Chapter 15

Introduction Host defense mechanisms Ways in which the body protects itself from pathogens— referred to as three lines of defense. The first two lines of defense are nonspecific. The third line of defense, the immune response, is very specific. In the third line of defense, special proteins called antibodies are produced in response to foreign substances called antigens.

Lines of Defense

Nonspecific Host Defense Mechanisms Nonspecific host defense mechanisms are general and serve to protect the body against many harmful substances. Example: innate or inborn resistance Exact factors that produce innate resistance are not well understood. Other nonspecific host defense mechanisms include mechanical and physical barriers to invasion, chemical factors, microbial antagonism, fever, the inflammatory response, and phagocytic white blood cells.

First Line of Defense Skin and mucous membranes as physical barriers Cellular and chemical factors In addition to the skin as a physical barrier, there are other factors (e.g., pH and temperature of skin, perspiration, cilia, and various enzymes in secretions such as lysozyme) that are components of the first line of defense. Microbial antagonism When indigenous microbiota prevent colonization of “new arrivals” as a result of competition for sites and nutrients and production of lethal substances

Second Line of Defense Transferrin Levels of this glycoprotein increase in response to systemic bacterial infections; it binds to iron depriving pathogens of this vital nutrient. Fever Stimulated by pyrogenic (fever-producing) substances (e.g., pathogens and interleukin 1 [IL-1]) Augments host’s defenses by stimulating leukocytes, reducing available free plasma iron, and inducing the production of IL-1

Second Line of Defense (cont.) Interferons These are small antiviral proteins produced by virus-infected cells; they prevent viruses from multiplying. There are three types (alpha, beta, and gamma), produced by three different types of cells. These three types are induced by different stimuli (e.g., viruses, tumors, bacteria, and foreign cells). Interferons are not virus-specific, but they are species-specific. Interferons can cause nonspecific flu like symptoms.

Second Line of Defense (cont.) The complement system It is a group of about 30 different proteins found in normal blood plasma — “complementary” to the immune system. Complement components interact with each other in a stepwise manner known as the complement cascade. The complement system assists in the destruction of many different pathogens. Opsonization is a process by which phagocytosis is facilitated by the deposition of opsonins (e.g., antibodies or certain complement fragments) onto objects (e.g., pathogens).

Second Line of Defense (cont.) Acute-phase proteins Plasma proteins that increase rapidly in response to infection, inflammation, or tissue injury; (e.g., is C-reactive protein). Cytokines These are chemical mediators released from many different types of cells in the body; they enable cells to communicate with each other—within the immune system and between the immune system and other systems of the body. Some cytokines (called chemokines) are chemoattractants; they recruit phagocytes to sites where they are needed.

Second Line of Defense Inflammation The body responds to any local injury, irritation, microbial invasion, or bacterial toxin by a complex series of events referred to as inflammation; the three major events in acute inflammation are An increase in the diameter of capillaries, (vasodilation) which increases blood flow to the site Increased permeability of the capillaries, allowing the escape of plasma and plasma proteins Exit of leukocytes from the capillaries and their accumulation at the site of injury

Inflammation (cont.) The primary purposes of the inflammatory response are to Localize an infection Prevent the spread of microbial invaders Neutralize any toxins being produced at the site Aid in the repair of damaged tissue The four major signs and symptoms of inflammation are redness, heat, swelling (edema), and pain. Plasma that escapes from the capillaries into the site causes the area to become edematous (swollen).

Sequence of Events in Inflammation Tissue injury Vasodilation Increased permeability Emigration of leukocytes Chemotaxis Phagocytosis

Inflammation (cont.) The accumulation of fluid, cells, and cellular debris at the inflammation site is known as an inflammatory exudate. If the exudate is thick and greenish-yellow, containing many live and dead leukocytes, it is known as a purulent exudate or pus. In many inflammatory responses (e.g., arthritis or pancreatitis), there is no exudate and no invading microbes. Pyogenic microbes (pus-producing microbes) such as staphylococci and streptococci result in additional pus formation.

Phagocytosis Phagocytic white blood cells are called phagocytes, and the process by which they surround and engulf (ingest) foreign material is called phagocytosis. The three major categories of leukocytes (white cells) found in blood are monocytes, lymphocytes, and granulocytes. The three types of granulocytes are eosinophils, basophils, and neutrophils. The most important groups of phagocytes in the human body are macrophages and neutrophils.

Table 15-1 Four steps in Phagocytosis

Mechanisms by Which Pathogens Escape Destruction by Phagocytes Capsules initially serve to protect the organism from phagocytosis (i.e., they serve an antiphagocytic function). Some bacteria produce an exoenzyme called leukocidin, which kills phagocytes. Some bacteria (e.g., Mycobacterium tuberculosis) are not destroyed within the phagolysosome. The mechanism by which each pathogen evades digestion by lysosomal enzymes differs from pathogen to pathogen, and is not yet fully understood.

Disorders and Conditions That Adversely Affect Phagocytic and Inflammatory Processes Leukopenia—an abnormally low number of circulating leukocytes Disorders and conditions affecting leukocyte motility and chemotaxis Inability of leukocytes to migrate in response to chemotactic agents may be related to a defect in the production of actin, a structural protein associated with motility. Disorders and conditions affecting intracellular killing by phagocytes (e.g., chronic granulomatous disease, CGD) Additional factors

Additional Factors That Can Impair Host Defense Mechanisms Nutritional status Increased iron levels Stress Cancer and cancer chemotherapy Various genetic defects Age AIDS Drugs (e.g., steroids)