What gave mankind the discovery of immunity. The natural history of immunity. What is the theory of immunity
During the second half of the 19th century, doctors and biologists of that time actively studied the role of pathogenic microorganisms in the development of infectious diseases, as well as the possibility of creating artificial immunity to them. These studies led to the study of facts about the body's natural defense against infections. Pasteur proposed to the scientific community the idea of the so-called "exhausted force". According to this theory, viral immunity is a condition in which human body is not a beneficial breeding ground for infectious agents. However, this idea could not explain a number of practical observations.
Mechnikov: cellular theory of immunity
This theory appeared in 1883. The creator of the cellular theory of immunity relied on the teachings of Charles Darwin and was based on the study of the processes of digestion in animals, which are located at different stages of evolutionary development. The author of the new theory found a certain similarity in the intracellular digestion of substances in endoderm cells, amoebas, tissue macrophages and monocytes. Actually, immunity was created by the famous Russian biologist Ilya Mechnikov. His work in this area continued for a long time. They started in the Italian city of Messina, in which the microbiologist observed the behavior of the larvae.
The pathologist discovered that the wandering cells of the observed creatures surrounded by foreign bodies and then engulfed them. In addition, they dissolve and then destroy those tissues that the body no longer needs. He put a lot of effort into developing his concept. The creator of the cellular theory of immunity introduced, in fact, the concept of "phagocytes", derived from the Greek words "phages" - to eat and "kitos" - a cell. That is, the new term literally meant the process of eating cells. The scientist came to the idea of such phagocytes a little earlier, when he studied intracellular digestion in various connective tissue cells in invertebrates: sponges, amoebas and others.
In representatives of the higher animal world, white blood cells, that is, leukocytes, can be called the most typical phagocytes. Later, the creator of the cellular theory of immunity proposed to divide such cells into macrophages and microphages. The correctness of such a division was confirmed by the achievements of the scientist P. Ehrlich, who differentiated different types leukocytes by staining. In his classic works on the pathology of inflammation, the creator of the cellular theory of immunity was able to prove the role of phagocytic cells in the elimination of pathogens. Already in 1901, his fundamental work on immunity to infectious diseases was published. In addition to Ilya Mechnikov himself, a significant contribution to the development and dissemination of the theory of phagocytic immunity was made by I.G. Savchenko, F.Ya. Chistovich, L.A. Tarasevich, A.M. Berezka, V.I. Isaev and a number of other researchers.
Good afternoon, dear friends! So, today we will again focus on an important component for human health - its immunity.
Of course, we all understand that it is necessary to monitor our health, and each of us has repeatedly heard and uttered this phrase himself - increasing immunity. Today our topic will be one of the sides of this issue, namely, what is humoral immunity?
This term is especially often heard in medical institutions. Let's try and understand what it means and how it works. The classification of the types of the human defense system is quite extensive, and includes several points.
Humoral factors of immunity, expressed in simple words, this is the constant production of antibodies designed to destroy pathogenic viruses and infectious manifestations. The confrontation must be constant, the only way to maintain health and prevent dangerous diseases. Human immunity is a link that should not be weak.
In connection with this type of protective system, it is impossible not to mention the second type, which is somewhat different in its functionality, but is inextricably linked with the above. This is a cellular type of defense system. Together they achieve a great effect. What is the difference between cellular and humoral immune protective action?
- Cellular has the ability to recognize and infect fungi, viruses, foreign cells and tissues in its own cellular structures.
- The humoral theory of immunity is associated with the defeat of bacteria located in the pericellular space, and mainly in the plasma.
The theory is based on the processes of specific interaction of antibodies. The basis of immunity B - lymphocytes synthesized with native proteins, are able to instantly respond to the appearance of foreign proteins.
At the same time, as soon as a foreign substance appears in the blood, even regardless of its harmfulness, antibodies are immediately formed. And such a reaction can cause the defeat of the "foreigner" without much effort.
