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Revision as of 16:51, 4 November 2006 by ClockworkSoul (talk | contribs) (Reverted edits by 129.105.234.70 (talk) to last version by ClockworkSoul)(diff) ← Previous revision | Latest revision (diff) | Newer revision → (diff)The immune system protects the body from infection by pathogenic organisms. It is composed of a complex constellation of cells, organs and tissues, arranged in an elaborate and dynamic communications network. The immune system is, in its simplest form, a cascade of detection and adaptation, culminating in a system that is remarkably effective.
Overview of the immune system
The immune system protects the body from infection by creating and maintaining barriers that prevent bacteria and viruses from entering the body. If a pathogen breaches the barriers, and gets into the body, the innate immune system is equipped with specialized cells that detect, and often eliminate, the invader before it is able to reproduce, potentially causing serious injury to the host. A pathogen that successfully evades the innate immune cells faces a second, adaptive immune system. It is through the adaptive response that the immune system gains the ability to recognize a pathogen, and to mount stronger attacks each time that pathogen is encountered.
| Innate immune system | Adaptive immune system |
|---|---|
| Response is non-specific | Pathogen and antigen specific response |
| Exposure leads to immediate maximal response | Lag time between exposure and maximal response |
| Cell-mediated and Humoral components | Cell-mediated and Humoral components |
| Cells are called leukocytes | Cells are called lymphocytes |
| No immunological memory | Exposure leads to immunological memory |
Surface barriers
Several barriers protect the host from infection; including mechanical, chemical and biological barriers.
The skin is a mechanical barrier and is often the first line of defense against infection. The skin is made up of the epidermis, outer layer, and dermis, and most infectious agents find it to be impenetrable. Coughing and sneezing causes tiny hairs, called cilia, to move in an upward motion mechanically ejecting both living things and other irritants from the respiratory tract. The flushing action of saliva, tears, and urine also mechanically expel pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to protect the host by trapping microorganisms.
The skin is comprised of tightly packed cells rich in keratin, this serves as a chemical barrier, because it impedes water and is slightly acidic, which inhibit bacterial growth. Enzymes, in saliva and tears and breast milk are antibacterial. Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains spermine and zinc which repel pathogens. Gastric acid, the low pH and destructive enzymes that exist in the stomach, are powerful chemical defenses against ingested pathogens.
Within the intestines, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space, diminishing the probability that pathogens will be able to reach sufficient numbers to cause illness. Antibiotics do not discriminate between pathogenic bacteria and the normal gut flora, and ingestion of oral antibiotics can sometimes lead to an “overgrowth” of fungus (fungus is not affected by antibiotics), such as a yeast infection.
Innate immunity
Further information: Innate immune system
If microorganisms successfully breach the surface barriers, the cells and mechanisms of the innate immune system are present, and ready to be mobilized to defend the the host. Innate immune defenses are non-specific, meaning that the innate system recognizes and responds to, pathogens in a generic way. The innate system does not confer long-lasting or protective immunity to the host. It is thought to constitute an evolutionarily older defense strategy, and is the dominant system of host defense in plants, fungi, insects, and in primitive multicellular organisms. The innate immune system protects the host by establishing humoral, chemical and cellular barriers to infection.
Humoral and chemical barriers
Inflammation
Inflammation, characterized by redness and swelling, is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors, including specialized chemical mediators, called cytokines, released by injured cells and serves to; establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the removal of pathogens.
Complement system
The complement system is a biochemical cascade that helps, or “complements”, the ability of antibodies to clear pathogens or mark them for destruction by other cells. The complement system "tag" pathogens for destruction by other cells by opsonizing, or coating, the surface of the pathogen, triggers the recruitment of inflammatory cells, and rids the body of neutralized antigen-antibody complexes. Activation of complement often results in disruption of the plasma membrane of infected cells, resulting in cytolysis of the infected cell, and causing the death of the pathogen.
Elements of the complement cascade can be found in many species evolutionarily older than mammals including plants, fish and some species of invertebrates.
