Contagious Diseases Sourcebook, 4th Ed.

Chapter 1

Understanding Microbes

Chapter Contents

Section 1.1—What Are Microbes?

Section 1.2—Microbes Can Cause Different Kinds of Infections

Section 1.3—Preventing Microbial Diseases

Section 1.4—General Symptoms, Diagnosis, and Treatment of Microbial Diseases

Section 1.1

What Are Microbes?

This section includes text excerpted from Understanding Microbes in Sickness and in Health, National Institute of Allergy and Infectious Diseases (NIAID), January 2006. Reviewed July 2019.

Microbes are tiny organisms—too tiny to see without a microscope, yet they are abundant on Earth. They live everywhere—in air, soil, rock, and water. Some live happily in searing heat, while others thrive in freezing cold. Some microbes need oxygen to live, but others do not. These microscopic organisms are found in plants and animals, as well as in the human body.

Some microbes cause disease in humans, plants, and animals. Others are essential for a healthy life, and we could not exist without them. Indeed, the relationship between microbes and humans is delicate and complex. Some microbes keep us healthy, while others can make us sick.

Most microbes belong to one of four major groups: bacteria, viruses, fungi, or protozoa. A common word for microbes that cause disease is germs. Some people refer to disease-causing microbes as bugs. I have got the flu bug, for example, is a phrase you may hear during the wintertime to describe an influenza virus infection.

Since the 19th century, we have known that microbes cause infectious diseases. Near the end of the 20th century, researchers began to learn that microbes also contribute to many chronic diseases and conditions. Mounting scientific evidence strongly links microbes to some forms of cancer, coronary artery disease, diabetes, multiple sclerosis, and chronic lung diseases.

Bacteria

Microbes belonging to the bacteria group are made up of only 1 cell. Under a microscope, bacteria look like balls, rods, or spirals. Bacteria are so small that a line of 1,000 could fit across the eraser of a pencil. Life in any form on Earth could not exist without these tiny cells.

Scientists have discovered fossilized remains of bacteria that date back more than three and a half billion years, placing them among the oldest living things on Earth. Bacteria can inhabit a variety of environments, including extremely hot and cold areas.

Psychrophiles, or cold-loving bacteria, can live in the subfreezing temperature of the Arctic.

Thermophiles are heat-loving bacteria that can live in extreme heat, such as in the hot springs in Yellowstone National Park.

Extreme thermophiles, or hyperthermophiles, thrive at 235 degrees Fahrenheit near volcanic vents on the ocean floor.

Many bacteria prefer the milder temperature of the healthy human body

As with humans, some bacteria (aerobic bacteria) need oxygen to survive. Others (anaerobic bacteria), however, do not. Amazingly, some can adapt to new environments by learning to survive with or without oxygen.

As with all living cells, each bacterium requires food for energy and building materials. There are countless numbers of bacteria on Earth—most are harmless, and many are even beneficial to humans. In fact, less than one percent of bacteria cause diseases in humans. For example, harmless anaerobic bacteria, such as Lactobacillus acidophilus, live in our intestines, where they help to digest food, destroy disease-causing microbes, fight cancer cells, and give the body needed vitamins. Healthy food products, such as yogurt, sauerkraut, and cheese, are made using bacteria.

Some bacteria produce poisons called toxins, which also can make us sick.

Are Toxins Always Harmful?

Certain bacteria give off toxins that can seriously affect your health. Botulism, a severe form of food poisoning, affects the nerves and is caused by toxins from Clostridium botulinum bacteria. Under certain circumstances, however, bacterial toxins can be helpful. Several vaccines that protect us from getting sick are made from bacterial toxins. One type of pertussis vaccine, which protects infants and children from whooping cough, contains toxins from Bordetella pertussis bacteria. This vaccine is safe and effective and causes fewer reactions than other types of pertussis vaccine.

Viruses

Viruses are among the smallest microbes, much smaller even than bacteria. Viruses are not cells. They consist of one or more molecules of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), which contain the virus’s genes surrounded by a protein coat. Viruses can be rod-shaped, sphere-shaped, or multisided. Some viruses look like tadpoles.

Unlike most bacteria, most viruses do cause disease because they invade living, normal cells, such as those in your body. They then multiply and produce other viruses similar to themselves. Each virus is very particular about which cell it attacks. Various human viruses specifically attack particular cells in your body’s organs, systems, or tissues, such as the liver, respiratory system, or blood.

Although types of viruses behave differently, most survive by taking over the machinery that makes a cell work. Briefly, when a piece of a virus, called a virion, comes in contact with a cell it likes, it may attach to special landing sites on the surface of that cell. From there, the virus may inject molecules into the cell, or the cell may swallow the virion. Once inside the cell, viral molecules, such as DNA or RNA, direct the cell to make new virus offspring. That is how a virus infects a cell.

Viruses can even infect bacteria. These viruses, called bacteriophages, may help researchers develop alternatives to antibiotic medicines for preventing and treating bacterial infections.

Many viral infections do not result in disease. For example, by the time most people in the United States become adults, they have been infected by cytomegalovirus (CMV). Most of these people, however, do not develop CMV-disease symptoms.

Other viral infections can result in deadly diseases, such as acquired immunodeficiency syndrome (AIDS) or Ebola hemorrhagic fever.

Fungi

A fungus is actually a primitive plant. Fungi can be found in the air, in soil, on plants, and in water. Thousands, perhaps millions, of different types of fungi exist on Earth. The most familiar ones to us are mushrooms, yeast, mold, and mildew. Some live in the human body, usually without causing illness. Fungal diseases are called mycoses.

Mycoses can affect your skin; nails; body hair; internal organs, such as your lungs; and body systems, such as your nervous system. Aspergillus fumigatus, for example, can cause aspergillosis, a fungal infection in your respiratory system.

