Adaptive immune system

Adaptive immune system

The adaptive immune system refers to T cells , which contribute to cell-mediated immunity , and B cells which are responsible for humoral-mediated immunity . These two cell populations have properties and functions distinct from cells of the innate immune system .

There are two main major characteristics of adaptive immunity:

The genes encoding the lymphocyte antigen receptors are subject to somatic and random DNA recombination , called somatic recombination . As the nature of the lymphocyte antigen receptors is not entirely genetically predetermined, adaptive immunity is also known as acquired immunity .

The activation of a lymphocyte is accompanied by a clonal expansion (allowing to amplify the specific immune response to the antigen), and the establishment of a memory , or anamnestic response (on which the principle is based of vaccination ). This is what we talk about adaptive immunity .

The adaptive immune system helps build lifelong acquired immunity, which together with the innate immune system constitutes the immune phenotype of individuals.

The adaptive immune system only exists in vertebrate gnathostomes .

Features of the adaptive immune system

Image of a lymphocyte obtained by scanning electron microscopy .

Adaptive immunity is activated following the recognition of infectious agents by the innate immune system 1 . Although innate immunity makes it possible to recognize families of pathogens thanks to specific receptors of which there are several types corresponding to several classes of pathogen, it cannot recognize a particular species: for example it can recognize gram-negative bacteria, but she cannot distinguish which gram negative species causes the infection.

Adaptive immunity is specific for a given species and has a memory mechanism. The adaptive immune system makes it possible to amplify the immune response and confers both a specific response to the antigen, and therefore particularly adapted to the infectious agent, and a memory response allowing a more efficient elimination of the same infectious agent if the organism is confronted again 2 . The cells of adaptive immunity thus constitute an essential complement to the innate immune response.

Specificity and memory are the two main characteristics of the adaptive immune system.

Another important characteristic of adaptive immunity is the need to use a large number of specific cells to fight a specific pathogen. This specific multiplication is clonal expansion. It takes several days, which explains why the effects of adaptive immunity only appear after about 7 days.

The production of the immune repertoire

What is the immune repertoire?

At the beginning of the XX th century, biologists thought that in view of the very large number of possible pathogens, it was not possible for the organism to produce, in advance, receptors for all the pathogenic antigens. Biologists thought that the penetration of a microbe led to the production of receptors by the organism capable of recognizing the microbe, then in a second time these newly synthesized receptors signaled the presence of a microbe to the lymphocytes which finally produced antibodies. This theory was called the interventionist theory. This theory is false.

The body produces receptors in advance for all present and future microbes. If this production depended on the genome present in the lymphocytes, the size of the lymphocyte genome containing less than 25,000 genes would be insufficient. It would take millions of genes to store that much information;

The body can make billions of receptors through a mechanism called somatic recombination, which occurs in the DNA of B and T lymphocytes in the lymph nodes. The production of B and T lymphocyte receptors is accompanied by changes in the DNA of these lymphocytes.

The immune repertoire is the set formed by B and T lymphocytes having a membrane receptor specific for a pathogen. Only part of the lymphocyte repertoire can recognize a given antigen, therefore only part of the lymphocyte repertoire is activated by a given antigen in an infectious context.

Immunoglobulins

The immunoglobulins are proteinaceous structures which there are two forms: the membrane immunoglobulins in lymphocytes naive B who will receive the pathogen antigen and soluble immunoglobulins which are secreted into the plasma by the plasma cells (cells derived from B lymphocytes). Soluble immunoglobulins are called antibodies and will attach to the pathogen.

Immunoglobulin is made up of two protein chains: the heavy chain and the light chain.

Membrane immunoglobulin

There are 5 classes, sometimes called isotypes, of immunoglobulins designated by a letter of the alphabet (this letter of the alphabet is in fact the first letter of the name of the Greek letter given by biologists to each heavy chain): immunoglobulin A, immunoglobulin D, immunoglobulin E, immunoglobulin G, immunoglobulin M.

Membrane immunoglobulins attach to naive B lymphocytes through a small area: the membrane anchoring area ( B Cell Receptor). The vertical portion of an immunoglobulin, consisting solely of heavy chain, is called the Fc domain. The Fc domain determines the function of the immunoglobin: it is for example on this part that the proteins of the complement system are fixed and the cells having a phagocytic action such as for example the Fc receptors of a macrophage ( Fc Recepto r) . It is on the end of the variable portions that the antigens of the pathogen are recognized.

The immunoglobulin is divided into two regions: the constant region (in purple on the diagram) identical for all immunoglobulins of the same class and a variable region (in green on the diagram). The synthesis (formation) of the variable part is a complex process because it includes a hypervariable region (at the end of the variable region) called CDR ( Complementary Determining Regions ) where the antigen is fixed.

Antigen

An antigen is any molecule recognized by B or T lymphocytes via secretory and / or membrane immunoglobulins. The parts of the antigen that are recognized by an antibody are called epitopes and the part of the antibody that recognizes the epitope is called a paratope . Most antigens have multiple epitopes.

