Immune system

The immune system is a network of biological processes 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 (non-specific) provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system (acquired or specific) 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. Innate immunity is present in all multicellular animals, while adaptive immunity is found only in vertebrates.

The immune system is responsible for our immunity and works in conjunction with other  organ systems in the human body. (An organ system is a group of organs that have a common origin, a single structural plan and perform a common function. Five of ten organ systems are regulatory: nervous, circulatory, endocrine, lymphatic, and immune. It should be clarified that the lymph organs and lymph nodes, of which there are about 600, are functionally part of the immune system).

Immunity is the capability of multicellular organisms to resist harmful microorganisms.

The innate immunity is the same in all people and reacts in the same way to any “enemies”. The reaction begins immediately after the penetration of the microbe into the body and does not form an immunological memory. That is, if the same microbe enters the body again, the nonspecific immunity system “does not recognize” it and will react “as usual”. Nonspecific immunity is very important – it is the first to signal danger and immediately begins to repulse the penetrated microbes.

However, these reactions cannot protect the body from serious infections, so after non-specific immunity, acquired immunity comes into play. Here, the reaction of the body is individual for each “enemy”, therefore, the “arsenal” of specific immunity in different people differs and depends on what kind of infections a person has encountered in life and what vaccinations he did. Adaptive immunity takes time to study the infection that has entered the body, so reactions at the first contact with the infection develop more slowly, but they work much more efficiently. But the most important thing is that, once destroying a microbe, the immune system “remembers” it and the next time it encounters the same, it reacts much faster, often destroying it even before the first symptoms of the disease appear.

The immune system includes central and peripheral organs.

1. The central organs of the immune system (responsible for the formation and maturation of cells): red bone marrow and thymus.
2. Peripheral organs (provide protection, that is, the immune response): spleen, tonsils, lymph nodes and lymphoid tissue, Peyer’s patch, appendix.

• Bone marrow. It is the central organ of immunogenesis. All cells involved in immune responses are formed in the bone marrow. Bone marrow is a storage of stem cells from which blood cells are formed. Depending on the situation, the stem cells are transformed into immune B-lymphocytes. If necessary, a certain part of B-lymphocytes is converted into plasma cells, which are capable of producing antibodies.
• Thymus (thymus gland). Is one of the main organs of the immune system which is responsible for the formation of T-cells of the immune system in the lymphoid tissues of the body. In the thymus, some immune cells (T-lymphocytes) mature after they have formed in the bone marrow. This type of bone marrow is found mostly in your flat bones, like your pelvis, scapula, skull, and sternum.
• Spleen. In the spleen, immune cells (B-lymphocytes) also mature. In addition, the process of phagocytosis is actively taking place in it – when special cells of the immune system catch and digest microbes that have entered the body, fragments of their own dead cells, and so on.
• Tonsils. The tonsils are a set of lymphoid organs facing into the aerodigestive tract and perform a protective function, are involved in the formation of local and general immunity. A person has six tonsils: adenoid tonsil, two tubal tonsils, two palatine tonsils, and the lingual tonsils.
• The lymph nodes. In their structure, they resemble a sponge through which lymph is constantly filtered. In the pores of this “sponge” there are a lot of immune cells that also catch and digest microbes that have entered the body. In addition, memory cells are located in the lymph nodes – these are special cells of the immune system that store information about microbes that have already entered the body earlier.
• Peyer’s patch. Because the lumen of the gastrointestinal tract is exposed to the external environment, much of it is populated with potentially pathogenic microorganisms. Peyer’s patches thus establish their importance in the immune surveillance of the intestinal lumen and in facilitating production of the immune response within the mucosa.
• Appendix. Has a protective function. accumulations of lymphoid tissue in it are part of the peripheral parts of the immune system. It is more difficult for people with a removed appendix to restore intestinal microflora after infection.

