Immune system

The immune system is composed of a complex constellation of cells, organs and tissues, arranged in an elaborate and dynamic communications network and equipped to optimize the response against invasion by pathogenic organisms. The immune system is, in its simplest form, a cascade of detection and adaptation, culminating in a system that is remarkably effective.

The immune system protects the body from infection by employing three basic strategies:

Creating and maintaining a barrier that prevents 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 and cause potentially serious injury to the host.
If a pathogen is able to successfully evade the innate immune cells, the immune system activates a second, adaptive immune response against the pathogen. It is through the adaptive immune response that the immune system gains the ability to recognize a pathogen, and to mount an even stronger attack each time the pathogen is encountered.

Surface Barriers and Mucosal Immunity

The skin is the first line of immunological defense. The surface of the skin is made up of the epidermis, or outer layer, and the dermis. The epidermis is comprised of tightly packed cells rich in keratin, which impedes water from entering the skin, and is slightly acidic which inhibits bacterial growth. The dermis contains the sebaceous glands from which hairs grow, and from which sebum, an acidic substance comprised of fatty acids, is secreted. Sebum inhibits the growth of some type of bacteria and fungi. Areas of the body not covered with hair (i.e. lacking sebaceous glands) such as the palms and the soles of the feet, are more susceptible to fungal growth, such as athlete’s foot.
Pathogens are mechanically expelled from the lungs through a process known as ciliary action. Coughing and sneezing causes tiny hairs, called cilia, to move in an upward motion ejecting both living things and other irritants from the respiratory tract.
The flushing action of saliva, tears, and urine also mechanically expel pathogens.
In addition saliva and tears contain antibacterial enzymes, such as lysozyme, which destroy bacterial cell walls. Vaginal secretions become slightly acidic following menarche, while semen contains spermine and zinc which repells some pathogens. Mother’s milk contains the powerful enzyme lactoperoxidase.
Mucus secreted by the respiratory and gastrointestinal tract serves to protect the host by trapping many microorganisms.
Gastric acid, produced in the stomach, is a powerful defense against ingested pathogens. Few species are able to survive the low pH and destructive enzymes that exist in the stomach.
Within the intestines, commensal flora are protective by competing with pathogenic bacteria for food and space, diminishing the probability that the pathogenic bacteria will be able to reach sufficient numbers to cause illness. Antibiotics do not discriminate between pathogenic bacteria and the normal gut flora. It is for this reason that ingestion of oral antibiotics can sometimes lead to an “overgrowth” of fungus (fungus is not affected by antibiotics), such as a yeast infection.

The Lymphatic System

The lymphatic system is a complex network of organs, lymph nodes, lymph ducts, and lymph vessels that produce and transport fluid from tissues to the circulatory system.

The primary organs are the bone marrow (in the hollow center of bones) and the thymus gland (located behind the breastbone and above the heart).
The secondary immune organs lie near all of the possible portals of entry for pathogens: adenoids, tonsils, spleen (located in the upper left of the abdomen), lymph nodes (along the lymphatic vessels and concentrated in the neck, armpits, abdomen, and groin), the Peyer's patches (lining the intestines), and the appendix.

When micro-organisms invade the body or the body encounters other antigens (such as pollen), the antigens are transported from the tissue in the lymph fluid by the lymphatic system. The lymph is carried in the lymph vessels to regional lymph nodes. The lymph nodes filter the lymph fluid and remove foreign material, such as bacteria and cancer cells. The organs of the lymphatic system also serve both as, the site of final maturation for some types of white blood cells, and the site at which a number of the innate and adaptive immune functions are initiated.

Innate Immunity

The innate immune system is comprised of the cells and mechanisms that defend the host from infection by other organisms, in a non-specific manner. This means that the cells of the innate system recognize, and respond to, pathogens in a generic way. The innate system does not confer long-lasting or protective immunity to the host. The innate system is thought to constitute an evolutionarily older defense strategy, and is the dominant immune system found in plants, fungi, insects, and in primitive multicellular organisms.

Inflammation

Inflammation is one of the first responses of the immune system to infection or irritation. Inflammation results in the recruitment of cells, called neutrophils, to the site of injury, neutrophils then trigger the immune system by releasing factors that summon other innate immune cells and lymphocytes. Inflammation also serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens.