Some fungi have made our lives easier. Penicillin and other antibiotics, which kill harmful bacteria in our bodies, are made from fungi. Other fungi, such as certain yeasts, also can be helpful. For example, when a warm liquid, such as water, and a food source are added to certain yeasts, the fungus ferments. The process of fermentation is essential for making healthy foods, such as some breads and cheeses.

Protozoa

Protozoa are a group of microscopic one-celled animals. Protozoa can be parasites or predators. In humans, protozoa usually cause disease.

Some protozoa, such as plankton, live in water environments and serve as food for marine animals, such as some kinds of whales. Protozoa also can be found on land in decaying matter and in soil, but they must have a moist environment to survive. Termites would not be able to do such a good job of digesting wood without these microorganisms in their guts.

Malaria is caused by a protozoan parasite. Another protozoan parasite, Toxoplasma gondii, causes toxoplasmosis in humans. This is an especially troublesome infection in pregnant women because of its effects on the fetus and in people with human immunodeficiency virus (HIV) infection or other immune deficiency disorder.

Table 1.1. Microbes in the Healthy Human Body*

* A selection of usually harmless microbes, some of which help keep our bodies functioning normally. If their numbers become unbalanced, however, these microbes may make us sick. All are bacteria, unless otherwise noted.

Section 1.2

Microbes Can Cause Different Kinds of Infections

This section includes text excerpted from Understanding Microbes in Sickness and in Health, National Institute of Allergy and Infectious Diseases (NIAID), January 2006. Reviewed July 2019.

Microbes Infections

Some disease-causing microbes can make you very sick quickly and then not bother you again. Some can last for a long time and continue to damage tissues. Others can last forever, but you will not feel sick anymore, or you will feel sick only once in a while. Most infections caused by microbes fall into three major groups.

Acute infections

Chronic infections

Latent infections

Acute Infections

Acute infections are usually severe and last a short time. They can make you feel very uncomfortable, with signs and symptoms such as tiredness, achiness, coughing, and sneezing. The common cold is such an infection. The signs and symptoms of a cold can last for 2 to 24 days (but usually a week), though it may seem such as a lot longer. Once your body’s immune system has successfully fought off one of the many different types of rhinoviruses or other viruses that may have caused your cold, the cold does not come back. If you get another cold, it is probably because you have been infected with other cold-causing viruses.

Chronic Infections

Chronic infections usually develop from acute infections and can last for days to months to a lifetime. Sometimes, people are unaware they are infected but still may be able to transmit the germ to others. For example, hepatitis C, which affects the liver, is a chronic viral infection. In fact, most people who have been infected with the hepatitis C virus do not know it until they have a blood test that shows antibodies to the virus. Recovery from this infection is rare—about 85 percent of infected persons become chronic carriers of the virus. In addition, serious signs of liver damage, such as cirrhosis or cancer, may not appear until as long as 20 years after the infection began.

The Difference between Infection and Disease

A disease occurs when cells or molecules in your body stop working properly, causing symptoms of illness. Many things can cause a disease, including altered genes, chemicals, aging, and infections. An infection occurs when a microbe—such as a virus, bacterium, fungus, or parasite—enters your body and begins to reproduce. The invading microbe can directly damage cells, or the immune system can cause symptoms, such as fever, as it tries to rid your body of the invader. Some infections do not cause disease because the microbe is quickly killed or it remains dormant.

Latent Infections

Latent infections are hidden or silent and may or may not cause symptoms again after the first acute episode. Some infectious microbes, usually viruses, can wake up—become active again but not always causing symptoms—off and on for months or years. When these microbes are active in your body, you can transmit them to other people. Herpes simplex viruses, which cause genital herpes and cold sores, can remain latent in nerve cells for short or long periods of time, or for forever.

Chickenpox is another example of a latent infection. Before the chickenpox vaccine became available in the 1990s, most children in the United States got chickenpox. After the first acute episode, usually, when children are very young, the Varicella zoster virus goes into hiding in the body. In many people, it emerges many years later when they are older adults and causes a painful disease of the nerves called herpes zoster, or shingles.

Emerging and Reemerging Microbes

By the mid-20th century, some scientists thought that medicine had conquered infectious diseases. With the arrival of antibiotics and modern vaccines, as well as improved sanitation and hygiene, many diseases that formerly posed an urgent threat to public health were brought under control or largely eliminated.

The emergence of new microbes and the reemergence of old microbes has continued, however, as it has throughout history. Several pressures are contributing to the emergence of new diseases such as:

Rapidly changing human demographics

Rapid global travel

Changes in land use patterns

Ecological, environmental, and technological changes

Even public health practices, such as widespread antibiotic, use are contributing to this emergence. These pressures are both shaping the evolution of microbes and bringing people into closer and more frequent contact with microbes.

Table 1.2. Common Diseases and Infections and Their Microbial Causes

Unsanitary conditions in animal agriculture and increasing commerce in exotic animals (for food and as pets) have also contributed to the rise in opportunity for animal microbes to jump from animals to humans. From time to time, with the right combination of selective pressures, a formerly harmless human or animal microbe can evolve into a pathogen that can cause a major outbreak of human disease. At times, changes in societal and environmental factors can also lead to the reemergence of diseases that were previously under control.

Section 1.3

Preventing Microbial Diseases

This section includes text excerpted from Understanding Microbes in Sickness and in Health, National Institute of Allergy and Infectious Diseases (NIAID), January 2006. Reviewed July 2019.

You Can Prevent Catching or Passing on Germs

Handwashing

Handwashing is one of the simplest, easiest, and most effective ways to prevent getting or passing on many germs. Amazingly, it is also one of the most overlooked. Healthcare experts recommend scrubbing your hands vigorously for at least 15 seconds with soap and water, about as long as it takes to recite the English alphabet. This will wash away cold viruses and staph and strep bacteria, as well as many other disease-causing microbes.