That is, to make it completely clear, the mechanism of action is simple, the protection of our blood and cells during humoral immunity is carried out by proteins antigens. They are part of the blood composition and other fluids of our body with you.
humoral immunity - This is the recognition of bacteria in any body fluid, whether it be blood, lymph, saliva or another. The name "humoral" is liquid, moisture. With the widespread formation of antibodies or immunoglobulins, whether in the bone marrow, lymph nodes or intestines, protein compounds "stick" to foreign bacterial structures. Successfully destroy them, then removing them from the body with the same fluid. There are five main types of immunoglobulins:
A, D, E, G, M. Of all the lymphocytes we have, they are determined in the body by about 15%.
A bit of history
The history of the study of the humoral link of immunity goes back to the years when, in the 19th century, a dispute arose between two prominent scientists, Ilya Mechnikov and Paul Erlich. At that time, so much attention was paid to the issue of immunity and people suffered from constant severe diseases and infectious lesions.
On the basis of this intractable task, the opinions of pundits agreed in a dispute. Mechnikov's evidence was based on the fact that the immune properties of the human body work exclusively at the level of cellular processes. That is, cells are the basis of immunity.
Ehrlich argued with his opponent and argued that blood plasma is the main engine of protective processes, and immunity depends on its composition. This went on for many years, and neither of them became the winner of an important dispute, or rather, they both turned out to be winners and received the Nobel Prize.
Like this true story from the life of great scientists, which made it possible, through a long study, to make an important discovery. It is believed that humoral immunity was discovered by P. Ehrlich.
Turned out one was proving the benefits cellular immunity and the other humoral. We know the outcome of the dispute, both protective systems are of great importance for a person and are closely interconnected with each other. The regulation of protective processes occurs in two systems, cellular and molecular.
It was only through the interaction of this symbiosis that a multicellular creature arose, capable of withstanding the endless attacks of viruses and pathogenic microbes. And the name of this creature is Man. Our unique system has allowed us to survive and pass through the millennia, constantly adapting to the environment.
Humoral specific and nonspecific immunity
We all react differently to external negative factors that can cause disease. Some begin to mope and experience signs of illness from the slightest breath of a breeze, others can withstand an ice hole. All this is the mechanism of action of the protective background.
Today, the work of the human body, physicians classify as specific and non-specific. Let's take a closer look at each of the concepts.
- A specific reaction or form is directed to any single factor. An example is a person who had chicken pox as a child, after which he built a strong immunity to this disease. This can also include all those vaccinations and vaccinations that we were given in childhood.
- The non-specific form implies universal protection given by nature and the body's reaction to the penetration of infection into the body.
Let's look at the principle of operation of these two forms in more detail.
The factors of a specific property, first of all, belong to immunoglobulins or antibodies. They are engaged in the blood by white cells, otherwise they can be called B - lymphocytes. How are antibodies produced in the body?
The first part always appears by transmission at birth from the mother, the second through breast milk. Time passes, and a person becomes able to produce them himself from stem cells or after exposure to a vaccine.
Non-specific factors include substances without a clear specialization, these are: tissue particles of the body, blood serum and proteins in it, glands and their secretory ability to inhibit the growth of microbes, lysozyme, which contains an antibacterial enzyme.
The humoral link of immunity plays an important role in both cases and is built up by constant education during internal systems body of "smart" antibodies.
Violations
Methods of study allow to reveal violations in humoral immunity. This is done using a special analysis - an immunogram. This examination allows you to understand the number of B-lymphocytes, immunoglobulins in the body, the interferon index and other important parameters.
This test is done by drawing blood from a vein. This is done on an empty stomach in the morning, so that before that there were 8 hours of abstinence from food, alcohol and smoking.
All these are rather difficult concepts for the perception of an ordinary person; rather, this is the prerogative of specialists. But still, it is interesting to understand the principle of immunity and expand your horizons a little in this matter. Do not forget to support your body, and remember that your health depends on the state of humoral immunity!