The inflammatory response is characterized by the following quintet: redness (rubor), heat (calor), swelling (tumor), pain (dolor) and possible dysfunction of the organs or tissues involved (functio laesa). Inflammation is stimulated by chemical factors released by injured cells. These factors (histamine, bradicine) sensitize pain receptors, cause vasodilatation of the blood vessels at the scene, and attract phagocytes, especially neutrophils. ^[1]

Complement System

The complement system is a biochemical cascade of the immune system that helps clear pathogens or mark them for destruction by other cells. The cascade is composed of many small plasma proteins, sythesized in the liver, primarily by hepatocytes, which work together:

To trigger the recruitment of inflammatory cells.
To tag the pathogen for destruction by coating, or opsonizing, the surface of the pathogen.
Or to disrupt the target cell's plasma membrane resulting in cytolysis, and death, of the pathogen.

Other specific proteins include Protease C3-convertase, which is sythesized in the liver and connects to other molecules that are commonly found in bacteria but non-existent in humans, stimulating the complement system and phagocytosis.

Cells of the Innate Immune system

All white blood cells (WBC) are known officially as leukocytes. Leukocytes are unlike other cells of the body, and are not exclusively associated with any organ or tissue- in fact they actually act like independent, single-celled organisms. Leukocytes are able to move, interact, and even capture things on their own. Also unlike many other cells in the body, most innate immune leukocytes cannot divide or reproduce on their own, but rely instead on the pluripotent hemopoietic stem cells present in the bone marrow to produce new cells.

Mast cells

Mast cells reside in the connective tissue and in the mucous membranes, and are intimately associated with pathogen defense and wound healing. They are often associated with allergy and anaphylaxis. When activated, mast cells rapidly release characteristic granules, rich in histamine and heparin, along with various hormonal mediators, and chemokines, or chemotactic cytokines into the environment. Histamine dilates blood vessels, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages.

Natural killer cells

Natural killer cells, or NK cells, are a component of the innate immune system, and are distinctive in that NK cells attack host cells that have been infected by microbes, but do not attack microbes themselves. NK cells attack and destroy tumor cells, and virally infected cells, through a process known as "missing-self", a term used to describe cells with low levels of a cell-surface marker called MHC (major histocompatibility complex)—a situation which can arise due to viral infection of the host cell, or in tumors under strong selection pressure from T cells. They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self."

Phagocytes

The word 'phagocyte' literally means 'eating cell', originating from the Greek word 'phagein', meaning 'eat', and ‘cyte’ meaning ‘cell’. Thus, phagocytes are immune cells that engulf, or eat, pathogens or particles. To phagocytose a particle or pathogen, a phagocyte extends portions of its plasma membrane, wrapping the membrane around the particle until the entire particle is enveloped (i.e. the particle is now inside the cell). Once inside the cell, the invading pathogen is contained inside a vacuole which merges with another type of vacuole called a lysosome. The lysosome contains enzymes and acids that kill and digest the particle or organism. Phagocytes generally patrol the body searching for pathogens, but are also able to react to a group of highly specialized molecular signals, called cytokines, produced by other cells.

In addition to eating bacteria, phagocytes often engulf the hosts’ own cells. When cells die, either during normal processes (called apoptosis) or due to a bacterial or viral infection of the cell, phagocytic cells are responsible for their removal from the system. In much the same way, phagocytosis is also an important part of the healing process following tissue injury, by helping to remove the dead cells to make room for the new healthy cells.

The phagocytic cells of the immune system include Macrophages, Neutrophils and Dendritic cells.

Macrophages

Macrophages and Monocytes are large phagocytic leukocytes, that are able to travel out of the circulatory system by moving across the cell membrane of capillary vessels and entering the interstitial fluid in pursuit of invading pathogens. Once a monocyte has left the circulatory system, it is properly termed a macrophage, from the Greek, meaning "large eating cell". Macrophages are the most efficient of the phagocytes, and can eat substantial numbers of bacteria or other cells. The binding of bacterial molecules, to receptors on the surface of macrophages, triggers to macrophage to engulf and destroy the bacteria through the generation of a “respiratory burst”. Pathogens also stimulate the macrophage to produce chemokines, which summon other cells to the site of infection.

