20.2: Introduction to the Immune System - Biology

Worm Attack!

Does this organism look like a space alien? A scary creature from a nightmare? In fact, it’s a 1-cm long worm in the genus Schistosoma. It may invade and take up residence in the human body, causing a very serious illness known as schistosomiasis. The worm gains access to the human body while it is in a microscopic life stage. It enters through a hair follicle when the skin comes into contact with contaminated water. The worm then grows and matures inside the human organism, causing disease.

Host vs. Pathogen

The Schistosoma worm has a parasitic relationship with humans. In this type of relationship, one organism, called the parasite, lives on or in another organism, called the host. The parasite always benefits from the relationship and the host is always harmed. The human host of the Schistosoma worm is clearly harmed by the parasite when it invades the host’s tissues. The urinary tract or intestines may be infected, and signs and symptoms may include abdominal pain, diarrhea, bloody stool, or blood in the urine. Those who have been infected a long time may experience liver damage, kidney failure, infertility, or bladder cancer. In children, Schistosoma infection may cause poor growth and difficulty learning. Table (PageIndex{1}) lists some of the microscopic pathogens, their images, description, and the diseases that they cause.

Like the Schistosoma worm, many other organisms can make us sick if they manage to enter our body. Any such agent that can cause disease is called a pathogen. Most pathogens are microorganisms, although some, such as the Schistosoma worm, are much larger. In addition to worms, common types of pathogens of human hosts include bacteria, viruses, fungi, and single-celled organisms called protists. You can see examples of each of these types of pathogens in Table (PageIndex{1}). Fortunately for us, our immune system is able to keep most potential pathogens out of the body or to quickly destroy them if they do manage to get in. When you read this chapter, you’ll learn how your immune system usually keeps you safe from harm — including from scary creatures like the Schistosoma worm!

Table (PageIndex{1}): Types of Pathogens
Type of PathogenExample and their ImageDescriptionHuman Disease caused by pathogens of that type


such as Escherichia coli

Single-celled organisms without a nucleusStrep throat, staph infections, tuberculosis, food poisoning, tetanus, pneumonia, syphilis


such as Herpes simplex

Particles that reproduce by taking over living cells.Common cold, flu, genital herpes, cold sores, measles, AIDS, genital warts, chickenpox, smallpox


such as Trichophyton rubrum

Organisms with a nucleus that grow as single cells or tread-like filamentsRingworm, athlete's foot, tineas, candidiasis, histoplasmosis


Such as Giarida lamblia

A single-celled organism with a nucleusMalaria, Traveler's diarrhea, giardiasis, trypanosomiasis (sleeping sickness)

What is the Immune System?

The immune system is a host defense system. It comprises many biological structures —ranging from individual white blood cells to entire organs — as well as many complex biological processes. The function of the immune system is to protect the host from pathogens and other causes of disease such as tumor cells. To function properly, the immune system must be able to detect a wide variety of pathogens. It also must be able to distinguish the cells of pathogens from the host’s own cells and also to distinguish cancerous or damaged host cells from healthy cells. In humans and most other vertebrates, the immune system consists of layered defenses that have increased specificity for particular pathogens or tumor cells. The layered defenses of the human immune system are usually classified into two subsystems called the innate immune system and the adaptive immune system.

Innate Immune System

Any discussion of the innate immune response usually begins with the physical barriers that prevent pathogens from entering the body, destroy them after they enter, or flush them out before they can establish themselves in the hospitable environment of the body’s soft tissues. Barrier defenses are part of the body’s most basic defense mechanisms. The barrier defenses are not a response to infections, but they are continuously working to protect against a broad range of pathogens.

The phagocytes are the body’s fast acting first line of immunological defense against organisms that have breached barrier defenses and have entered the vulnerable tissues of the body. For example, certain leukocytes (white blood cells) engulf and destroy pathogens they encounter in the process called phagocytosis. The body's response again a pathogen's breach is also called Inflammation. Phagocytosis and Inflammation will be discussed in detail in concept Innate Immune System.

Adaptive Immune System

The adaptive immune system is activated if pathogens successfully enter the body and manage to evade the general defenses of the innate immune system. An adaptive response is specific to the particular type of pathogen that has invaded the body or to cancerous cells. It takes longer to launch a specific attack, but once it is underway, its specificity makes it very effective. An adaptive response also usually leads to immunity. This is a state of resistance to a specific pathogen due to the ability of the adaptive immune system to “remember” the pathogen and immediately mount a strong attack tailored to that particular pathogen if it invades again in the future.

