Resistance above all!

What is the immune system?

Complex living organisms are exposed to various external influences of various factors, which may result in their damage and diseases. The system that organizes and directs defense in these organisms in response to the aggression of these factors is the immune system.

Like the nervous or endocrine system, it is also included in the integration systems of a complex living organism: having the ability to distinguish between the body’s own structures and strangers, it ensures the integrity of the entire system, and takes care of its integrity.

It is a system that can locate an “aggressor” or “intruder” by various mechanisms, recognize it as “foreign” (learn its alien nature), apply neutralizing measures to it, and finally – get rid of it. Factors referred to as “foreign” or “hostile” to the body are primarily various viruses, bacteria, fungi, protozoa and larger parasitic organisms, as well as various chemical molecules: proteins, polysaccharides and lipids. The immune system, as a guardian of the body’s integrity, controls phenomena that can lead to carcinogenesis – cancer (the “enemy” is cancer cells), and affects pregnancy. Probably involved in embryogenesis. Modern research shows that its cells – lymphocytes – participate in the phenomenon of programmed cell death – apoptosis.

Specific and non-specific immunity

The immune system is made up of a network of cells (lymphocytes) whose genes control their defense functions.
Lymphocytes are specialized ubiquitous cells, dispersed in body fluids and tissues or forming their own organs, central and peripheral. There are as many as 1012 cells in the body, which is about 1% of the total body weight. The immune system primarily organizes the specific immunity associated with lymphocytes, thanks to which the “aggressor”, “intruder”, whenever it intrudes into the body is, after precise recognition, eliminated as a result of the immune response. In addition to specific immunity, the system has other mechanisms by which it fights “foreign”. They create an old phylogenetic non-specific immunity, which, however, is also significantly influenced by the immune system.

This type of immunity is, among others associated with mechanisms and structures affecting the continuity of barriers separating the system from the external environment, such as skin or mucous membranes. It is also based on the stereotypical activities of various cells exhibiting phagocytic properties, so-called phagocytes, e.g. macrophages or neutrophils (multinucleated).

Simple defense mechanisms

The simplest defense against “intruders” is to keep your skin and mucous membranes intact. The skin is acidic, which is not beneficial for bacteria. In addition, sebaceous glands secrete bactericidal unsaturated fatty acids. Permanent peeling of the epidermis makes it easier to get rid of bacteria and other microorganisms on the skin. Mucous membranes are covered with protective mucus, which is sometimes an insurmountable obstacle for many aggressors. Individual organs have additional and characteristic defense mechanisms. For example, in the airways, epithelial shutter cells help the body to get rid of inhaled foreign particles and microbes. Acid gastric juice has very strong bactericidal properties. Similarly, the acid reaction of urine to some extent insures the body against the aggression of many pathogens. Numerous protective substances are present in body secretions, which are important in immunity. These include strongly bactericidal lysozyme present in most secretions or lactoferrin present in breast milk.

phagocytosis

Phagocytosis involves the absorption of the “intruder” by the appropriate cell, followed by its digestion in its interior. Many body cells have phagocytic abilities, but only some of them are real “professionals” who are specially (immunologically) prepared for this function. Phagocytic cells are the primary guardians of the system. They take immediate action when the “intruder” overcomes the protective barriers. Phagocytes have inter-tissue mobility. Their penetrating abilities are huge. Phagocytes show some specialization in their defense interactions. For example, neutrophils absorb and digest primarily extracellular bacteria, while macrophages – bacteria and intracellular parasites and viruses.

The most important stage of phagocytosis is digestion. During it, numerous intracellular digestive enzymes are activated, which degrade the aggressor molecules. Phagocytic cells, especially granulocytes, use killer free radical systems to destroy bacteria, primarily hydrogen peroxide – such intracellular “hydrogen peroxide”. Neutrophils use microbes to combat microbes. cationic proteins, or defensins, with which they destroy bacterial cell membranes and virus envelopes by creating holes in them.

Complement system

Non-specific immunity also consists of the activity of some enzyme systems in the blood, especially the complement (complement) system. This system is formed by 30 components that are subsequent substrates and enzymes that act on them. The activation of the complement system in response to the presence of an aggressor cell leads to the formation of a protein complex in the blood, which is crucial for the disintegration of this cell. At the same time, the individual components of the complement system play an independent role in various physiological phenomena in the blood, including immune processes. It is important that the complement system, although originally independent of the immune system, most efficiently functions only within a specific type of immune-based immunity.

