Basic immunology and immune system disorders

CHAPTER 1 Basic immunology and immune system disorders

The immune system is a Western medical concept. Chinese medicine never discusses immunity directly. Instead it describes the clinical symptoms of the body’s response to an invasion by external pathogens in terms of Zheng Qi, vital Qi, which protects human health by fending off invasion.¹

In Western medical theory, the immune system has a defensive function; the cells of the immune system work together with different proteins to seek out and destroy anything foreign or dangerous that enters the body. It may take some time for the immune cells to be activated – anywhere from minutes to days – but once they are operating at full strength there are very few hostile organisms that stand a chance against them.

The immune system protects against infection by killing pathogens and eliminating foreign substances. It detects pathogens, including viruses, bacteria and parasites, and distinguishes them from the organism’s normal cells and tissues. Detection by the immune system is sometimes frustrated as pathogens adapt and evolve new ways in which they can successfully infect the host organism.

The first response of the immune system to infection is inflammation. The symptoms of inflammation are redness, swelling, heat and pain. This reaction is caused by increased blood flow to the affected tissue. Infected cells, injured cells or fragments of cells produce eicosanoids and cytokines. Eicosanoids include prostaglandins that produce a feeling of heat, fever and the dilatation of blood vessels; cytokines include interleukins that are responsible for communication between white blood cells.

1 The immune system process

The immune system is a complex of organs and tissues that includes highly specialized cells and even a circulatory system separate from the cardiovascular system. These all work in concert to clear infection and cancer cells from the body. The organs of the immune system, which are called lymphoid organs, are positioned throughout the body and include lymph nodes, the spleen, thymus, tonsils and appendix.

The specialized cells of the immune system, lymphocytes, initially form in the bone marrow and then differentiate into two major classes, T cells and B cells. T cells mature in the thymus, high in the chest behind the sternum, and B cells grow to maturity in the bone marrow. T cells are involved in a process called cell-mediated immune response. B cells are involved in a process called humoral immune response, which refers to immunity conferred by proteins called antibodies.

(1) Cell-mediated immunity

All T cells, also called thymocytes because of the location of their maturation, originate from stem cells in the bone marrow. The least mature thymocytes express neither CD4 nor CD8, an abbreviation for specific cluster differentiations. Cluster differentiations are various molecular substances that exist on the surface of T and B cells. Initially, T cells are classed as double-negative (CD4⁻ CD8⁻) cells. As they develop, they become double-positive thymocytes (CD4⁺ CD8⁺). Finally they mature to single-positive (CD4⁺ CD8⁻ or CD4⁻ CD8⁺) thymocytes that are then released from the thymus to peripheral tissues, where they circulate until needed, awaiting activation by other immune system cells.

A macrophage is one type of cell that can activate T cells. Macrophages are large immune system scavenger cells that travel through the body. When a macrophage comes into contact with an antigen, or foreign protein in the body, it engulfs the antigen. Once engulfed, the macrophage processes the antigen internally and then displays parts of the molecule on the cell surface together with some of its own proteins. This process of displaying parts of an engulfed antigen sensitizes T cells, essentially turning them on to recognize the antigens.

One factor that allows T cells to recognize an almost infinite number of antigens is their cluster differentiation (CD). Various molecules coat the surfaces of all cells, including immune system cells. Every T and B cell has about 10⁵ (100 000) molecules on its surface, one type of which is CD. There are more than 160 CD types, each of which is a different chemical molecule. T cells have CD2, CD3, CD4, CD28 and CD45R, as well as other non-CD molecules on their surface. B cells are coated with CD21, CD35, CD40 and CD45 in addition to other non-CD molecules.

The large and varied number of molecules existing on the surface of lymphocytes results in huge variability in the shape of their receptor sites, with which they bind to antigens. Additionally, as lymphocytes mature, their receptor sites develop random configurations, resulting in some 10¹⁸ possible structurally different receptors. Essentially, any antigen may find a near-perfect fit on a lymphocyte receptor, although, given the possible number of antigens in the world, that near-perfect fit may be with a very small number of lymphocytes, perhaps as few as one or two. Once a T cell has bound to an antigen, it communicates with other cells in the immune system, ordering them to assist in the fight against the antigen.

