Mechanical Barriers

Mechanical barriers are the first line of defense against pathogens, and they physically block pathogens from entering the body. The skin is the most important mechanical barrier. In fact, it is the single most important defense the body has. The outer layer of skin, the epidermis, is tough and very difficult for pathogens to penetrate. It consists of dead cells that are constantly being shed from the body surface. This helps remove bacteria and other infectious agents that have adhered to the skin. The epidermis also lacks blood vessels and is usually lacking moisture, so it does not provide a suitable environment for most pathogens. Hair, which is an accessory organ of the skin, also helps to keep out pathogens. Hairs inside the nose may trap larger pathogens and other particles in the air before they can enter the airways of the respiratory system.

Mucous membranes provide a mechanical barrier to pathogens and other particles at body openings. These membranes also line the respiratory, gastrointestinal, urinary, and reproductive tracts. Mucous membranes secrete mucus, which is a slimy and somewhat sticky substance that traps pathogens. Many mucous membranes also have hair-like cilia that sweep mucus and trapped pathogens toward body openings where they can be removed from the body. When you sneeze or cough, mucus, and pathogens are mechanically ejected from the nose and throat, as you can see in the photo below. Other mechanical defenses include tears, which wash pathogens from the eyes, and urine, which flushes pathogens out of the urinary tract.

Chemical Barriers

Chemical barriers also protect against infection by pathogens. They destroy pathogens on the outer body surface, at body openings, and on inner body linings. Sweat, mucus, tears, saliva, and breastmilk all contain antimicrobial substances, such as the enzyme lysozyme, that kill pathogens, especially bacteria. Sebaceous glands in the dermis of the skin secrete acids that form a very fine, slightly acidic film on the surface of the skin that acts as a barrier to bacteria, viruses, and other potential contaminants that might penetrate the skin. Urine and vaginal secretions are also too acidic for many pathogens to endure. Semen contains zinc, which most pathogens cannot tolerate, as well as defensins, which are antimicrobial proteins that act mainly by disrupting bacterial cell membranes. In the stomach, stomach acid and digestive enzymes called proteases, which break down proteins, kill most pathogens that enter the gastrointestinal tract in food or water.

Biological Barriers

Biological barriers are living organisms that help protect the body from pathogens. Trillions of harmless bacteria normally live on the human skin and in the urinary, reproductive, and gastrointestinal tracts. These bacteria use up food and surface space that help prevent pathogenic bacteria from colonizing the body. Some of these harmless bacteria also secrete substances that change the conditions of their environment, making it less hospitable to potentially harmful bacteria. For example, they may release toxins or change the pH. All of these effects of harmless bacteria reduce the chances that pathogenic microorganisms will be able to reach sufficient numbers to cause illness.

Phagocytosis

Phagocytosis is an important feature of innate immunity that is performed by cells classified as phagocytes. In the process of phagocytosis, phagocytes engulf and digest pathogens or other harmful particles. Phagocytes generally patrol the body searching for pathogens, but they can also be called to specific locations by the release of cytokines when inflammation occurs. Some phagocytes reside permanently in certain tissues.

As shown in the figure below, when a pathogen such as a bacterium is encountered by a phagocyte, the phagocyte extends a portion of its plasma membrane, wrapping the membrane around the pathogen until it is enveloped. Once inside the phagocyte, the pathogen becomes enclosed within an intracellular vesicle called a phagosome. The phagosome then fuses with another vesicle called a lysosome, forming a phagolysosome. Digestive enzymes and acids from the lysosome kill and digest the pathogen in the phagolysosome. The final step of phagocytosis is the excretion of soluble debris from the destroyed pathogen through exocytosis.

Leukocytes

Types of leukocytes that kill pathogens by phagocytosis include neutrophils, macrophages, and dendritic cells. Macrophages and dendritic cells are the derivatives of monocytes.

 

Dendritic Cells

Like macrophages, dendritic cells develop from monocytes. They reside in tissues that have contact with the external environment, so they are located mainly in the skin, nose, lungs, stomach, and intestines. Besides engulfing and digesting pathogens, dendritic cells also act as antigen-presenting cells that trigger adaptive immune responses.

Naturally Acquired Active Immunity

Active immunity is acquired naturally when a pathogen invades the body and activates the adaptive immune system. When the initial infection is over, memory B cells and memory T cells remain that provide immunological memory of the pathogen. As long as the memory cells are alive, the immune system is ready to mount an immediate response if the same pathogen tries to infect the body again.

Artificially Acquired Active Immunity

Active immunity can also be acquired artificially through immunization. Immunization is the deliberate exposure of a person to a pathogen in order to provoke an adaptive immune response and the formation of memory cells specific to that pathogen. The pathogen is introduced in a vaccine — usually by injection, sometimes by nose or mouth (see the photo below) — so immunization is also called vaccination.