It is especially important to wash your hands:

Before preparing or eating food

After coughing or sneezing

After using the bathroom

After changing a diaper

Healthcare providers should be especially conscientious about washing their hands before and after examining any patient. Workers in child care and elder care settings, too, should be vigilant about handwashing around those in their care.

Medicines

There are medicines on the market that help prevent people from getting infected by germs. For example, you can prevent getting the flu (influenza) by taking an antiviral medicine. Vaccines, however, are the best defense against influenza viruses.

Under specific circumstances, healthcare providers may prescribe antibiotics to protect people from getting certain bacteria, such as Mycobacterium tuberculosis, which causes tuberculosis (TB). Healthcare experts usually advise people traveling to areas where malaria is present to take antiparasitic medicines to prevent possible infection.

Vaccines

In 1796, Edward Jenner laid the foundation for modern vaccines by discovering one of the basic principles of immunization. He had used a relatively harmless microbe, cowpox virus, to bring about an immune response that would help protect people from getting infected by the related but deadly smallpox virus.

Dr. Jenner’s discovery helped researchers find ways to ease human disease suffering worldwide. By the beginning of the 20th century, doctors were immunizing patients with vaccines for diphtheria, typhoid fever, and smallpox.

Nowadays, safe and effective vaccines prevent childhood diseases, including measles, whooping cough, chickenpox, and the form of meningitis caused by Haemophilus influenzae type b (Hib) virus.

Vaccines, however, are not only useful for young children. Adolescents and adults should get vaccinated regularly for tetanus and diphtheria. A vaccine to prevent meningococcal meningitis is now available and recommended for all adolescents. In addition, adults who never had diseases such as measles or chickenpox during childhood or those who never received vaccines to prevent them should consider being immunized. Childhood diseases can be far more serious in adults.

More people travel all over the world today. So, finding out which immunizations are recommended for travel to your destination(s) is even more important than ever. Vaccines also can prevent yellow fever, polio, typhoid fever, hepatitis A, cholera, rabies, and other bacterial and viral diseases that are more prevalent abroad than in the United States.

In the Fall, many adults and children may benefit from getting the flu vaccine. Your healthcare provider also may recommend immunizations for pneumococcal pneumonia and hepatitis B if you are at risk of getting these diseases.

Some Vaccine-Preventable Infectious Diseases

Bacterial meningitis

Chickenpox

Cholera

Diphtheria

Haemophilus influenzae type b

Hepatitis A

Hepatitis B

Flu

Measles

Mumps

Pertussis (whooping cough)

Pneumococcal pneumonia

Polio

Rabies

Rubella

Tetanus (lockjaw)

Yellow fever

Some People Are Immune to Certain Diseases

We become immune to germs through natural and artificial means. As long ago as the 5th century B.C., Greek doctors noticed that people who had recovered from the plague would never get it again—they seemed to have become immune or resistant to the germ. You can become immune, or develop immunity, to a microbe in several ways. The first time T cells and B cells in your immune system meet up with an antigen, such as a virus or bacterium, they prepare the immune system to destroy the antigen. Because the immune system often can remember its enemies, those cells become active if they meet that particular antigen again. This is called naturally acquired immunity.

Another example of naturally acquired immunity occurs when a pregnant woman passes antibodies to the fetus. Babies are born with weak immune responses, but they are protected from some diseases for their first few months of life by antibodies received from their mothers before birth. Babies who are nursed also receive antibodies from breast milk that help protect their digestive tracts.

Artificial immunity can come from vaccines. Immunization with vaccines is a safe way to get protection from germs. Some vaccines contain microorganisms or parts of microorganisms that have been weakened or killed. If you get this type of vaccine, those microorganisms (or their parts) will start your body’s immune response, which will demolish the foreign invader but not make you sick. This is a type of artificially acquired immunity.

Immunity can be strong or weak and short- or long-lived, depending on the type of antigen, the amount of antigen, and the route by which it enters your body. When faced with the same antigen, some people’s immune system will respond forcefully, others feebly, and some not at all.

The genes you inherit also can influence your likelihood of getting a disease. In simple terms, the genes you get from your parents can influence how your body reacts to certain microbes.

Section 1.4

General Symptoms, Diagnosis, and Treatment of Microbial Diseases

This section includes text excerpted from Understanding Microbes in Sickness and in Health, National Institute of Allergy and Infectious Diseases (NIAID), January 2006. Reviewed July 2019.

When You Should Go to the Doctor

You should call a healthcare provider immediately if:

You have been bitten by an animal.

You are having difficulty breathing.

You have a cough that has lasted for more than a week.

You have a fever higher than 100 degrees Fahrenheit.

You have episodes of rapid heartbeat.

You have a rash (especially if you have a fever at the same time).

You have swelling.

You suddenly start having difficulty with seeing (blurry vision, for example).

You have been vomiting.

Generally, you should consult your healthcare provider if you have or think you may have an infectious disease. These trained professionals can determine whether you have been infected, determine the seriousness of your infection, and give you the best advice for treating or preventing disease. Sometimes, however, a visit to the doctor may not be necessary.

Some infectious diseases, such as the common cold, usually do not require a visit to your doctor. They often last a short time and are not life-threatening, or there is no specific treatment. We have all heard the advice to rest and drink plenty of liquids to treat colds. Unless there are complications, most victims of colds find that their immune systems successfully fight off the viral culprits. In fact, the coughing and sneezing that make you feel miserable are part of your immune system’s way of fighting off the culprits.

If, however, you have other conditions in which your immune system does not function properly, you should be in contact with your healthcare provider whenever you suspect you have any infectious disease, even the common cold. Such conditions can include asthma and immune deficiency diseases, like human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS).