The term "immunity" originated from the Latin word "immunitas" - liberation, getting rid of something. It entered medical practice in the 19th century, when it began to mean "liberation from illness" (French Dictionary Litte, 1869). But long before the appearance of the term, physicians had the concept of immunity in the sense of a person's immunity to disease, which was designated as "the self-healing power of the body" (Hippocrates), " life force"(Galen) or "healing power" (Paracelsus). Doctors have long known the inherent immunity (resistance) to animal diseases (for example, chicken cholera, dog distemper) inherent in people from birth. Now this is called innate (natural) immunity. Since ancient times Physicians knew that a person does not get sick with certain diseases twice.So, back in the 4th century BC, Thucydides, describing the plague in Athens, noted the facts when people who miraculously survived could take care of the sick without the risk of getting sick again. showed that people can become resistant to re-infection after suffering severe infections, such as typhus, smallpox, scarlet fever. This phenomenon is called acquired immunity.
There is evidence that the first smallpox inoculations were carried out in China a thousand years before the birth of Christ. The sores of a person who had recovered from smallpox were scratched into the skin of a healthy person, who usually then suffered a mild infection, after which he recovered and remained resistant to subsequent smallpox infections. The inoculation of the contents of smallpox pustules to healthy people in order to protect them from the acute form of the disease then spread to India, Asia Minor, Europe, and the Caucasus. However, the reception of artificial infection with natural (human) smallpox did not give positive results in all cases. Sometimes, after inoculation, an acute form of the disease, and even death, was noted.
Inoculation was replaced by the vaccination method (from Latin vacca - cow), developed at the end of the 18th century. English doctor E. Jenner. He drew attention to the fact that thrush nurses who cared for sick animals sometimes fell ill in an extremely mild form of cowpox, but never got sick with smallpox. Such an observation gave the researcher a real opportunity to fight the disease of people. In 1796, 30 years after the start of his research, E. Jenner decided to test the vaccination method on a boy who was vaccinated with cowpox, and then infected him with smallpox. The experiment was successful, and since then the method of vaccination according to E. Jenner has been widely used throughout the world.
It should be noted that long before E. Jenner, the outstanding scientist-physician of the Medieval East, Razi, by inoculating children with cowpox, protected them from human smallpox. E. Jenner did not know about the Razi method.
After 100 years, the fact discovered by E. Jenner formed the basis of L. Pasteur's experiments on chicken cholera, which culminated in the formulation of the principle of prevention infectious diseases- the principle of immunization with weakened or killed pathogens (1881).
The birth of infectious immunology is associated with the name of the outstanding French scientist Louis Pasteur. The first step towards a targeted search for vaccine preparations that create stable immunity to infection was made after Pasteur's well-known observation on the pathogenicity of the causative agent of chicken cholera. It was shown that infection of chickens with a weakened (attenuated) culture of the pathogen creates immunity to the pathogenic microbe (1880). In 1881 Pasteur demonstrated an effective approach to immunizing cows against anthrax, and in 1885. he managed to show the possibility of protecting people from rabies.
By the 40-50s of our century, the principles of vaccination laid down by Pasteur found their manifestation in the creation of a whole arsenal of vaccines against the widest range of infectious diseases.
Although Pasteur is considered the founder of infectious immunology, he did not know anything about the factors involved in the process of defense against infection. Behring and Kitasato were the first to shed light on one of the mechanisms of resistance to infection. In 1890, Emil von Behring reported that after introducing into the body of an animal not whole diphtheria bacteria, but only a certain toxin isolated from them, something appears in the blood that can neutralize or destroy the toxin and prevent the disease caused by the whole bacterium. Moreover, it turned out that preparations (serums) prepared from the blood of such animals healed children already ill with diphtheria. A substance that neutralized the toxin and appeared in the blood only in its presence was called an antitoxin. In the future, substances similar to it began to be called by the general term - antibodies. And the agent that causes the formation of these antibodies came to be called an antigen. For these works, Emil von Behring was awarded the Nobel Prize in Physiology or Medicine in 1901.
Later, P. Ehrlich developed the theory of humoral immunity on this basis, i.e. immunity provided by antibodies, which, moving through the liquid internal media of the body, such as blood and lymph (from Latin humor - liquid), strike foreign bodies at any distance from the lymphocyte that produces them.
