IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 1. General Properties of the Immune System

■ The Immune System evolved to protect the host against pathogenic microbes. Some of these, such as Viruses, invade host Cells, whereas others, like many Bacteria, multiply extracellularly in Tissues or Body Cavities.

■ Lymphocytes and phagocytes participate in maintaining Immunity. Lymphocytes recognize Antigens of pathogenic microorganisms, while phagocytes ingest and destroy the pathogens themselves.

■ The Immune Response consists of two phases. In the early phase, the antigen is recognized by specifically reacting lymphocytes and they become activated; in the late (effector) phase, these lymphocytes perform their coordinating function to eliminate the source of foreign antigens from the body.

■ Specificity and memory are two KEY FEATURES OF adaptive immunity. Upon re-exposure to the same antigen, the immune system responds much more effectively.

■ Lymphocytes are functionally specialized. B cells produce Antibodies. Cytotoxic T lymphocytes destroy virus-infected cells. Helper T lymphocytes coordinate the immune response through direct Cell-to-cell contact and by releasing cytokines into the extracellular environment, which, for example, help B cells produce antibodies.

■ Antigens are molecules recognized by lymphocyte receptors. B lymphocytes typically recognize intact antigen molecules, whereas T lymphocytes are usually capable of recognizing antigenic molecules only as fragments presented On the surface of other cells.

■ Recognition of antigen molecules by specific lymphocytes triggers the selective proliferation of lymphocyte clones; clonal expansion is accompanied by the differentiation of lymphocytes into effector cells and immunological memory cells.

■ Malfunctions can occur during the functioning of the immune system, leading to immunodeficiency states, hypersensitivity, or autoimmune diseases.

Our environment contains an enormous variety of pathogenic microbes—viruses, bacteria, Fungi, Protozoa—and multicellular parasites. They are capable of causing disease and, if they multiply unchecked within the body's tissues, ultimately lead to its death. However, under normal conditions, thanks to the immune system protecting us against pathogenic microbes, most infections are short-lived and practically devoid of health-damaging consequences.

Because microorganisms exist in a multitude of forms, the body possesses a wide array of anti-infective resistance factors and forms of the immune response. First and foremost, the body's outer coverings serve as an effective barrier against most infectious agents—only a very few pathogen species can penetrate through intact Skin (Fig. 1.1). However, many pathogenic microbes are capable of invading the epithelium of the digestive and urogenital tracts, as well as infecting the nasopharynx and Lungs. Certain pathogens, such as the malaria parasite and hepatitis B virus, cause infection only when introduced directly into the bloodstream.

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Fig. 1.1. Most disease-causing agents do not penetrate the internal environment of The Human Body due to various physical and biochemical barriers. The growth of many potentially pathogenic microorganisms is effectively suppressed (through competition) by commensal microbes, toward which the host is tolerant.

Which form of immune response will be effective depends largely on the site of infection and the type of pathogen. Most crucially, this depends on whether the microbes invade the host's cells or not. To eradicate an intracellular infection—such as those caused by all viruses, certain bacteria, and A number of parasitic protozoa—the immune system must recognize and destroy the infected cells. In the case of extracellular multiplication of the infectious agent in tissues, fluids, or body cavities—which is characteristic of many bacteria and larger pathogens—the immune response is entirely different. Nevertheless, during The Development of an infection, even intracellular pathogens must travel via the bloodstream and tissue fluid to reach their target cells, and during this transit, they are vulnerable to the immune system components primarily tailored against extracellular pathogens (Fig. 1.2).

Fig. 1.2

The task of the immune system is to recognize pathogens and respond to infection regardless of its Location. For instance, viruses must enter a cell to replicate. An intracellular developmental stage is also characteristic of protozoa, such as malaria parasites (Plasmodium spp.) or trypanosomes (Trypanosoma cruzi, the CAUSATIVE AGENT OF Chagas disease), and bacteria such as Salmonella typhi. Some parasitic protozoa (including trypanosomes, the agents of African sleeping sickness) parasitize the Blood, whereas many large multicellular parasites inhabit the tissues or cavities of specific Organs (e.g., tapeworms). Many bacteria colonize epithelial surfaces and can invade the internal environment of the body to multiply within tissues.

