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Nonspecific defenses are present from birth, and they include physical barriers, phagocytic cells, immuno-logic surveillance, liberation of a variety of chemi-cals, inflammation, and fever.
Physical barriers prevent or make it difficult for for-eign organisms to enter the body. For example, the skin is multilayered, and the epithelial cells are inter-locked or held together by tight junctions that make it difficult for organisms to enter the body. The pres-ence of keratin in the epidermis provides resistance against bacterial enzymes, acids, and alkalis. Also, the skin’s accessory structures provide additional protection. The hair protects against mechanical abrasion. Secretions from sebaceous glands contain chemicals (lysozymes) that have antibiotic proper-ties. Even if microorganisms penetrate the epidermis, they are confined to one area by the fascia.
Entry of organisms through the mucous membranes of the respiratory, gastrointestinal, urinary, and reproductive tracts is also effectively prevented. The respiratory tract is lined by mucus-secreting cells. The microorganisms that enter tend to settle on the mucus.
Cilia—hairlike projections on the surface of respiratory cells—help move the mucus toward the mouth, and it is then swallowed. Reflexes, such as coughing and sneezing, also help as defense mecha-nisms in the respiratory tract. Nasal hair filters and traps microorganisms in the nasal passages.
In the digestive tract, saliva has antimicrobial prop-erties. The highly acidic environment and the protein-digesting enzymes in the stomach kill pathogens. Defe-cation and vomiting also help expel microbes from the body. The genitourinary tract is frequently flushed with urine, which is a deterrent for growth of microorgan-isms, and the pH of the vagina is not conducive to mi-crobial growth. Other secretions, such as tears, sweat, and nasal secretions, contain lysozyme, an enzyme ca-pable of breaking down the cell walls of bacteria. They also help to wash away microorganisms.
Phagocytes are white blood cells that patrol the tissue. If they encounter foreign or dead organisms, phagocytes engulf them into their cyto-plasm and digest them. Phagocytes are attracted to the site of infection by chemicals, such as microbial products, components of white blood cells, damaged tissue cells, and activated complement proteins, in a process known as chemotaxis. The phagocytes then adhere to the plasma membrane of the organism a process called adherence. The cell membrane then extends around the microorganism to engulf it (in-gestion), after which lysosomes containing digestiveenzymes fuse with the vacuole containing the organ-ism. The organism is then killed and digested, and the residue (residual body) is extruded from the cell by exocytosis. Neutrophils and eosinophils are the smallest phagocytic cells; often referred to as the mi-crophages. They serve as the “first line” of defense.
The larger macrophages are modified monocytes of the circulation that have wandered into the tissues. Almost all tissue harbors macrophages and this dif-fuse collection of phagocytic cells is known as the reticuloendothelial system. Wandering or free macro-phages are attracted to sites of injury or in-fection by chemicals liberated in the affected tissue (chemotaxis). They then squeeze out from the blood between the endothelium of capillaries in a process called emigration, or diapedesis. Fixed macro-phages are modified monocytes that remain in thesame location.
The fate of microorganisms engulfed by phago-cytic cells varies. Some organisms are engulfed and destroyed by lysosomal enzymes. Other microorgan-isms, such as those in tuberculosis, may not be de-stroyed inside the cell unless other cells assist the macrophage. At times, the macrophages secrete tox-ins into the interstitial fluid in the vicinity of the or-ganism in order to destroy them. Fixed macrophages rely on the fluid movement around them to phagocy-tize the organisms.
Another form of nonspecific immunity is immuno-logic surveillance. Cells known as natural killer (NK) cells constantly survey the tissue of the body. These lymphocytes recognize any antigen that is for-eign to the body. At times, the body’s own cells may become abnormal. These cells, too, are recognized by NK cells and destroyed. NK cells are different from other lymphocytes in that they recognize all cells that look different. These cells are important in destroying cancer cells and cells infected by viruses, among oth-ers. NK cells are present in the blood, spleen, lymph nodes, and red bone marrow.
Chemicals liberated by different cells are important in immunity. There are many different types of chem-icals, some of which are described below.
Cytokines are small proteins that inhibit or facilitatenormal cell function, such as cell growth and differ-entiation. For example, certain cytokines (chemotac-tic agents) attract phagocytes to the area, some cause fever by affecting the hypothalamus, and others stim-ulate proliferation of white blood cells. Cytokines are secreted by cells such as lymphocytes, macrophages, fibroblasts, and endothelial cells. Interleukin, tumor necrosis factor, lymphotoxins, perforin, macrophage migration-inhibiting factor, and interferons are ex-amples of cytokines.
Interferons are small proteins released by acti-vated lymphocytes, macrophages, and tissue cells in-fected by viruses. Interferons bind to surface recep-tors on normal cells and trigger the cell to release antiviral proteins in the cytoplasm. These proteins prevent the virus from multiplying inside the cells. Interferons also help to activate macrophages and NK cells. Certain types of interferons reduce inflam-mation in an injured area.
The complement system is similar to the clotting sys-tem. It includes a number of inactive enzymes in the blood plasma, one of which, when activated, triggers a sequence of events that activate the other enzymes of the system. There are 11 enzymes belonging to this system, labeled from C1–C9 (C1 has 3 subtypes). When C1 is activated, it sequentially activates the other en-zymes. The activated enzymes trigger the necessary defense mechanisms. For example, one consequence of complement activation is inserting pore-forming molecules into the cell membranes of foreign cells that literally punch holes through the membrane. Another is stimulating granulocytes, mast cells, and platelets to release histamine. Histamine dilates the blood vessels (redness) and allows fluid to leak out (swelling). Some of the activated complements and enzymes attract leukocytes to the site. By “sticking” to the surface of the organisms, the enzymes alert the leukocytes to the “enemy.”
Histamine is a chemical liberated by a variety of tis-sue cells, including mast cells, basophils (a type of white blood cell), and platelets. Histamine causes va-sodilatation (which brings more blood to the area of injury or infection), increases vascular permeability (which allows fluid to enter the injured area and di-lute the toxins released; it also allows white blood cells to migrate to the area easily), and increases glandular secretion. Other actions include contrac-tion of smooth bronchi muscles in the respiratory tract and attraction of eosinophils.
Kinins are derived from plasma protein and have ef-fects similar to those of histamine: increase in vascular permeability, vasodilatation, attraction of white blood cells to the area, and stimulation of pain receptors.
Prostaglandins are lipids that are secreted by almost all cells. These chemicals have varied actions, such as smooth muscle relaxation, vasodilatation, and stimu-lation of pain receptors.
Similar to prostaglandins, leukotrienes are also lipids and have similar actions. Mast cells and basophils primarily secrete leukotrienes.
Pyrogens are chemicals released by white blood cells (and other cells) that cause an increase in body tem-perature (fever). An example of a pyrogen is inter-leukin-1, a type of cytokine.
Inflammation is discussed eariler.
A person has “fever” if his body temperature is main-tained above 37.2°C (99°F). Pyrogens reach the hypo-thalamus—the temperature-regulating area of the brain—and reset the “thermostat” to a higher tem-perature. This increase in temperature tends to in-hibit some viruses and bacteria and also speeds the body’s metabolism and, thereby, the activity of de-fense cells.
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