Most molecules, proteins , glycoproteins , polysaccharides , lipoprotein , lipopolysaccharide , nucleic acids can be antigens. This is even the case for chemicals such as heavy metals or narcotics .

Different types of antigen

Self antigens are antigens that are part of one’s own body: these are the antigens of the self.

The antigens that do not belong to one’s own body are the antigens of the non-self of which there are two categories:

Those belonging to a different species: the exogenous (antigen coming from outside)

Those belonging to the same species: the aliens. Allogens trigger rejection of the graft in organ transplants or are responsible for reactions during the transfusion of a blood group that does not belong to the same group as the recipient.

Immunogenicity

Immunogenicity is the ability of an antigen to produce a response by the adaptive system. Some antigens do not produce an immune response. Haptene is a low molecular weight antigen that needs a carrier to elicit an immune response from the adaptive system.

Variable part of immunoglobulin

In order for the adaptive immune response to recognize, eliminate, and “remember” the multiple antigens expressed by the multiple infectious agents encountered during existence, the immune system must be able to recognize a very large number of different antigens. A human being is a priori capable of producing nearly one trillion different antibodies.

The multitude of antigenic receptors is produced by a process called clonal selection . According to the theory of clonal selection, at birth, an animal randomly generates an immense diversity of lymphocytes, each of which expresses a unique antigenic receptor from a limited number of genes. In order to generate unique antigen receptors, these genes are subjected to the process of somatic recombination , during which each gene segment recombines with the other to form a unique gene. The product of this gene thus gives a unique antigen receptor or antibody for each lymphocyte, even before the body is confronted with an infectious agent, and prepares the body to recognize an almost unlimited number of different antigens.

Secretory forms of immunoglobulins

Different classes

There are 5 classes or isotypes of immunoglobulins. This classification depends on the constant area of   the immunoglobulin (purple).

Immunoglobulin D only exists in membrane form. There are no soluble immunoglobulins D (in the blood).

Immunoglobulin M. The secreted form of immunoglobulin M is different from the membrane form. Immunoglobulin M soluble is made up of 5 immunoglobulins M, or pentamer. Each pentamer therefore has ten antigen recognition sites making this immunoglobulin particularly effective for the recognition of pathogenic antigens.

Immunoglobulins D and immunoglobulins M are the immunoglobulins found on the surface of naive B lymphocytes.

Immunoglobulin A in its soluble form is a dimer. The bond connecting the 2 immunoglobulins is called the J chain. It is the most common antibody in the respiratory, digestive and genital mucosa 3 .

Immunoglobulins E and G are secreted as a monomer.

Greed antibodies

The greed of antibodies is a very important concept. Greed is the ability (binding force) of an antibody to bind to an antigen.

The avidity of the antibody depends on two factors :,

The affinity of the antibody which is the probability (percentage) of the antibody to bind to an antigen. This probability of settling depends on the hypervariable region (at the end of the variable region) called CDR.

The number of antigenic sites carried by the antibody. The number of antigenic sites is called valence in immunology. Immunoglobulins D, E, G have 2 antigenic sites. Immunoglobulin A has 4 antigenic sites. Immunoglobulin M has 10 antigenic sites.

The greed of immunoglobulins G is widely used to determine the dating of a viral (rubella , chickenpox, etc.) or parasitic ( toxoplasmosis ) infection in pregnant women. Strong greed signals an old infection. This eliminates the hypothesis of an infection in early pregnancy by locating the infection before pregnancy. The appearance of a strong greed for immunoglobulins varies depending on the infection. For example, for toxoplasmic antibodies, greed becomes strong 4 months after infection. Strong avidity of toxoplasmic antibodies in a 10 week (2.5 month) pregnant woman suspected of

BCR-CD79 B cell complex

Structure of B and T lymphocyte receptors

B-cell or BCR receptors

Remember that B lymphocytes are responsible for humoral immunity by the production of antibodies. This immunity mainly attacks the extracellular microbe or before it enters the cell like viruses.

BCR is the receptor located on the surface of naive B lymphocytes (before any stimulation by a microbe). The antigen binding site is a membrane immunoglobulin fixed by a small area: the membrane anchoring area ( B Cell Receptor). This area does not enter the cell. He is unable on his own to report to the cell that a germ has settled on him. The immunoglobulins of the naive B lymphocyte BCRs are immunoglobulins M and D 4 .

The membrane immunoglobulin needs a co-receptor to signal the presence of a microbe: CD79. It is made up of two chains: alpha and beta. Inside the cell, CD79 has an area called ITAM ( Design Activation of immune receptors based on Tyrosine or (immunoreceptor tyrosine-based activation pattern ) that can signal the presence of a microbe by phosphorization.

T lymphocyte or TCR cell receptor

Main article: B cell receptor .

T or TCR receptors

The TCR-CD3 complex of T lymphocytes

Remember that T cells are responsible for cellular immunity. This immunity mainly attacks the intracellular microbe.

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