In addition, some common, usually mild infectious diseases, such as chickenpox or flu, can cause serious harm in very young children and the elderly.

Diagnosis of Microbial Diseases

Sometimes your healthcare provider can diagnose an infectious disease by listening to your medical history and doing a physical exam. For example, listening to you describe what happened and any symptoms you have noticed plays an important part in helping your doctor find out what is wrong.

Blood and urine tests are other ways to diagnose an infection. A laboratory expert can sometimes see the offending microbe in a sample of blood or urine viewed under a microscope. One or both of these tests may be the only way to determine what caused the infection, or they may be used to confirm a diagnosis that was made based on taking a medical history and doing a physical exam.

In another type of test, your healthcare provider will take a sample of blood or other body fluid, such as vaginal secretion, and then put it into a special container called a Petri dish to see if any microbe grows. This test is called a culture. Certain bacteria, such as chlamydia and strep, and viruses, such as herpes simplex, usually can be identified using this method.

X-rays, scans, and biopsies (taking a tiny sample of tissue from the infected area and inspecting it under a microscope) are among other tools the doctor can use to make an accurate diagnosis.

All of the above procedures are relatively safe, and some can be done in your doctor’s office or a clinic. Others pose a higher risk to you because they involve procedures that go inside your body. One such invasive procedure is taking a biopsy from an internal organ. For example, one way a doctor can diagnose Pneumocystis carinii pneumonia, a lung disease caused by a fungus, is by doing a biopsy on lung tissue and then examining the sample under a microscope.

Treatment of Microbial Diseases

How an infectious disease is treated depends on the microbe that caused it and sometimes on the age and medical condition of the person affected. Certain diseases are not treated at all but are allowed to run their course, with the immune system doing its job alone. Some diseases, such as the common cold, are treated only to relieve the symptoms. Others, such as strep throat, are treated to destroy the offending microbe, as well as to relieve symptoms.

By Your Immune System

Your immune system has an arsenal of ways to fight off invading microbes. Most begin with B and T cells and antibodies whose sole purpose is to keep your body healthy. Some of these cells sacrifice their lives to rid you of disease and restore your body to a healthy state. Some microbes normally present in your body also help destroy microbial invaders. For example, normal bacteria, such as lactobacillus in your digestive system, help destroy disease-causing microbes.

Other important ways your body reacts to an infection include fever and coughing and sneezing.

Fever

Fever is one of your body’s special ways of fighting an infectious disease. Many microbes are very sensitive to temperature changes and cannot survive in temperatures higher than normal body heat, which is usually around 98.6 degrees Fahrenheit. Your body uses fever to destroy flu viruses, for example.

Coughing and Sneezing

Another tool in your immune system’s reaction to invading infection-causing microbes is mucus production. Coughing and sneezing help mucus move those germs out of your body efficiently and quickly.

Other methods your body may use to fight off an infectious disease include:

Inflammation

Vomiting

Diarrhea

Fatigue

Cramping

By Your Healthcare Provider

For Bacteria

The last century saw an explosion in our knowledge about how microbes work and in our methods of treating infectious diseases. For example, the discovery of antibiotics to treat and cure many bacterial diseases was a major breakthrough in medical history. Doctors, however, sometimes prescribe antibiotics unnecessarily for a variety of reasons, including pressure from patients with viral infections. Patients may insist on being prescribed an antibiotic without knowing that it will not work on viruses. Colds and flu are two notable viral infections for which some doctors send their patients to the drugstore with a prescription for an antibiotic.

Because antibiotics have been overprescribed or inappropriately prescribed for many years, bacteria have become resistant to the killing effects of these drugs. This resistance, called antibiotic resistance or drug resistance, has become a very serious problem, especially in hospital settings.

Bacteria that are not killed by the antibiotic become strong enough to resist the same medicine the next time it is given. Because bacteria multiply so rapidly, changed or mutated bacteria that resist antibiotics will quickly outnumber those that can be destroyed by those same drugs.

For Viruses

Viral diseases can be very difficult to treat because viruses live inside your body’s cells where they are protected from medicines in the bloodstream. Researchers developed the first antiviral drug in the late 20th century. The drug, acyclovir, was first approved by the U.S. Food and Drug Administration (FDA) to treat herpes simplex virus infections. Only a few other antiviral medicines are available to prevent and treat viral infections and diseases.

Healthcare providers treat HIV infection with a group of powerful medicines that can keep the virus in check. Known as highly active antiretroviral therapy (HAART), this treatment has improved the lives of many suffering from this deadly infection.

Viral diseases should never be treated with antibiotics. Sometimes, a person with a viral disease will develop a bacterial disease as a complication of the initial viral disease. For example, children with chickenpox often scratch the skin lesions (sores) caused by the viral infection. Bacteria, such as staph, can enter those lesions and cause a bacterial infection. The doctor may then prescribe an antibiotic to destroy the bacteria. The antibiotic, however, will not work on the chickenpox virus. It will work only against staph.

Although safe and effective treatments and cures for most viral diseases have eluded researchers, there are safe vaccines to protect you from viral infections and diseases.

For Fungi

Medicines applied directly to the infected area are available by prescription and over-the-counter (OTC) for treating skin and nail fungal infections. Unfortunately, many people have had limited success with them. During the 1990s, oral prescription medicines became available for treating fungal infections of the skin and nails.

For many years, very powerful oral antifungal medicines were used only to treat systemic (within the body) fungal infections, such as histoplasmosis. Doctors usually prescribe oral antifungal medications cautiously because all of them, even the milder medicines for skin and nail fungi, can have very serious side effects.

For Protozoa

Diseases caused by protozoan parasites are among the leading causes of death and disease in tropical and subtropical regions of the world. Developing countries within these areas contain three-quarters of the world’s population, and their people suffer the most from these diseases. Controlling parasitic diseases is a problem because there are no vaccines for any of them.