Polymorphonuclear cells

Neutrophils, along with two other cell types; eosinophils and basophils, are known as granulocytes or polymorphonuclear cells (PMNs), due to their lobed nuclei. 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. ^[1] Similar to macrophages, neutrophils destroy foreign substances or pathogens by activating a "respiratory burst". The main product of the neutrophil respiratory burst is hydrogen peroxide, produced through a series of reactions, which also releases free oxygen radicals and hypochlorite. Hydrogen peroxide, with its release of oxygen ion, and hypochlorite, are strong oxidizing agents which efficiently cause the destruction of foreign substances and pathogens. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day, and more than 10 times that many per day during acute inflammation.^[1]

Basophils possess very little phagocytic activity, but when activated release histamine, and are important in defense against parasites, and play a role in allergic reactions (such as asthma). Eosinophils are non-consuming cells related to the neutrophil. Upon activation, eosinophils secrete a range of highly toxic proteins and free radicals that are highly effecttive against bacteria and parasites, but are also responsible for most of the tissue damage during allergic reactions. Activation and toxin release by eosiniphils is tightly regulated to prevent any inappropriate tissue destruction. ^[1]

Dendritic cells

Dendritic cells (DC) are phagocytic cells that are present in tissues that are in contact with the external environment, mainly the skin (where they are often called Langerhans cells) and the inner lining of the 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. In humans, and some other mammals, dendritic cells are divided into two major subsets; myeloid DC and plasmacytoid DC, each thought to have distinct roles in protecting the host from inflection. Dendritic cells are also very important in the process of antigen presentation (see below), and serve as a link between the innate and adaptive immune systems.

Innate immune evasion

Cells of the innate immune system are very effective for preventing the free growth of most bacteria within the body, but are often unable to adequately control bacterial infection. In fact, many species of bacteria have evolved mechanisms that allow them to evade the innate immune system^[2]. Some of these strategies involve:

Inhibiting phagocytosis, by affecting the receptors that the phagocytes use to engulf bacteria, or by mimicking host cells, so that the immune system does not perceive them to be foreign (Bacteroides)
Inhibiting the ability of the phagocyte to respond to chemokines signals (Staphylococcus aureus)
Inhibiting the mechanisms that phagocytes use to destroy the bacteria (Mycobacterium tuberculosis), and multiplying within the phagocyte.
Directly killing the phagocyte (M. tuberculosis, Streptococcus pyogenes and Bacillus anthracis).

Also, the innate immune system, with the exception of NK cells, is completely ineffective against viral infections. Further, initiation of the innate system does not provide any long-lived immunity to control recurrent infections. To recognize and fight a wide range of pathogens the body has evolved an adaptive immune system.

Specific or Adaptive Immune System

Adaptive immunity is triggered when a pathogen evades the innate immune system and generates a threshold level of antigen. The basis of adaptive immunity lies in the capacity of immune cells to distinguish between the body's own cells, and the unwanted invaders. The host’s cells express “self” antigens that identify them as such. These antigens are different from those on the surface of bacteria ("non-self" antigens) or on the surface of virally infected host cells (“missing self”). The adaptive immune system works by clonal selection. According to this theory, beginning at birth an animal randomly generates a vast diversity of lymphocytes. Throughout the lifetime of the animal those lymphocytes that can react against the foreign antigens that the animal actually encounters, are specifically selected for action, usually destruction, directed against anything that expresses that antigen (see Immunolgical Diversity, below).

Cells of the Adaptive Immune System

The cells of the adaptive immune system are a type of leukocyte, called a lymphocyte. B cells and T cells are the two major types of lymphocytes. In the human body there are about 2 trillion lymphocytes, constituting 20–40% of the body’s WBCs, their total mass is about the same as that of the brain or liver. The peripheral blood contains 20–50% of circulating lymphocytes; the rest move within the lymphatic system.

B cells and T cells are derived from same pluripotent hemopoietic stem cells, and are indistinguishable from one another until after they are activated. B cells play a large role in the humoral immune response, and T-cells are involved in the cell-mediated immune response. B-cells may be named for the bursa of Fabricius, an organ unique to birds, where the cells were first found to develop. However, in nearly all other vertebrates, B cells (and T-cells) are produced by stem cells in the bone marrow. T-cells travel to and develop in, the thymus, from which they derive their name. In an adult animal, the peripheral lymphoid organs contain a mixture of B- and T cells in at least three stages of maturation: naive cells, effector cells and memory cells.