Pathogenic microorganisms and other antigens entering the intestinal tract encounter macrophages, dendritic cells, B-lymphocytes, and T-lymphocytes found in Peyer’s patches and other sites of gut-associated lymphoid tissue (GALT). Peyer’s patches thus act for the gastrointestinal system much as the tonsils act for the respiratory system, trapping foreign particles, surveilling them, and destroying them.

Thus, the organs of the immune system provide the formation, maturation and place of life of immune cells. So, in the bone marrow, B-lymphocytes are formed from its stem cells. In the thymus, differentiation of T-lymphocytes occurs, formed from the stem cells of the bone marrow that entered this organ. Then B- and T-lymphocytes with blood flow enter the peripheral organs of the immune system, which include the tonsils, lymph nodes and spleen, as well as numerous leukocytes that move freely in organs and tissues in order to search, recognize and destroy foreign substances. Leukocytes – white blood cells.

The main functions of leukocytes:

• detection and destruction of bacteria, viruses and other foreign agents by phagocytosis;
• destruction of altered cells (cancerous, etc.);
• destruction of dead body cells;
• participation in allergic reactions;
• participation in inflammatory reactions with tissue damage;
• the production of antibodies;
• the formation of the body’s immune memory.

Types of leukocytes. Leukocytes are divided into three main groups: granulocytes, monocytes, lymphocytes, dendritic cells.

• Granulocytes contain numerous lysosomes, secretory vesicles and granules. In accordance with the different nature of the color of these granules, granulocytes are divided into neutrophils, basophils and eosinophils.

1. Eosinophils (pink granules) protect the body from parasites and contribute to the development of allergic reactions. They provide anthelmintic immunity.
2. Basophils (blue-violet granules) secrete histamine, which is involved in inflammatory reactions.
3. Neutrophils (purple-pink color of granules) are capable of phagocytosis. They capture, kill and digest microorganisms (mainly bacteria). They constantly patrol the organism for signs of microbial infections, and when found, these cells quickly respond to trap and kill the invading pathogens.

• Monocytes are the largest of the white blood cells. Coming out of the bloodstream, they become macrophages (large blue-gray cells). Like neutrophils, they are capable of phagocytosis. However, macrophages are much larger and live longer than neutrophils.
• Lymphocytes are involved in the immune response and are divided into:
• B-lymphocytes produce antibodies (immunoglobulins). These are special proteins that “stick” to microbes and cause their death. Antibodies can also neutralize some toxins.
•  T-lymphocytes kill cells infected with the virus and regulate the activity of other white blood cells.
•  Natural killer (NK) cells are able to contact target cells, secrete proteins that are toxic to them, kill them or send them into apoptosis. NK recognize viral and tumor cells.
• Dendritic cells (also known as accessory cells) are bone marrow-derived leukocytes and are the most potent type of antigen-presenting cells. DCs are specialised to capture and process antigens, converting proteins to peptides that are presented on major histocompatibility complex (MHC) molecules recognised by T-cells. DC can be found in practically all tissues, where they detect homeostatic imbalances and process antigens for presentation to T-cells, establishing a link between innate and adaptive immune responses. Regardless of localization, all dendritic cells differentiate in tissues from blood monocytes, where they are in an immature state. The main function of immature dendritic cells is to recognize and absorb antigens that enter the body through barrier zones (skin, mucous membranes).

T-lymphocytes are classified into:

• T-helpers   promote the development of an immune response; help the immune system recognize specific types of microbes.
• T-suppressors  (Regulatory – cells)  suppress the development of the immune response, regulate the strength and duration of the immune response (i.e., it is a type of immune cell that blocks the action of certain other types of lymphocytes so that the immune system does not become overly active).
• Killer T-cells   kill viral-infected cells that carry antigens to stop the progression of infection.

How do the cells of the immune system distinguish “us” from “strangers” and understand with whom to fight? There are two main mechanisms of immunity within the adaptive immune system – humoral and cellular.