In many cases, controlling the insects that transmit these diseases is difficult because of pesticide resistance, concerns regarding environmental damage, and lack of adequate public health systems to apply existing insect control methods. Thus, disease control relies heavily on the availability of medicines. Healthcare providers usually use antiparasitic medicines to treat protozoal infections. Unfortunately, there are very few medicines that fight protozoa, and some of those are either harmful to humans or are becoming ineffective.

The fight against the protozoan Plasmodium falciparum, the cause of the most deadly form of malaria, is a good example. This protozoan has become resistant to most of the medicines currently available to destroy it. A major focus of malaria research is on developing a vaccine to prevent people from getting the disease. In the meantime, many worldwide programs hope to eventually control malaria by keeping people from contact with infected mosquitoes or preventing infection if contact cannot be avoided.

Chapter 2

Immunity: An Overview

Chapter Contents

Section 2.1—The Immune System

Section 2.2—Immune System Response to Infection

Section 2.1

The Immune System

This section includes text excerpted from Overview of the Immune System, National Institute of Allergy and Infectious Diseases (NIAID), December 30, 2013. Reviewed July 2019.

Function

The overall function of the immune system is to prevent or limit infection. An example of this principle is found in immune-compromised people, including those with genetic immune disorders; immune-debilitating infections, such as human immunodeficiency virus (HIV); and even pregnant women, who are susceptible to a range of microbes that typically do not cause infection in healthy individuals.

The immune system can distinguish between normal, healthy cells and unhealthy cells by recognizing a variety of danger cues called danger-associated molecular patterns (DAMPs). Cells may be unhealthy because of infection or because of cellular damage caused by noninfectious agents, such as sunburn or cancer. Infectious microbes, such as viruses and bacteria, release another set of signals recognized by the immune system called pathogen-associated molecular patterns (PAMPs).

When the immune system first recognizes these signals, it responds to address the problem. If an immune response cannot be activated when there is sufficient need, problems arise, such as an infection. On the other hand, when an immune response is activated without a real threat or is not turned off once the danger passes, different problems arise, such as allergic reactions and autoimmune disease.

The immune system is complex and pervasive. There are numerous cell types that either circulates throughout the body or reside in a particular tissue. Each cell type plays a unique role, with different ways of recognizing problems, communicating with other cells, and performing their functions. By understanding all the details behind this network, researchers may optimize immune responses to confront specific issues, ranging from infections to cancer.

Location

All immune cells come from precursors in the bone marrow and develop into mature cells through a series of changes that can occur in different parts of the body.

Skin

The skin is usually the first line of defense against microbes. Skin cells produce and secrete important antimicrobial proteins, and immune cells can be found in specific layers of skin.

Bone Marrow

The bone marrow contains stems cells that can develop into a variety of cell types. The common myeloid progenitor stem cell in the bone marrow is the precursor to innate immune cells—neutrophils, eosinophils, basophils, mast cells, monocytes, dendritic cells, and macrophages—that are important first-line responders to infection.

The common lymphoid progenitor stem cell leads to adaptive immune cells—B cells and T cells—that are responsible for mounting responses to specific microbes based on previous encounters (immunological memory). Natural killer (NK) cells also are derived from the common lymphoid progenitor and share features of both innate and adaptive immune cells, as they provide immediate defenses similar to innate cells but also may be retained as memory cells like adaptive cells. B, T, and NK cells also are called lymphocytes.

Bloodstream

Immune cells constantly circulate throughout the bloodstream, patrolling for problems. When blood tests are used to monitor white blood cells (WBCs), another term for immune cells, a snapshot of the immune system is taken. If a cell type is either scarce or overabundant in the bloodstream, this may reflect a problem.

Thymus

T cells mature in the thymus, a small organ located in the upper chest.

Lymphatic System

The lymphatic system is a network of vessels and tissues composed of lymph, an extracellular fluid, and lymphoid organs, such as lymph nodes. The lymphatic system is a conduit for travel and communication between tissues and the bloodstream. Immune cells are carried through the lymphatic system and converge in lymph nodes, which are found throughout the body.

Lymph nodes are a communication hub where immune cells sample information brought in from the body. For instance, if adaptive immune cells in the lymph node recognize pieces of a microbe brought in from a distant area, they will activate, replicate, and leave the lymph node to circulate and address the pathogen. Thus, doctors may check patients for swollen lymph nodes, which may indicate an active immune response.

Spleen

The spleen is an organ located behind the stomach. While it is not directly connected to the lymphatic system, it is important for processing information from the bloodstream. Immune cells are enriched in specific areas of the spleen, and upon recognizing blood-borne pathogens, they will activate and respond accordingly.

Mucosal Tissue

Mucosal surfaces are prime entry points for pathogens, and specialized immune hubs are strategically located in mucosal tissues, such as the respiratory tract and gut. For instance, Peyer’s patches are important areas in the small intestine where immune cells can access samples from the gastrointestinal tract.

Section 2.2

Immune System Response to Infection

This section includes text excerpted from Overview of the Immune System, National Institute of Allergy and Infectious Diseases (NIAID), December 30, 2013. Reviewed July 2019.

Features of an Immune Response

An immune response is generally divided into innate and adaptive immunity. Innate immunity occurs immediately, when circulating innate cells recognize a problem. Adaptive immunity occurs later, as it relies on the coordination and expansion of specific adaptive immune cells. Immune memory follows the adaptive response, when mature adaptive cells, highly specific to the original pathogen, are retained for later use.

Innate Immunity

Innate immune cells express genetically encoded receptors, called Toll-like receptors (TLRs), which recognize general danger- or pathogen-associated patterns. Collectively, these receptors can broadly recognize viruses, bacteria, fungi, and even noninfectious problems. However, they cannot distinguish between specific strains of bacteria or viruses.