When mature naive cells encounter antigen for the first time, they differentiate into “armed”-effector cells, capable of controlling the spread of infection. Upon resolution of the infection, most of the effector cells will die and be cleared away by phagocytes, but a few of these cells will be retained as memory cells. These memory cells are able to quickly differentiate into effector cells upon a later encounter with the same antigen, dramatically shortening the time required to mount an effective immune response. Memory cells, like naïve cells, give rise to either effector cells or more memory cells.

Antigen Presentation

Although phagocytes play a major role in the innate immune system, they are also important for the development of adaptive immunity. Dendritic cells and B-cells, and to a lesser extent macrophages, act as professional antigen presenting cells (APC), which present antigen to T cells, leading to the activation of adaptive immunity.

Exogenous Antigens

Dendritic cells engulf exogenous (outside the cell) pathogens in the tissues and then migrate, via chemokine signals, to the lymph nodes. During migration, DCs undergo a process of maturation in which they lose most of their ability to engulf other pathogens and develop an increased ability to communicate with T-cells in the lymph nodes. The DC also uses enzymes to chop the pathogen into smaller pieces. In the lymph node the DC will display these small pieces of the pathogen on its surface by coupling them to a receptor called the Major histocompatibility complex, or MHC (also known in humans as Human leukocyte antigen (HLA)). This MHC:antigen complex is then recognized by T-cells passing through the lymph node. Exogenous antigens are usually displayed on MHC Class II molecules, which interact with CD4+ helper T-cells.

Endogenous Antigens

Endogenous antigens (from inside the cell) are produced by viruses replicating within a host cell. Like the DC, the host cells use enzymes to digest virally associated proteins. The infected cell displays these small pieces of the virus, coupled to MHC, on its surface, to T-cells. Endogenous antigens are typically displayed on MHC Class I molecules, which interact with CD8+ cytotoxic T-cells. With the exception of some cell types, such as non-nucleated cells (including erythrocytes), Class I MHC is expressed by all host cells.

CD8+ T Lymphocytes and Cytotoxicity

File:Cytotoxic T cell.jpg

Killer T cells—also called cytotoxic T lymphocytes or CTLs-directly attack other cells carrying certain foreign or abnormal molecules on their surfaces.

Cytotoxic T cells (also known as TC, killer T cell, or cytotoxic T-lymphocyte (CTL)) are a sub-group of T cells which are capable of inducing the death of infected cells; they kill cells that are infected with viruses (or other pathogens), or are otherwise damaged or dysfunctional, and are thus defined as cyto- or “cell”-toxic.

Cytotoxic T cells express T-cell receptors (TCR) that recognize, and have high affinity for, a specific peptide antigen bound to Class I MHC molecules. This affinity is what keeps the CTL and the infected cell bound closely together, and allows for antigen-specific activation or the CTL.

Cytotoxic T cell activation

Cytotoxic T cells are activated when their TCR strongly interacts with a peptide-bound MHC class I molecule. Once activated CTL undergoes a process called clonal expansion in which the cell divides rapidly. The activated CTLs will then travel throughout the body in search of other cells bearing the same MHC Class I + peptide complex that initially activated it.

When exposed to infected/dysfunctional somatic cells, CTL release perforin and granulysin, cytotoxins which form pores in the target cell's plasma membrane; causing ions and water to flow into the infected cell, causing it to burst or lyse. CTL also release granzyme, a serine protease that enters target cells via the perforin-formed pore and induces apoptosis (cell death).

CD4+ “helper” T-cells

File:T cell activation.jpg

The T lymphocyte activation pathway. T cells contribute to immune defenses in two major ways: some direct and regulate immune responses; others directly attack infected or cancerous cells.

CD4+ Lymphocytes, or 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 or phagocytic activity; and cannot kill infected cells or clear pathogens, but, in essence, direct these responses by other cells.

Helper T cells express T-cell receptors (TCR) that recognize a specific peptide antigen bound to Class II MHC molecules. The activation of the helper T-cell causes it to release cytokines, which in turn, influence the activity of many other cell types, including the APC that activated it. Helper T-cells require a much milder stimulus than do cytotoxic T-cells, thus, helper T-cells are sometimes required to provide extra signals that activate the cytotoxic cells. HIV is able to subvert the immune system by directly attacking the CD4+ T cells, precisely the cells that could drive the destruction of the virus, but also the cells that drive immunity against all of the other pathogens encountered during ones lifetime.