How does the immune system work?

antigens

For the immune system to function efficiently, it must first be able to distinguish between its own structures: cells, molecules (structurally separated fragments), and structures for foreign bodies. The substances subject to constant control by this system in terms of their structural compliance with the genetic record of lymphocytes, i.e. with what lymphocytes “know” about them, are so-called antigens. In essence, an antigen is any substance that, as a result of contact with cells of the immune system, can trigger an immune response on its part. In turn, generally speaking, it consists first of all in the production of a substance opposite to an antigen – the so-called antibodies – and, secondly, on sensitizing lymphocytes, i.e. making them immunologically active, including those capable of memorizing the structure of the encountered and recognized antigen.

The immune response occurs in several stages. In the first phase, during the induction period, the antigen is recognized. In the second phase, during the activation period, the cells, upon contact with the antigen, begin to multiply, gradually passing into the final forms, immunologically active, i.e. effector. They also include immune memory cells that store antigen knowledge. In the third, effector, executive phase, mechanisms that ultimately eliminate the antigen are activated.

Own and foreign antigens are distinguished. Each cell in the body carries its own antigens called autoantigens. They remain, like any antigen, under the control of the immune system and under normal conditions, recognized as “their”, are not the subject of its attack (do not cause an immune response).

On the surface of the membranes of the cells of each complex living organism, genetically encoded (by a gene complex located on the 6th chromosome, called MHC (Major Histocompatibility Complex)) protein molecules in the number of 50 to 200, which have a strictly defined genetically specific structure, characteristic for each individual .

These molecules are called histocompatibility antigens (in short – HLA, Human Leukocyte Antigen – the first of them have been recognized on leukocyte cell membranes) and determine tissue individuality. They are tissue identifiers, just as the identifiers are blood groups in the AB0 Rh system.

A significant part of them are so-called transplant antigens. They are found on most membranes of somatic cells and if they are recognized as foreign, i.e. tissue incompatible, they will be eliminated by an immune reaction. At the tissue or organ level, this means rejection of the transplant. In addition to autoantigens, other antigens are “read” as “foreign” after reading them, and are the reason for the immune response that eliminates them. However, sometimes the antigen does not cause the immune system to respond, for example because it is not recognized. On the other hand, it happens that despite the detection of a foreign antigen, there is no classic immune response. This antigen is simply tolerated by the immune system. Immune tolerance is a permanent phenomenon with both positive and negative aspects. It is needed because it protects the body against autoimmune phenomena in which its own antigens are read as foreign with all serious pathological consequences. On the other hand, some microorganisms can use persistent tolerance for uncontrolled reproduction. The immune system has great recognition capabilities. It is believed that he is able to respond to any antigen. Given that there are as many as 1016 antigens in nature – the possibilities of the system are simply limitless.

Not all antigens are equally able to cause a full immune response. Those that are not directly immunogenic are called haptens. To trigger an immune response, haptens need a suitable carrier. Haptens are usually small molecules, sometimes even single atoms, and their carrier is usually an immunogenic protein or polysaccharide.

Not the whole antigen, but only a small part (fragment), called the antigenic determinant, causes an immune response, including the production of an antibody. In a sense, the antigenic determinant plays the role of a hapten, the rest – a carrier.

It happens that one antigen has several, several dozen or even several hundred antigenic determinants, so as a result of the immune reaction, a sufficient number of different antibodies may appear. Often, however, among numerous antigenic determinants the so-called dominant determinants against which the immune response is mainly directed. There are many different antigens. They may differ in chemical structure (some are proteins, others are multi-sugars or have a lipid structure), may be a separate chemical molecule or be a separate fragment of a larger cellular structure, may finally have bacterial, plant or viral origin, etc.

Body antigen – is an autoantigen that, as already mentioned, does not cause an immune response. Identical twins have so-called isoantigens, which also do not cause a response from the twin immune system. Other antigens, so-called alloantigens belonging to individuals of the same species and heteroantigens belonging to different species cause very strong immune responses.

Autoantigens are essentially (under health conditions) non-immunogenic; the immunogenicity of other antigens varies. For example, high molecular antigens are generally more immunogenic than medium-sized or small antigens. Additionally – smaller particles are eliminated faster from the body (e.g. by the kidneys), which means that their contact with the immune system is shortened sufficiently to make them even less immunogenic. Protein antigens outweigh the immunogenicity of other chemical compounds, but they must be proteins with a higher molecular weight. The antigen’s high or low immunogenicity may be determined by its spatial structure and current electrical charge, which usually reduces immunogenicity.

