Let’s have a look at the topics to be covered under cells of the immune system….

 

Overview

 

 
 

Lymphocytes

 

Lymphocytes constitute 20%–40% of the body’s white blood cells and 99% of the cells in the lymph. There are approximately 1011 (range depending on body size and age: ~1010–1012) lymphocytes in the human body. These lymphocytes continually circulate in the blood and lymph and are capable of migrating into the tissue spaces and lymphoid organs, thereby integrating the immune system to a high degree. The lymphocytes can be broadly subdivided into three populations—B cells, T cells, and natural killer cells—on the basis of  function and cell-membrane components. [1]

 

B and T lymphocytes that have not interacted with antigen— referred to as naive, or unprimed—are resting cells in the G0 phase of the cell cycle. Known as small lymphocytes, these cells are only about 6 _m in diameter; their cytoplasm forms a barely discernible rim around the nucleus. Small lymphocytes have densely packed chromatin, few mitochondria, and a poorly developed endoplasmic reticulum and Golgi apparatus. The naive lymphocyte is generally thought to have a short life span. Interaction of small lymphocytes with antigen, in the presence of certain cytokines discussed later, induces these cells to enter the cell cycle by progressing from G0 into G1 and subsequently into S, G2, and M. As they progress through the cell cycle, lymphocytes enlarge into 15 _m-diameter blast cells, called lymphoblasts; these cells have a higher cytoplasm: nucleus ratio and more organellar complexity than small lymphocytes Lymphoblasts proliferate and eventually differentiate into effector cells or into memory cells. Effector cells function in various ways to eliminate antigen. These cells have short life spans, generally ranging from a few days to a few weeks. Plasma cells—the antibody-secreting effector cells of the Bcell lineage—have a characteristic cytoplasm that contains abundant endoplasmic reticulum (to support their high rate of protein synthesis) arranged in concentric layers and also many Golgi vesicles. The effector cells of the T-cell lineage include the cytokine-secreting T helper cell (TH cell) and the T cytotoxic lymphocyte (TC cell). Some of the progeny of B and T lymphoblasts differentiate into memory cells. The persistence of this population of cells is responsible for life-long immunity to many pathogens. Memory cells look like small lymphocytes but can be distinguished from naive cells by the presence or absence of certain cell membrane molecules. [1]

 

Fate of Antigen activated lymphocytes

Source: Chapter 2, Cells and Organs of Immune System, Immunology, Kuby, 5^th Edition.

 

 

B LYMPHOCYTES

 

How do they mature?

 

B lymphocytes (B cells) are an essential component of the humoral immune response. Produced in the bone marrow, B cells migrate to the spleen and other secondary lymphoid tissues where they mature and differentiate into immunocompetent B cells. Part of the adaptive immune system, B cells are responsible for generating antibodies to specific antigens, which they bind via B cell receptors (BCR). [3]

 

And after that?

 

Activation of B cells occurs via antigen recognition by BCRs and a required co-stimulatory, secondary activation signal provided by either helper T cells or the antigen itself. This results in stimulation of B cell proliferation and the formation of germinal centers where B cells differentiate into plasma cells or memory B cells. Importantly, all B cells derived from a specific progenitor B cell are clones that recognize the same antigen epitope.

Plasma cells are found in the spleen and lymph nodes and are responsible for secreting different classes of clonally unique antibodies that are found in the blood. Following the primary response, a small number of B cells develop into memory B cells, which express high-affinity surface immunoglobulins (mainly IgG), survive for a longer period of time, and enable a rapid secondary response. [3]

 

About mature B cells…

 

The B lymphocyte derived its letter designation from its site of maturation, in the bursa of Fabricius in birds; the name turned out to be apt, for bone marrow is its major site of maturation in a number of mammalian species, including humans and mice. Mature B cells are definitively distinguished from other lymphocytes by their synthesis and display of membrane-bound immunoglobulin (antibody) molecules, which serve as receptors for antigen. Among the other molecules expressed on the membrane of mature B cells are the following:

 

§  B220 (a form of CD45) is frequently used as a marker for B cells and their precursors. However, unlike antibody, it is not expressed uniquely by B-lineage cells.

§  Class II MHC molecules permit the B cell to function as an antigen-presenting cell (APC).

§  CR1 (CD35) and CR2 (CD21) are receptors for certain complement products.

§  Fc_RII (CD32) is a receptor for IgG, a type of antibody.

§   B7-1 (CD80) and B7-2 (CD86) are molecules that interact with CD28 and CTLA-4, important regulatory molecules on the surface of different types of T cells, including TH cells.

§  CD40 is a molecule that interacts with CD40 ligand on the surface of helper T cells. In most cases this interaction is critical for the survival of antigenstimulated B cells and for their development into antibody-secreting plasma cells or memory B cells.[1]

 

Interaction between antigen and the membrane-bound antibody on a mature naive B cell, as well as interactions with T cells and macrophages, selectively induces the activation and differentiation of B-cell clones of corresponding specificity. In this process, the B cell divides repeatedly and differentiates over a 4- to 5-day period, generating a population of plasma cells and memory cells. Plasma cells, which have lower levels of membrane-bound antibody than B cells, synthesize and secrete antibody. All clonal progeny from a given B cell secrete antibody molecules with the same antigen-binding specificity. Plasma cells are terminally differentiated cells, and many die in 1 or 2 weeks. [2]

Source: Chapter 2, Cells and Organs of Immune System, Immunology, Kuby, 5^th Edition.

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T LYMPHOCYTES

 

How do they mature?