Self vs. Non-Self

Both innate and adaptive immune responses depend on the ability of the immune system to distinguish between self and non-self molecules. Self molecules are those components of an organism’s body that can be distinguished from foreign substances by the immune system. Virtually all body cells have surface proteins that are part of a complex called the major histocompatibility complex (MHC). These proteins are one way the immune system recognizes body cells as self. Non-self proteins, in contrast, are recognized as foreign because they are different from self-proteins.

Antigens and Antibodies

Many non-self molecules comprise a class of compounds called antigens. Antigens, which are usually proteins, bind to specific receptors on immune system cells and elicit an adaptive immune response. Some adaptive immune system cells (B cells) respond to foreign antigens by producing antibodies. An antibody is a molecule that precisely matches and binds to a specific antigen. This may target the antigen (and the pathogen displaying it) for destruction by other immune cells.

Antigens on the surface of pathogens are how the adaptive immune system recognizes specific pathogens. Antigen specificity allows for the generation of responses tailored to the specific pathogen. It is also how the adaptive immune system ”remembers” the same pathogen in the future.

Immune Surveillance

Another important role of the immune system is to identify and eliminate tumor cells. This is called immune surveillance. The transformed cells of tumors express antigens that are not found on normal body cells. The main response of the immune system to tumor cells is to destroy them. This is carried out primarily by aptly named killer T cells of the adaptive immune system.

Lymphatic System

The lymphatic system is a human organ system that is a vital part of the adaptive immune system. It is also part of the cardiovascular system and plays a major role in the digestive system (see the concept Lymphatic System).

Feature: Human Biology in the News

“They’ll have to rewrite the textbooks!”

That sort of response to scientific discovery is sure to attract media attention, and it did. It’s what Kevin Lee, a neuroscientist at the University of Virginia, said in 2016 when his colleagues told him they had discovered human anatomical structures that had never before been detected. The structures were tiny lymphatic vessels in the meningeal layers surrounding the brain.

How these lymphatic vessels could have gone unnoticed when all human body systems have been studied so completely is amazing in its own right. The suggested implications of the discovery are equally amazing:

  • The presence of these lymphatic vessels means that the brain is directly connected to the peripheral immune system, presumably allowing a close association between the human brain and human pathogens. This suggests an entirely new avenue by which humans and their pathogens may have influenced each other’s evolution. The researchers speculate that our pathogens may have even influenced the evolution of our social behaviors.
  • The researchers think there will also be many medical applications of their discovery. For example, the newly discovered lymphatic vessels may play a major role in neurological diseases that have an immune component, such as multiple sclerosis. The discovery might also affect how conditions such as autism spectrum disorders and schizophrenia are treated.


  1. What is a pathogen?
  2. State the purpose of the immune system.
  3. Compare and contrast the innate and adaptive immune systems.
  4. Explain how the immune system distinguishes self molecules from non-self molecules.
  5. What are antigens?
  6. Define tumor surveillance.
  7. Briefly describe the lymphatic system and its role in immune function.
  8. Identify the neuroimmune system.
  9. Which of the following is NOT a function of the immune system?
    1. Protecting the body against fungi
    2. Protecting the body against bacteria
    3. Protecting the body against cancerous cells
    4. None of the above
  10. What does it mean that the immune system is not just composed of organs?
  11. What are the general relationships between the terms lymphocytes, leukocytes, and white blood cells?
  12. True or False. Phagocytosis occurs in the innate immune system.
  13. True or False. Major histocompatibility complex proteins are antibodies.
  14. True or False. Only the adaptive immune response requires the ability to distinguish between self and non-self.
  15. Why is the immune system considered to be “layered?”

Explore More

Scientists predict we may be facing an antibiotic apocalypse, learn more here:

122 Chapter 12: Introduction to the Immune System and Disease

Figure 12.1 (a) This smallpox (variola) vaccine is derived from calves exposed to cowpox virus. Vaccines provoke a reaction in the immune system that prepares it for a subsequent infection by smallpox. (b) Viewed under a transmission electron microscope, you can see the variola’s dumbbell-shaped structure that contains the viral DNA. (credit a: modification of work by James Gathany, CDC credit b: modification of work by Dr. Fred Murphy Sylvia Whitfield, CDC scale-bar data from Matt Russell)

Organisms have a wide array of adaptations for preventing attacks of parasites and diseases. The vertebrate defense systems, including those of humans, are complex and multilayered, with defenses unique to vertebrates. These unique vertebrate defenses interact with other defense systems inherited from ancestral lineages, and include complex and specific pathogen recognition and memory mechanisms. Research continues to unravel the complexities and vulnerabilities of the immune system.

