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The term immune system refers to the collection organs and tissues involved in the adaptive defense of a body against foreign biological material. It may be broken down into the adaptive immune system, composed of four lymphoid organs (thymus, lymph nodes, spleen and submucosal lymphoid nodules) and the group motile cells that are involved in the body's defense against foreign bodies. It may also be used to refer to the totality of a body's defense systems, encompassing both the adaptive immune system and other passive defenses, such as the skin.
Types of systems
In multicellular organisms, the immune system is an organ system that acts as a defense against foreign pathogens (such as viruses, bacteria, parasites), some poisons, as well as cancer. Components of the immune system also function in the return of extracellular fluid to the blood.
Bacteria and monocellular organisms have an "immune system" designed to combat bacteriophages (viruses that infect bacteria). They do this by simultaneously expressing enzymes that cut DNA at certain sequences, and enzymes that protect DNA from this enzyme by methylating the same sequence. Therefore, the bacterium's DNA will not be damaged by the first enzyme because of the presence of the second enzyme. However, when a bacteriophage attempts to infect this bacterium, the viral DNA has not been protected, and gets degraded by the first enzyme.
However, when we talk about immune systems we are usually referring to the immune systems of multicellular organisms, usually vertebrates.
Recognizing self and non-self
To prevent the body's immune system from attacking itself, the plasma membrane of every cell contains molecules of a large glycoprotein called the major histocompatibility complex (MHC) These proteins have configurations and amino acid sequences that are unique to every individual. During development, B cells and T cells are tested for self-reactivity. If a cell contains receptors that identify an existing molecule in the body, they are rendered non-functional or destroyed by apoptosis. Cells that do not contain the MHC of the individual are recognised as foreign by lymphocytes and macrophages.
- See Major histocompatibility complex for more information
Structure of the immune system
Most multicellular organisms possess an immune system consisting of innate immunity which generally consists of a set of genetically-encoded responses to pathogens and does not change during the lifetime of the organism. Adaptive immunity, in which the response to pathogens changes during the lifetime of an individual, appeared somewhat abruptly in evolutionary time with the appearance of cartilaginous (jawed) fish. Organisms that possess an adaptive immunity also possess an innate immunity and many of the mechanisms between the systems are common, so it not always possible to draw a hard and fast boundary between the individual components involved in each, despite the clear difference in operation. Higher vertebrates and all mammals have both an innate and an adaptive immune system.
Innate immune system
The adaptive immune system may take days or weeks after an initial infection to have an effect. However, most organisms are under constant assault from pathogens, which must be kept in check by the faster-acting innate immune system. Innate immunity fights pathogens using defenses that are quickly mobilized and triggered by receptors that recognize a broad spectrum of pathogens. Plants and many lower animals do not possess an adaptive immune system and instead rely on innate immunity.
The study of the innate immune system has recently flourished. Earlier studies of innate immunity utilized model organisms that lack adaptive immunity such as the plant Arabidopsis thaliana, the fly Drosophila melanogaster, and the worm Caenorhabditis elegans. Recent advances have been made in the field of innate immunology with the discovery of the toll-like receptors, which are the receptors in mammals that are responsible for a large proportion of the innate immune recognition of pathogens. There is strong evidence that these toll-like receptors are responsible for sensing the "pathogen-associated molecular patterns" and/or providing the "danger signal" as speculated by Janeway and Matzinger, respectively.
The first defense includes barriers to infection such as skin and mucus coating of the gut and airways, physically preventing the interaction between the host and pathogen. Pathogens which penetrate these barriers encounter constitutively expressed anti-microbial molecules that restrict the infection.
The second-line defense includes phagocytic cells, which includes macrophages and neutrophil granulocytes (polymorphonuclear leukocytes, PMN) that can engulf (phagocytose) foreign substances. Macrophages are thought to mature continuously from circulating monocytes.
Phagocytosis involves chemotaxis, where phagocytic cells are attracted to microorganisms by means of chemotactic chemicals like microbial products, complements, damaged cells and white blood cell fragments; chemotaxis is followed by adhesion, where the phagocyte sticks to the microorganism. Adhesion is enhanced by opsonization, where proteins like opsonins are coated on the surface of the bacterium. This is followed by ingestion, in which the phagocyte extends projections, forming pseudopods that engulf the foreign organism. Finally the bacterium is digested by the enzymes in the lysosome.