There are numerous types of innate immune cells with specialized functions. They include neutrophils, eosinophils, basophils, mast cells, monocytes, dendritic cells, and macrophages. Their main feature is the ability to respond quickly and broadly when a problem arises, typically leading to inflammation. Innate immune cells also are important for activating adaptive immunity. Innate cells are critical for host defense, and disorders in innate cell function may cause chronic susceptibility to infection.

Adaptive Immunity

Adaptive immune cells are more specialized, with each adaptive B or T cell bearing unique receptors, B-cell receptors (BCRs) and T-cell receptors (TCRs), that recognize specific signals rather than general patterns. Each receptor recognizes an antigen, which is simply any molecule that may bind to a BCR or TCR. Antigens are derived from a variety of sources, including pathogens, host cells, and allergens. Antigens are typically processed by innate immune cells and presented to adaptive cells in the lymph nodes.

The genes for BCRs and TCRs are randomly rearranged at specific cell maturation stages, resulting in unique receptors that may potentially recognize anything. Random generation of receptors allows the immune system to respond to new or unforeseen problems. This concept is especially important because environments may frequently change, for instance when seasons change or a person relocates, and pathogens are constantly evolving to survive. Because BCRs and TCRs are so specific, adaptive cells may only recognize one strain of a particular pathogen, unlike innate cells, which recognize broad classes of pathogens. In fact, a group of adaptive cells that recognize the same strain will likely recognize different areas of that pathogen.

If a B or T cell has a receptor that recognizes an antigen from a pathogen and also receives cues from innate cells that something is wrong, the B or T cell will activate, divide, and disperse to address the problem. B cells make antibodies, which neutralize pathogens, rendering them harmless. T cells carry out multiple functions, including killing infected cells and activating or recruiting other immune cells. The adaptive response has a system of checks and balances to prevent unnecessary activation that could cause damage to the host. If a B or T cell is autoreactive, meaning its receptor recognizes antigens from the body’s own cells, the cell will be deleted. Also, if a B or T cell does not receive signals from innate cells, it will not be optimally activated.

Immune memory is a feature of the adaptive immune response. After B or T cells are activated, they expand rapidly. As the problem resolves, cells stop dividing and are retained in the body as memory cells. The next time this same pathogen enters the body, a memory cell is already poised to react and can clear away the pathogen before it establishes itself.

Vaccination

Vaccination, or immunization, is a way to train your immune system against a specific pathogen. Vaccination achieves immune memory without an actual infection, so the body is prepared when the virus or bacterium enters. Saving time is important to prevent a pathogen from establishing itself and infecting more cells in the body.

An effective vaccine will optimally activate both the innate and adaptive response. An immunogen is used to activate the adaptive immune response so that specific memory cells are generated. Because BCRs and TCRs are unique, some memory cells are simply better at eliminating the pathogen. The goal of vaccine design is to select immunogens that will generate the most effective and efficient memory response against a particular pathogen. Adjuvants, which are important for activating innate immunity, can be added to vaccines to optimize the immune response. Innate immunity recognizes broad patterns, and without innate responses, adaptive immunity cannot be optimally achieved.

Immune Cells

Granulocytes include basophils, eosinophils, and neutrophils. Basophils and eosinophils are important for host defense against parasites. They also are involved in allergic reactions. Neutrophils, the most numerous innate immune cell, patrol for problems by circulating in the bloodstream. They can phagocytose, or ingest, bacteria, degrading them inside special compartments called vesicles.

Mast cells also are important for defense against parasites. Mast cells are found in tissues and can mediate allergic reactions by releasing inflammatory chemicals, such as histamine.

Monocytes, which develop into macrophages, also patrol and respond to problems. They are found in the bloodstream and in tissues. Macrophages, which means big eater in Greek, are named for their ability to ingest and degrade bacteria. Upon activation, monocytes and macrophages coordinate an immune response by notifying other immune cells of the problem. Macrophages also have important nonimmune functions, such as recycling dead cells, like red blood cells (RBCs), and clearing away cellular debris. These housekeeping functions occur without activation of an immune response.

Neutrophils accumulate within minutes at sites of local tissue injury (center). They then communicate with each other using lipid and other secreted mediators to form cellular swarms. Their coordinated movement and exchange of signals then instruct other innate immune cells called macrophages and monocytes to surround the neutrophil cluster and form a tight wound seal.

Dendritic cells (DC) are an important antigen-presenting cell (APC), and they also can develop from monocytes. Antigens are molecules from pathogens, host cells, and allergens that may be recognized by adaptive immune cells. Similar to DCs, APCs are responsible for processing large molecules into readable fragments (antigens) recognized by adaptive B or T cells. However, antigens alone cannot activate T cells. They must be presented with the appropriate major histocompatibility complex (MHC) expressed on the APC. MHC provides a checkpoint and helps immune cells distinguish between host and foreign cells.

Natural killer (NK) cells have features of both innate and adaptive immunity. They are important for recognizing and killing virus-infected cells or tumor cells. They contain intracellular compartments called granules, which are filled with proteins that can form holes in the target cell and also cause apoptosis, the process for programmed cell death. It is important to distinguish between apoptosis and other forms of cell death, such as necrosis. Apoptosis, unlike necrosis, does not release danger signals that can lead to greater immune activation and inflammation. Through apoptosis, immune cells can discreetly remove infected cells and limit bystander damage. Recently, researchers have shown in mouse models that NK cells, similar to adaptive cells, can be retained as memory cells and respond to subsequent infections by the same pathogen.

Adaptive Cells

B cells have two major functions: They present antigens to T cells, and more importantly, they produce antibodies to neutralize infectious microbes. Antibodies coat the surface of a pathogen and serve three major roles: neutralization, opsonization, and complement activation.