Despite a poor understanding of the workings of the body in the early 18th century in Europe, the practice of inoculation as a method to prevent the often-deadly effects of smallpox was introduced from the courts of the Ottoman Empire. The method involved causing limited infection with the smallpox virus by introducing the pus of an affected individual to a scratch in an uninfected person. The resulting infection was milder than if it had been caught naturally and mortality rates were shown to be about two percent rather than 30 percent from natural infections. Moreover, the inoculation gave the individual immunity to the disease. It was from these early experiences with inoculation that the methods of vaccination were developed, in which a weakened or relatively harmless (killed) derivative of a pathogen is introduced into the individual. The vaccination induces immunity to the disease with few of the risks of being infected. A modern understanding of the causes of the infectious disease and the mechanisms of the immune system began in the late 19th century and continues to grow today.

20.2: Introduction to the Immune System - Biology

Introduction to the Immune System

Do you remember the last time you were sick? Chances are you remember having had a head cold or the flu, or maybe even a stomach virus. You might have thought that you were never going to recover, but in a few days, you were feeling yourself again, thanks to your immune system!

Pathogens - What makes you sick?

Bacteria and viruses are usually to blame for bringing on nasty colds, fevers and fatigue, and many serious infections. There are other life forms that can infect you as well, such as parasites and fungi, and also non-living things like chemical toxins. Any microorganism that causes infection is called a pathogen. Some common pathogens are the Influenza virus that causes the Flu, or the bacterium Streptococcus pneumoniae which causes Pneumonia.

Transmission - How do you get sick?

Pathogens can infect you in many ways which . Sometimes kissing, sneezing, coughing, or touching contaminated areas can spread infection. This is how the common cold is mainly spread. Many bacterial diseases can come from leaving open wounds untreated and eating contaminated food also blood poisoning or food poisoning can develop. Yet more chronic diseases can spread through transferring blood or sexual contact, like the HIV virus. There are many ways pathogens spread from person to person, and each pathogen is different, but sometimes all we have to do to get sick is breathe in air-born particles!

With so many points of entry and so many dangerous microbes out there, it seems that we should be sick all the time. Luckily, our immune system is working &lsquoround the clock to fend off infections from outside particles and clean the body of dead or old cells.

What is the immune system?

The immune system is not located in a specific organ. It&rsquos easiest to think of our bodies&rsquo immune system as a complex constellation of different types of cells like B and T cells and tissues like the lymphatic system and the thymus that work together to protect nearly every area of our body. Each type of cell is prepared to perform certain functions, such as killing damaged or infected cells, carrying messages, making antibodies, or carrying away debris.

You might ask, how does each cell know what job to do? Are they just born that way? And how do they differentiate between &ldquogood&rdquo and &ldquobad&rdquo cells, knowing not to attack your own healthy cells?

Distinguishing self from non-self

In fact, this is the most important function of the immune system: to distinguish what cells and substances belong to your body and are healthy, and which aren&rsquot! What belongs to the body is referred to as &ldquoself,&rdquo and something that doesn&rsquot belong as &ldquonon-self.&rdquo Think of the wide variety of different tissues and cells that can be found in your body: hair cells, teeth cells, bone cells, blood cells, calcium in your bone, there are even some friendly bacteria that live in our intestine to help us eat! Your immune system has to be very smart to be able to discern such a variety of things!

Understanding how the immune system works could reveal the key to curing many infections and diseases. But if you are just beginning to explore the many functions of the immune system, the most important idea to keep in mind is that our immune system has &ldquolearned to learn&rdquo in other words, through millions of years of evolution, our immune system has acquired the ability to learn and remember information about the billions of different cells and substances it comes into contact with every day. Without the ability to learn and remember, you&rsquod keep getting sick from the same thing over and over!

This project is funded by Science Education Partnership Award (SEPA) award from the National Center for Research Resources, a component of the National Institutes of Health


The immune system has two components: innate and adaptive immunity. The innate immunity is present in all metazoans, [2] while the adaptive immunity only occurs in vertebrates.