Th1 and Th2: Helper T cell responses

There are essentially two types of CD4+ T helper cells. The Th1 response is characterized by the production of cytokines, namely Interferon-gamma, which activates the bactericidal activities of macrophages, and induces B-cells to make opsonizing (coating) antibodies, leading to "cell-mediated immunity". The Th2 response is characterized by the release of Interleukin-4, which results in the activation of B-cells to make neutralizing (killing) antibodies, leading to "humoral immunity".

The factors that dictate whether an infection will trigger a Th1 or Th2 type response are not fully understood, but clearly the type of response generated plays an important role in the clearance of different kinds of pathogens. The Th1 response is very efficient in elimination of intracellular pathogens (viruses and bacteria that are inside the host cells), while the Th2 response is more effective against pathogens present outside cells, such as extracellular bacteria, parasites and toxins.

For example, Leishmania is a protozoan parasite responsible for the disease leishmaniasis. During infection the protozoa are engulfed by macrophages that must be activated by the T helper cells in order to destroy the protozoa and eliminate the infection. If Th2 type response is activated against the leishmania, these helper T-cells are not able to activate macrophages that destroy the parasite and control the infection, and leishmaniasis develops. On the other hand, if a Th1 type of response is generated the CD4 T-cell is able to activate the macrophage, effectively controlling the spread of the infection.

A third type of T lymphocyte, the regulatory T cells (Treg), limits and suppresses the immune system, and may control aberrant immune responses to self-antigens; an important mechanism in controlling the development of autoimmune diseases.

B Lymphocytes and Antibody Production

File:B cell activation.jpg

The B lymphocyte activation pathway. B cells produce antibodies that identify and neutralize foreign objects like bacteria and viruses.

Humoral immunity (the creation of antibodies that circulate in blood plasma and lymph) involves B cell activation. B Cells secrete antibodies (or immunoglobulin, Ig), large Y-shaped proteins used by the immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. In mammals there are five types of antibody: IgA, IgD, IgE, IgG, and IgM, each of which differ in biological properties and have evolved to handle different types of antigens.

Like T-cells, each B cell has a unique receptor protein, an antibody molecule that is bound to the surface of the B cell and referred to as the B cell receptor (BCR). The BCR will recognize and bind to only one particular antigen. A critical difference between B cells and T cells is how each cell "sees" an antigen. B cells recognize their cognate antigen in its native form. In contrast, T cells recognize their cognate antigen in a processed form - as a peptide in the context of an MHC molecule. Once a B cell encounters its cognate (or specific) antigen and receives additional signal from a helper T cell (predominatyly Th2 type), it can further differentiate into an effector cell, known as a plasma cell.

Plasma cells are short lived cells (2-3 days) which secrete antibodies that assist in the destruction of antigens by binding to them and making them easier targets for phagocytes or by triggering the complement cascade.

About 10% of these plasma cells will survive to become long-lived memory B-cells, which are specific to the antigen encountered during the primary immune response; these cells respond quickly upon a second exposure to the antigen, and by producing specific antibodies, can rapidly eliminate the infectious agent.

Immunological Diversity

Most large molecules, including virtually all proteins and many polysaccharides, can serve as antigens. The parts of an antigen that combine with the antigen-binding site; either on an antibody molecule or a lymphocyte receptor, are called epitopes. Most antigens have a variety of epitopes that can stimulate the production of antibodies, specific T cell responses, or both. Only a very small proportion (less than 0.01%) of the total lymphocytes in the body bind to each antigen, suggesting that only a very small number of cells are responsive to each specific antigen.

For the adaptive response to efficiently eliminate and "remember" pathogens the immune system must be able to distinguish between many different antigens. Therefore, the receptors used to recognize antigens must be produced in a huge variety of configurations, essentially one receptor for each different pathogen that might ever be encountered. Even in the absence of antigen stimulation, a human is capable of producing more than 1 trillion different antibody molecules, while the entire human genome contains fewer than 50,000 genes. So how are so many different antibodies produced? The immense diversity of each type of possible receptor could not be encoded in the genome of a cell, as millions of genes would be required to produce the sum total of receptors.

The clonal selection theory describes how this myriad of receptors might feasibly be produced. According to the theory, a small family of genes encodes all antigen receptors. Unique and specific antigen receptors emerge through a process called combinatorial diversification; in which one gene segment from each gene family recombine, to form a single unique gene. This assembly process effectively generates the enormous diversity of receptors and antibodies, even before the body encounters antigen, enabling the immune system to respond to an almost unlimited diversity of antigens.