Cellular barriers of the innate system
All white blood cells (WBC) are known officially as leukocytes. Leukocytes are not exclusively associated with any organ or tissue and act like independent, single-celled organisms. The innate leukocytes include; mast cells, eosinophils, basophils, natural killer cells, and the phagocytes (macrophages, neutrophils and dendritic cells) and function by identifying pathogens that might cause infection. Pathogens are eliminated by direct killing or by engulfment and destruction. Innate cells are also important mediators in the adaptive immune system, which they are able to activate through a process known as antigen presentation.
Mast cells reside in the connective tissue and the mucous membranes, and are intimately associated with pathogen defense, wound healing, and often associated with allergy and anaphylaxis. Basophils and Eosinophils are related to the neutrophil (see below), and secrete chemical mediators that are particularly important in defense against parasites. They also play a role in allergic reactions (such as asthma). Although not part of the inflammatory response, natural killer or NK cells, non-specifically attack and destroy tumor cells or cells that have been infected by viruses.
The word 'phagocyte' literally means 'eating cell'. These are cells that engulf, or eat, pathogens or particles. Once inside the cell, the pathogen is digested by enzymes and acids. Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines.
Macrophages are the most efficient phagocytes, and are able to travel within the tissues and the areas between cells in pursuit of invading pathogens. Neutrophils, are the most abundant type of phagocyte, normally representing 50 to 60% of the total circulating leukocytes, and are usually the first cells to arrive at the scene of infection. The binding of bacterial molecules to receptors on the surface of a macrophage or neutrophil triggers it to engulf and destroy the bacteria, through the generation of a “respiratory burst”.
Dendritic cells (DC) are phagocytes present in tissues that are in contact with the external environment, mainly the skin, nose, lungs, stomach and intestines. They are named for their resemblance to neuronal dendrites, but dendritic cells are in no way connected to nervous system function. Dendritic cells serve as a link between the innate and adaptive immune systems, in the process of antigen presentation.
Specific or Adaptive immunity
Further information: Adaptive immune system
The innate immune system is brought into play at the earliest stages of infection. Many pathogens, however, have developed strategies that allow them to elude or escape from innate immune control. Under these circumstances the early innate response often sets the scene for the specialized adaptive immune system.
The adaptive immune system is antigen specific and requires the recognition of specific “non-self” antigens in the presence of “self”, during the process of antigen presentation. This antigen specificity allows for; the generation of responses that are tailored to maximally eliminate specific pathogens or pathogen infected cells, and the development of immunological memory, in which each pathogen is “remembered” by a signature antigen. These memory cells can be called upon to quickly eliminate a pathogen should subsequent infections occur.
Lymphocytes
The cells of the adaptive immune system are a type of leukocyte, called a lymphocyte. B cells and T cells are the major types of lymphocytes, and are derived from pluripotential hemopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response, whereas T-cells are involved in cell-mediated immune responses.
Both B cells and T cells carry customized receptor molecules that allow them to recognize and respond to their specific targets.
T cells recognize a “non-self” target only after antigens (small fragments of the pathogen) have been processed and presented in combination with a special type of “self” receptor called a major histocompatibility complex (MHC) marker. There are two major subtypes of T-cells; the killer T cell, and the helper T cell. Killer T cells only recognize antigens coupled to Class I MHC markers, while helper T cells only recognize antigens coupled to Class II MHC markers. This arrangement ensures the target antigen is acted upon by the T-cells that can most efficiently eliminate it.
The B cell's antigen-specific receptor is quite different; it is actually an antibody molecule that sits on the B-cell’s surface, and recognizes antigens in their natural state. The B-cell antigen receptor is a “sample” of the antibodies that the cell is prepared to manufacture.
Killer T cells
Killer T cells are a sub-group of T cells which induce the death of cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional. Resting killer T cells are activated when their T-cell receptor (TCR) strongly interacts with a peptide-bound MHC Class I molecule. The MHC:peptide complex is recognized and bound to the T cell by a receptor on the T-cell, called CD8. This binding helps to activate the cell. Activated killer T-cells then travel throughout the body in search of infected or damaged cells bearing that unique MHC Class I/peptide. When exposed to infected cells, killer cells release cytotoxins, which form pores in the target cell's plasma membrane, allowing ions, water and toxins to flow into the cell, causing the cell to burst, or to undergo apoptosis (cell death). In the case of virally infected cells, the death of the host cell also results in the death of the virus (viruses lack the means for self-reproduction outside a host cell).