The innate system relies on the recognition of certain foreign molecules to stimulate two types of innate immune responses: inflammatory responses and phagocytosis. [3] The adaptive system, on the other hand, is composed of more advanced lymphatic cells that are programmed to distinguish between specific "non-self" substances in the presence of "self". The reaction to foreign substances is etymologically described as inflammation, meaning to set on fire. The non-reaction to self substances is described as immunity - meaning to exempt. These two components of the immune system create a dynamic biological environment where "health" can be seen as a physical state where the self is immunologically spared, and what is foreign is inflammatorily and immunologically eliminated. "Disease" can arise when what is foreign cannot be eliminated or what is self is not spared. [4]

Innate immunity, also known as native immunity, is a semi-specific and widely distributed form of immunity. It is defined as the first line of defense against pathogens, representing a critical systemic response to prevent infection and maintain homeostasis, contributing to the activation of an adaptive immune response. [5] It does not adapt to specific external stimulus or a prior infection, but relies on genetically encoded recognition of particular patterns. [6]

Adaptive or acquired immunity is the active component of the host immune response, mediated by antigen-specific lymphocytes. Unlike the innate immunity, the acquired immunity is highly specific to a particular pathogen, including the development of immunological memory. [7] Like the innate system, the acquired system includes both humoral immunity components and cell-mediated immunity components.

Adaptive immunity can be acquired either 'naturally' (by infection) or 'artificially' (through deliberate actions such as vaccination). Adaptive immunity can also be classified as 'active' or 'passive'. Active immunity is acquired through the exposure to a pathogen, which triggers the production of antibodies by the immune system. [8] Passive immunity is acquired through the transfer of antibodies or activated T-cells derived from an immune host either artificially or through the placenta it is short-lived, requiring booster doses for continued immunity.

The diagram below summarizes these divisions of immunity. Adaptive immunity recognizes more diverse patterns. Unlike innate immunity it is associated with memory of the pathogen. [6]

The concept of immunity has intrigued mankind for thousands of years. The prehistoric view of disease was that supernatural forces caused it, and that illness was a form of theurgic punishment for "bad deeds" or "evil thoughts" visited upon the soul by the gods or by one's enemies. [9] Between the time of Hippocrates and the 19th century, when the foundations of the scientific methods were laid, diseases were attributed to an alteration or imbalance in one of the four humors (blood, phlegm, yellow bile or black bile). [10] Also popular during this time before learning that communicable diseases came from germs/microbes was the miasma theory, which held that diseases such as cholera or the Black Plague were caused by a miasma, a noxious form of "bad air". [9] If someone were exposed to the miasma in a swamp, in evening air, or breathing air in a sickroom or hospital ward, they could get a disease.

The modern word "immunity" derives from the Latin immunis, meaning exemption from military service, tax payments or other public services. [11] The first written descriptions of the concept of immunity may have been made by the Athenian Thucydides who, in 430 BC, described that when the plague hit Athens: "the sick and the dying were tended by the pitying care of those who had recovered, because they knew the course of the disease and were themselves free from apprehensions. For no one was ever attacked a second time, or not with a fatal result". [11] The term "immunes", is also found in the epic poem "Pharsalia" written around 60 B.C. by the poet Marcus Annaeus Lucanus to describe a North African tribe's resistance to snake venom. [10]

The first clinical description of immunity which arose from a specific disease-causing organism is probably A Treatise on Smallpox and Measles ("Kitab fi al-jadari wa-al-hasbah'', translated 1848 [12] [13] ) written by the Islamic physician Al-Razi in the 9th century. In the treatise, Al Razi describes the clinical presentation of smallpox and measles and goes on to indicate that exposure to these specific agents confers lasting immunity (although he does not use this term). [10] The first scientist who developed a full theory of immunity was Ilya Mechnikov after he revealed phagocytosis in 1882. With Louis Pasteur's germ theory of disease, the fledgling science of immunology began to explain how bacteria caused disease, and how, following infection, the human body gained the ability to resist further infections. [11]

The birth of active immunotherapy may have begun with Mithridates VI of Pontus (120-63 B.C.). [14] To induce active immunity for snake venom, he recommended using a method similar to modern toxoid serum therapy, by drinking the blood of animals which fed on venomous snakes. [14] He is thought to have assumed that those animals acquired some detoxifying property, so that their blood would contain transformed components of the snake venom that could induce resistance to it instead of exerting a toxic effect. Mithridates reasoned that, by drinking the blood of these animals, he could acquire a similar resistance. [14] Fearing assassination by poison, he took daily sub-lethal doses of venom to build tolerance. He is also said to have sought to create a 'universal antidote' to protect him from all poisons. [10] [15] For nearly 2000 years, poisons were thought to be the proximate cause of disease, and a complicated mixture of ingredients, called Mithridate, was used to cure poisoning during the Renaissance. [16] [10] An updated version of this cure, Theriacum Andromachi, was used well into the 19th century.