Arne Tiselius (Nobel Prize in Chemistry in 1948) showed that antibodies are just ordinary proteins, but with a very large molecular weight. The chemical structure of antibodies was deciphered by Gerald Maurice Edelman (USA) and Rodney Robert Porter (UK), for which they received the Nobel Prize in 1972. It was found that each antibody consists of four proteins - 2 light and 2 heavy chains. Such a structure in an electron microscope resembles a "slingshot" in its appearance. The portion of an antibody molecule that binds to an antigen is highly variable and is therefore called variable. This area is contained at the very tip of the antibody, so the protective molecule is sometimes compared to tweezers grasping with sharp ends. the smallest details the most intricate clockwork. The active center recognizes small regions in the antigen molecule, usually consisting of 4-8 amino acids. These parts of the antigen fit into the structure of the antibody "like a key to a lock". If antibodies cannot cope with the antigen (microbe) on their own, other components will come to their aid, and, first of all, special "eating cells".
Later, the Japanese Susumo Tonegawa, based on the achievement of Edelman and Porter, showed what no one, in principle, could even expect: those genes in the genome that are responsible for the synthesis of antibodies, unlike all other human genes, have an amazing ability to repeatedly change their structure in individual human cells during his life. At the same time, they, varying in their structure, are redistributed in such a way that they are potentially ready to ensure the production of several hundred million different protein-antibodies, i.e. much more than the theoretical amount of potentially acting on the human body from the outside of foreign substances - antigens. In 1987, S. Tonegawa was awarded the Nobel Prize in Physiology or Medicine "for the discovery of the genetic principles of antibody generation."
Our compatriot I.I. Mechnikov developed the theory of phagocytosis and substantiated the phagocytic theory of immunity. He proved that animals and humans have special cells - phagocytes - capable of absorbing and destroying pathogenic microorganisms and other genetically alien material that has appeared in our body. Phagocytosis has been known to scientists since 1862 from the works of E. Haeckel, but only Mechnikov was the first to associate phagocytosis with the protective function of the immune system. In the subsequent long-term discussion between supporters of phagocytic and humoral theories, many mechanisms of immunity were revealed.
In parallel with Mechnikov, the German pharmacologist Paul Ehrlich developed his theory of immune defense against infection. He was aware of the fact that in the blood serum of animals infected with bacteria, protein substances appear that can kill pathogenic microorganisms. These substances were subsequently named by him "antibodies". The most characteristic property of antibodies is their pronounced specificity. Formed as a protective agent against one microorganism, they neutralize and destroy only it, remaining indifferent to others. In an attempt to understand this phenomenon of specificity, Ehrlich put forward the theory of "side chains", according to which antibodies in the form of receptors preexist on the surface of cells. In this case, the antigen of microorganisms acts as a selective factor. Having come into contact with a specific receptor, it ensures enhanced production and circulation of only that particular receptor (antibody).
Ehrlich's foresight is astounding, since with some modifications this generally speculative theory has now been confirmed.
Phagocytosis, discovered by Mechnikov, was later called cellular immunity, and antibody formation, discovered by Ehrlich, was called humoral immunity. Two theories - cellular (phagocytic) and humoral - in the period of their emergence stood on antagonistic positions. The schools of Mechnikov and Erlich fought for scientific truth, unaware that every blow and every parry brought the opponents closer together. In 1908 both scientists were simultaneously awarded the Nobel Prize.
New stage The development of immunology is associated primarily with the name of the outstanding Australian scientist M. Burnet (Macfarlane Burnet; 1899-1985). It was he who largely determined the face of modern immunology. Considering immunity as a reaction aimed at differentiating everything "one's own" from everything "alien", he raised the question of the significance of immune mechanisms in maintaining the genetic integrity of the organism during the period of individual (ontogenetic) development. It was Burnet who drew attention to the lymphocyte as the main participant in a specific immune response, giving it the name "immunocyte". It was Burnet who predicted, and the Englishman Peter Medawar and the Czech Milan Hasek experimentally confirmed the state opposite to immune reactivity - tolerance. It was Burnet who pointed out the special role of the thymus in the formation of the immune response. And finally, Burnet remained in the history of immunology as the creator of the clonal selection theory of immunity. The formula of such a theory is simple: one clone of lymphocytes is able to respond only to one specific antigenic specific determinant.
