Regulation of adaptive immunity

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In this article, I briefly describe adaptive immunity and its regulation.

Adaptive immunity and its disparity with innate immunity

The adaptive immunity is marked by an antigen-specific response, depending primarily on B and T lymphocytes. When a pathogen attacks and invades a body, the adaptive immunity gives a response within a week, unlike innate immunity.

It is a slower response in comparison to innate immunity, which quickly acts upon infections. The innate immunity is genetically inherited, constituting an agile response, which includes recognition of the pathogen and subsequent phagocytosis.

The adaptive response is slower than the innate response because it is dependent upon the T cells and B cells possessing the antigen-specific receptors. The responses are fewer in number when compared to innate responses. The adaptive response is also slower because it depends partly on the innate immunity that encounters and categorizes antigens previously.

The T cells and B cells first encounter antigen, then followed by a process of selection and proliferation. They can acquire the infection perfectly only after selection and replication, which helps them to sharpen their attack skills.

Besides the T cells and B cells, a small population of T cells known as NKT cells have some features of innate immune cells. Clonal selection is a process in which Each T and B-lymphocyte interacts with the antigen and makes a cloned population of antigen-reactive cells.

As the name suggests, adaptive immunity adapts for betterment. It doesn’t work fast like innate immunity. However, it works more precisely. It perfectly recognizes, invades the antigen, and also keeps it in memory.

Adaptive immunity and immunologic memory

Immunologic memory is the key feature of adaptive immunity, which helps the immune system to work smoothly and with higher efficiency when a repeated attack of the same pathogen takes place.

When a foreign antigen first invades our body, adaptive immunity goes through a primary response in which the B and T-lymphocytes are clonally selected and honed to clear the infection.

When our body undergoes a repeated attack by the same pathogen, the adaptive response occurs through a secondary response through memory cells. The memory cells remain in the body for a long period and provide quick antigen-specific responses at that time.

Cells regulating adaptive immunity

The lymphocytes ( type of white blood cells) are the principal cells in adaptive immunity that provide immunologic memory. Among the total white blood cells, 20-40% are lymphocytes, whereas 99% of cells in the lymph represent them. They can mainly divided into three categories, i.e., B-lymphocytes (B cells), T-lymphocytes (T cells), and innate lymphoid cells (ILCs).

B cells (B-lymphocytes)

The B cells derive their names from their site of maturation, which is in the bursa of Fabricius in birds and the bone marrow in the case of humans and other mammals. When B cells attain maturity, they express a membrane-bound immunoglobulin known as the B-cell receptor, which binds to antigen. Each B-lymphocyte expresses a surface antibody that possesses a unique specificity for antigen.

The activated B-lymphocytes possess antigen-specific receptors through which they internalize antigens efficiently and process the antigens. Then, the antigen is presented at the cell surface. B cells differentiate into plasma cells, which secrete antibodies and memory cells when stimulated by cytokines.

When activated B-cells present antigen to T-cells, T-cells get activated, proliferated, and differentiated into cytotoxic T lymphocytes (effector cells). These effector cells produce cytokines that help differentiate into plasma and memory cells. Plasma cells lack the surface of immunoglobulins as they are highly specialized for secreting antibodies.

T-cells (T-lymphocytes)

Like B cells, T cells derive their names from their site of maturation in the thymus. After attaining maturity, T cells express specific antigen-binding receptors known as T cell receptors. However, unlike the B-cell receptor (BCR), the T cell receptor (TCR) is unable to recognize soluble antigens, rather it can only recognize processed pieces of antigen bound to cell-membrane proteins called the MHC (Major histocompatibility complex) molecules.

MHC molecules are categorized into MHC1 and MHC2 molecules. MHC class 1 molecules are expressed by nearly all nucleated cells of vertebrates, whereas MHC 2 molecules are expressed by antigen-presenting cells.

There are two different types of membrane glycoproteins, i.e., CD4 and CD8, present on the surface of T cells. Based on the type of glycoproteins present on the surface, T-cells can be differentiated into T-helper cells (TH cells) and T-cytotoxic cells (TC cells).

TH cells express CD4 membrane glycoproteins, which recognize antigens in complex with MHC-class II. TC cells express CD8 membrane glycoproteins, which recognize antigens in complex with MHC-class I molecules.

Activation of TC cells to Cytotoxic T lymphocytes (CTLs)

Naïve TC cells with their T-cell receptors bind to an MHC-peptide complex, which activates them. As a result, they start proliferating and finally get differentiated into effector cells known as cytotoxic-T-lymphocytes (CTLs). CTLs eliminate virus-infected cells, tumor cells, and cells of a foreign tissue graft. These cells are complexed with MHC1, which CTLs recognize and eliminate.

Activation of TH cells

Like TC cells, naïve TH cells, when recognizing an MHC-peptide complex, they get activated and start to proliferate. Finally, they get differentiated into effector T cells, like TH1, TH17, TH2, and T follicular helper cells. These effector cells regulate our response to intracellular pathogens and extracellular pathogens respectively.

NKT cells

NKT cells have features of both adaptive and innate immunity. These cells possess TCRs, and some of them express CD4. NKT cells express less diverse TCRs, unlike T cells.

They recognize specific lipids and glycolipids presented by a molecule known as CD1, which is related to the MHC molecule. When NKT cells are activated, they release cytotoxic granules and cytokines. Cytotoxic granules kill target cells, whereas cytokines can enhance or suppress the immune response.

Innate lymphoid cells

NK Cells

Natural killer cells, or NK cells, are the innate lymphoid cells and constitute 5% to 10% of the lymphocytes in human peripheral blood.

NK cells attack abnormal cells

NK cells use a two-way strategy to kill a variety of abnormal cells, like some infected cells and tumor cells. First, they attack cells that lack MHC class-I molecules, like tumor cells. Tumor cells lack the MHC class I molecules due to the mutations in them or the occurrence of any viral infections.

NK cells possess receptors for self-MHC class-I molecules, which inhibit their activity of killing cells associated with MHC class-I molecules. Tumor cells lacking MHC class-I molecules are killed by NK cells due to the cytotoxic granules secreted by them. Due to the absence of an MHC class I molecule, receptors present in NK cells are no longer engaged, which activates the NK cells to release cytotoxic granules and kill the target cell.

As a second approach to killing, NK cells with their FC receptors can kill the target cell. Fc receptors are meant for only antibodies through which NK cells can target infected cells.

Infected cells contain viral proteins and NK cells possess Fc receptors. Through these viral proteins, NK cells come in contact with their target cells. After encountering their target cells, NK cells release cytotoxic granules causing target cell death. This process of killing target cells is known as antibody-dependent cell-mediated cytotoxicity (ADCC).

Innate lymphoid cells (ILCs) can be categorized into ILC1, ILC2, and ILC3 depending upon their secreted cytokines. NK cells are classified under the ILC1 group. NK cells are efficient cell killers.

Conclusion

Adaptive immunity is an antigen-specific response depending primarily on B and T lymphocytes. Adaptive immunity is slower than innate immunity. Immunologic memory is the key feature of adaptive immunity which helps the immune system to work smoothly and with higher efficiency when the repeated attack of the same pathogen takes place.

Three types of cells regulate adaptive immunity, e.g., T lymphocytes, B lymphocytes, and innate lymphoid cells. Innate lymphoid cells (ILCs) can be categorized into ILC1, ILC2, and ILC3 depending upon their secreted cytokines. NK cells, also called natural killer cells are the innate lymphoid cells. These constitute 5% to 10% of lymphocytes in human peripheral blood. NK cells efficiently kill target cells.

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