Neutralization occurs when the pathogen, because it is covered in antibodies, is unable to bind and infect host cells. In opsonization, an antibody-bound pathogen serves as a red flag to alert immune cells, such as neutrophils and macrophages, to engulf and digest the pathogen. Complement is a process for directly destroying, or lysing, bacteria.

Antibodies are expressed in two ways. The B-cell receptor (BCR), which sits on the surface of a B cell, is actually an antibody. B cells also secrete antibodies to diffuse and bind to pathogens. This dual expression is important because the initial problem, for instance, a bacterium, is recognized by a unique BCR and activates the B cell. The activated B cell responds by secreting antibodies, essentially the BCR but in soluble form. This ensures that the response is specific against the bacterium that started the whole process.

Every antibody is unique, but they fall under general categories: IgM, IgD, IgG, IgA, and IgE. (Ig is short for immunoglobulin, which is another word for antibody.) While they have overlapping roles, IgM generally is important for complement activation; IgD is involved in activating basophils; IgG is important for neutralization, opsonization, and complement activation; IgA is essential for neutralization in the gastrointestinal tract; and IgE is necessary for activating mast cells in parasitic and allergic responses.

T cells have a variety of roles and are classified by subsets. T cells are divided into two broad categories: CD8+ T cells or CD4+ T cells, based on which protein is present on the cell’s surface. T cells carry out multiple functions, including killing infected cells and activating or recruiting other immune cells.

CD8+ T cells also are called cytotoxic T cells or cytotoxic lymphocytes (CTLs). They are crucial for recognizing and removing virus-infected cells and cancer cells. CTLs have specialized compartments, or granules, containing cytotoxins that cause apoptosis, i.e., programmed cell death. Because of its potency, the release of granules is tightly regulated by the immune system.

The four major CD4+ T-cell subsets are TH1, TH2, TH17, and Treg, with TH referring to T helper cell. TH1 cells are critical for coordinating immune responses against intracellular microbes, especially bacteria. They produce and secrete molecules that alert and activate other immune cells, such as bacteria-ingesting macrophages. TH2 cells are important for coordinating immune responses against extracellular pathogens, such as helminths (parasitic worms), by alerting B cells, granulocytes, and mast cells. TH17 cells are named for their ability to produce interleukin 17 (IL-17), a signaling molecule that activates immune and nonimmune cells. TH17 cells are important for recruiting neutrophils.

Regulatory T cells (Tregs), as the name suggests, monitor and inhibit the activity of other T cells. They prevent adverse immune activation and maintain tolerance or the prevention of immune responses against the body’s own cells and antigens.

Communication

Immune cells communicate in a number of ways, either by cell-to-cell contact or through secreted signaling molecules. Receptors and ligands are fundamental for cellular communication. Receptors are protein structures that may be expressed on the surface of a cell or in intracellular compartments. The molecules that activate receptors are called ligands, which may be free-floating or membrane-bound.

Ligand-receptor interaction leads to a series of events inside the cell involving networks of intracellular molecules that relay the message. By altering the expression and density of various receptors and ligands, immune cells can dispatch specific instructions tailored to the situation at hand.

Cytokines are small proteins with diverse functions. In immunity, there are several categories of cytokines important for immune cell growth, activation, and function.

Colony-stimulating factors are essential for cell development and differentiation.

Interferons are necessary for immune-cell activation. Type I interferons mediate antiviral immune responses, and type II interferon is important for antibacterial responses.

Interleukins, which come in over 30 varieties, provide context-specific instructions, with activating or inhibitory responses.

Chemokines are made in specific locations of the body or at a site of infection to attract immune cells. Different chemokines will recruit different immune cells to the site needed.

The tumor necrosis factor (TNF) family of cytokines stimulates immune-cell proliferation and activation. They are critical for activating inflammatory responses, and as such, TNF blockers are used to treat a variety of disorders, including some autoimmune diseases.

Toll-like receptors are expressed on innate immune cells, such as macrophages and dendritic cells. They are located on the cell surface or in intracellular compartments because microbes may be found in the body or inside infected cells. TLRs recognize general microbial patterns, and they are essential for innate immune-cell activation and inflammatory responses.

B-cell receptors and T-cell receptors are expressed on adaptive immune cells. They are both found on the cell surface, but BCRs also are secreted as antibodies to neutralize pathogens. The genes for BCRs and TCRs are randomly rearranged at specific cell maturation stages, resulting in unique receptors that may potentially recognize anything. Random generation of receptors allows the immune system to respond to unforeseen problems. They also explain why memory B or T cells are highly specific and, upon re-encountering their specific pathogen, can immediately induce a neutralizing immune response.

Major histocompatibility complex (MHC), or human leukocyte antigen (HLA), proteins serve two general roles.

Major histocompatibility complex proteins function as carriers to present antigens on cell surfaces. MHC class I proteins are essential for presenting viral antigens and are expressed by nearly all cell types, except red blood cells. Any cell infected by a virus has the ability to signal the problem through MHC class I proteins. In response, CD8+ T cells (also called CTLs) will recognize and kill infected cells. MHC class II proteins are generally only expressed by antigen-presenting cells, such as dendritic cells and macrophages. MHC class II proteins are important for presenting antigens to CD4+ T cells. MHC class II antigens are varied and include both pathogen- and host-derived molecules.

Major histocompatibility complex proteins also signal whether a cell is a host cell or a foreign cell. They are very diverse, and every person has a unique set of MHC proteins inherited from her or his parents. As such, there are similarities in MHC proteins between family members. Immune cells use MHC to determine whether or not a cell is friendly. In organ transplantation, the MHC or HLA proteins of donors and recipients are matched to lower the risk of transplant rejection, which occurs when the recipient’s immune system attacks the donor tissue or organ. In stem cell or bone marrow transplantation, improper MHC or HLA matching can result in graft-versus-host disease, which occurs when the donor cells attack the recipient’s body.