There is a phenomenon of crossing immunological reactions. There are different antigens whose antigenic determinants have identical or similar chemical structure. The resulting antibody that is directed against one antigen may also be directed against another, to which the system has not yet been able to, or simply could not respond.

lymphocytes

The main textured components of the immune system are B and T lymphocytes.

They are small mononuclear cells with a diameter of 8 to 15 microns. This variation in lymphocyte size is one of the grounds for their division into small, medium and large. Some of them have a short, day-long life. They are usually larger lymphocytes. Others, usually small, live long, e.g., immune memory lymphocytes. Lymphocytes are found primarily in the lymph organs: lymph nodes and spleen, as well as in loose lymph tissue groups, e.g. in the digestive tract. A large proportion of lymphocytes have no specific organ affiliation. They are in constant motion, move, circulate in the blood and lymphatic vessels. Adult lymphocytes are formed in the bone marrow – which plays a central role in the immune system, as a result of the division of omnipotent stem cells. These divisions and differentiation, which also result in, besides lymphocytes, other cells, such as erythrocytes, granulocytes, monocytes and platelets, are induced and controlled by growth factors produced by some cells associated with stem cells. Some lymphocytes mature and reach adulthood on the spot, ie in the bone marrow. They are B lymphocytes.

Some immature, undifferentiated lymphocytes, however, leave the bone marrow and migrate to the thymus, the other, apart from the bone marrow, “central” lymphatic organ located in the upper mediastinum. Here they go through the next stage of puberty, transforming into the so-called T lymphocytes. B and T lymphocytes have in their cell membrane characteristic antigens and receptors for each of the groups. The phenomena of lymphocyte maturation inside the thymus are regulated by the thymus hormone thymopoietin. T-cells ripening in the thymus are sometimes called thymus-dependent lymphocytes. It turns out that for about 1% of T cells, the thymus is not the final settlement. These lymphocytes leave the thymus and after reaching the lymph nodes and spleen undergo further, final maturation process. The remaining 99% of lymphocytes remaining in the thymus die after 2-3 days in it.

Lymph nodes and spleen

Man has a huge number of lymph nodes, small (the size and texture of peas or small beans) of well-defined peripheral lymphatic organs. Some subcutaneous nodes are palpable: especially the submandibular, cervical, under armpits and groin. Lymph nodes are located along the blood vessels, near the internal organs, and are connected by a separate network of lymph vessels in which the lymph (lymph) flows. Lymph nodes along with lymphatic vessels and lymphatic papules located in the wall of the digestive system form the peripheral lymphatic system, which is connected to the venous part of the circulatory system. Another important peripheral lymphoid organ is the spleen, located in the abdominal cavity on its left side, just below the diaphragm. There are T-dependent and B-dependent zones in the lymph nodes. In these zones, the immune system (lymphocytes) reacts to the antigen delivered to the node. As a result of contact with the antigen presented, lymphocytes pass into active forms capable of multiplication. Subsequent daughter cells acquire different properties. They become immunocompetent, i.e. capable of immune response. There are also T-dependent areas in the spleen, reserved for T lymphocytes, and separate groups of B lymphocytes. Antigens reach the spleen through the bloodstream, and the nodes – lymphatic vessels.

Some lymphocytes constantly circulate through lymphatic and blood pathways. Most of them are T cells. Immune memory cells constitute a very important part of circulating lymphocytes.

B lymphocytes

B lymphocytes are of myeloid origin. On their surface they have protein receptors, which are called antideterminants for individual antigens, and more precisely – for their antigenic determinants. It is very important that each lymphocyte is monospecific, i.e. it has only one antideterminant.

B lymphocytes undergo several developmental stages as they mature. The mature form of B lymphocyte, if it doesn’t come in contact with the antigen, lives short. However, if such contact occurs, the lymphocyte is transformed into the antibody-producing plasma cell or becomes a long-lived B-cell.

T lymphocytes

T lymphocytes are a separate population of immune cells that is different from B lymphocytes, which is not at all homogeneous because it includes functionally different smaller subpopulations. Each of them has different surface (membrane) molecules (markers), which are their identifiers. The most characteristic of them are proteins with the symbols CD8 and CD4.

