In this article, I briefly describe the effector cells of the immune system.
Effector cells
The effector cells of the immune system are the differentiated cells mounting precise responses in the presence of a stimulus. Our immune system generates effector cells as a response against harmful pathogens. Effector cells are also produced against self-cells in case of autoimmune disorders.
When our body is under a pathogen attack, immune cells proliferate and differentiate into effector and memory cells. Effector cells carry out specific functions in response to the pathogen. In contrast, memory cells are retained in the body and undergo division only when the body suffers a repeated attack of the same pathogen.
T lymphocytes, B lymphocytes, and NK cells are the major effector cells of adaptive immunity. Effector cells are characterized by their less stringent activation requirements, increased cell adhesion molecule expression, and membrane-bound and soluble effector molecule production.
T cells
T lymphocytes play a central role in cell-mediated immunity. It expresses a unique antigen-binding receptor on its surface, known as T cell receptor. T lymphocytes can be grouped into T helper cells (TH cells) and T cytotoxic cells (TC cells). These two cell types can be distinguished from each other by the presence of either CD4 or CD8 membrane glycoproteins on their surfaces. The three types of effector T cells are CD4+ TH1 cells, CD4+ TH2 cells, and CD8+ Cytotoxic lymphocytes.
Naïve T cells require two signals, i.e., a primary signal and a co-stimulatory signal for activation. After activation, naïve T cells undergo proliferation and differentiation to produce effector T lymphocytes. T-cell receptors only recognize processed pieces of antigen bound to cell membrane proteins called major histocompatibility complex (MHC) molecules. The T lymphocytes displaying CD4 membrane glycoproteins function as T helper (TH) cells and recognize antigens in complex with class-II MHC. The T lymphocytes displaying CD8 membrane glycoproteins function as cytotoxic (TC) cells and recognize antigens in complex with class-I MHC.
The interaction of a TCR complex (T cell with a CD4 or CD8 co-receptor) with a foreign peptide-MHC molecule complex generates a primary signal. The interaction between particular membrane molecules on the T cell and the antigen-presenting cell generates a co-stimulatory signal. T helper cells help to mature B cells and also activate cytotoxic T lymphocytes and macrophages. Activated T cells secrete cytokines that regulate an active immune response.
Differentiation of T helper cells into several effector subtypes
Naïve CD4+TH cells, when coming across an MHC-peptide complex, they get activated and proliferate. Then they get differentiated into one of a variety of effector T-cell subsets. CD4+TH cells can be differentiated into several subtypes, e.g., TH1, TH2, and TH17, which produce cytokines of different types and take part in several immune reactions (figure 1).
TH1 cells or T helper type 1 cells and TH17 cells regulate our response to intracellular pathogens. TH2 cells and T follicular helper cells (TFH) regulate our response to extracellular pathogens, like bacteria and parasitic worms.
Another type of CD4+ T cell, also known as regulatory T cell (TREG), can inhibit immune responses. These cells are called natural TREG cells, which arise during maturation in the thymus from autoreactive cells (the cells that bind self-proteins with high affinity). At the site of an immune response, these cells can be induced in an antigen-dependent manner. Regulatory T cells can be identified by the presence of CD4 and CD25 surface markers on their surfaces and the expression of the internal transcription factor FoxP3 as well. TREG cells put down auto-reactive responses and limit our normal T-cell responses to pathogens.
Cytotoxic lymphocytes and their activation into effector cells
The cytotoxic T lymphocytes or TC cells are the CD8+subset of T cells, also known as CD8+cytoxic lymphocytes. Most cytotoxic T cells express T-cell receptors (TCRs) that can recognize a specific antigenic peptide bound to class I MHC molecules, present on all nucleated cells, and a glycoprotein called CD8, which is attracted to non-variable portions of the class I MHC molecule. Naïve CD8+ TC cells (CTL precursors) when bound to an MHC-peptide complex, they get activated. After that, they proliferate and differentiate into the type of effector cells called cytotoxic T lymphocytes (CTLs).
The CTL has a vital function in monitoring the cells of the body and eliminating cells that display non-self-antigen complexed with class-I MHC, such as virus-infected cells, tumor cells, and cells of a foreign tissue graft. The affinity between CD8 and the MHC molecule keeps the TC cell and the target cell bound closely together during antigen-specific activation.
Activation of CTL precursors into effector CTLs
CTL precursors do not show any cytotoxic activity. Thus, they don’t express Interleukin-2 (IL-2) or IL-2 receptors. The cytokine IL-2 plays an important role in the activation and proliferation of CTL-precursors into effector cytotoxic lymphocytes. The CTL precursors after an encounter with antigen-class I MHC complexes on appropriate target cells, begin to express IL-2 receptors. When a CTL precursor interacts with a target cell, two types of costimulatory signals are generated (figure 2), which help in the activation of the CTL precursor into an effector CTL.
When the TCR complex present on the CTL precursor recognizes a peptide-class I MHC complex, it generates an antigen-specific signal that helps to activate the CTL precursor. When the CD28 receptor on the CTL precursor interacts with the co-stimulatory B7 molecule on the antigen-presenting cell, a co-stimulatory signal is transmitted. However, the activation and proliferation of the CTL precursors into effector CTLs need another important signal.
The signal induced by IL-2
This second signal is induced by the interaction between the IL-2 and the IL-2 receptor. However, few IL-2s are produced by the antigen-activated CTL precursors. So, they require additional IL-2 secreted by TH1 cells, resulting from antigen activation and proliferation of CD4+T cells.
