Nonspecific Host Defenses and Host Systems

Important words and concepts from Chapter 16, Black, 1999 (3/28/2003):

by Stephen T. Abedon (abedon.1@osu.edu) for Micro 509 at the Ohio State University

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(1) Chapter title: Nonspecific Host Defenses and Host Systems

Nonspecific resistance	Prevention of entrance to the body	Physical barriers	· skin barrier · mucous membranes · one-way valves
		Removal by washing	· washing of the eyes · washing of the mouth · washing of the respiratory tract · washing of the urogenital tract
		Chemical barriers	· antimicrobials of the skin · lysozyme made by the body · gastric juices
	Inhibition within the body	---	· leukocytosis · phagocytosis · inflammation · fever · complement · interferon
Specific resistance (next chapter)	Cellular arm of the immune system	---	---
Specific resistance (next chapter)	Antibodies	---	---

(a) [nonspecific host defenses and host systems (Google Search)] [index]

(2) Host defenses

(a) Host defenses to pathogens may be divided categorically into specific host defenses and non-specific ones

(b) This chapter considers the latter

(3) Non-specific host defenses (constitutive defenses)

(a) "In the case of many threats to an individual's well being, specific defenses [e.g., antibodies or cellular immunity] do not need to be called on because the body is adequately protected by its nonspecific defenses—those that act against any type of invading agent. Often such defenses perform their function before specific body defense mechanisms are activated."

(b) Non-specific host defenses include:

(i) Physical barriers

(ii) Chemical barriers

(iii) Cellular defenses

(iv) Inflammation

(v) Fever

(vi) Molecular defenses

(c) See Figure 16.10, A summary of the body's nonspecific defenses

(d) [non-specific host defenses, constitutive defenses (Google Search)] [index]

(4) Physical barriers (mucous membranes)

(a) Physical barriers act to prevent pathogens from entering the body

(b) Physical barriers include the skin and mucous membranes

(c) Physical barriers additionally include the viscous mucous that covers mucous membranes, giving these membranes their name

(d) Movement of substances out of the body additionally serve as physical barriers, including the movement of mucous out of the lungs, the movement of urine down the urethra and out of the body, vomiting, diarrhea, and even the movement of blood out of a wound

(e) Usually physical barriers do a good job of preventing pathogens from entering the body

(f) However, some pathogens are capable of breaching these physical barriers, and sometimes physical barriers are not functional or are not as present as one would otherwise hope (e.g., cuts in the skin, drying out of mucous membranes, not voiding one's bladder when necessary, etc.); for example:

(i) A number of viruses specifically infect mucous-membranes or via them {e.g., polio virus (intestine), chickenpox (lungs)}

(ii) A number of viruses infect via skin abrasions (e.g., warts, smallpox, herpes, hepatitis B, HIV)

(g) [“Air begins its journey to the respiratory system through the nose, which filters, warms, and moistens our inhalations before they pass through the pharynx, larynx, and trachea into the bronchi and the lungs. For this purpose, the external nose contains a septum (the wall dividing the two nostrils) composed of cartilage and bone covered by a layer of mucous membrane, and six or eight turbinates. ¶ The turbinates are thin curlicues of bone, also covered by thick mucous membranes, that curve from the outer part of the nose in toward the septum. Under the mucous membrane is erectile tissue that is sensitive to temperature and causes tissues of the area to swell with the influx of blood when there is an abundance of cold, dry, or contaminated air. This narrows the passages and thus slows the incoming air, allowing the turbinates to warm and humidify it. When the turbinates become erect they give rise to large amounts of mucus, which is why noses tend to run on cold days. ¶ The sticky mucous lining of the nose and nasal passages acts as a filter, trapping bacteria and airborne dirt particles. The mucus is then moved by the action of hair-like cilia either to the front of the nose where it can be blown out, or to the back of the nose where it enters the throat and is swallowed.” (Columbia University Home Medical Guide)]

(h) [physical barriers to infection (Google Search)] [index]

(5) Chemical barriers

(a) Chemical barriers are antimicrobial chemical defenses

(b) These defenses include lysozyme in sweat, tears, and saliva; the low pH of the lumen of the stomach, etc.

(6) Cellular defenses

(a) Various blood cells as well as platelets play an active role in defending the body from pathogen invaders

(b) Platelets are involved in blood clotting, which can serve as a barrier to pathogens

(c) Various white blood cells (a.k.a., leukocytes) are involved in phagocytosis (which is essentially intracellular killing of pathogens) or an extracellular killing of pathogens

(d) "Cellular defense mechanisms usually prevent an infection from spreading or from getting worse. However, sometimes these nonspecific defense mechanisms are overwhelmed by sheer numbers of microbes or are inhibited by virulence factors that the microbes possess. The pathogen can then invade other parts of the body."

