**2. Mechanism of activation of adapted immunity**

Adaptive immune responses carried out by lymphocytes are of two broad classes:


During an immune response, the B cells are activated to secrete immunoglobulins, which circulate in blood, permeate to other body fluids, and bind specifically to foreign antigen that stimulated their production in the first place. This binding inactivates viruses and microbial toxins by blocking their interaction with the host cells. Antibody binding also marks invading pathogens for destruction by phagocytic cells of the innate immune system [3].

Cell-mediated reactions depend on direct interactions between T lymphocytes and cells bearing the antigen that the T cells recognize. T cells are specialized to recognize foreign antigens as peptide fragments bound to proteins of the major histocompatibility complex (MHC). The cytotoxic T cells recognize any infected cells with the help of viral antigens displayed on the surface of the infected cells [1]. Other T lymphocytes that activate the cells they recognize are marked by the expression of the cell-surface molecule CD4 on helper T cells. The CD4 T lymphocytes can be divided into two subsets, which carry out different functions by defending the body particularly from bacterial infections. Bacteria phagocytosed by macrophages are destroyed in the lysosomes, which contain several enzymes and antimicrobial substances. The intracellular bacteria, as in case of tuberculosis (Mtb), survive, because the vesicles they occupy do not fuse with the lysosomes. These infections are modified by a subset of CD4 T cells, namely TH1 cells, which activate macrophages, induce fusion of lysosomes and phagocytic vesicles containing the bacteria, and at the same time stimulate other antibacterial mechanisms of the phagocyte. CD4+ T cells play critical role during Mtb infection by mediating protection, contributing to inflammation, and regulating immune response. Th1 and Th17 cells are the main effector CD4+ T cells during Mtb. Th1 cells release cytokines and chemokines that attract phagocytes to the site of infection and impart protection from Mtb by secreting IFN-γ and activating antimycobacterial action in macrophages.

**83**

*Immune Cell Activation: Stimulation, Costimulation, and Regulation of Cellular Activation*

T cells not only destroy intracellular pathogens by killing infected cells and by activating macrophages, but they also have a central role in the destruction of extracellular pathogens by activating B cells. This is the specialized role of the second subset of CD4 T cells called TH2 cells with special properties that can activate naive B lymphocytes. Most antigens require an accompanying signal from helper T cells before they can stimulate B cells to proliferate and differentiate into cells secreting antibody. Cytotoxic T cells and TH1 cells interact with antigens produced by pathogens that have infected the target cell or that have been ingested by it. Helper T cells, in contrast, recognize and interact with B cells that have bound and internalized

Antigen-specific activation of effector T cells is aided by coreceptors that distinguish between the two classes of MHC molecule—CD8 coreceptor bearing cytotoxic cells that binds MHC class I molecules, whereas TH1 and TH2 cells express the CD4 coreceptor with specificity for MHC class II molecules. The maturation of T cells into either CD8 or CD4 T cells reflects the type of T-cell receptor specificity that occurs during development, and the selection of T cells that can receive survival signals from self-MHC molecules. On recognizing their targets, the three types of T cell are stimulated to release different sets of effector molecules namely, cytokines, which play crucial role in the clonal expansion of lymphocytes as well as in the innate immune responses. T cells are thus crucially important for both humoral and cell-mediated responses of adaptive immunity. The adaptive immune response seems to have engrafted specific antigen recognition by highly diversified receptors onto innate defense systems, which have a central role in the effector actions of both B and T lymphocytes. The vital role of adaptive immunity in fighting infection is illustrated by the immunodeficiency and/or autoimmune diseases and the problems caused by pathogens that succeed in evading or subverting an adaptive immune response. The antigen-specific suppression of adaptive immune responses is the goal of treatment for important human diseases involving inappropriate activation of lymphocytes, whereas the specific stimulation of an adaptive immune response is the basis of successful vaccination for several childhood infections.

As early as 1987, Jankovic and Maric [4] showed that the neuropeptides methionine-enkephalin, and leucine-enkephalin, exhibit a protective action against anaphylactic shock in rats sensitized to ovalbumin. Subsequent studies have shown that enkephalins can act both as suppressors and potentiators of immune response in a dose-dependent manner. Animal studies, where nutritional status, environmental influences, history of drug abuse, and genetic variability can be controlled more easily, have shown that morphine treatment results in significant immune deficits. Chronic morphine use has been shown to result in severe immunosuppression, posing as a significant risk factor for opportunistic infection [5], and this finding is also supported by epidemiological studies that show an increased prevalence of opportunistic infections in opiate users [6]. Chronic morphine has been shown to effect early reactions of innate immunity and later responses of adaptive immunity against microbes [7]. In addition, morphine has also been shown to affect the brainimmune axis by an IL-1β-dependent pathway [8]. Various studies support the idea that chronic morphine exposure in vivo attenuates lymphocyte proliferation [9], NK cell cytotoxicity [10], antibody and serum hemolysin formation [11], and phagocytic properties of peripheral mononuclear leukocytes [12]. Morphine exposure has also been shown to increase mortality of infected mice [12–14]. Novick et al. [15] showed that long-term abuse of opiates results in impaired NK cell activity and altered CD4+

*DOI: http://dx.doi.org/10.5772/intechopen.81568*

foreign antigen by means of their surface immunoglobulin.

**3. Opioid receptor and immune function**

#### *Immune Cell Activation: Stimulation, Costimulation, and Regulation of Cellular Activation DOI: http://dx.doi.org/10.5772/intechopen.81568*

T cells not only destroy intracellular pathogens by killing infected cells and by activating macrophages, but they also have a central role in the destruction of extracellular pathogens by activating B cells. This is the specialized role of the second subset of CD4 T cells called TH2 cells with special properties that can activate naive B lymphocytes. Most antigens require an accompanying signal from helper T cells before they can stimulate B cells to proliferate and differentiate into cells secreting antibody. Cytotoxic T cells and TH1 cells interact with antigens produced by pathogens that have infected the target cell or that have been ingested by it. Helper T cells, in contrast, recognize and interact with B cells that have bound and internalized foreign antigen by means of their surface immunoglobulin.

Antigen-specific activation of effector T cells is aided by coreceptors that distinguish between the two classes of MHC molecule—CD8 coreceptor bearing cytotoxic cells that binds MHC class I molecules, whereas TH1 and TH2 cells express the CD4 coreceptor with specificity for MHC class II molecules. The maturation of T cells into either CD8 or CD4 T cells reflects the type of T-cell receptor specificity that occurs during development, and the selection of T cells that can receive survival signals from self-MHC molecules. On recognizing their targets, the three types of T cell are stimulated to release different sets of effector molecules namely, cytokines, which play crucial role in the clonal expansion of lymphocytes as well as in the innate immune responses.

T cells are thus crucially important for both humoral and cell-mediated responses of adaptive immunity. The adaptive immune response seems to have engrafted specific antigen recognition by highly diversified receptors onto innate defense systems, which have a central role in the effector actions of both B and T lymphocytes. The vital role of adaptive immunity in fighting infection is illustrated by the immunodeficiency and/or autoimmune diseases and the problems caused by pathogens that succeed in evading or subverting an adaptive immune response. The antigen-specific suppression of adaptive immune responses is the goal of treatment for important human diseases involving inappropriate activation of lymphocytes, whereas the specific stimulation of an adaptive immune response is the basis of successful vaccination for several childhood infections.