In 1888 Emile Roux and Alexandre Yersin isolated diphtheria toxin, and following the 1890 discovery by Behring and Kitasato of antitoxin based immunity to diphtheria and tetanus, the antitoxin became the first major success of modern therapeutic Immunology. [10]

In Europe, the induction of active immunity emerged in an attempt to contain smallpox. Immunization, however, had existed in various forms for at least a thousand years. [11] The earliest use of immunization is unknown, however, around 1000 A.D. the Chinese began practicing a form of immunization by drying and inhaling powders derived from the crusts of smallpox lesions. [11] Around the fifteenth century in India, the Ottoman Empire, and east Africa, the practice of inoculation (poking the skin with powdered material derived from smallpox crusts) became quite common. [11] This practice was first introduced into the west in 1721 by Lady Mary Wortley Montagu. [11] In 1798, Edward Jenner introduced the far safer method of deliberate infection with cowpox virus, (smallpox vaccine), which caused a mild infection that also induced immunity to smallpox. By 1800 the procedure was referred to as vaccination. To avoid confusion, smallpox inoculation was increasingly referred to as variolation, and it became common practice to use this term without regard for chronology. The success and general acceptance of Jenner's procedure would later drive the general nature of vaccination developed by Pasteur and others towards the end of the 19th century. [10] In 1891, Pasteur widened the definition of vaccine in honour of Jenner and it then became essential to qualify the term, by referring to polio vaccine, measles vaccine etc.

Passive immunity is the transfer of immunity, in the form of ready-made antibodies, from one individual to another. Passive immunity can occur naturally, when maternal antibodies are transferred to the foetus through the placenta, and can also be induced artificially, when high levels of human (or horse) antibodies specific for a pathogen or toxin are transferred to non-immune individuals. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. [17] Passive immunity provides immediate protection, but the body does not develop memory, therefore the patient is at risk of being infected by the same pathogen later. [18]

Naturally acquired Edit

Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus by its mother during pregnancy. Maternal antibodies (MatAb) are passed through the placenta to the fetus by an FcRn receptor on placental cells. This occurs around the third month of gestation. IgG is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its antibodies. Colostrum present in mothers milk is an example of passive immunity. [18]

Artificially acquired Edit

Artificially acquired passive immunity is a short-term immunization induced by the transfer of antibodies, which can be administered in several forms as human or animal blood plasma, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, and in the form of monoclonal antibodies (MAb). Passive transfer is used prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia. [19] It is also used in the treatment of several types of acute infection, and to treat poisoning. [17] Immunity derived from passive immunization lasts for only a short period of time, and there is also a potential risk for hypersensitivity reactions, and serum sickness, especially from gamma globulin of non-human origin. [18]

The artificial induction of passive immunity has been used for over a century to treat infectious disease, and before the advent of antibiotics, was often the only specific treatment for certain infections. Immunoglobulin therapy continued to be a first line therapy in the treatment of severe respiratory diseases until the 1930s, even after sulfonamide lot antibiotics were introduced. [19]

Transfer of activated T-cells Edit

Passive or "adoptive transfer" of cell-mediated immunity, is conferred by the transfer of "sensitized" or activated T-cells from one individual into another. It is rarely used in humans because it requires histocompatible (matched) donors, which are often difficult to find. In unmatched donors this type of transfer carries severe risks of graft versus host disease. [17] It has, however, been used to treat certain diseases including some types of cancer and immunodeficiency. This type of transfer differs from a bone marrow transplant, in which (undifferentiated) hematopoietic stem cells are transferred.

When B cells and T cells are activated by a pathogen, memory B-cells and T- cells develop, and the primary immune response results. Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and can mount a strong secondary response if the pathogen is detected again. The primary and secondary responses were first described in 1921 by English immunologist Alexander Glenny [20] although the mechanism involved was not discovered until later. This type of immunity is both active and adaptive because the body's immune system prepares itself for future challenges. Active immunity often involves both the cell-mediated and humoral aspects of immunity as well as input from the innate immune system.

Naturally acquired Edit

Naturally acquired active immunity occurs when a person is exposed to a live pathogen and develops a primary immune response, which leads to immunological memory. [17] This type of immunity is "natural" because deliberate exposure does not induce it. Many disorders of immune system function can affect the formation of active immunity such as immunodeficiency (both acquired and congenital forms) and immunosuppression.

