Introduction
The vertebrate, including human, immune system is a complex multilayered system for defending against external and internal threats to the integrity of the body. The human immune system is a host defense system, i.e. is able to keep most potential pathogens out of the body or quickly destroy them if they do manage to get in. A pathogen is an organism that can make humans sick if it manages to enter their body. Most pathogens are microorganisms, although some are much larger. Common types of pathogens of human hosts include bacteria, viruses, fungi, and single-celled organisms called protists. Examples of each of these types of pathogens are presented in Table 10.1.
| Type of pathogen | Description | Disease caused |
|---|---|---|
| Bacteria Example: Escherichia coli | single cell organisms without a nucleus | strep throat, staph infections, tuberculosis, food poisoning, tetanus, pneumonia, syphilis |
| Viruses Example: Herpes simplex | non-living particles that reproduce by taking over living cells | common cold, flu, genital herpes, cold sores, measles, AIDS, genital warts, chicken pox, small pox |
| Fungi Example: Death cap mushroom | simple organisms, including mushrooms and yeast, that grow as single cells or thread-like filaments | ringworm, athletes foot, tinea, candidiasis, histoplasmosis, mushroom poisoning |
| Protozoa Example: Giardia lamblia | single cell organisms with a nucleus | malaria, “traveller’s diarrhea”, giardiasis, typano somiasis (“sleeping sickness”) |
Table 10.1: Types of disease-causing pathogens.
The immune system comprises many biological structures – ranging from individual leukocytes 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 (cancer) 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 increasing specificity for particular pathogens or tumor cells. The system can be divided into two types of defense systems: the innate immune system, which is nonspecific toward a particular kind of pathogen, and the adaptive immune system, which is specific.
Innate immunity is not caused by an infection or vaccination and depends initially on physical and chemical barriers that work on all pathogens, sometimes called the first line of defense. The second line of defense of the innate system includes chemical signals that produce inflammation and fever responses as well as mobilizing protective cells and other chemical defenses.
The adaptive immune system mounts a highly specific response to substances and organisms that do not belong in the body. The adaptive system takes longer to respond and has a memory system that allows it to respond with greater intensity should the body encounter a pathogen again, even years later.
The innate immune system
When pathogens enter the body, the innate immune system responds through a variety of barriers and internal defense mechanisms. The barriers to pathogens are usually categorized into two groups: anatomical and cellular. The internal defense mechanisms are: the inflammatory response, phagocytosis, the complement system, and the natural killer cells.
Anatomical barriers
The body’s first line of defense consists of three different types of barriers that keep most pathogens out of body tissues. These types of barriers are: mechanical, chemical, and biological.
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 skin contains the protein keratin, which resists physical entry into cells. The outer layer of skin – the epidermis – is tough, and very difficult for pathogens to penetrate. It consists of dead cells that are constantly shed from the body surface, a process that 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 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, preventing their movement deeper into the body. 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. A sneeze can travel as fast as 160 Km/hr (about 99 mi/hour) and expel as many as 100,000 droplets into the air around you (a good reason to cover your sneezes!). Other mechanical defenses include tears, which wash pathogens from the eyes, and urine, which flushes pathogens out of the urinary tract.
Despite these defenses, pathogens may enter the body through skin abrasions or punctures, or by collecting on mucosal surfaces in large numbers that overcome the protections of mucus or cilia.
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 breast milk contain antimicrobial substances (such as the enzyme lysozyme) that kill pathogens, especially bacteria.
In the stomach, stomach acid and digestive enzymes called proteases (which break down proteins) create a highly acidic environment, which kills most of the pathogens that enter the gastrointestinal tract in food or water.
Sebaceous glands in the dermis of the skin secrete acids that form a very fine, slightly acidic film on the surface of the skin. This film 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.
Biological barriers
Biological barriers are living organisms that help protect the body from pathogens. The surface of the body and the urinary, reproductive, and lower gastrointestinal tracts have a community of trillions of microorganisms, such as bacteria, archaea, and fungi, that coexist without harming the body. These harmless microorganisms use up food and surface space that help prevent pathogenic bacteria from colonizing the body. Some of them also secrete substances that change the conditions of their environment, making it less hospitable to potentially harmful bacteria – for instance, they may release toxins or change the pH. All these effects of these harmless microorganisms make them highly beneficial to their host by reducing the chances that pathogenic microorganisms are able to reach sufficient numbers and cause illness.
