, cytomegalovirus, etc.). The natural blood group antibody is IgM, and the hemolytic reaction caused by blood transfusion of incompatible blood group is also caused by this antibody. When the body is infected by a pathogen, IgM is the earliest antibody produced in the humoral immune response. The clinical detection of this antibody can specifically diagnose and treat the disease early.   

Clinical significance: The increase is seen in macroglobulinemia, autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome), viral infection, chronic lymphocytic leukemia and malignant lymphoma. Decrease is seen in multiple myeloma, burns, malnutrition and immunocompromised diseases.

4. IgE

IgE is also called reactin. When the body encounters allergens, IgE can cause cells to release a variety of active substances, causing allergic reactions. 

Reference value: 0.13~0.93 g/L for adults.

The normal content is very stable. It is the immunoglobulin with the least content in normal human serum, and has a strong affinity with mast cells, alkaloid granulocytes and other cells, which causes type I hypersensitivity. 

Increased IgE is seen in bronchial asthma, urticaria, eczema and other allergic diseases and parasitic diseases (roundworms, hookworms) and so on. IgE reduction is seen in primary agammaglobulinemia.  

5. IgD

It may have the function of regulating immunity. 

Reference value: 0.6~2.0 g/L for adults.

It is an antibody that can be produced at any time of individual development, but its content in the body is very low, easily hydrolyzed by proteases, and has a short half-life (only 3 days). Its main physiological functions are not yet fully understood.

Clinical significance: Increased IgD can be seen in multiple myeloma, chronic osteomyelitis, epidemic hemorrhagic fever, cirrhosis, certain connective tissue diseases, allergic diseases, Hashimoto's thyroiditis and viral infectious diseases. Decrease can be seen in primary agammaglobulinemia, silicosis, etc.

Conclusion

Measuring the content of human serum immunoglobulin is an important method to understand the immune function of the body and has certain value in the diagnosis of autoimmune diseases, especially for the diagnosis of plasma cell malignant transformation and humoral immune deficiency.

In addition, it has certain value for observing the curative effect of disease. However, serum immunoglobulins have a large range of variation with marginal specificity. Therefore, the diagnosis and analysis of its significance must be closely integrated with clinical diseases.

Want to learn more about antigens and antibodies? Read about monoclonal and polyclonal antibodies.

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