T lymphocytes having CD4 molecules on their surface, i.e. positive CD4 lymphocytes (CD4 +), are called helper lymphocytes. Their tasks are particularly varied. The CD4 lymphocyte is thought to be the central cell of the immune response.

By means of the active substances it produces and secreted, the so-called cytokines, affect various immune processes. Among others, they affect B lymphocytes, stimulating their division and maturation in the presence of antigen, macrophages and their phagocytic properties, neutrophils, modulating their participation in inflammation and phagocytosis, and finally the T lymphocytes forming the second large subpopulation – CD8. Among the CD4 lymphocytes are long-lived immune memory cells. The second sub-population of T lymphocytes, CD8 positive (CD8 +) lymphocytes are so-called cytotoxic or suppressive lymphocytes. Cytotoxicity means the ability to kill other cells when a foreign antigen is recognized on their surface. Suppression is a more complex phenomenon, which includes such functions as: control of autoimmune, allergic and immune tolerance processes. In a word, suppressive lymphocytes regulate the immune response.

NK lymphocytes

A small percentage of lymphocytes do not have on their surface any proteins characteristic of B lymphocytes or T lymphocytes. For this reason they are called “zero” cells. Because of the role they play in fighting “aliens”, they are called NK (Natural Killers), or “natural killers.” It is interesting that NK lymphocytes do not require contact with the antigen for their activation. They kill cells with proteins (antibodies) on their surface directed against their own surface antigens. Their activity is called antibody-dependent cytotoxicity.

antibodies

Antibodies, protein molecules directed against antigens, are produced primarily by plasma cells (plasmocytes), which are ultimately (effector) altered B lymphocytes. Plasmocytes are located primarily in the lymphatic organs, as well as in the digestive wall. They are larger than lymphocytes, live short – up to several weeks.

Antibodies are also B lymphocytes themselves. Antibodies are so-called immunoglobulins, i.e. immunogenic globulins (globulins form a group of globular proteins, constituting the majority of body proteins), which have a specific specificity, which means that their structure “corresponds” to the structure of a specific antigen. There are different immunoglobulins. They belong to different classes, depending on the construction. Most immunoglobulins belong to the gamma class – these are gamma immunoglobulins (IgG). In addition, there are also alpha immunoglobulins (IgA), mi immunoglobulins (IgM), delta immunoglobulins (IgD) and epsilon immunoglobulins (IgE).

Immunoglobulins have quite a complicated structure. They are composed of polypeptide chains formed by long strings of amino acids: heavy, i.e. high molecular weight, and light – low weight. The membership of an immunoglobulin in a particular class depends on the structure of the heavy chain.

The immunoglobulin prototype has the shape of the capital letter Y, whose arms are formed from the outside with two light chains, from the inside – with two heavy chains, longer, because they also form the “letter”, from which the arms extend. At the ends of both arms, immunoglobulins have so-called immunoglobulin variable parts. Each of them is a small polypeptide fragment consisting of only about 100 amino acids. It depends on the part of the variable that the specificity of the immunoglobulin for the specific antigen with which the lymphocyte has come into contact. The final formation of the variable part of the immunoglobulin makes it become an antibody.

The plasma cell is very efficient. It synthesizes about 2000 immunoglobulins in one second. The synthesis process is genetically controlled, including variable parts – by several separate genes. This is a very complicated process given that the antibody produced must be compatible with the specific antigen. Antibody production as a result of lymphocyte antigenic activation ultimately resembles matching the right key to a particular lock. However, it should be remembered that the antibodies nevertheless show significant heterogeneity, which means that they can be “matched” to different antigens, given that different antigens may have the same or very similar determinants.

However, there are very specific and fully homogeneous antibodies. They are so-called monoclonal antibodies, produced by clones of homogeneous cancer cells of the lymphatic system.

Modern biology has provided an interesting method of producing highly specific antibodies directed against a specific antigen. This method involves combining a plasma cell taken from a multiple myeloma focus (cancer of the lymphatic system), which has immortal characteristics, with a B-cell, which in turn produces a specific antibody. The resulting cell hybrid provides a virtually unlimited number of identical highly specific antibodies. The production of an antibody as a result of lymphocyte contact with an antigen is called a humoral immune response. This is a very complex reaction, which consists of various mechanisms. The antigen does not reach the lymphocyte in the usual way, passively transported by blood or lymph. After entering the body, it is first “caught” by the feeding cells (among others – macrophages or by cells with protrusions, so-called dendritic cells), endowed with the ability to penetrate tissues and is bound to their cell membrane. In the event that a bacterial cell or other above-organized infectious agent is “caught”, it is absorbed into the food cell and digested. Residues from this particular intracellular “feast” are emerged outside the cell, constituting the correct antigen.