Killer T cell activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T-cells (see below).
Helper T cells
Helper T cells are immune response mediators, and play an important role in establishing and maximizing the capabilities of the adaptive immune response. These cells have no cytotoxic activity; and cannot kill infected cells or clear pathogens, but, in essence "manage" the immune response by directing other cells to perform these tasks. Helper T cells express T-cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. This complex is recognized by the helper cell’s CD4 receptor. The activation of a resting helper T-cell causes it to release cytokines, which influences the activity of many cell types. Helper T-cells require a much milder activation stimulus than killer T-cells, and can provide extra signals to "help" activate both killer cells and antibody producing B cells.
B lymphocytes and antibody production
When a B cell identifies its target antigen it is engulfed and processed. The B cell then produces millions of copies of antibody, specifically directed against the antigen, that circulate in blood plasma and lymph, in search of any other copies of that antigen. By binding to their specific antigens, antibodies mark the invader or infected cell for destruction by killer T cells or by complement.
Immunological memory
When B cells and T cells are activated some will become memory cells. Throughout the lifetime of an animal these memory cells will “remember” each specific pathogen encountered, and are able to mount a strong response if the pathogen is detected again. This is "adaptive" because the body's immune system prepares itself for future challenges. Immunological memory can either be in the form of passive short-term memory or active long-term memory.
Passive memory
Passive memory is usually short-term, lasting between a few days and several months. Newborn infants have had no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. In utero, maternal IgG is transported directly across the placenta, so that at birth, human babies have high levels of antibodies, with the same range of antigen specificities as their mother. Breast milk contains antibodies that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies.
This is passive immunity because the fetus does not actually make any memory cells or antibodies, it only borrows them. Short-term passive immunity can also be transferred artificially from one individual to another via antibody-rich serum.
Active Memory
Active immunity is generally long-term and can be acquired by infection followed by B cells and T cells activation, or artificially acquired by vaccines, in a process called immunization.
Immunization
Historically, infectious disease has been the leading cause of death in the human population. Over the last century, two important factors have been developed to combat thier spread; sanitation and immunization. Immunization (commonly referred to as vaccination) is the deliberate induction of an immune response, and represents the single most effective manipulation of the immune system mankind has developed. Immunizations are successful because they utilize the immune system's natural specificity as well as its inducibility.
The principle behind immunization is to introduce an antigen, derived from a disease causing organism, that stimulates the immune system to develop protective immunity against that organism, but which does not itself cause the pathogenic effects of that organism. An antigen (short for antibody generator), is defined as any substance that binds to a specific antibody and elicits an adaptive immune response.
Most viral vaccines are based on live attenuated viruses, while many bacterial vaccines are based on acellular components of micro-organisms, including harmless toxincomponents. Many antigens derived from acellular vaccines do not strongly induce an adaptive response, and most bacterial vaccines require the addition of adjuvants that activate the antigen presenting cells of the innate immune system to enhance immunogenicity.
Disorders of the human immune system
The immune system is a remarkably effective structure that incorporates specificity, induciblity and adaptation. That being said, failures of host defense do occur and fall into three broad categories: immunodeficiencies, autoimmunity and hypersensitivities.
Immunodeficiencies
Immunodeficiencies occur when one or more of the components of the immune system is defective.
Nutrition is a critical determinant of immune system function and malnutrition the most common cause of immunodeficiency worldwide. Diets lacking sufficient protein sources are associated with a significant impairment of cell-mediated immunity, phagocyte function, the complement system, IgA antibody concentrations, and cytokine production. Deficiency of single nutrients such as zinc; selenium; iron; copper; vitamins A, C, E, and B-6; and folic acid (vitamin B-9) also results in inhibition of immune responses.
The ability of the immune system to respond to pathogens is diminished in both the young and elderly. In fact, immune response to immunization begins to decline at around age 50. Obesity, Alcohol and Drug abuse also contribute to poor immune function.
In developed countries, inherited (or 'congenital') and 'acquired' forms of immunodeficiencies are more common. Chronic granulomatous disease, in which phagocytes have trouble destroying pathogens, is an example of a congenital immunodeficiency. AIDS "Acquired Immune Deficiency Syndrome" and some types of cancer are examples of acquired immunodeficiency.