Of particular note are Burnet's views on immunity as such an organism's reaction, which distinguishes everything "own" from everything "alien". After Peter Medawar proved the immune nature of rejection of a foreign transplant and the accumulation of facts on the immunology of malignant neoplasms, it became obvious that the immune response develops not only to microbial antigens, but also when there are any, albeit insignificant, antigenic differences between the body and that biological material (transplant, malignant tumor) that the body encounters.
Strictly speaking, scientists of the past, including Mechnikov, understood that the purpose of immunity is not only the fight against infectious agents. However, the interests of immunologists in the first half of our century concentrated mainly on the development of problems of infectious pathology. It took time for the natural course of scientific knowledge to make it possible to put forward the concept of the role of immunity in individual development. And the author of the new generalization was Burnet.
A great contribution to the development of modern immunology was also made by Robert Koch (Robert Koch; 1843-1910), who discovered the causative agent of tuberculosis and described the skin tuberculin reaction; Jules Bordet (1870-1961), who made important contributions to the understanding of complement dependent bacterial lysis; Karl Landsteiner (1868-1943), who received the Nobel Prize for the discovery of blood groups and developed approaches to study the fine specificity of antibodies using haptens; Rodney Porter (1917-1985) and Gerald Edelman (1929), who studied the structure of antibodies; George Snell, Baruj Benacerraf and Jean Dausset, who described the major histocompatibility complex in animals and humans and discovered immune response genes. Among domestic immunologists, the studies of N.F. Gamalei, G.N. Gabrichevsky, L.A. Tarasevich, L.A. Zilber, G.I. Abelev are especially significant.
The phylogenesis of immunity is inseparable from the history of the emergence and development of multicellular organisms. The emergence of Metazoa (multicellular) means the formation of autonomous organisms that have an internal environment filled with cells belonging to this organism and limited by a barrier separating it from the environment. The environment is a priori hostile to the organism, since it serves as a source of aggression, competition, and so on. Aggression may consist in the penetration of other organisms (primarily unicellular) into the internal environment of a multicellular organism, followed by competition for territory and resources, as well as possible active damage to cells or their poisoning with toxins and metabolites. Thus, the very fact of the emergence of a separate community of cells, having at least elementary integrating systems and reproducing as a whole, served as a sufficient basis for the emergence of a “service” to maintain the cellular and molecular constancy of the internal environment. This "service" became the prototype of the immune system.
It follows from the above that the first condition for the formation of immunity is the presence of a “protected” closed territory with its mandatory delimitation from external environment. The second condition is the emergence of factors specialized to ensure the constancy of the protected internal environment by freeing it from agents coming from outside (that is, to ensure immunity in its direct original sense - release). Since the time of I.I. Mechnikov, it is generally accepted that such a factor was specialized cells of mesenchymal origin - mobile amoebocytes, the ancestors of mammalian phagocytes. They have a pronounced ability to phagocytosis - a mechanism that ensures the elimination of potentially aggressive cells that have penetrated into the internal environment of the body.
An important condition for the effective operation of this homeostatic mechanism is the ability of protective cells to distinguish potentially aggressive foreign cells from their own. The principle on which such recognition is based has become the basis of immunity in all its manifestations. Thus, the immune system, not being able to “wait” for the manifestation of the aggressiveness of cells that have penetrated from the outside, it considers any foreign cells and molecules as potentially dangerous. Apparently, such a "solution" of evolution is the most universal and justified: truly alien objects are almost always harmful, even if they do not show active aggression.
The emergence of receptors that allow "recognizing" someone else's was the third fundamental event on the path to the formation of immunity (after the emergence of the internal environment of multicellular and specialized phagocyte cells). Indeed, the presence of pathogen-recognizing receptors, as they are now called, is an extremely ancient "invention" of evolution, common to animals and plants. Let us immediately note that the immunity of plants and animals subsequently evolved in different ways, but the general principle of recognition of foreign objects was preserved.