Disorders of the human immune system

It is important to note that the innate and adaptive portions of the immune system work together and not in spite of each other. The adaptive arm, B and T cells, would be unable to function without the input of the innate system. T cells are useless without antigen-presenting cells to activate them; and B cells are crippled without T-cell help. On the other hand the innate system would likely be overrun with pathogens without the specialized action of the adaptive immune response. That being said, failures of host defense do occur. These disorders fall into two broad categories that are characterized by:

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.^[3] Diets lacking sufficient protein sources are associated with a significant impairment of cell-mediated immunity, phagocyte function, the complement system, secretory immunoglobulin A 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 also results in altered immune responses. ^[3]

Obesity, Alcohol and Drug abuse also contribute to poor immune function.
Finally, 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 age 50. ^[3]

In developed countries, inherited (or 'congenital') or '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 and Hypersensitivity

Overactive immune responses comprise the other end of the immune dysfunction spectrum, 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. 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 the young lymphocytes with self antigens that might be produced throughout the body and eliminate T-cells that react strongly with self-antigens.

Other examples of overzealous immune responses in disease include hypersensitivities, such as allergies and asthma.

Manipulation of the immune response

The immune response can be manipulated to suppress unwanted responses in autoimmunity, allergy and transplant rejection, and to stimulate protective responses against pathogens that largely elude the immune system.

Immunosupression

Immunosuppression (suppression of the immune system) is often used to control autoimmune disorders or inflammation when excessive tissue damage occurs, and to prevent transplant rejection after an organ transplant.

The drugs most commonly used to negatively regulate the immune system are anti-inflammatory drugs, which control the effects of inflammation. The corticosteroids are the most powerful of these drugs, however the use of these drugs must be tightly controlled as they can have many toxic side-effects. Therefore, 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 cell killing induced by these drugs is indiscriminate and other organ systems may be affected. Immunossupressive 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 than the cytotoxic drugs.

Immunization

Infectious disease is the leading cause of death in the human population. The two most important factors to combat these diseases have been developed over the last century; sanitation and immunization. Immunization, the deliberate induction of an immune response, is the single most effective manipulation of the immune system mankind has developed, because it utilizes both the immune system’s natural specificity and its inducibility.

Immunization involves the injection of antigen into an animal or human. Any substance that elicits an immune response is said to be immunogenic and is called an immunogen, but a clear difference exists between an antigen and an immunogen. An antigen is defined as any substance that binds to a specific antibody, and all antigens are not immunogenic. Thus 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 that does not cause the pathogenic effects of the disease.

Immunity and Pregnancy

Given that the cornerstone of the immune system is the recognition of “self” versus “non-self” the mechanisms which protect the human fetus, which is clearly, “non-self” from attack by the immune system, are particularly interesting. Although no comprehensive explanation has emerged that explains this mysterious lack of rejection, it is thought that the fetus is tolerated for two main reasons. The first is that the fetus occupies a portion of the body that is protected by a non-immunological barrier, the uterus, which the immune system does not routinely patrol. The second is that the fetus likely promotes local immunosuppression in the mother, perhaps by a process of active nutrient depletion (see malnutrition above).

Because they have had no prior exposure to microbes, newborn infants are particularly vulnerable to infection. However, the mother provides her baby several layers of protection against infection. 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. Further, breast milk contains antibodies that are transferred to the gut of the infant and protect it against bacterial infections until the newborn can synthesize its own protective antibodies.

References and further reading

The majority of information used to compile this article came from the following excellent sources:

Immunobiology; Sixth Edition. New York and London: Garland Science. 2001. ISBN 0815341016. {{cite book}}: |first= missing |last= (help); Text "whatever" ignored (help)

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)

The NIAID resource booklet "Understanding the Immune System (pdf)" was the source of the diagrams used in this article. This resource also includes information regarding the techniques used to study immunological systems.

Where noted the following references were consulted.

^ ^a ^b ^c ^d 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)
^ Kennedy, Alan. "Immune Evasion by bacteria".
^ ^a ^b ^c 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)

Template:Link FA Template:Link FA

[IandF-1] 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)

[Evasion-2] Kennedy, Alan. "Immune Evasion by bacteria".

[nutrition-3] 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)

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