When helper T cells interact with antigen-presenting cells, they produce IL-2, which interacts with the IL-2 receptors. The IL-2 receptors in the antigen-activated CTL precursors interact with the IL-2 produced by the TH1 cells (figure 2), and a signal is induced that causes the generation of effector CTLs from antigen-activated CTL precursors. Sometimes IL-2 secreted by the CTL precursors is sufficient for their proliferation and differentiation into effector CTLs. These CTL precursors are the memory CTL precursors that do not require the IL-2 secreted by TH cells. Antigen-activated memory CTL precursors secrete sufficient IL-2 to stimulate their proliferation and differentiation into effector CTLs.
Cytokines secreted by effector cells
TH1 and TH2 subsets secrete largely non-overlapping sets of cytokines. CTLs secrete the soluble effectors as perforins and granzymes, IFN-γ and TNF-β. The membrane-bound molecules expressed by the effector T cells belong to the tumor necrosis factor (TNF) family of membrane proteins. They include the Fas ligand (FASL) on CD8+CTLs, TNF-β on TH1 cells, and the CD40 ligand on TH2 cells. The membrane-bound and the soluble effector molecules play an important role in various T cell effector functions.
B lymphocytes
The B lymphocyte matures in the bursa of Fabricius in birds and bone marrow in humans, mice, and many other mammals. Mature B cells express the B-cell receptor (BCR), a membrane-bound immunoglobulin molecule that binds to antigen. Activated B lymphocytes are the only non-myeloid cells that can act as professional antigen-presenting cells.
They are quite efficient in internalizing antigens through their antigen-specific receptor. They process and present antigenic peptides at the cell surface. Activated B cells express co-stimulatory molecules that are required to activate T cells. B cells when presenting antigens directly to T cells, get help from the T cells as cytokines. They then differentiate into antibody-secreting plasma cells and memory cells.
Activated B cells differentiate into effector cells known as plasma cells. Plasma cells can not express surface immunoglobulin and become highly specialized for antibody secretion. A single cell can secrete from a few hundred to more than a thousand molecules of antibody per second. Plasma cells do not divide further, though some travel to the bone marrow and live there for years, whereas others die within one or two weeks.
NK cells
Natural killer cells, or NK cells are bone marrow-derived effector lymphocytes critical to the innate immune system. They have a large granular morphology and provide immune defenses against viruses and tumors. NK cells do not require activation to kill cells that are missing ”self” markers of MHC class-I. Thus, they are called natural killer cells. This is an important role played by NK cells, as harmful cells missing MHC I markers can not be detected and destroyed by T lymphocytes.
NK cells are known to differentiate and mature in the bone marrow, lymph node, spleen, tonsils, and thymus, where they then enter into the circulation. NK cells constitute 5%-10% of lymphocytes in human peripheral blood. They do not express the membrane molecules and receptors that distinguish T-cell and B-cell lineages. They express surface markers CD16 and CD57 in humans. Different NK cells express different sets of membrane molecules as CD2, 75kDa β subunit of the IL-2 receptor, and CD16 (a receptor for the FC region of IgG).
NK cells produce many immunologically important cytokines. They play important roles in immune regulation and influence both innate and adaptive immunity. The cytokines IFN-α, IFN-β, and IL-12 stimulate the activity of NK cells. Cytokines released by cells upon viral infection give signals to NK cells about the presence of viral pathogens in the affected area. NK cells are the first line of defense against virus infection, controlling viral replication during the time required for activation, proliferation, and differentiation of CTL precursors into effector CTLs. They contain viral infections, whereas the adaptive immune response generates antigen-specific cytotoxic T cells that clear the infection.
The function of NK cell
The natural killer cell uses a cell-killing mechanism known as antibody-dependent cell-mediated cytotoxicity. In this method, certain receptors (CD16) expressed on NK cells recognize antibodies that bind to antigens. This recognition activates NK cells, which causes them to release cytotoxic granules, ultimately leading to cell apoptosis. NK cells are cytotoxic cells, which have small granules in their cytoplasm. These granules contain proteins such as perforins and proteases known as granzymes. Perforin forms pores in the cell membrane of the target cell, thus creating an aqueous channel. Through this channel the granzymes and associated molecules can enter, inducing either apoptosis or osmotic cell lysis.
Conclusion
The effector cells of the immune system are the differentiated cells mounting precise responses in the presence of a stimulus. Our immune system generates effector cells as a response against harmful pathogens. T lymphocytes, B lymphocytes, and NK cells are the major effector cells of adaptive immunity.
T lymphocytes can be grouped into T helper cells (TH cells) and T cytotoxic cells (TC cells). These two cell types can be distinguished from each other by the presence of either CD4 or CD8 membrane glycoproteins on their surfaces. Naïve CD4+TH cells, when coming across an MHC-peptide complex, get differentiated into one of a variety of effector T-cell subsets.
Naïve CD8+ TC cells (CTL precursors) when bound to an MHC-peptide complex, they get activated. After that, they proliferate and differentiate into the type of effector cells called cytotoxic T lymphocytes (CTLs). The cytokine IL-2 plays an important role in the activation and proliferation of CTL-precursors into effector cytotoxic lymphocytes.
Activated B cells express co-stimulatory molecules that are required to activate T cells. B cells when presenting antigens directly to T cells, get help from the T cells as cytokines. They differentiate with the help of cytokines into antibody-secreting plasma cells and memory cells.
NK cells are bone marrow-derived effector lymphocytes. They have a large granular morphology and provide immune defenses against viruses and tumors. NK cells are cytotoxic cells, which have small granules in their cytoplasm. These granules contain proteins such as perforins and proteases known as granzymes.
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I, Swagatika Sahu (author of this website), have done my master’s in Biotechnology. I have around twelve years of experience in writing and believe that writing is a great way to share knowledge. I hope the articles on the website will help users in enhancing their intellect in Biotechnology.