In the process of evolution of a species, genes encoding molecules were fixed, designed to recognize not just “foreign”, but obviously dangerous for a given organism. These receptors are membrane or soluble molecules that have spatial affinity (and therefore are able to recognize them) for the most common and pathogenicity-related molecular markers of foreign agents: components of the bacterial cell wall, endotoxins, nucleic acids, etc. Each receptor recognizes not an individual molecule, but a whole group of similar molecules that serve as images (patterns) of pathogenicity. Receptor molecules are present not only on the surface of immune effector cells, but also in granules into which foreign agents enter during phagocytosis. Pathogen-recognizing molecules are also present in body fluids and are capable of inactivating toxins and killing foreign cells. A relatively small number of genes encoding such receptors ensures the recognition of almost all pathogens without being an excessive "burden" for a multicellular organism.
As a result of pattern recognition of pathogenicity, cells - immunocytes - are activated, which allows them to kill and then eliminate pathogens. This happens with the help of cytolysis - intracellular (the most advanced, associated with phagocytosis), extracellular (caused by secreted factors) and contact. Pathogens can be killed or prepared for phagocytosis by soluble bactericidal factors and receptor molecules. In all cases, the final splitting of the killed pathogens occurs in the process of phagocytosis.
Rice. 1.1. Phylogeny of innate and adaptive immunity. On a simplified phylogenetic tree (only those taxa in which immunity was studied are indicated), the zones of action of innate and adaptive immunity are marked. Cyclostomes are singled out as a special group as animals in which adaptive immunity did not develop along the “classical” path.
So, schematically, you can imagine the immune system, which is commonly called innate. This form of immunity is characteristic of all multicellular animals (in a slightly different form - and for plants). Its age is 1.5 billion years. The innate immune system very effectively protected protostomes metazoans, as well as lower deuterostomes, which often had large sizes (Fig. 1.1). Manifestations of innate immunity at different stages of evolution and in different taxa are extremely diverse. However general principles its functioning is the same at all stages of development of multicellular organisms. The main components of innate immunity:
- recognition of foreign agents in the internal environment of the body with the help of receptors specialized in recognizing "patterns" of pathogenicity;
- elimination of identified foreign agents from the body by phagocytosis and cleavage.
Table 1.2. Main properties of innate and adaptive immunity
|
Characteristic |
innate immunity |
adaptive immunity |
|
Conditions formation |
Formed in ontogeny, regardless of the "request" |
Formed in response to a "request" (receipt of alien agents) |
|
An object recognition |
Groups of foreign molecules associated with pathogenicity |
Individual molecules (antigens) |
|
Effector cells |
Myeloid, partially lymphoid cells |
Lymphoid cells |
|
Cell population response type |
The cell population responds as a whole (not clonally) |
Response to antigen clonal |
|
recognizable molecules |
Images of pathogenicity; stress molecules |
Antigens |
|
Recognizing receptors |
Pathogen-recognizing receptors |
Antigen-recognizing receptors |
|
The threat of auto-aggression |
Minimum |
Real |
|
Memory availability |
Absent |
Immunological memory is formed |
A significant difference between adaptive immunity and innate immunity is the method of recognizing someone else (Table 1.3). In adaptive immunity, it is mediated by a specific type of molecule (immunoglobulins or other proteins of the immunoglobulin superfamily) that recognizes not patterns but individual molecules or small groups of similar molecules called antigens. There are about 106 different antigens. Such a number of receptors not only cannot be present on one cell, but also cannot be encoded in the vertebrate genome, which contains only tens of thousands of genes. That is why, in the process of evolution of adaptive immunity, a complex mechanism for generating a variety of antigen-specific receptors has been formed: with the development of specialized cells (lymphocytes), their genes encoding antigen-recognizing receptors are rearranged, which leads to the formation of a receptor with unique specificity in each cell. When activated, each cell can give rise to a clone, all cells of which will have receptors of the same specificity. Thus, each specific antigen is not recognized by all lymphocytes, but only by their individual clones that have specific antigen-recognizing receptors.