(e) ["cellular defenses" against infection (Google Search)] [index]

(7) Phagocytes

(a) Cells capable of effecting phagocytosis are called phagocytes

(b) Included among the phagocytes are the neutrophils and the macrophages

(c) Typically neutrophils serve as a first line of defense at the site of a wound whereas macrophages serve as a second, much larger line of defense

(d) Ideally, the act of phagocytosis results in the ingestion and subsequent killing of the pathogen

(e) This ideal is not always achieved, and in such cases the interior of the phagocyte can serve as a immunologically protected zone within a body

(f) [phagocytes (Google Search)] [index]

(8) Wandering macrophages

(a) These are the macrophages that migrate to a wound to effect cellular defenses against invading pathogens

(b) [wandering macrophages (Google Search)] [index]

(9) Fixed macrophages

(a) These cells remain within tissues, essentially waiting, ideally futilely, for breaches in the physical and chemical barriers that bring pathogens to them

(b) [fixed macrophages (Google Search)] [index]

(10) Phagocytosis

(a) Phagocytosis is the engulfing of debris or pathogens

(b) Phagocytosis occurs in four steps

(i) The phagocyte must first find the pathogen (or cell debris) meaning that it comes into physical contact with it (chemotaxis)

(ii) The phagocyte must then chemically adhere to the pathogen (adherence)

(iii) Next, the pathogen is ingested (endocytosed into a phagosome)

(iv) Finally, ideally, the pathogen in digested intracellularly (digestion)

(c) See Figure 16.3, Phagocytosis of two bacterial cells by a neutrophil

(d) [phagocytosis (Google Search)] [index]

(11) Chemotaxis

(a) The phagocytes find wounds or infections by following chemical signals released from cells present at the site

(b) Mostly these chemicals are soluble proteins and phagocytes follow the protein gradient (up the gradient) to the site

(d) [chemotaxis and phagocytosis (Google Search)] [index]

(12) Adherence (engulfment, ingestion, phagosome)

(a) Phagocytes adhere to pathogens by adhering to specific chemicals found on the surface of pathogens (many, most, all? of these chemicals are actively placed there by the body, e.g., complement or antibodies)

(b) A means of interfering with adherence is via the secretion of a capsule (by a bacterium) which prevents the chemical attachment of the phagocyte to the pathogen

(d) The vesicle in which the pathogen is now present, within the phagocyte following ingestion/engulfment, is called a phagosome

(e) [adherence and phagocytosis, engulfment and phagocytosis, ingestion and phagocytosis, phagosome (Google Search)] [index]

(13) Digestion (phagolysosome)

(a) Ideally, ingestion of the pathogen is followed by the digestion (destruction) of the pathogen

(b) Destruction involves the use of digestive enzymes, e.g., by the fusing the phagosome with a lysozome (thus forming a phagolysosome)

(d) Some pathogens avoid digestion and some can even replicate within the phagocyte

(e) This avoidance may be accomplished either by resisting digestion (e.g., via protection from capsule of acid-fast cell envelopes) or by releasing toxins that actively destroy the phagocyte before digestion proceeds

(f) [digestion and phagocytosis, phagolysosome (Google Search)] [index]

(14) Lymph nodes

(a) Pathogens may be filtered from lymph at lymph nodes where phagocytes actively phagocytize pathogens

(b) Lymph nodes can swell when actively battling an infection so consequently swollen lymph nodes serve as an indicator for serious systemic infection

(15) Spleen

(a) The spleen is an organ that, serving a similar purpose to the blood as lymph nodes serve for lymph, actively remove pathogens from blood via phagocytosis effected by phagocytes present within the spleen

(b) [spleen (Google Search)] [index]

(16) Extracellular killing

(a) Extracellular killing is employed particularly against virus-infected cells and helminths

(b) Extracellular killing is accomplished by the secreting of chemical toxins

(c) This secretion is either into the vicinity of helminths, or is directed against virus-infected cells, which are sacrificed to stop the viral-infected cell from making additional viral progeny

(d) This killing of host cells to kill viruses is one way that viral infections effect their damage upon their hosts

(e) [extracellular killing (Google Search)] [index]

(17) Inflammation

(a) The inflammation of tissues is a defensive response that serves to protect damaged tissues against infection (or a worsening of an existing infection)

(b) The four indications of the occurrence of localized inflammation are

(i) Warming of the area

(ii) Reddening of the area

(iii) Swelling of the area

(iv) Pain in the area (e.g., to touch)

(i) Kill pathogens (kill)

(ii) Remove tissue debris (clean)

(iii) Repair damaged tissue (repair)

