It took more than 400 million years of evolution for our immune system to develop into the highly complex and adaptable defense mechanism that it is today. Its primary task is to protect us from foreign and harmful substances, microorganisms, toxins, and malignant cells. Only through the continuous development ofthe immune system was it possible to protect living organisms against constant attacks from both the external and internal environments. In the process, the immune system has learned to inactivate destructive responses to endogenous substances and to prevent irreparable damage to the surrounding tissue. Most immunological responses are of limited duration and are restricted by regulatory mechanisms to prevent overreactions.
An essential task of the immune system is to distinguish dangerous from harmless. Infiltration with microorganisms or bacterial toxins, for example, is a dangerous attack on an organism, whereas the inhalation of pollen or the infiltration offood antigens from the stomach into the blood system is harmless. The destruction of malignant cells or foreign cell material is desirable (e.g., in parasite infestation), but direct at-tacks against the host tissue are undesirable (e.g., in autoimmune disease). The processes by which the immune system avoids the development of destructive self-reactivity are collectively referred to as tolerance. The large majority of lymphocytes directed against self-antigens present throughout the primary lymphoid organs are destroyed in a process known as central tolerance. Peripheral tolerance is still another mechanism that occurs in less common endogenous structures or in those present only in certain regions of the body.
Nonspecific (innate) immune system. The historically older congenital defense mechanisms are defined as nonspecific because they become active independently of the invading pathogen. They are also called nonclonal defense mechanisms because no individual cell clone is required for their specific development. Some examples include the acid layer of the skin, the intact epidermis, the complement system, antimicrobial enzyme systems, and non-specific mediators such as interferons and interleukins. Examples on the cellular level include granulocytes, the monocyte-macrophage system, and natural killer (NK) cells. The latter represent an interface between the specific and nonspecific immune systems.
The inflammatory response permits an on-the-site concentration of defensive forces via the complex interplay of soluble and cellulareomponents; this is an important nonspecific defense mechanism. The first step in this process is the release of mediators that dilate the blood vessels and make the capillary walls more permeable. The site of infection is then pe-netrated by granulocytes, which are replaced by macrophages in the later course of the reaction The granulocytes carry out the “first line of defense” in which the majority of invading pathogens are destroyed. The remaining pathogenic organisms and waste products of this firstline defense are phagocytosed by macrophages.
Specific (adaptive) immune system. The process ofsuch an immune response paves the way for the specific immune response. In a specific cytokine environment, the body can decide whether to proceed to a more humoral line of defense or a more cellular line of defense. The migration of antigen-presenting cells (APC) to the lymphoid organs first triggers a systemic immune response, then a memory response. The specific immune system consisting of T and B lymphocytes is responsible for this. These cell systems can produce highly specific reactions to their respective antigens and undergo clonal expansion, thus achieving a highly effective response to and memory for those antigens.
Origin of Cells of the Immune System Cells of the immune system originate in the bone marrow. Once mature these cells patrol tissues, circulating in blood and lymphatic vessels. Haematopoietic stem cells (HSCs) found mainly in the bone marrow give rise to all blood cells and cells of the immune system. HSCs differentiate into both myeloid and lymphoid progenitors (Figure 1. 1).