Cellular barriers
Cellular responses of the innate immune system involve a variety of types of leukocytes. Leukocytes are white blood cells made in the bone marrow and found in the blood and lymph tissue. They have the ability to recognize pathogens as foreign to the body. A white blood cell is larger than a red blood cell, is nucleated, and is typically able to move using amoeboid locomotion. Because they can move on their own, white blood cells can leave the blood to go to infected tissues. Many of these leukocytes circulate in the blood and act like independent, single-celled organisms, searching out and destroying pathogens in the human host. These and other immune cells of the innate system identify pathogens or debris, and then help to eliminate them in some way. Various types of cells involved in innate immune are shown in Figure 10.1.
Figure 10.1: Cells involved in the innate immune response include mast cells, natural killer cells, and white blood cells, such as monocytes, macrophages and neutrophils.
Monocytes
A monocyte is a type of white blood cell that circulates in the blood and lymph and can differentiate into macrophages and conventional dendritic cells. Monocytes are the largest type of leukocyte. They compose 2% to 10% of all leukocytes in the human body and serve multiple roles in immune function. Such roles include: replenishing resident macrophages under normal conditions; migration within approximately 8–12 hours in response to inflammation signals from sites of infection in the tissues; and differentiation into macrophages or dendritic cells to effect an immune response. In an adult human, half of the monocytes are stored in the spleen. These monocytes change into macrophages after entering into infected tissue and can transform into foam cells in the endothelium.
Neutrophils
Neutrophils are leukocytes that travel throughout the body in the blood. They are usually the first immune cells to arrive at the site of an infection. They are the most numerous types of phagocytes, and they normally make up at least half of the total circulating leukocytes. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day. During acute inflammation, more than ten times that many neutrophils may be produced each day. Many neutrophils are needed to fight infections, because after a neutrophil phagocytizes just a few pathogens, it generally dies.
Macrophages
Macrophages are large phagocytic leukocytes that develop from monocytes. Macrophages spend much of their time within the interstitial fluid in body tissues. They are the most efficient phagocytes, and they can phagocytize substantial numbers of pathogens or other cells. Macrophages are also versatile cells that produce a wide array of chemicals – including enzymes, complement proteins, and cytokines – in addition to their phagocytic action. As phagocytes, macrophages act as scavengers that rid tissues of worn-out cells and other debris, as well as pathogens. In addition, macrophages act as antigen-presenting cells that activate the adaptive immune system.
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.
Eosinophils
Eosinophils are non-phagocytic leukocytes that are related to neutrophils. They specialize in defending against parasites. They are very effective in killing large parasites (such as worms) by secreting a range of highly-toxic substances when activated. Eosinophils may become overactive and cause allergies or asthma.
Basophils
Basophils are non-phagocytic leukocytes that are also related to neutrophils. They are the least numerous of all white blood cells. Basophils secrete two types of chemicals that aid in body defenses: histamine and heparin. Histamine is responsible for dilating blood vessels and increasing their permeability in inflammation. Heparin inhibits blood clotting, and also promotes the movement of leukocytes into an area of infection.
Mast cells
Mast cells are non-phagocytic leukocytes that help initiate inflammation by secreting histamines. In some people, histamines trigger allergic reactions as well as inflammation in response to physical injury. Mast cells may also secrete chemicals that help defend against parasites. Mast cells are produced in the same way as white blood cells, but unlike circulating white blood cells, mast cells take up residence in connective tissues and especially mucosal tissues.
References:
- Fowler, Samantha, et al. Concepts of Biology. OpenStax College, Rice University, 2013. Download for free at: https://openstax.org/details/books/concepts-biology.
- Miller, Christine, Human Biology, 2020. Terms of use: This work is licensed under a Creative Commons Attribution NonCommercial. The original version can be found here.