Autoimmunity
Overactive immune responses comprise the other end of immune dysfunction, particularly the autoimmune disorders. In this situation, the immune system fails to properly distinguish between self and non-self, and attacks a part of the host. Under normal circumstances, many T cells and antibodies react with “self” peptides. One of the functions of specialized cells (located in the thymus and bone marrow) is to present young lymphocytes with self antigens produced throughout the body, and to eliminate those T-cells that react strongly with self-antigens, curbing the potential for autoimmunity to develop.
Hypersensitivity
Hypersensitivity is an immune response that damages the body's own tissues. They are divided into four classes (Type I-IV) based on the mechanisms involved and the time course of the hypersensitive reaction.
Type I hypersensitivity is classified as an immediate or anaphylactic reaction, and is often associated with allergy. Symptoms can range from mild discomfort to death. Type I hypersensitivity is mediated by IgE released from mast cells and basophils. Type II hypersensitivity occurs when antibodies bind to antigens on the patient's own cells, marking them for destruction by other cells. This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated IgG and IgM antibodies. Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions. Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop. Type IV reactions are involved in the pathogenesis of many autoimmune and infectious diseases, but may also involve contact dermatitis (poison ivy). These reactions are mediated by T cells, monocytes and macrophages.
Manipulation of the immune response
The immune response can be manipulated to suppress unwanted responses resulting from autoimmunity, allergy and transplant rejection, and to stimulate protective responses against pathogens that largely elude the immune system.
Immunosuppression (suppression of the immune system) is used to control autoimmune disorders or inflammation when excessive tissue damage occurs, and to prevent transplant rejection after an organ transplant.
Anti-inflammatory drugs are often used to control the effects of inflammation. The corticosteroids are the most powerful of these drugs, however these drugs can have many toxic side-effects and their use must be tightly controlled. Therefore, lower doses of anti-inflammatory drugs are often used in conjunction with cytotoxic or immunosuppressive drugs. Cytotoxic drugs inhibit the immune response by killing dividing cells. However, the killing is indiscriminate and other organ systems may be affected. Immunosuppressive drugs act by inhibiting the ability of T-cells to respond to signals correctly. These drugs are usually less harmful but affect all T-cells, regardless of antigen specificity, and are generally more expensive.
See also
Other mechanisms of host defense
- Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life.
- Pattern recognition receptors are proteins used by organisms to identify molecules associated with microbial pathogens.
- Toll-like receptors are a major class of pattern recognition receptor.
- The Complement system is a biochemical cascade of the immune system that helps clear pathogens from an organism.
- Systemic acquired resistance is found in plants and is analogous to the innate immune system. See also: Plant defense against herbivory
- The Restriction modification system is used by bacteria, and perhaps other prokaryotic organisms to protect themselves from foreign DNA, such as bacteriophages.
References and further reading
- ^ Microbiology and Immunology On-Line Textbook: USC School of Medicine
- ^ Alberts, Bruce (2002). Molecular Biology of the Cell; Fourth Edition. New York and London: Garland Science. ISBN 0815332181.
{{cite book}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Janeway, Charles (2001). Immunobiology; Fifth Edition. New York and London: Garland Science. ISBN 0815341016.
{{cite book}}: Unknown parameter|coauthors=ignored (|author=suggested) (help). - ^ Stvrtinová, Viera (1995). Inflammation and Fever from Pathophysiology: Principles of Disease. Computing Centre, Slovak Academy of Sciences: Academic Electronic Press.
{{cite book}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Janeway CA, Jr.; et al. (2005). Immunobiology (6th ed. ed.). Garland Science. ISBN 0-443-07310-4.
{{cite book}}:|edition=has extra text (help); Explicit use of et al. in:|author=(help) - ^ The NIAID resource booklet "Understanding the Immune System (pdf)".
- ^ Chandra, RK (1997). "Nutrition and the immune system: an introduction". American Journal of Clinical Nutrition. Vol 66: 460S – 463S.
{{cite journal}}:|volume=has extra text (help) - ^ Microbiology and Immunology On-Line Textbook Hypersensitivity Reactions: USC School of Medicine
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