(d) Inflammation results from local histamine release from damaged cells which causes vasodilation (a widening of blood vessels), an increase in blood flow to the area that accounts for the warming, swelling, and redness associated with inflammation

(e) The chemicals produced upon cellular injury, along with inducing inflammation, additionally attract neutrophils and ultimately attract wandering macrophages

(f) [inflammation, cardinal signs of inflammation (Google Search)] [index]

(18) Leukocytosis (leukocyte)

(a) Leukocytosis is an increase in the number of leukcocyotes (white blood cells) found in the blood

(b) Tissue inflammation stimulates leukocytosis, which in turn represents a systemic immune response

(19) Pus

(a) Accumulated dead neutrophils are collectively called pus

(b) Note that pus will continue to accumulate until an infection has been brought under control

(c) Note additionally that viral infections do not result in the production of pus because viral infections are not combated by engulfment by neutrophils

(d) [pus and infection (Google Search)] [pus (Parents’ Common Sense Encyclopedia)] [index]

(20) Abscess (pimple, boil)

(a) An accumulation of pus within a cavity formed by tissue damage is a called an abscess

(b) Note that abscesses, e.g., pimples and boils, are typically inflamed

(21) Fever

(a) Fever is a systemic rise in temperature (i.e., of the whole body)

(b) The high temperature of fevers

(i) Can interfere with pathogen growth

(ii) Can inactivate some pathogen toxins

(iii) Effects a more intense immune system response

(iv) Causes the individual to take it easy so that body energy may be devoted to fighting the infection rather than toward other uses (e.g., eating, mating, etc.)

(c) "For the beneficial effects cited above, many physicians now recommend allowing fevers to run their course. Evidence shows that medication can delay recovery. However, if a fever goes above 40ºC or if the patient has disorder that might be worsened by fever, antipyretics (anti-fever medication) are still used."

(d) [fever and temperature (Google Search)] [index]

(22) Pyrogen

(a) Fevers may be caused by body exposure to pathogens, immunological reactions, or tissue injuries

(b) Fevers are typically induced by substances called pyrogens

(c) Pyrogens are either products of microorganisms (e.g., toxins) or products of the body (e.g., pyrogens are produced by macrophages)

(d) Pyrogens are released into the body and have their effect on a region of the brain known as the hypothalamus

(e) [pyrogen and fever (Google Search)] [index]

(23) Molecular defenses

(a) Many molecules are associated with immune responses, including the antibodies associated with specific immunity

(b) Non-specific immune defenses include the molecules interferon and complement

(d) [molecular defenses (Google Search)] [index]

(24) Interferon

(a) "As early as the 1930s, scientists observed that infection by one virus prevented for a time infection by another virus. Then, in 1957, a small, soluble protein was discovered that was responsible for this viral interference. This protein, called interferon (in-ter-fer'on), 'interfered' with virion replication in other cells."

(b) Humans make three types of interferon, termed alpha, beta, and gamma (a, b, and g, respectively)

(c) Both a-interferon and b-interferon are secreted by virus-infected cells; these molecules bind to other body cells, stimulating those cells to produce antiviral proteins, which act to interfere with the subsequent viral replication of those cells

(d) See figure 16.7, The mechanisms by which interferons a and b act

(e) Gamma-interferon differs in that it is secreted by uninfected immune system cells (stimulated by the binding of these cells to pathogen antigens) and has a broader effect (i.e., in addition to stimulating the production of antiviral proteins)

(f) Interferons are used as treatments for certain viral diseases and some cancers

(g) [interferon (Google Search)] [index]

(25) Complement

(a) Complement refers to a variety of highly prevalent blood proteins that are involved in the non-specific defense against especially bacterial pathogens

(b) The effects of complement action are extensive, varied, and most easily understood in the context of their mechanism of action

(d) The classical pathway involves the binding of specific antibody to bacterial cells while the alternative pathway involves the binding of non-specific complement molecules to bacterial cells; that is, the alternative pathway involves molecules that preferentially bind to bacterial cells, but not by bonding to specific molecules that are unique to a particular pathogen (e.g., as antibodies do)

(e) Regardless of the mechanism of initiation, the result of complement activation includes

(i) Opsonization

(ii) Inflammation

(iii) Attack complexes

(f) See Figure 16.8, The complement system

(g) "A great advantage of the complement system to host defenses is that, once activated, the reaction cascade occurs rapidly."

(h) [complement immunology (Google Search)] [index]

(26) Opsonization

(a) Opsonization is the complement- (or antibody-) mediated adherence of pathogens to phagocytes which stimulates phagocytosis

(b) Thus, one effect of complement adherence to a pathogen is the stimulation of the phagocytosis of the pathogen