Macrophages or dendritic cells provide and “present” antigen to B lymphocytes. However, it turns out that presentation alone is sometimes not enough for this lymphocyte to respond. Additional signals are still needed, including those from the T helper cell.

The antigen first binds to the membrane receptor (nb. It is an immunoglobulin) of the B lymphocyte, and then is absorbed into its interior and this is an impulse for cell activation.

The B lymphocyte divides every several hours and after 8-12 divisions produces a very large number of daughter effector cells, some of which are capable of producing antibodies, while others “learn” and remember the structure of the antigen. It is not known what mechanisms lead to such differentiation.

Some progeny B lymphocytes that lose contact with the antigen become unnecessary and undergo programmed death, i.e. apoptosis. For the activation of B lymphocytes, in addition to antigen presentation, the presence of T lymphocytes is generally needed. However, some B lymphocytes do not need their participation for activation. In the immune response, B and T lymphocytes stimulate and support each other. B-lymphocyte presents antigen to T-lymphocyte, which in response – secreting active substances, so-called lymphokines (cytokines) – controls the division and differentiation of B lymphocytes into a plasma cell.

Antibody production has specific dynamics. If the body first comes into contact with the antigen, the production of antibodies is not immediate, although in the immunoglobulin class M it begins after a day. The peak of production of antibodies from the immunoglobulin G class is reached after about 3 weeks from contact of the body with the antigen.

In the case of repeated contact of the body with the antigen – the production of antibodies is almost immediate and very intense, even if the amount of antigen that has entered the body is small. Secondary response to the antigen is associated with the activation of immune memory cells. Hence its other name – the amnestic immune response. Antibodies arising as a result of subsequent contact of the body with the antigen show much greater affinity for the antigen.

The use of antibodies

The humoral response of the immune system plays an important role in fighting bacterial infections. The resulting antibodies, by binding to bacterial antigens, can cause a variety of phenomena that are unfavorable to bacteria. For example, they can block the action of bacterial endotoxins (neutralize them), they can, by coating the bacteria, facilitate their phagocytosis. Still other antibodies facilitate the penetration of the bacterial cell membrane by bactericidal lysozyme, and by activating the complement system, they promote the influx of phagocytic cells, especially granulocytes.

Some antibodies, by binding to surface antigens with microbes, prevent them from binding to susceptible tissues, especially mucous membranes. This is another way to reduce germ infestation.

In relation to viruses, antibodies can neutralize, i.e. inactivate, by inhibiting the virus from attaching to the cell being attacked or by preventing viral nucleic acid from being “injected” into the cell.

The complexes formed as a result of the reaction of the antigen with the antibody may be separate structures that circulate in body fluids, especially in the blood. They are removed in various ways from the body, among others by phagocytosis.

Dangers of Antigen-Antibody Reactions

Circulating antigen-antibody complexes may not always be removed. For this to happen – the complexes must be balanced, i.e. the ratio of antibody to antigen must be (numerically and spatially) optimal in them. The balanced complex is generally insoluble in plasma, easily precipitates and is captured by the phagocytic cells. However, if the complex is not balanced (it has a predominance of antigen over the antibody, or vice versa – the antibody over the antigen), it does not form large spatial structures, but is small and easily soluble in plasma. Circulating in the blood, it settles in the walls of the vessels and tissues and causes destructive reactions there.

Cellular immunity

In addition to humoral immunity, associated with the production of antibodies directed against specific antigens, the immune system can respond to the presence of an “intruder”, to a “foreign” antigen, yet another way. In this other response, the central role is no longer played by antibodies, organic inanimate structures, but immunocompetent cells themselves. Therefore, this other immune response to a “foreign” antigen is called cell-type immunity (OTK) and is mediated by T lymphocytes.

Cellular immunity complements humoral immunity, broadens the body’s defense capabilities. It often happens that a foreign antigen is not available for an antibody, so the effectiveness of humoral immunity is not sufficient. A different fighting method is needed. OTK is not a homogeneous phenomenon, it covers several types of reactions in which various subpopulations of T cells are involved. But for an immune response to occur, the immune system must also come into contact with the antigen. The antigen must reach the lymphocyte and be presented to it. After recognition of the antigen, the lymphocyte migrates to the lymph node, here it divides and undergoes differentiation. The result is a number of daughter effector cells that either take on the final fight against the antigen or transform into immune memory cells.