Cellular immunity occurs within infected cells and is mediated by T-lymphocytes. The major histocompatibility complex of the first type (MHC-I) helps them in this. This is a group of proteins that is located on the surface of every cell in our body and is unique for each person. This is a kind of “passport” of the cell, which allows the immune system to understand that it has “its own” in front of it. If something bad happens to a cell of the body, for example, it is affected by a virus or degenerates into a tumor cell, then the configuration of MHC-I changes or it disappears altogether. “Natural killer” T-cells and “killer” T-cells are able to recognize the MHC-I receptor, and as soon as they find a cell with altered or missing MHC-I, they kill it. This is how cellular immunity works.

But we have another type of immunity – humoral. Humoral immunity is also called antibody-mediated immunity. With assistance from helper T cells, B cells will differentiate into plasma B cells that can produce antibodies against a specific antigen. The humoral immune system deals with antigens from pathogens that are freely circulating, or outside the infected cells. Antibodies produced by the B cells will bind (stick) to antigens, neutralizing them, or causing lysis (dissolution or destruction of cells by a lysin) or phagocytosis.

How does our immune system understand the antigen structure and select the appropriate antibody for it?

Let’s consider this process using the example of the development of a bacterial infection. For example, you scratched your finger. When the skin is damaged, bacteria are most likely to enter the wound. When any tissue in the body is damaged, an inflammatory response is immediately triggered. Damaged cells secrete a large number of different substances – cytokines, to which neutrophils and macrophages are very sensitive. Reacting to cytokines, they penetrate the walls of the capillaries, “swim” to the site of injury and begin to absorb and digest bacteria that have got into the wound – this is how nonspecific immunity is triggered, but it has not yet come to the synthesis of antibodies.

Cracking down on bacteria, macrophages bring out different pieces of them to their surface in order to acquaint T-helpers and B-lymphocytes with the structure of these bacteria. This process is called antigen presentation. The T-helper and the B-lymphocyte study pieces of the digested bacteria and select the appropriate structure of the antibody so that later it “sticks” well to the same bacteria. This is how specific humoral immunity is triggered. This is a rather lengthy process, so at the first contact with an infection, it may take up to two weeks for the body to pick up the structure and start synthesizing the necessary antibodies.

After that, the B-lymphocyte that successfully coped with the task turns into a plasma cell and begins to synthesize antibodies in large quantities. They enter the bloodstream, are carried throughout the body and bind to all penetrated bacteria, causing their death. In addition, bacteria with adhered antibodies are absorbed much faster by macrophages, which also contributes to the destruction of the infection.

Are there any other mechanisms?

Specific immunity would not be so effective if each time it encounters an infection, the body synthesizes the required antibody for two weeks. But here we are rescued by another mechanism: some of the B-lymphocytes activated by the T-helper turn into the so-called memory cells. These cells do not synthesize antibodies, but carry information about the structure of the bacteria that has entered the body. Memory cells migrate to lymph nodes and can persist there for decades. When a second encounter with the same type of bacteria, thanks to memory cells, the body begins to synthesize the necessary antibodies much faster and the immune response starts earlier.

Thus, our immune system has a whole arsenal of different cells, organs and mechanisms to distinguish the cells of our own organism from genetically foreign objects, destroying the latter and performing its main function – maintaining genetic homeostasis.

Immune system disorders in humans

Immune system disorders can be divided into three categories: immunodeficiencies, autoimmune diseases, and hypersensitivity reactions.

Immunodeficiencies

Immunodeficiency is a decrease in quantitative indicators and/or functional activity of the main components of the immune system, leading to a violation of the body’s defense against pathogenic microorganisms and manifested by an increased infectious morbidity.

Primary immunodeficiencies (PIDs) are hereditary diseases caused by defects in genes that control the immune response. Basically, PIDs manifest themselves already in early childhood, but sometimes only by the age of 30-40.

