Innate (Nonspecific) Defenses

Innate (Nonspecific) Defenses

Our innate or nonspecific defenses prevent or limit microorganisms and other environmental hazards from approaching, entering, or spreading. These defenses are often able to prevent infection by destroy-ing pathogens, without needing the help of any other defenses. Sometimes, however, the adaptive immune system is needed to assist the nonspecific defenses. Nonspecific defenses are the first line of defense and include intact skin and mucosae. When pathogens penetrate the skin or mucosae, the second line of defense is activated. This relies on internal defenses, including antimicrobial proteins and phagocytes. Inflammation is the most important process in thesecond line of defense. The nonspecific defenses are classified as mechanical barriers, which cover body surfaces, and chemical substances, which are involved with invading pathogens.

Mechanical Barriers

Also known as physical barriers, mechanical bar-riers include the skin and the mucous membranes that line the respiratory system, digestive system, urinary system basement membranes, and repro-ductive passageways. They protect against certain infectious agents. The body’s hair, sweat, and mucus also act as mechanical barriers. The mechanical bar-riers of immunity are ready to act when we are born. The skin’s keratinized epithelial membrane stops most microorganisms on the skin from penetrating it. Keratin itself resists many weak bases and acids as well as toxins and bacterial enzymes. Inside the body, the mucous membranes function in much the same capacity.

Chemical Barriers

Provided by enzymes and other chemical substances in body fluids, these include pepsin and hydrochloric acid in the stomach; tears; lysozyme in tears, saliva, breast milk, and mucus; salt in perspiration; interferons; mucin; defensins; certain lipids in sebum; dermicidin; and complement. Interferons and complement ­proteins are the most important antimicrobial pro-teins in the body:

■■ Interferons are small proteins that bind to uninfected cells and stimulate them to make protective proteins. Interferons are secreted by infected cells and diffuse to nearby cells, stimulating protein synthesis that interferes with viral replication. Interferons block viral RNA from synthesizing proteins and also degrade the viral RNA itself. Interferon-α and -β also activate NK cells. Interferon-γ, also known as immune interferon, is secreted by lymphocytes. It activates macrophages and has wide ranging immune mobilization effects.

■■ Acid mantle components inhibit bacterial growth. These consist of the acidity of the skin, stomach secretions, and vagina.

■■ Enzymes such as lysozyme destroy bacteria. Lysozyme is found in the respiratory mucus, lacrimal fluid of the eye, and saliva. In the stomach, protein digesting enzymes kill a variety of different microorganisms.

■■ Mucin is a substance that forms mucus when dissolved in water. This mucus is thick and sticky,lining the passageway of the digestive and respiratory systems. It functions to trap a variety of microorganisms. The mucin of the saliva is dif-ferent in that it traps microorganisms but washes them from the mouth to the stomach, where they are digested.

Defensins are broad-spectrum antimicrobialpeptides secreted from the skin and mucous membranes. They are produced in much higher quantities when surface barriers are breached and inflammation develops. They help to control col-onization by bacteria and fungi in different ways, including disruption of the membranes of these microorganisms.

■■ Dermicidin found in eccrine sweat is toxic to bac-teria, similar to the effects of certain lipids in the body’s sebum.

■■ Complement is a group of proteins in plasma andother body fluids that interact to cause inflam-mation and phagocytic activities. Plasma con-tains at least 20 special complement or C proteins that comprise the complement system, includ-ing proteins C1 through C9; factors called B, D, and P; and also several proteins that have a reg-ulatory effect. The term complement refers to the way this system “complements” the action of antibodies. The complement proteins interact in chain reactions or cascades that are similar to those of the clotting system. Activated com-plement also acts by lysing and killing certain cells and ­bacteria. There are additional chemical barriers in the respiratory tract mucosae. When microorganisms make it past the chemical barri-ers, the internal innate defenses begin to combat them. Interferons are not virus-specific, and those produced against a certain virus protect against other viruses as well. The interferons are a group of immune modulating proteins with slightly different effects. They also play an indirect role in fighting cancer. The actions of the adaptive immune system greatly increase the inflamma-tory response. Most complement activation also occurs because of this system.

■■ Complement activation involves the classical pathway and the alternative pathway. Theclassical pathway is the fastest and most effec-tive pathway, beginning with binding of comple-ment protein C1 to an antibody, already attached to its specific antigen, which may be a bacterial cell wall. When antibody molecules are absent, the alternative or properdin pathway activates the complement system. This slow, less effective path-way begins when properdin or factor P, factor B, and factor D interact in the plasma. These are all various types of complement proteins. This inter-action may be triggered by exposure to foreign materials. The alternative pathway also ends, like the classical pathway, with conversion of inactive C3 protein into activated C3b protein. The activa-tion of complement results in formation of pores, increased phagocytosis, and release of histamine.