In a vaccine, only part of a pathogen, a weakened form of the pathogen, or a dead pathogen is typically used. This causes an adaptive immune response without making the immunized person sick. This is how you most likely became immune to diseases such as measles, mumps, and chickenpox. Immunizations may last for a lifetime or require periodic booster shots to maintain immunity. While immunization generally has long-lasting effects, it usually takes several weeks to develop full immunity.

Immunization is the most effective method ever discovered in preventing infectious diseases. As many as 3 million deaths are prevented each year because of vaccinations. Widespread immunity due to vaccinations is largely responsible for the worldwide eradication of smallpox and the near elimination of several other infectious diseases from many populations, including such diseases as polio and measles. Immunization is so successful because it exploits the natural specificity and inducibility of the adaptive immune system.

Naturally Acquired Passive Immunity

Passive immunity is acquired naturally by a fetus through its mother’s blood. Antibodies are transported from mother to fetus across the placenta, so babies have high levels of antibodies at birth. Their antibodies have the same range of antigen specificity as their mother’s. Passive immunity may also be acquired by an infant through the mother’s breast milk. This gives young infants protection from common pathogens in their environment while their own immune system matures.

Artificially Acquired Passive Immunity

Older children and adults can acquire passive immunity artificially through the injection of antibodies or activated T cells. This may be done when there is a high risk of infection and insufficient time for the body to develop active immunity through vaccination. It may also be done to reduce symptoms of ongoing disease or to compensate for immunodeficiency diseases (for the latter, see the concept Disorders of the Immune System).

Allergens

Any antigen that causes an allergy is called an allergen. Common allergens are plant pollens, dust mites, mold, specific foods (such as peanuts or shellfish), insect stings, and certain common medications (such as aspirin and penicillin). Allergens may be inhaled or ingested, or they may come into contact with the skin or eyes. Symptoms vary depending on the type of exposure and the severity of the immune system response. Two common causes of allergies are ragweed and poison ivy. Inhaling ragweed pollen may cause symptoms of allergic rhinitis, such as sneezing and red itchy eyes. Skin contact with oils in poison ivy may cause an itchy rash. This type of allergy is called contact dermatitis.

Prevalence of Allergies

There has been a significant increase in the prevalence of allergies over the past several decades, especially in the rich nations of the world, where allergies are now very common disorders. In the developed countries, about 20 percent of people have or have had hay fever, another 20 percent have had contact dermatitis, and about 6 percent have food allergies. In the poorer nations of the world, on the other hand, allergies of all types are much less common.

One explanation for the rise in allergies in the developed world is called the hygiene hypothesis. According to this hypothesis, people in developed countries live in relatively sterile environments because of hygienic practices and sanitation systems. As a result, people in these countries are exposed to fewer pathogens than their immune system evolved to cope with. To compensate, their immune system “keeps busy” by attacking harmless antigens in allergic responses.

How Allergies Occur

The diagram in Figure 20.6.320.6.3 shows how an allergic reaction occurs. At the first exposure to an allergen, B cells are activated to form plasma cells that produce large amounts of antibodies to the allergen. These antibodies attach to leukocytes called mast cells. Subsequently, every time the person encounters the allergen again, the mast cells are already primed and ready to deal with it. The primed mast cells immediately release cytokines and histamines, which in turn cause inflammation and recruitment of leukocytes, among other responses. These responses are responsible for the signs and symptoms of allergies.

Treating Allergies

The symptoms of allergies can range from mild to life-threatening. Mild allergy symptoms are often treated with antihistamines. These are drugs that reduce or eliminate the effects of the histamines that produce allergy symptoms.

Immunotherapy for Allergies

Another way to treat allergies is called immunotherapy, commonly called “allergy shots.” This approach may actually cure specific allergies, at least for several years if not lifelong. It may be particularly beneficial for allergens such as pollen that are difficult or impossible to avoid. First, however, patients must be tested to identify the specific allergens that are causing their allergies. As shown in the photo below, this may involve scratching tiny amounts of common allergens into the skin and then observing whether there is a localized reaction to any of them. Each allergen is applied in a different numbered location on the skin so if there is a reaction, such as redness or swelling, the responsible allergens can be identified. Then, through periodic injections (usually weekly or monthly), patients are gradually exposed to larger and larger amounts of the allergens. Over time, generally from months to years, the immune system becomes desensitized to the allergens. This method of treating allergies is often effective for allergies to pollen or insect stings, but its usefulness for allergies to food is unclear.

Common Autoimmune Diseases

An estimated 15 million or more people worldwide have one or more autoimmune diseases. Two of the most common autoimmune diseases are type I diabetes and multiple sclerosis. Both are localized diseases in terms of the specific body cells that are attacked by the immune system. In the case of type I diabetes, the immune system attacks and destroys insulin-secreting islet cells in the pancreas. In the case of multiple sclerosis, the immune system attacks and destroys the myelin sheaths that normally insulate the axons of neurons and allow rapid transmission of nerve impulses.