Artificially acquired Edit

Artificially acquired active immunity can be induced by a vaccine, a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease. [17] Richard Dunning coined the term vaccination, a colleague of Edward Jenner, and adapted by Louis Pasteur for his pioneering work in vaccination. The method Pasteur used entailed treating the infectious agents for those diseases, so they lost the ability to cause serious disease. Pasteur adopted the name vaccine as a generic term in honor of Jenner's discovery, which Pasteur's work built upon.

In 1807, Bavaria became the first group to require that their military recruits be vaccinated against smallpox, as the spread of smallpox was linked to combat. [21] Subsequently, the practice of vaccination would increase with the spread of war.

There are four types of traditional vaccines: [22]

  • Inactivated vaccines are composed of micro-organisms that have been killed with chemicals and/or heat and are no longer infectious. Examples are vaccines against flu, cholera, plague, and hepatitis A. Most vaccines of this type are likely to require booster shots.
  • Live, attenuated vaccines are composed of micro-organisms that have been cultivated under conditions which disable their ability to induce disease. These responses are more durable, however, they may require booster shots. Examples include yellow fever, measles, rubella, and mumps. are inactivated toxic compounds from micro-organisms in cases where these (rather than the micro-organism itself) cause illness, used prior to an encounter with the toxin of the micro-organism. Examples of toxoid-based vaccines include tetanus and diphtheria. , recombinant, polysaccharide, and conjugate vaccines are composed of small fragments or pieces from a pathogenic (disease-causing) organism. [23] A characteristic example is the subunit vaccine against Hepatitis B virus.
  • DNA vaccines: DNA vaccines are composed of DNA encoding protein antigens from the pathogen. These vaccines are inexpensive, relatively easy to make and generate a strong, long-term immunity. [23]
  • Recombinant vector vaccines (platform-based vaccines): These vaccines are harmless live viruses that encode a one/or a few antigens from a pathogenic organism. They are used widely in veterinary medicine. [23][24][25]

Most vaccines are given by hypodermic or intramuscular injection as they are not absorbed reliably through the gut. Live attenuated polio and some typhoid and cholera vaccines are given orally in order to produce immunity based in the bowel.

20.2: Introduction to the Immune System - Biology

The Chinese are credited with making the observation that deliberately infecting people with mild forms of smallpox could prevent infection with more deadly forms and provide life long protection. Knowledge of the technique, known as variolation, worked its way west to Turkey by the 18th century.

Lady Mary Wortley Montagu, the wife of the British Ambassador to Turkey and who had once survived smallpox, had her children treated and brought the ideas back to Britain, where research began on how to reduce the inoculation's sometimes-awful side effects.

In 1798, the British physician Edward Jenner published his long-term observation that cowpox exposure protected milkmaids from smallpox. To see if this protection could be artificially induced, he exposed a "healthy boy" to cowpox virus from a milkmaid, and then attempted to infect the boy with smallpox. (Obviously, this experimental method is unethical by today's standards.) This method works because cowpox shares antigens with smallpox, but doesn't cause the disease.

Discrimination of self from nonself

The success of the immune system depends on its ability to discriminate between foreign (nonself) and host (self) cells.
Survival requires both the ability to mount a destructive immune response against nonself and the inability to mount a destructive response against self.
-David Huston, Biology of the Immune System , JAMA 278 (22)

When an organism is threatened by microorganisms, viruses, or cancer cells, the immune response acts to provide protection.

Normally, the immune system does not mount a response against self. This lack of an immune response is called tolerance .

In some cases, the immune system does mount an immune response against self. If an error is made, and an immune response is made against self, tolerance to self is lost. This condition is called autoimmunity (from Greek, "self-immunity"). Examples of autoimmune diseases in humans are: asthma, lupus, and arthritis.

The nude mouse cannot mount an immune response

The nude mouse has a defect in its immune system, and can only live if protected from pathogens. The mouse to the right has a transplant of rabbit skin, and can't reject the foreign tissue. Mice with immune deficiencies are very useful in cancer research because human cancer cells can grow into tumors allowing new ways to test cancer therapy.