This chapter provides only the most fundamental information about the immune system and the immune response. These topics are discussed in greater detail in Chapters 2–20. Various Disorders of the immune system leading to immunopathological reactions are covered In the second half of the book. It is important to note, however, that The primary function of the immune system is the elimination of infectious agents and the reduction of the harm they cause.

ADAPTIVE AND INNATE IMMUNITY

As a rule, the immune response consists, firstly, of recognizing the pathogen or other foreign material and, secondly, of deploying a cascade of reactions aimed at their elimination. Broadly speaking, all the diverse forms of the immune response can be divided into two types: innate and adaptive reactions. The fundamental difference between these Two Types of immunoreactivity is that adaptive immunity is highly specific for each particular pathogen. Furthermore, re-exposure to a given pathogenic microbe does not alter innate immunity, but enhances adaptive immunity: the immune system essentially "remembers" the pathogen to prevent future Infections caused by it. For example, individuals who recover from measles or diphtheria often acquire lifelong adaptive immunity to these diseases. The two core features of adaptive immunity are specificity and immunological memory.

The immune response is executed primarily by leukocytes, which comprise several distinct types.

Phagocytes and innate immunity. An important group of leukocytes consists of phagocytic cells: monocytes, macrophages, and polymorphonuclear neutrophils. They are capable of binding microorganisms on their surface and subsequently ingesting and destroying them. This function relies on simple, non-specific recognition mechanisms that allow the binding of A wide variety of microbial products, and represents a manifestation of innate immunity. Phagocytes form the first line of defense against infection.

Lymphocytes and adaptive immunity. Another crucial group of leukocytes is the lymphocytes. They play a leading role in all adaptive immunity reactions because they specifically recognize a particular pathogen wherever it may be located—inside or outside cells, in tissue fluid or in the blood. There are various types of lymphocytes, but the two main populations are T lymphocytes (or T cells) and B lymphocytes (or B cells). The latter combat extracellular pathogens and the effects of their products by producing antibodies, molecules capable of specifically recognizing and binding particular target molecules—antigens. Antigens can be molecules on The surface of microbial cells or toxins produced by them. T lymphocytes, or more precisely their various populations combined, possess a wide repertoire of activities. Some T cells participate in regulating B lymphocyte differentiation and antibody production. Others interact with phagocytes, helping them destroy ingested microbial cells. A third group of T lymphocytes recognizes and destroys virus-infected cells.

Interaction between lymphocytes and phagocytes. The Scope of such interactions is substantial. For example, certain types of phagocytic cells, after capturing antigens, can present them to T lymphocytes in a form suitable for recognition. This process is called antigen presentation. Upon recognizing the antigen, T lymphocytes in turn release soluble factors (cytokines) that activate phagocytes and induce them to destroy the engulfed microbes. In another type of interaction, phagocytes utilize antibodies produced by B lymphocytes to more efficiently recognize pathogens themselves (Fig. 1.3). Consequently, the Immune Response to an infection is most often composed of various interconnected effects of both innate and adaptive immunity. In the Cytology/cytology/16.html">Early stages of infection, innate immunity mechanisms dominate, but later lymphocytes mount a specific response characteristic of adaptive immunity. In doing so, they "remember" the pathogen, and if the body is subsequently reinfected with the same microbe, they "recall" it and mount a more effective and rapid immune response.

Fig. 1.3. B lymphocytes secrete antibodies that interact with pathogenic microorganisms and their metabolic products. By doing so, B lymphocytes assist phagocytes—capable of binding antibodies via their Fcγ-receptors—in recognizing foreign antigens. Cytokines released by T lymphocytes activate phagocytic cells to destroy the material they have engulfed. In turn, mononuclear phagocytes can present the fragmented antigen to T cells, thereby triggering their activation.