9: The immune response

Chapter 9 The immune response

Chapter 8 described the development of B and T cell repertoires. At birth, the immature immune system consists of B cells selected for low-affinity antibody production, while the T cell repertoire consists of T cell antigen receptors (TCRs) potentially able to recognize foreign but usually not self peptides presented by major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs). The latter must also provide co-stimulatory signals for full T cell activation.

During the vulnerable few months following birth, while immune system maturation is continuing, the infant receives protection against pathogens from the mother’s ‘experienced’ immune system. Maternal immunoglobulin G (IgG) antibodies cross the placenta and provide passive immunity. The IgA antibodies in mother’s milk protect the infant’s digestive system. By the age of 9 months, all maternal IgG antibodies will have been catabolized and suckling may have been terminated. The infant must now be able to mobilize its own adaptive immune response mechanisms to fight off potential pathogens.

Antibodies

Antibodies, or immunoglobulins (Igs), are the secreted products of B lymphocytes, which have become activated following binding of antigen to their B cell receptors (BCRs). The specificity for antigen of the secreted antibody is the same as that of the BCR, so they will bind to the same antigen that induced their production. The formation of the antigen–antibody complex may result in:

The basic Y-shaped, four-chain structure of the antibody molecule is shown in Figure 9.1. Antigen-binding specificity is provided by the combined variable (V) regions of heavy (H) and light (L) chains. Since the basic Ig unit has two such pairings, the molecule can bind two identical epitopes; i.e. it is bivalent. The Ig heavy-chain constant region, particularly domains 2 and 3, which make up the Fc region, largely determines the biological activity of the molecule.

There are five distinct classes of Ig (IgG, IgA, IgM, IgD, IgE), four subclasses of IgG (IgG1, IgG2, IgG3, IgG4) and two subclasses of IgA (IgA1, IgA2). These are derived from usage of different heavy-chain genes, as described in Chapter 8. The different structures and properties of Ig molecules are summarized in Figure 9.2.

Cytokines

Cytokines are low-molecular-weight hormone-like glycoproteins secreted by leukocytes and various other cells in response to a number of stimuli, which are involved in communication between cells, particularly those of the immune system. Lymphocyte-derived cytokines are known as lymphokines, those produced by monocyte/macrophages as monokines. Many of the cytokines are referred to as interleukins (ILs), a name indicating that they are secreted by some leukocytes and act upon other leukocytes. They are required for the initiation and regulation of all stages of the immune response, from stem cell differentiation to effector cell activation. Their action is mediated by binding to specific receptors on target cells; often the receptor may be released from the target cell in soluble form so that it may intercept the cytokine and act as an inhibitor. There are also other forms of cytokine inhibitors responsible for keeping these molecules under tight regulation. Each cytokine has several different activities (pleiotropy), and the same activity may be produced by several different cytokines (redundancy). The response of a cell to an individual cytokine depends on the context in which it receives the signal, e.g. its state of differentiation and activation and the presence of other cytokines in the microenvironment.

Chemokines are a family of low-molecular-weight, structurally related cytokines that promote adhesion of cells to endothelium, chemotaxis and activation of leukocytes. They are involved in leukocyte trafficking, providing specific signals for lymphocyte entry into lymphoid and other tissue.

Table 9.1 outlines the main sources and activities of cytokines. It is not exhaustive, and new cytokines and activities are undoubtedly awaiting discovery. The exciting field of cytokine research has led to the isolation of genes for cytokines and their receptors and inhibitors and the ability to manufacture these molecules by recombinant DNA technology. There is optimism that therapeutic use of these reagents will, in the near future, benefit patients with infections, autoimmunity, allergy and other immunologically mediated diseases.

Table 9.1 Main producers and major actions of cytokines

Cytokine Main producers Major actions
IL-1 Macrophages Mediator of inflammation; augments immune response
IL-2 T cells T cell activation and proliferation
IL-3 T cells Haematopoiesis (early progenitors)
IL-4 T cells T cell, B cell, mast cell proliferation; IgE production
IL-5 T cells B cell proliferation; IgA production; eosinophil, basophil differentiation
IL-6 Macrophages, T cells Mediator of inflammation; B cell differentiation
IL-7 Bone marrow cells, thymic stroma Haematopoiesis (lymphocytes)
IL-8 Macrophages Neutrophil chemotaxis
IL-9 T cells T cell proliferation
IL-10 Macrophages, T cells Inhibitor of cytokine production
IL-11 Bone marrow stromal cells Haematopoiesis (early progenitors)
IL-12 Macrophages T cell differentiation
IL-13 T cells Similar to IL-4
IL-14 T cells Proliferation of activated B cells
IL-15 Stromal cells Similar to IL-2
IL-16 T cells T cell chemotaxis
IL-17 T cells Mediator of inflammation and haematopoiesis
IL-18 Macrophages Similar to IL-12
IFN-α Leukocytes Activation of macrophages, NK cells; upregulation of MHC expression; protection of cells against virus infection
IFN-β Fibroblasts
IFN-γ T cells, NK cells
LT T cells Mediator of inflammation; killing of tumour cells; inhibition of tumour growth
OSM Macrophages, T cells
TGF-β Macrophages, lymphocytes, endothelial cells, platelets Wound healing; IgA production; suppression of cytokine production
TNF-α Macrophages, T cells Mediator of inflammation; killing of tumour cells
gCSF Macrophages Haematopoiesis (granulocytes)
mCSF Monocytes Haematopoiesis (monocyte/macrophages)
gmCSF T cells Haematopoiesis (granulocytes, monocyte/macrophages)

IL, interleukin; IFN, interferon; LT, lymphotoxin; OSM, oncostatin M; TGF, transforming growth factor; TNF, tumour necrosis factor; CSF, colony-stimulating factor; g, granulocyte; m, monocyte/macrophage; NK, natural killer; Ig, immunoglobulin; MHC, major histocompatibility complex.

Jan 4, 2015 | Posted by in General Dentistry | Comments Off on 9: The immune response
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