Important definitions

The immune system Cells in our bone marrow, thymus, and the lymphatic system of ducts and nodes, spleen, and blood that function to protect us. Antigen Anything causing an immune response, usually foreign material but may be our own tissues. Pathogen Any disease causing micro-organism. Tolerance Non-reactivity of the immune system, usually refers to "self" but may include foreign tissue in organ transplants. Autoimmunity A failure of tolerance, the immune system reacts to self. Chemokines Molecules released by pathogens and infected tissues to attract cells of the immune system. Cytokines Signaling molecules released by one cell to cause a response in another. Signaling is extremely important in our immune response. Innate immunity Protection that is always present. Includes phagocytic (cells that eat other cells) macrophages and dendritic cells. Adaptive immunity Protection that arises by an immune response, including humoral immunity producing antibodies and cellular immunity.
Begin Problem Set

Since it was first discovered to play a role in the dilation of blood vessels many new roles for Nitric Oxide (NO) have been discovered. Nitric oxide has been found to be produced by virtually every cell type in the body and plays an important role in controlling the normal function of cells as well as in regulating larger scale processes such as the nervous and immune systems. Some of these biological roles for NO are described in more detail below.

The Immune System

Nitric oxide plays many important roles in the immune system. It is produced in high amounts from specialised cells of the immune system called macrophages. Following a bacterial infection, for example, the body produces chemicals known as cytokines which activate the cells of the immune system, including macrophaes, and help guide them to the site of infection. The high amounts of nitric oxide produced by the macrophages is actually toxic to the bacteria and plays an important role in their destruction (see image on the right). The production of nitric oxide in this way also help protect against other types of infection including viruses and parasites.

However, too much nitric oxide production has also been implicated in conditions where the immune system is too active - diseases like arthritis and the so-called autoimmune diseases.

The Nervous System

Nitric oxide has been shown to be involved in both the central and peripheral nervous system. Of the three types of enzyme that produce nitric oxide in humans, one type is found almost exclusively in the nervous system. It appears to play a role in promoting the transfer of nerve signals from one neuron to another. It does this be stimulating the release of molecules called neurotransmitters which are released from one nerve cell, diffuse across the gap between the cell and stimulate the neighbouring nerve cell to transmit the signal. Nitric oxide has been implicated in diseases of the nervous system like Parkinson's and Alzheimer's.

Reproductive Biology

Nitric oxide is involved in many aspects of reproduction. It is thought to play a role in the implantation of the early embryo in the uterus and it functions to relax blood vessels and thereby helps to regulate maternal blood pressure. During pregnancy nitric oxide may also play a role in promoting the formation of new blood vessels, a process known as angiogenesis. It is also known to be an important survival factor for specialist cells called trophoblasts which form the placenta. There is also evidence that complications of pregnancy such as preeclampsia may be associated with reduced production of nitric oxide.

In addition drugs such as Viagra help overcome erectile dysfunction by affecting nitric oxide signalling.

Cellular function

A wide range of cellular activity can be regulated by nitric oxide including cell division, cell survival and cell movement .

Most cells have an in-built self-destruct system or cell suicide mechanism. This mechanism, usually called apoptosis or programmed cell death, exists to prevent damaged or infected cells from affecting the proper functioning of the rest of the tissue. Once triggered the apoptotic pathway leads to the breakdown of the structure of the cell in an organised manner, leading to a cell that is smaller and more neatly "packaged" ready for removal by cell of the immune system.

Nitric oxide has been shown to inhibit apoptosis and therefore is important in promoting cell survival. However, high doses of nitric oxide have been reported as being toxic to many cell types and in these circumstances may promote cell death instead.

How do antibiotics help fight infections?

Antibiotics can be used to help your child's immune system fight infections by bacteria. However, antibiotics don’t work for infections caused by viruses. Antibiotics were developed to kill or disable specific bacteria. That means that an antibiotic that works for a skin infection may not work to cure diarrhea caused by bacteria. Using antibiotics for viral infections or using the wrong antibiotic to treat a bacterial infection can help bacteria become resistant to the antibiotic so it won't work as well in the future. It is important that antibiotics are taken as prescribed and for the right amount of time. If antibiotics are stopped early, the bacteria may develop a resistance to the antibiotics and the infection may come back again.

Note: Most colds and acute bronchitis infections will not respond to antibiotics. You can help decrease the spread of more aggressive bacteria by not asking your child’s healthcare provider for antibiotics in these cases.

The body's other defences against microbes

As well as the immune system, the body has several other ways to defend itself against microbes, including:

  • skin - a waterproof barrier that secretes oil with bacteria-killing properties
  • lungs - mucous in the lungs (phlegm) traps foreign particles, and small hairs (cilia) wave the mucous upwards so it can be coughed out
  • digestive tract - the mucous lining contains antibodies, and the acid in the stomach can kill most microbes
  • other defences - body fluids like skin oil, saliva and tears contain anti-bacterial enzymes that help reduce the risk of infection. The constant flushing of the urinary tract and the bowel also helps.