Table 1.3. Main types of immunological recognition
|
Characteristic |
Group (pattern) |
Individual (antigenic) |
|
Recognition object |
Conservative molecular structures - images of pathogenicity |
Antigenic epitopes (as part of free molecules or embedded in MHC molecules) |
|
Discrimination "one's own" |
Perfect, developed in phylogenesis |
Imperfect, formed in ontogeny |
|
The need for costimulation |
No |
Eat |
|
Effect realization time |
Immediately |
Takes time (adaptive immune response) |
|
Communication with various forms immunity |
Associated with innate immunity |
Associated with adaptive immunity |
|
Formation of receptor genes |
determined genetically |
Formed during cell differentiation |
|
Cells that carry receptors |
Any nucleated cells (predominantly myeloid) |
Only B and T lymphocytes |
|
Distribution on cells |
All cells in a population express the same receptors |
Clonal |
|
Receptors |
TLR, NLR, CLR, RIG, DAI, Seavenger receptors, soluble receptors |
BCR (on B cells), TCR-yS, (on y8T cells), TCR-ap (on arT cells) |
If the pattern-recognizing receptors of innate immunity were formed in the course of evolution as molecules that recognize foreign, but not the body's own molecules, then the specificity of antigen-recognizing receptors of the adaptive immunity system is formed by chance. This required the development of additional selection mechanisms to eliminate "unnecessary" and "dangerous" (directed against "one's own") clones of lymphocytes. Such mechanisms are quite effective, but still do not completely eliminate the risk of developing autoimmune processes - immune reactions directed against self-antigens that cause damage to the host organism.
Both types of immunity form an integral system, while innate immunity serves as the foundation for the development of adaptive immunity. Thus, lymphocytes recognize the antigen in the process of presentation, carried out mainly by cells of innate immunity. The removal of an antigen and its carrying cells from the body occurs through reactions based on the mechanisms of innate immunity that have received a specific component, i.e. directed to a specific antigen and acting with increased efficiency.
The clonal nature of the adaptive immune response created the possibility of immunological memory. With innate immunity, memory does not develop, and each time the reaction to the introduction of a foreign
ny molecules develop as for the first time. In the process of adaptive immunity, clones of cells are formed that retain the "experience" of the previous immune response, which allows them to respond to a second encounter with an antigen much faster than during the initial contact, and at the same time form a stronger response. The presence of memory cells makes the body resistant to a fairly wide range of pathogens. Probably, it was the possibility of the formation of immunological memory that served as an advantage that allowed such an “expensive” for the body, cumbersome, largely unreliable and even dangerous mechanism to gain a foothold in the evolutionary process as an adaptive immune response.
Thus, adaptive immunity is based on three main processes:
- recognition of antigens (usually foreign to the body), regardless of their relationship with pathogenicity, using clonally distributed receptors;
- elimination of recognized foreign agents;
- the formation of an immunological memory of contact with an antigen, which allows faster and more efficient removal of it upon re-recognition.
Early 1880s Mechnikov in Messina, Italy, sending his family to watch a circus performance, calmly examined a transparent larva under a microscope starfish. He saw how mobile cells surround a foreign particle that has entered the body of a larva. The phenomenon of absorption was observed even before Metchnikov, but it was generally accepted that this was simply a preparation for the transport of particles by blood. Unexpectedly, Mechnikov had an idea: what if this is not a mechanism of transport, but of protection? Mechnikov immediately introduced into the body of the larva pieces of thorns of a tangerine tree, which he had prepared instead of a New Year tree for his children. The moving cells again surrounded the alien bodies and engulfed them.
If the motile cells of the larvae, he thought, were protecting the body, they must also absorb the bacteria. And this assumption was confirmed. Mechnikov has repeatedly observed how white blood cells - leukocytes - also gather around a foreign particle that has entered the body, forming a focus of inflammation. In addition, after many years of work in the field of comparative embryology, he knew that these motile cells in the body of the larva and human leukocytes come from the same germ layer - the mesoderm. It turned out that all organisms that have blood or its precursor - hemolymph, have a single protection mechanism - the absorption of foreign particles by blood cells. Thus, a fundamental mechanism was discovered by which the body protects itself from the penetration of foreign substances and microbes into it. At the suggestion of Professor Klaus from Vienna, to whom Mechnikov told about his discovery, the defender cells were called phagocytes, and the phenomenon itself was called phagocytosis. The mechanism of phagocytosis has been confirmed in humans and higher animals. Human leukocytes surround the microbes that have entered the body and, like amoeba, form protrusions, cover a foreign particle from all sides and digest it.