Not all antigens are able to induce cellular immunity. But surely these include viral antigens, fungi, some bacteria. Sometimes they are simple haptens that, when combined with a protein carrier, are able to cause cellular reactions. What is the effector phase of cell-type immunity?

Lymphocyte, as a result of contact with the antigen, begins to produce active substances, cytokines, which affect the activity of various other cells, e.g. endothelial cells or macrophages. It is interesting that some cytokines activate subsequent T cells. This is a special gift of autoactivation, thanks to which antigen-sensitized individual lymphocytes cause changes in a huge number of subsequent cells. This is a very efficient amplification mechanism.

The immune system involves not lymphocytes but other cells for direct elimination (destruction) of the antigen. The “warrior” fighting the antigen and its carrier is a germ cell – macrophage. However, before a macrophage can fight an antigen, it must obtain the appropriate instruction from the lymphocyte. This instruction is transmitted by chemical signals, cytokines, of which the most potent is gamma interferon.

The instructed macrophages absorb antigens and their carriers (e.g. some bacteria) and digest them, ultimately destroying them. However, it happens that even the best instructed macrophages are not able to destroy the antigen. This is the case with tuberculosis infection. As cytokine stimulation continues, the number of active macrophages increases, which leads to tuberculosis. Another form of cellular immunity is a cytotoxic reaction involving CD8 lymphocytes. It is a reaction to the presence of primarily own but altered body cells. The changes are caused by the appearance of foreign antigens on the cell surface, e.g. bacterial, viral or cancerous. CD8 + lymphocytes also exhibit cytotoxic properties against allogeneic transplants, because on the surface of foreign transplanted cells (tissues, organs) there are, of course, different tissue compatibility antigens. The mechanism of cytotoxicity is the contact of the lymphocyte with the target cell and the introduction into it of substances that induce apoptosis, or programmed death.

This contact of a lymphocyte with a “foreign” cell is called by some “a kiss of death.” Cell killing has its own dynamics and phases. First, a substance is released that paves the way for killing agents. It is a perforin because it perforates the cell membrane. During the “death kiss”, substances (granzymes) are poured into the foreign cell through the holes, which initiate transformations, resulting in dramatic destruction of the affected cell in the genetic code (DNA).

Antigen-activated lymphocytes produce cytokines that affect various structures, in particular the various cells that are in the vicinity of the immune response. For example, endothelial cells undergo some changes. As a result, there is a significant permeability of capillaries. From blood to tissues, leukocytes and monocytes can easily pass and participate in the immune process, which takes the form of inflammation. In addition, nearby mast cells are activated and their products (e.g. histamine) intensify inflammatory processes.

All phenomena leads to so-called late-type responses, which are characterized by infiltration and high activity of various inflammatory cells aimed at combating the aggressor. Benefits of cell type immunity

Fighting viruses

Cell-type immunity is of great importance in fighting viral infections. Both CD4 and CD8 lymphocytes are involved in responding to the virus infection. Viruses are intracellular infectious agents, which is why lymphocyte interactions are infected with viruses of the body’s cells. They are killed mainly by cytotoxic lymphocytes, also by natural killers (NK lymphocytes) and by instructed macrophages. Cytokines, especially interferon gamma, play a very important role in controlling viruses. Similarly to viral infections, defense based on cell-type responses also becomes most important in intracellular bacterial infections. Also here, both types of T cells, NK lymphocytes and instructed macrophages participate.

Fighting cancer

Immune surveillance of cancer is associated with T lymphocytes. It is known that cancer cells have their own (altered) transplant antigens. Circulating T cells recognize the antigenicity of cancer cells and destroy them immediately, including by cytotoxic effect. NK lymphocytes are also involved in combating cancers, which are also a cellular front guard protecting the body against cancer.

Other cells, such as macrophages and mast cells, may be involved in the destruction of cancer cells. Various cytokines produced by lymphocytes are involved in this complex process, among which gamma interferon and tumor necrosis factor play a huge role.

Fighting cancer cells is a fragment of cell-type immunity, which does not mean that there is no place for humoral immunity. Antibodies directed against tumor cell antigens coat these cells, inducing the cytotoxic activity of a wide variety of cells, such as macrophages, monocytes, neutrophils and NK lymphocytes.