B Cells

B cells are immune cells that function primarily by producing antibodies. An antibody is any of the group of proteins that binds specifically to pathogen-associated molecules known as antigens. An antigen is a chemical structure on the surface of a pathogen that binds to T or B lymphocyte antigen receptors. Once activated by binding to antigen, B cells differentiate into cells that secrete a soluble form of their surface antibodies. These activated B cells are known as plasma cells.

The immune system protects the body from possibly harmful substances by recognizing and responding to antigens. Antigens are substances (usually proteins) on the surface of cells, viruses, fungi, or bacteria. Nonliving substances such as toxins, chemicals, drugs, and foreign particles (such as a splinter) can also be antigens. The immune system recognizes and destroys, or tries to destroy, substances that contain antigens.

Your body's cells have proteins that are antigens. These include a group of antigens called HLA antigens. Your immune system learns to see these antigens as normal and usually does not react against them.

Innate, or nonspecific, immunity is the defense system with which you were born. It protects you against all antigens. Innate immunity involves barriers that keep harmful materials from entering your body. These barriers form the first line of defense in the immune response. Examples of innate immunity include:

  • Enzymes in tears and skin oils
  • Mucus, which traps bacteria and small particles
  • Skin
  • Stomach acid

Innate immunity also comes in a protein chemical form, called innate humoral immunity. Examples include the body's complement system and substances called interferon and interleukin-1 (which causes fever).

If an antigen gets past these barriers, it is attacked and destroyed by other parts of the immune system.

Acquired immunity is immunity that develops with exposure to various antigens. Your immune system builds a defense against that specific antigen.

Passive immunity is due to antibodies that are produced in a body other than your own. Infants have passive immunity because they are born with antibodies that are transferred through the placenta from their mother. These antibodies disappear between ages 6 and 12 months.

Passive immunization may also be due to injection of antiserum, which contains antibodies that are formed by another person or animal. It provides immediate protection against an antigen, but does not provide long-lasting protection. Immune serum globulin (given for hepatitis exposure) and tetanus antitoxin are examples of passive immunization.

The immune system includes certain types of white blood cells. It also includes chemicals and proteins in the blood, such as antibodies, complement proteins, and interferon. Some of these directly attack foreign substances in the body, and others work together to help the immune system cells.

Lymphocytes are a type of white blood cell. There are B and T type lymphocytes.

  • B lymphocytes become cells that produce antibodies. Antibodies attach to a specific antigen and make it easier for the immune cells to destroy the antigen.
  • T lymphocytes attack antigens directly and help control the immune response. They also release chemicals, known as cytokines, which control the entire immune response.

As lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that are not normally found in your body. Once B cells and T cells are formed, a few of those cells will multiply and provide "memory" for your immune system. This allows your immune system to respond faster and more efficiently the next time you are exposed to the same antigen. In many cases, it will prevent you from getting sick. For example, a person who has had chickenpox or has been immunized against chickenpox is immune from getting chickenpox again.

The inflammatory response (inflammation) occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause. The damaged cells release chemicals including histamine, bradykinin, and prostaglandins. These chemicals cause blood vessels to leak fluid into the tissues, causing swelling. This helps isolate the foreign substance from further contact with body tissues.

The chemicals also attract white blood cells called phagocytes that "eat" germs and dead or damaged cells. This process is called phagocytosis. Phagocytes eventually die. Pus is formed from a collection of dead tissue, dead bacteria, and live and dead phagocytes.


Immune system disorders occur when the immune response is directed against body tissue, is excessive, or is lacking. Allergies involve an immune response to a substance that most people's bodies perceive as harmless.

Vaccination (immunization) is a way to trigger the immune response. Small doses of an antigen, such as dead or weakened live viruses, are given to activate immune system "memory" (activated B cells and sensitized T cells). Memory allows your body to react quickly and efficiently to future exposures.


An efficient immune response protects against many diseases and disorders. An inefficient immune response allows diseases to develop. Too much, too little, or the wrong immune response causes immune system disorders. An overactive immune response can lead to the development of autoimmune diseases, in which antibodies form against the body's own tissues.

Complications from altered immune responses include:

  • Allergy or hypersensitivity , a life-threatening allergic reaction
  • Autoimmune disorders , a complication of a bone marrow transplant
  • Immunodeficiency disorders
  • Transplant rejection