Complement refers to a unique process that clears away pathogens or dying cells and also activates immune cells. Complement consists of a series of proteins found in the blood that forms a membrane-attack complex. Complement proteins are only activated by enzymes when a problem, such as an infection, occurs. Activated complement proteins stick to a pathogen, recruiting and activating additional complement proteins, which assemble in a specific order to form a round pore or hole. Complement literally punches small holes into the pathogen, creating leaks that lead to cell death. Complement proteins also serve as signaling molecules that alert immune cells and recruit them to the problem area.

Immune Tolerance

Tolerance is the prevention of an immune response against a particular antigen. For instance, the immune system is generally tolerant of self-antigens, so it does not usually attack the body’s own cells, tissues, and organs. However, when tolerance is lost, disorders such as autoimmune disease or food allergy may occur. Tolerance is maintained in a number of ways:

When adaptive immune cells mature, there are several checkpoints in place to eliminate autoreactive cells. If a B cell produces antibodies that strongly recognize host cells, or if a T cell strongly recognizes self-antigen, they are deleted.

Nevertheless, there are autoreactive immune cells present in healthy individuals. Autoreactive immune cells are kept in a nonreactive, or anergic, state. Even though they recognize the body’s own cells, they do not have the ability to react and cannot cause host damage.

Regulatory immune cells circulate throughout the body to maintain tolerance. Besides limiting autoreactive cells, regulatory cells are important for turning an immune response off after the problem is resolved. They can act as drains, depleting areas of essential nutrients that surrounding immune cells need for activation or survival.

Some locations in the body are called immunologically privileged sites. These areas, such as the eye and brain, do not typically elicit strong immune responses. Part of this is because of physical barriers, such as the blood-brain barrier, that limits the degree to which immune cells may enter. These areas also may express higher levels of suppressive cytokines to prevent a robust immune response.

Fetomaternal tolerance is the prevention of a maternal immune response against a developing fetus. Major histocompatibility complex proteins help the immune system distinguish between host and foreign cells. MHC also is called human leukocyte antigen. By expressing paternal MHC or HLA proteins and paternal antigens, a fetus can potentially trigger the mother’s immune system. However, there are several barriers that may prevent this from occurring: The placenta reduces the exposure of the fetus to maternal immune cells, the proteins expressed on the outer layer of the placenta may limit immune recognition, and regulatory cells and suppressive signals may play a role.

Transplantation of a donor tissue or organ requires appropriate MHC or HLA matching to limit the risk of rejection. Because MHC or HLA matching is rarely complete, transplant recipients must continuously take immunosuppressive drugs, which can cause complications such as higher susceptibility to infection and some cancers. Researchers are developing more targeted ways to induce tolerance to transplanted tissues and organs while leaving protective immune responses intact.

Chapter 3

Immunodeficiency and Contagious Diseases

Immunodeficiency is a disease wherein your body’s immune system is either absent or not functioning properly. This disease impairs the immune system’s ability to defend against foreign cells, such as cancer cells, bacteria, virus, and fungi, invading your body.

Types of Immunodeficiency Diseases

There are two types of immunodeficiency diseases:

Primary immunodeficiency (PID)

Secondary immunodeficiency (SID)

Primary Immunodeficiency

Primary immunodeficiency disorder is usually acquired from birth and is hereditary. Most PIDs manifest during childhood and infancy. There are many types of PIDs, and all are relatively rare.

Primary immunodeficiency disorders are sometimes caused by single-gene mutations, but mostly by the susceptibility of genes combined with environmental factors. Primary immunodeficiency disorders are categorized based on the part of the immune system that is affected. Examples of PIDs are:

Common variable immune deficiency (CVID). Common variable immune deficiencies (CVIDs) are the most commonly diagnosed form of PIDs, especially in adults, and are characterized by low levels of antibodies and serum immunoglobins, causing more susceptibility to infections.

B cell immunodeficiencies. The main role of the B cells is to produce antibodies, which helps the immune system to detect and kill invading microbes. Mutations in the B cells, which control genes, can affect the production of antibodies, which can in turn result in severe recurrent bacterial infections.

T cell immunodeficiencies. One role of the T cells is to activate the B cells and to pass information about the identity of the microbe, so that the B cells can produce the right antibodies. Some T cells get involved in killing the invading microbes. Mutations in the genes that control T cells can result in fewer T cells or in ones that have low functionality. This can cause disruptions in their killing ability and can also affect B cell functions.

Secondary Immunodeficiency

Secondary immunodeficiency is normally acquired after birth and is more common than PID. Secondary immunodeficiency is commonly acquired from primary illnesses such as human immunodeficiency virus (HIV). Examples of secondary immunodeficiency disorders are:

Malnutrition. One of the most common causes of SID is protein-calorie malnutrition. Deficiency in protein can affect the production of T cells and their functions. This leaves you susceptible to diarrhea and infections related to the respiratory tract.

Drug regimens. Taking certain drugs used for other primary illness, such as an immunosuppressive drug in cancer treatment, may result in SID. The immunosuppressive drug usage is to prevent transplant rejection, wherein the drug is used to suppress the immune system of the transplant recipient and prevent the immune system from attacking the transplanted tissue. These drugs have significant side effects and can suppress more areas of the immune system, leading to susceptibility to infections.

Signs and Symptoms of Immunodeficiency Diseases

Having infections that are longer lasting, frequent, and harder to treat are the most common signs that denote the presence of immunodeficiency diseases. You may also get infections that healthy people could fight off. The signs and symptoms of immunodeficiency diseases include:

Infection and inflammation of