T cells have two major roles in immune defence: regulation and communication. In the role of regulation, one type of T cell, regulatory (or suppressor) T cells, are essential for orchestrating the response of an elaborate system of immune cells. In the role of communication, another type of T cell, helper T cells, also known as CD4⁺ T cells, alert B cells to start producing antibodies. They also can activate other T cells, including CD8⁺ T cells, and macrophages, and influence the type of antibody that is produced. Once activated, CD8⁺ T cells can transform into killer T cells that attack and destroy infected cells. Killer T cells are also called cytotoxic T cells or cytotoxic lymphocytes (CTLs). Killer T cells directly attack other cells carrying foreign or abnormal antigens on their surface.

Regulatory T cells (T_reg cells), also known as suppressor T cells, are a specialized subpopulation of T cell, the job of which is to suppress continued activity of the immune system. They thereby maintain immune system homeostasis and tolerance to self-antigens; that is, they recognize which cells and proteins comprise the self and which are foreign. Their major role is to shut down T cell-mediated immunity towards the end of an immune reaction and to suppress the function of autoreactive T cells, as described below, that have escaped the process of negative selection in the thymus. Two major classes of T_reg cells have been described in the literature: naturally occurring and adaptive T_reg cells. Naturally occurring T_reg cells (also known as CD4⁺ CD25⁺ FoxP3⁺ T_reg cells) arise in the thymus, whereas adaptive T_reg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response. Understanding of the naturally occurring T_reg cell is important, because mutations of an intracellular molecule unique to T_reg cells called the FOXP3 gene can prevent regulatory T-cell development, causing the fatal autoimmune diseases discussed later in this book.

Helper T cells regulate both innate and adaptive immune responses and help to determine the immune response to a particular pathogen. Innate immunity results from natural barriers to pathogens created by all epithelial surfaces in the body: skin, the lining of the gastrointestinal and genitourinary tracts, and the lining of the nasal passages and lungs. Adaptive immunity is triggered in vertebrates when a pathogen evades the innate immune system and generates a threshold level of antigen. Helper T cells control the immune response by directing other cells to perform the tasks of killing infected cells and clearing away pathogens from the body.

Once a macrophage has engulfed and processed an antigen, it displays fragments of the antigen combined with a major histocompatibility complex (MHC) class II protein on its surface. The antigen–protein combination attracts the helper T cell and promotes its activation to produce antibodies. In organ or tissue transplant situations, the most rapid and severe rejection of foreign tissue occurs when there is a failure to match the donor and recipient properly for the MHC molecules. There are two categories: class I and class II.

Killer T cells are CD8⁺ T cells that have been activated by helper T cells. They kill cells infected with viruses and other pathogens, or that are otherwise damaged or dysfunctional. Killer T cells become activated when their T-cell receptor (TCR) binds to a specific antigen in a complex with the MHC class I receptor of another cell. Recognition of this MHC–antigen complex is aided by a co-receptor on the T cell, called CD8. The T cell then travels throughout the body in search of cells with MHC class I receptors that bear this antigen. When an activated T cell contacts such a cell, it releases cytotoxins that form pores in the target cell’s plasma membrane, allowing ions, water and toxins to enter. This causes the target pathogen or diseased cell to undergo lysis.

Memory T cells are a subset of antigen-specific T cells that persist long after an infection has resolved. They quickly reproduce large numbers of effector memory T cells upon re-exposure to their cognate antigen, thus providing the immune system with ‘memory’ against past infections. Memory T cells comprise two subtypes: central memory T cells (T_CM cells) and effector memory T cells (T_EM cells). Memory cells may be either CD4⁺ or CD8⁺.

To clarify, the relationship between killer T cells, helper T cells, regulator T cells, and memory T cells and their functions are:

• Cytotoxic or killer T cells (CD8⁺) work by releasing cytotoxins, which cause cell lysis.

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Tags: Treating Autoimmune Disease with Chinese Medicine

Jan 19, 2017 | Posted by admin in MUSCULOSKELETAL MEDICINE | Comments Off

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