Symptoms that may be signs of primary immunodeficiency:

• 4 or more cases of otitis during the year;
• 2 or more cases of sinusitis during the year;
• low effectiveness of antibiotics for two or more months of admission;
• 2 or more cases of pneumonia during the year;
• the child’s inability to gain weight and grow normally;
• frequent and deep abscesses of the skin and internal organs
• persistent candidiasis of the oral cavity and skin;
• the need for intravenous antibiotics to eliminate the infection;
• two or more systemic infections, including sepsis;
• hereditary predisposition.

Autoimmune pathology

Damage to the body’s own organs and tissues by the immune system is called an autoimmune process. About 5% of humanity suffers from this type of disease. In the patient’s body, military actions are developing, reminiscent of a civil war: “insiders against theirs” go on the attack. There are no winners in this struggle – only suffering.

• Autoantibodies can cause cell death by activating the complement system on their surface or by attracting macrophages;
• Receptors on the cell surface can become targets for antibodies.
• Autoantibodies, together with soluble antigens, can form immune complexes that settle in various organs and tissues (for example, in the renal glomeruli, joints, on the vascular endothelium), disrupting their work and causing inflammatory processes.

As a rule, autoimmune disease occurs suddenly, and it is impossible to determine exactly what caused it. It is believed that almost any stressful situation can serve as a trigger for starting, be it an infection, injury or hypothermia. An important role in the occurrence of an autoimmune disease is played by both a person’s lifestyle and a genetic predisposition – the presence of a certain variant of a gene.

Hypersensitivity

Hypersensitivity refers to an excessive immune response to an antigen. Hypersensitivity reactions are divided into several types, depending on their duration and the mechanisms underlying them:

• Type I hypersensitivity includes immediate anaphylactic reactions, often associated with allergies. Reactions of this type can be both mildly uncomfortable and even fatal. Type I hypersensitivity is based on immunoglobulins E (IgE), which cause degranulation of basophils and mast cells;
• type II hypersensitivity is characterized by the presence of antibodies that recognize its own proteins and mark the cells expressing them for destruction. Type II hypersensitivity is also called antibody-dependent or cytotoxic hypersensitivity, it is based on immunoglobulins G (IgG) and M (IgM);
• type III hypersensitivity is caused by immune complexes consisting of antigens, complement proteins, IgG and IgM;
• Type IV hypersensitivity, also known as delayed hypersensitivity, develops within 2–3 days. Type IV hypersensitivity reactions are observed in many autoimmune and infectious diseases, and they are based on T cells, monocytes and macrophages.

Effective methods of influencing immunity:

• regular vaccination in terms of the speed and quality of the reaction exceeds the natural process of forming immunity to a specific infection;
• balanced nutrition, ensuring the maintenance of normal metabolism;
• regular physical activity, ensuring the physiological functioning of all body systems, maintaining optimal body weight indicators;
• rejection of bad habits leading to addictions (alcoholic, nicotine, narcotic, toxic, computer);
• the regime of the day, especially the influence of circadian rhythms (change of day and night): during wakefulness, the number of T-killers and NK cells reaches the peak, as well as the concentration of anti-inflammatory substances such as cortisol and catecholamines; during sleep, the formation of memory T-cells reaches its peak.

Conclusion

The immune system is represented by three levels: organ, cellular and molecular with the most complex interactions between them.

Breakdowns in the structure of the immune system lead to the development of immunodeficiencies, autoimmune diseases or hypersensitivity reactions.

Immunodeficiency at the genetic level (primary) or acquired (secondary) can occur at any age and lead to increased infectious morbidity. In recent years, substitution therapies have emerged that extend the lives of these patients. Improving their quality of life requires not only the provision of expensive treatment, but also the organization of support from the family, psychologists and social institutions.

Autoimmune diseases and hypersensitivity are the inability of the body to resist the raging immune system, which has confused its own and that of others.

Unfortunately, medicine has not yet learned to cure any of the diseases of the immune system, but only to apply substitution therapy.

Vaccinations and a healthy lifestyle are effective preventive methods of influencing the immune system. So far, no one has managed to buy immunity at the pharmacy.