Unfortunately, macrophages can, paradoxically, promote cancer cells, regardless of anti-tumor interactions. By producing growth factors, they can promote rapid tumor proliferation.

Transplant Rejection
Another example of cellular immunity is the phenomenon of allogenic transplant rejection, i.e. originating from a genetically different member of the same species, or xenograft originating from a completely different species.

And here we are dealing with the difference in transplantation of transplanted cell antigens, which is recognized by the immune surveillance of T-lymphocytes. Stimulated lymphocytes trigger the phenomenon of cytotoxicity in which various cells and cytokines are involved.

Transplant rejection can be particularly acute (referred to as hyperacute rejection), which is associated with antibodies directed against endothelial antigens of the transplanted organ. The complement system is also involved in the immune response, which induces phenomena leading to extensive damage to the graft’s blood vessels.

Organ transplants are associated with a special phenomenon called the GvH (Graft Versus Host) reaction, the essence of which is the activation of donor lymphocytes present in the transplanted organ. These lymphocytes recognize the environment, i.e. the recipient cells (tissues) as foreign, and begin to act against them. The result of these activities is necrosis of many recipient tissues.

Immune system control

Internal control

The immune system shows great independence from other systems and is equipped with numerous built-in mechanisms of its own controlling the course of the immune response. Self-monitoring is necessary given the weapons at its disposal. Cytotoxic lymphocytes multiplied in large numbers, laden with deadly cytokines, must be controlled, otherwise they could direct their destructive action against healthy body cells.

Active immunocompetent cells, which become superfluous, are killed by induction of apoptosis in them. How?

Immunologically activated lymphocytes have on their surface a protein called Fas (CD95). Other cells of the immune system carry anti-Fas (Fas-ligand) proteins on their surface. When both cells meet, Fas joins with the protein directed against it. This fusion initiates dramatic intracellular processes in the active and redundant lymphocyte leading to his death.

External control

hormones
In addition to its own mechanisms, the immune system is influenced by other integration systems: endocrine and nervous. There are hormones that can directly affect immune function. For example, glucocorticoids, adrenocortical hormones, inhibit lymphocyte proliferation and cytokine production. Growth hormone – on the contrary – increases the proliferation of lymphocytes, increases the amount of lymph tissue. Both estrogens and androgens affect the immune system, which varies depending on the current needs of the body. Thyroxine, a hormone produced by the thyroid, enhances humoral immunity.

The nervous system
Nervous regulation of the immune system occurs primarily through the autonomic system, which fibers reach the lymph nodes.

Do the upper floors of the nervous system affect the immune system? There is no doubt today that this is happening. It also seems that the cerebral cortex can affect the functioning of immunity. Certain mental states are known in which immunity decreases or increases. For example, stress can have a beneficial or negative effect on immunity. The experience of yogis proves that meditation can be important in shaping immunity.
Recently, a new field of medical knowledge has been created – neuropsychoimmunology, which deals with these phenomena.

Pharmacological effect on the immune system

immunosupression

The immune system can be pharmacologically influenced. For example, it can be immunosuppressive, which means weakening immune responses. This is needed to fight autoimmune diseases in which the immune system attacks its own tissues, or to weaken the body’s defensive response against transplanted tissue or organs. The most known drugs that reduce immune responses are glucocorticoids.

Also, electromagnetic radiation (gamma, x-ray and ultraviolet with a wavelength of 250-400 nm) has a negative effect on the immune system.

There are various ways to suppress the immune response. Some agents negatively affect the cell division of activated lymphocytes, primarily through differentiated DNA effects, others inhibit cytokine secretion or lymphocyte migration, others affect lymphocyte effects on macrophages. Finally, there are biological agents such as anti-lymphocytic serum that directly damage or destroy lymphocytes.

immunostimulation

In addition to inhibiting the activity of the immune system, it can also be stimulating. Vaccines that stimulate the formation of antibodies and immune memory cells are a classic example of this.

There are also biological factors that, by binding to the antigen, contribute to a much stronger immune response. They are so-called immunological adjuvants of bacterial or non-bacterial origin. Some of them have found application in the treatment of cancer.

Immune system disorders can be dramatic and manifest as severe infections, e.g. viral, fungal or protozoal, which often lead to death despite treatment. Its reduced efficiency or warped action results in the manifestation of systemic diseases or is the reason for the ineffective fight of the body against malignant tumor.