Fever

Fever is the elevation of body temperature that reduces iron in the blood, which inhibits bacterial and fungal reproduction; fever also causes increased phagocy-tosis by macrophages. Fever is a systemic response to invading microorganisms. Exposure of leukocytes and macrophages to foreign substances causes the release of pyrogens, which cause the hypothalamus to raise the body temperature. As a result of fever, the spleen and liver keep iron and zinc away from the rest of the body somewhat so they cannot be used to sup-port bacterial growth. Cells are repaired more quickly because fever increases their metabolic rate. Active macrophages release a cytokine that is called endoge-nous pyrogen or interleukin-1, which produces a fever.

Inflammation

Inflammation is a tissue response to injury or infection that may include four cardinal signs: redness, swelling, heat, and pain. Infected cells attract white blood cells, which engulf them. Impaired function is a fifth occur-rence that many experts consider to be the fifth car-dinal sign of inflammation. When functions such as movement become impaired, the injured area may be temporarily forced to rest so it can heal. Masses of leu-kocytes, bacterial cells, and damaged tissue may form a thick fluid called pus. The body may react to inflam-mation by forming a network of fibrin threads where the infection is centered. This closes off the infected area to inhibit the spread of pathogens. An inflam-matory response is triggered when mast cells releasehistamine, serotonin, and heparin. The inflammatory response is a tissue-level reaction and is therefore related to the tissues and integumentary system. The inflammatory response helps to dispose off pathogens and cell debris, triggers the adaptive immune system to act, and prepares the body to repair damaged tis-sues. Neutrophils squeeze through capillary walls in response to inflammatory signals. This movement is called diapedesis.

Inflammatory chemicals may be released by injured tissue cells, stressed tissue cells, and immune cells. They can also be formed by mast cells. The strong inflam-matory chemical known as histamine is released by mast cells. Macrophages are able to ­recognize invaders and trigger a chemical response by using surface mem-brane or toll-like receptors. Additionally, inflammatory chemicals such as kinins, prostaglandins, and com-plement help to dilate localized arterioles and causeadditional leakage from localized capillaries. They may cause leukocytes to be attracted to an injured area for additional inflammatory actions.

The redness and heat of inflammation are caused by vasodilation. Local hyperemia occurs when local arterioles dilate, which means that there is congestion in the area with blood. Fluid containing clotting fac-tors and antibodies, known as exudate, leaks from the blood into the tissue spaces, causing local swelling or edema. This condition increases pain by pressing on nearby nerve endings. Bacterial toxins that are released also contribute to pain. Released prostaglandins and kinins contribute to sensitizing effects, and pain relief by aspirin or other anti-inflammatory drugs is based on the inhibition of prostaglandin synthesis.

Phagocytosis

Injured tissues attract neutrophils and monocytes, which engulf and digest particles such as pathogens and cell debris; monocytes influence the development of macrophages that attach to blood and lymphatic vessels. Neutrophils, along with eosinophils, are termed micro-phages because of their smaller size. Together, thesevarious phagocytic cells make up the mononuclearphagocytic system to remove foreign particles fromthe lymph and blood. Neutrophils are the most abun-dant and begin to engulf invaders when they find infectious material in the body tissues. Macrophages are larger in size, mostly derived from monocytes, and provide most phagocytic activities. Both free and fixed types of macrophages exist, which are similar in struc-ture and function. The free macrophages search tissue spaces for invaders or cellular debris. Fixed macro-phages live permanently inside certain organs, such as the liver’s stellate macrophages. All the various phago-cytes are collectively called the monocyte macrophagesystem or reticuloendothelial system.

Natural Killer Cells

Natural killer (NK) cells patrol the blood and lymphas part of immunologic surveillance. They are able to lyse and kill both cancer and viral cells before acti-vation of the adaptive immune system. They are part of the cells known as large granular leukocytes and have wider actions against pathogens than the lymphocytes of the adaptive immune system. They detect generalized abnormalities, such as when cell-surface proteins known as major histocompatibility complex (MHC) are lack-ing. However, they are not phagocytic and kill by con-tacting target cells directly, in the same way as cytotoxic T cells kill. Cytotoxic T cells secrete a poisonous lympho-toxin that kills target cells. The inflammatory response isincreased by strong ­chemicals secreted by NK cells. NK cells recognize abnormal cells, adhere to them, and use their Golgi apparatus to produce perforins, which are proteins that diffuse to the target cell. The perforins cre-ate holes or pores in the target cell’s membrane, resulting in lysis of the abnormal cell. NK cells attack cancer cells and those infected with viruses. The plasma membranes of cancer cells contain tumor-specific antigens, which the NK cells use to find them. Some cancer cells can destroy NK cells, via a process of either avoiding their detection or neutralizing body defenses. This process is called immunological escape.

Species Resistance

A final form of innate, nonspecific defense is speciesresistance. For example, a human may be resistantto certain diseases that affect other species of animals. A pathogen effective against a dog, for example, may be unable to survive in a human. In reverse, humans can be infected with measles, gonorrhea, mumps, and syphilis, none of which affects other animal species.

1. Which type of immunity is present at birth, and which develops over time?

2. Explain the most important antimicrobial proteins in the body.

3. Describe the effects of inflammation in the body, and list the cardinal signs.

4. What is the function of complement?