Paul Erlich
bright representative of the German school of microbiology was Paul Ehrlich (1854-1915). Since 1891, Ehrlich has been searching for chemical compounds capable of suppressing the life activity of pathogens. He introduced into practice the treatment of four-day malaria with methylene blue dye, the treatment of syphilis with arsenic.
Starting with work on diphtheria toxin at the Institute of Infectious Diseases. Ehrlich created the theory of humoral immunity (in his terminology - the theory of side chains). According to it, microbes or toxins contain structural units - antigens, which cause the formation of antibodies in the body - special proteins of the globulin class. Antibodies have stereospecificity, i.e., a conformation that allows them to bind only those antigens in response to the penetration of which they arose. So Ehrlich subordinated the aptigen-antibody interaction to the laws of stereochemistry. Initially, antibodies exist in the form of special chemical groups (side chains) on the surface of cells (fixed receptors), then some of them are separated from the cell surface and begin to circulate with the blood (freely retransferring receptors). Encountering microbes or toxins, antibodies bind to them, immobilize them and prevent their effect on the body. Ehrlich showed that the poisoning effect of the toxin and its ability to bind to the antitoxin is different functions and they can be treated separately. It was possible to increase the concentration of antibodies by repeated injections of the antigen - this is how Ehrlich solved the problem of obtaining highly effective sera that bothered Bering. Ehrlich introduced a distinction between passive immunity (administration of ready-made antibodies) and active immunity (administration of antigens to stimulate one's own antibody formation). Investigating the plant poison ricin, Ehrlich showed that antibodies do not appear immediately after the introduction of an antigen into the blood. He was the first to study the transfer of part of the immune properties from mother to fetus through the placenta and to the baby - with milk.
Between Mechnikov and Erlich a long and persistent discussion arose in the press about the "true theory of immunity." As a result, phagocytosis was called cellular, and antibody production - humoral immunity. Mechnikov and Erlich shared the 1908 Nobel Prize.
Bering was engaged in the creation of sera by selecting bacterial cultures and toxins, which he injected into animals. One of his greatest achievements is the creation in 1890 of anti-tetanus serum, which turned out to be very effective in the prevention of tetanus in wounds, although ineffective in a later period, with an already developed disease.
“Behring wanted the honor of discovering diphtheria serum to belong to German, not French scientists. In search of an inoculation with diphtheria-infected animals, Bering made sera from various substances, but the animals died. Once he used iodine trichloride for vaccination. True, this time the guinea pigs became seriously ill, but not one of them died. Encouraged by the first success, Bering, after waiting for the recovery of the experimental pigs, inoculated them from a broth with diphtheria toxin strained according to the Roux method, in which diphtheria bacilli had previously been grown. The animals withstood the vaccination admirably, despite the fact that they received a huge dose of the toxin. This means that they have acquired immunity against diphtheria, they are not afraid of either bacteria or the poison they secrete. Behring decided to improve his method. He mixed the blood of recovered guinea pigs with a filtered liquid containing diphtheria toxin and injected healthy guinea pigs with the mixture - none of them got sick. So, Bering decided, the blood serum of animals that have acquired immunity contains an antidote for diphtheria poison, some kind of “antitoxin”.
By vaccinating healthy animals with serum obtained from recovered animals, Bering became convinced that guinea pigs receive immunity not only when they are infected with bacteria, but also when they are exposed to a toxin. Later, he became convinced that this serum also has a therapeutic effect, that is, if sick animals are vaccinated, they recover. On December 26, 1891, a child dying of diphtheria was vaccinated from the serum of an ill mumps in the clinic for children's diseases in Berlin, and the child recovered. Emil Bering and his boss - Robert Koch won a triumphant victory over a formidable disease. Now Émile Roux took up the matter a second time. By inoculating horses with diphtheria toxin at short intervals, he gradually achieved complete immunization of the animals. Then he took several liters of blood from horses, isolated serum from it, from which he began to vaccinate sick children. Already the first results exceeded all expectations: mortality, which previously reached 60 to 70% with diphtheria, fell to 1-2%.
Behring received the Nobel Prize in Physiology or Medicine in 1901 for his work on serum therapy.
