The first line of defense against pathogens and foreign material is not directed

The body's nonspecific defenses include the following:

- Physical barriers keep hazardous materials and organisms outside the body (epithelium, hairs, secretions of sebaceous glands and sweat glands).  

- Phagocytes in peripheral tissues remove cellular debris and respond to invasion by foreign compounds or pathogens.  
           o   First line of cellular defense
           o   Two general classes: microphages and macrophages.
           o   Microphages are neutrophils (more abundant and mobile) and eosinophils.
           o   Macrophages are derived from circulating monocytes.
           o   Macrophages are either fixed (microglia in CNS or Kupffer cells in liver) or free.

- Immunological surveillance is the constant monitoring of normal tissues and involves the lymphocytes known as NK (natural killer) cells.
           o   NK cells recognize an abnormal cell by detecting the presence of antigens.
           o   NK secrete proteins called perforins, which kill the abnormal cell by creating  large pores in its cell membrane.  

- Interferons are small proteins released by activated lymphocytes, macrophages, and tissue cells infected with viruses
           o   Slow the spread of viral infections and stimulate the activities of macrophages and NK cells.
           o   Are cytokines that coordinate local activities.  

- The complement system consists of 11 special complement proteins.
           o   Complement proteins interact with one another in chain reactions.
           o   Reaction begins when a particular complement protein binds either to an antibody molecule attached to a bacterial cell wall or directly to bacterial cell walls.  The bound complement protein then interacts with a series of other complement proteins.  
           o   Complement activation is known to (1) attract phagocytes, (2) stimulate phagocytes, (3) destroy cell membranes, and (4) promote inflammation.
  
- Inflammation, or the inflammatory response, is a localized tissue response to injury.  
           o   Produces local swelling, redness, heat, and pain.  
           o   Can be produced by any stimulus that kills cells or damages loose connective tissue.
           o   Starts of when mass cells release chemicals, including histamine and heparin, into the interstitial fluid.
  
- Fever is the maintenance of a body temperature greater than 37.2°C (99°F).
           o   Hypothalamus (thermostat) contains nuclei that regulate body temperature.
           o   Pyrogens reset thermostat in the hypothalamus, causing a rise in body temperature.  
           o   Pathogens, bacterial toxins, and antigen-antibody complexes may act as pyrogens or stimulate the release of pyrogens by macrophages.  

Nonspecific defenses are directed against harmful substances without regard to their identity. The skin and mucous membranes form the body's first line of defense. While the skin cells act as a physical defense, the mucus traps foreign matter or pathogens. In addition, the secretions from sebaceous and sweat glands of the skin are quite acidic and can destroy many pathogens. If the pathogens get through the skin, another nonspecific defense is activated - the inflammatory response. The inflammatory response is initiated by macrophages in the tissue that destroy damaged cells by phagocytosis and release the cellular debris, which further stimulates the inflammatory response. Blood flow to the site of infection increases, as does the permeability of the capillary endothelial cells. This recruits additional leukocytes to the site of infection, and isolates the infected material by the release of clotting factors. A third form of nonspecific defense involves the release of interferons (\({\alpha}\) and \({\beta}\)) by virus-infected cells. Interferons act on nearby cells, making them resistant to viral replication due to the presence of RNA-degrading enzymes. Thus, while the virus-infected cells will die, the cells surrounding them are protected from infection. Another type of interferon (\({\gamma}\)) is secreted from T cells and NK cells, and activates cytotoxic T cells and NK cells to kill virus-infected cells and cancer cells. A fourth form of nonspecific defense involves the natural killer (NK) cells that recognize the general features of infected cells and cause them to lyse. The activity of the NK cells is enhanced by interleukin-2 and antibodies. Finally, the complement system is a form of nonspecific defense that involves a cascade of proteins. Those proteins lead to the incorporation of a membrane attack complex (MAC) into bacteria, causing them to lyse. The complement system can be activated by either the alternative or classical pathways. The alternative pathway is activated by directly binding to carbohydrates on the bacterium. The classical pathway is activated by the binding of an antibody to bacteria. Some complement proteins also play a role in chemotaxis or bind to mast cells to stimulate histamine release. At the same time, the complement protein C3b attaches to the surface of bacteria to induce opsonization, which enhances bacterial degradation by phagocytosis.