In addition, anti-microbial proteins may be activated if a pathogen pass through the barrier offered by skin. There are several class of antimicrobial proteins, such as acute phase proteins (C-reactive protein, for example, binds to the C-protein of S. pneumoniae - enhances phagocytosis and activates complement), lysozyme and the complement system.
The complement system is a very complex group of serum proteins which is activated in a cascade fashion. Three different pathways, the classical, alternative, and mannose-binding lectin pathways, are involved in complement activation. The first recognizes antigen-antibody complexes, the second spontaneously activates on contact with pathogenic cell surfaces, the third recognizes mannose sugars, which tend to appear only on pathogenic cell surfaces. A cascade of protein activity follows complement activation; this cascade can result in a variety of effects including opsonization of the pathogen, destruction of the pathogen by formation and activation of the membrane attack complex, and inflammation.
Adaptive immune system
The adaptive immune system, also called the acquired immune system, explains the interesting fact that when most mammals survive an initial infection by a pathogen, they are generally immune to further illness caused by that same pathogen. This fact is exploited by modern medicine through the use of vaccines. The adaptive immune system is based on immune cells called leukocytes (or white blood cells) that are produced by stem cells in the bone marrow. The immune system can be divided into two parts. Many species, including mammals, have the following type:
- The humoral immune system, which acts against bacteria and viruses in the body liquids (such as blood). Its primary means of action are immunoglobulins, also called antibodies, which are produced by B cells
- The cellular immune system, which takes care of other cells that are infected by viruses. This is done by T cells, also called T lymphocytes (T means they develop in the thymus). There are two major types of T cells:
- Cytotoxic T cells (TC cells) recognize infected cells by using T-cell receptors to probe the surface of other cells. If they recognize an infected cell, they release granzymes to signal that cell to become apoptotic ("commit suicide"), thus killing that cell and any viruses it is in the process of creating.
- Helper T cells (TH cells) interact with macrophages (which ingest dangerous material), and also produce cytokines (interleukins) that induce the proliferation of B and T cells.
- In addition, there are Regulatory T cells (Treg cells) which are important in regulating cell-mediated immunity.
The intersection between innate and adaptive immune systems
Although the dichotomy of the innate and adaptive immune systems has served to simplify and facilitate the reductionist approach to immunology, a number of fairly recent discoveries have helped to explain old mysteries of the immune system as well as blur the division between innate and adaptive immune systems.
- adjuvants - Although the text book explanation of the adaptive immune system would suggest that the adaptive immune system could raise antibodies and T-cells specific to any antigen, including artificial peptides, introduced to a mammal, the fact was that, in order to induce a robust immune response, the antigen had to be delivered with an adjuvant. The most commonly used adjuvant was Freund's Complete Adjuvant, an emulsion of oil and mycobacterium. It was later discovered that toll-like receptors, expressed on innate immune cells, are critical in the activation of adaptive immunity.
- antigen presentation - It was known that T-cell activation required other cells to process and present antigens. These cells were called antigen presenting cells (APC), and this function was thought to be performed by macrophages and/or B-cells in vivo. However, isolated macrophages and B-cells were not potent antigen presenting cells. The later discovery of dendritic cells (DC) (by Ralph Steinman) demonstrated that there existed a specialized cell type for this function. Dendritic cells are a type of myeloid cell derived (probably) from monocytes whose main function appears to be the activation of T-cells. Here you have an innate immune cell that is critical in the function of adaptive immunity.
Disorders of the human immune system
An ineffective immune system is a feature of immune deficiency; there are congenital (inborn) or acquired forms of immune deficiency, dependent on the cause. AIDS ("Acquired Immune Deficiency Syndrome") is an infectious disease, transmitted by HIV, which causes degeneration of the body's immune system.
On the other hand, an "overactive" immune system is a feature of a large number of different autoimmune disorders, such as lupus erythematosus, type I diabetes (sometimes called "juvenile onset diabetes"), multiple sclerosis, psoriasis, and rheumatoid arthritis. In these the self-recognition ability of the immune system fails and it attacks a part of the patient's own body.
People who are immunocompromised have a suppressed immune system. This may include people with acquired or inherited diseases which affect the immune system, and those who are taking medications to prevent rejection of transplanted organs.
- A standard textbook on the immune system is Immunobiology, by Charles Janeway, et al. The paperback of the sixth edition is ISBN 0815341016. NCBI makes the 5th edition availiable electronically at  (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10).