 

T lymphocytes also arise in the bone marrow; T cells migrate to the thymus gland to mature. During its maturation within the thymus, the T cell comes to express a unique antigen-binding molecule, called the T-cell receptor, on its membrane. T-cell receptors can recognize only antigen that is bound to cell-membrane proteins called major histocompatibility complex (MHC) molecules. MHC molecules that function in this recognition event, which is termed “antigen presentation,” are polymorphic (genetically diverse) glycoproteins found on cell membranes.[1]

MHC molecules (two types)

§  Class I MHC molecules, which are expressed by nearly all nucleated cells of vertebrate species, consist of a heavy chain linked to a small invariant protein called _2-microglobulin.

§  Class II MHC molecules, which consist of an alpha and a beta glycoprotein chain, are expressed only by antigen-presenting cells.

 

What about their proliferation?

 

When a naive T cell encounters antigen combined with a MHC molecule on a cell, the T cell proliferates and differentiates into memory T cells and various effector T cells. There are two well-defined subpopulations of T cells: T helper (TH) and T cytotoxic (TC) cells. Although a third type of T cell, called a T suppressor (TS) cell, has been postulated, recent evidence suggests that it may not be distinct from TH and TC subpopulations. T helper and T cytotoxic cells can be distinguished from one another by the presence of either CD4 or CD8 membrane glycoproteins on their surfaces. T cells displaying CD4 generally function as TH cells, whereas those displaying CD8 generally function as TC cells. [1]

 

What happens after recognition?

 

After a TH cell recognizes and interacts with an antigen– MHC class II molecule complex, the cell is activated—it becomes an effector cell that secretes various growth factors known collectively as cytokines. The secreted cytokines play an important role in activating B cells, TC cells, macrophages, and various other cells that participate in the immune response. [1]

 

Under the influence of TH-derived cytokines, a TC cell that recognizes an antigen–MHC class I molecule complex proliferates and differentiates into an effector cell called a cytotoxic T lymphocyte (CTL).  The CTL has a vital function in monitoring the cells of the body and eliminating any that display antigen, such as virus-infected cells, tumor cells, and cells of a foreign tissue graft. Cells that display foreign antigen complexed with a class I MHC molecules are called altered self-cells; these are targets of CTLs. [1]

 

 

More about T-cell receptor…

 

The T-cell system has developed to eliminate these altered self-cells, which pose a threat to the normal functioning of the body. T cells express distinctive membrane molecules. All T-cell subpopulations express the T-cell receptor, a complex of polypeptides that includes CD3; and most can be distinguished by the presence of one or the other of two membrane molecules, CD4 and CD8. In addition, most mature T cells express the following membrane molecules:

·      CD28, a receptor for the co-stimulatory B7 family of molecules present on B cells and other antigenpresenting cells

·         CD45, a signal-transduction molecule [2]

 

Source: Chapter 2, Cells and Organs of Immune System, Immunology, Kuby, 5^th Edition.

Do you want to know how many T cells you have?

check out the following link for the process:

https://www.nlm.nih.gov/medlineplus/ency/article/003516.htm

 

NATURAL KILLER CELLS

 

The natural killer cell was first described in 1976, when it was shown that the body contains a small population of large, granular lymphocytes that display cytotoxic activity against a wide range of tumor cells in the absence of any previous immunization with the tumor. NK cells were subsequently shown to play an important role in host defense both against tumor cells and against cells infected with some, though not all, viruses. These cells, which constitute 5%–10% of lymphocytes in human peripheral blood, do not express the membrane molecules and receptors that distinguish T- and B-cell lineages. [2]

 

NO Receptors? So how do they recognize?

 

Although NK cells do not have T-cell receptors or immunoglobulin incorporated in their plasma membranes,

they can recognize potential target cells in two different ways. In some cases, an NK cell employs NK cell receptors to distinguish abnormalities, notably a reduction in the display of class I MHC molecules and the unusual profile of surface antigens displayed by some tumor cells and cells infected by some viruses.

Another way in which NK cells recognize potential target cells depends upon the fact that some tumor cells and cells infected by certain viruses display antigens against which the immune system has made an antibody response, so that antitumor or antiviral antibodies are bound to their surfaces. Because NK cells express CD16, a membrane receptor for the carboxyl-terminal end of the IgG molecule, called the Fc region, they can attach to these antibodies and subsequently destroy the targeted cells. This is an example of a process known as antibody-dependent cell mediated cytotoxicity (ADCC). [2]

 

What are its roles?

 

Several observations suggest that NK cells play an important role in host defense against tumors. For example, in humans the Chediak-Higashi syndrome—an autosomal recessive disorder—is associated with impairment in neutrophils, macrophages, and NK cells and an increased incidence of lymphomas. Likewise, mice with an autosomal mutation called beige lack NK cells; these mutants are more susceptible than normal mice to tumor growth following injection with live tumor cells.[2]

 

About its cell type…

 

There has been growing recognition of a cell type, the NK1-T cell, which has some of the characteristics of both T cells and NK cells. Like T cells, NK1-T cells have T cell receptors (TCRs).Unlike most T cells, the TCRs of NK1-T cells interact with MHC-like molecules called CD1 rather than with class I or class II MHC molecules. Like NK cells, they have variable levels of CD16 and other receptors typical of NK cells, and they can kill cells. A population of triggered NK1-T cells can rapidly secrete large amounts of the cytokines needed to support antibody production by B cells as well as inflammation and the development and expansion of cytotoxic T cells. [2]

 

References:

 

1.   Chapter 1, Overview of the Immune System, Immunology, Kuby, 5^th Edition.

2.   Chapter 2, Cells and Organs of Immune System, Immunology, Kuby, 5^th Edition.

3.   Immunology, Microbiology and Immunology online, University of South Carolina School Of Medicine. Link : https://pathmicro.med.sc.edu/ghaffar/innate.htm

4.   R & D Systems (www.rndsystems.com)