Some relatively common autoimmune diseases are systemic, or body-wide, diseases. They include rheumatoid arthritis and systemic lupus erythematosus (SLE). In these diseases, many tissues and organs may be attacked and injured by the immune system. For example, as you can see in the figure below, symptoms of SLE may involve the muscular, skeletal, integumentary, respiratory, and cardiovascular systems.

Treatment for Autoimmune Diseases

None of these common autoimmune diseases can be cured, although all of them have treatments that may help relieve symptoms and prevent some of the long-term damage they may cause. Traditional treatments for autoimmune diseases include immunosuppressive drugs to block the immune response and anti-inflammatory drugs to quell inflammation. Hormone replacement may be another option. For example, type I diabetes is treated with injections of the hormone insulin because islet cells in the pancreas can no longer secrete it.

Causes of Immunodeficiency

Dozens of rare genetic diseases can result in a defective immune system. This type of immunodeficiency is called primary immunodeficiency. One is born with one of these diseases rather than acquiring it after birth. Probably the best known of these primary immunodeficiency diseases is severe combined immunodeficiency (SCID). It is also known as “bubble boy disease” because people with this disorder are extremely vulnerable to infectious diseases and some of them have become well known for living inside a bubble that provides a sterile environment. SCID is most often caused by an X-linked recessive mutation that interferes with normal B cell and T cell production.

Other types of immunodeficiency are not present at birth but acquired due to experiences or exposures that occur after birth. Acquired immunodeficiency is called secondary immunodeficiency because it is secondary to some other event or exposure. Secondary immunodeficiency may occur for a number of different reasons:

• The immune system naturally becomes less effective as people get older. This age-related decline, called immunosenescence, generally begins at about age 50 and worsens with increasing age. Immunosenescence is why older people are generally more susceptible to disease than younger people.
• The immune system may be damaged by another disorder, such as obesity, alcoholism, or the abuse of other drugs.
• In developing countries, malnutrition is the most common cause of immune system damage and immunodeficiency. Inadequate protein intake is especially damaging to the immune system. It can lead to impaired complement system activity, phagocyte malfunction, and lower-than-normal production of antibodies and cytokines.
• Surgical removal or disease of the thymus, where T lymphocytes normally mature, results in severe immunodeficiency. People without a functioning thymus are extremely susceptible to infections.
• Certain medications can suppress the immune system. This is the intended effect of immunosuppressant drugs given to people with transplanted organs so they do not reject them. In many cases, however, immunosuppression is an unwanted side effect of drugs used to treat other disorders.
• Some pathogens attack and destroy cells of the immune system. An example is a virus known as HIV, which attacks and destroys T cells.

Focus on HIV

Human immunodeficiency virus (HIV) is the most common cause of immunodeficiency in the world today, so it is the focus of the rest of this concept. It is also covered in the concept HIV and AIDS. HIV infections of human hosts are a relatively recent phenomenon. Scientists think that the virus originally infected monkeys but then jumped to human populations, probably sometime during the early to mid-1900s. This most likely occurred in West Africa, but the virus soon spread around the world. HIV was first identified by medical researchers in 1981. Since then, HIV has killed almost 40 million people worldwide, and its economic toll has also been enormous. The hardest hit countries are in Africa, where the virus has infected human populations the longest and medications to control the virus are least available.

HIV Transmission

HIV is transmitted through direct contact of mucous membranes or body fluids such as blood, semen, or breast milk. As shown in the figure below, the transmission of the virus can occur through sexual contact or the use of contaminated hypodermic needles. It can also be transmitted from an infected mother’s blood during late pregnancy or childbirth or through breast milk after birth. In the past, HIV was also transmitted occasionally through blood transfusions. Because donated blood is now screened for HIV, the virus is no longer transmitted this way.

HIV and the Immune System

HIV infects and destroys helper T cells, the type of lymphocytes that regulate the immune response. How this occurs is shown in Figure 20.6.820.6.8. The virus injects its own DNA into a helper T cell and uses the T cell’s “machinery” to make copies of itself. In the process, the helper T cell is destroyed, and the virus copies go on to infect other helper T cells. HIV is able to evade the immune system and keep destroying helper T cells by mutating frequently so its surface antigens keep changing and by using the host cell’s membrane to hide its own antigens.

Acquired immunodeficiency syndrome (AIDS) may result from years of damage to the immune system by HIV. It occurs when helper T cells fall to a very low level and opportunistic diseases occur (see the graph below). Opportunistic diseases are infections and tumors that are rare except in people with a damaged immune system. The diseases take advantage of the “opportunity” presented by people whose immune system cannot fight back. Opportunistic diseases are usually the direct cause of death of people with AIDS.