Supplemental Lecture (98/05/16 update) by Stephen T. Abedon (abedon.1@osu.edu)

  1. Chapter title: Nonspecific Defenses of the Host
    1. A list of vocabulary words is found toward the end of this document
  2. Lecture Review

specific resistance

cellular arm of the immune system

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antibodies

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nonspecific resistance

prevention of entrance to the body

barriers

Removal by washing

antimicrobials made by the body

inhibition within the body

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  1. Susceptibility
    1. Lack of resistance:
      1. Susceptibility is a measure of an individual's or population's inability to ward off disease given exposure to a pathogen.
      2. In other words, susceptibility represents a lack of resistance.
  2. Resistance
    1. Lack of susceptibility:
      1. Resistance is the ability of an individual or population to ward off disease given exposure to a pathogen.
      2. In other words, resistance represents a lack of susceptibility.
    2. Mechanisms of resistance:
      1. Mechanisms of resistance may be divided into:
        1. those that are specific to particular pathogens
        2. those that are not specific
      2. Specific resistance refers to actions of the immune system. These will not be covered in this lecture which deals instead with mechanisms of nonspecific resistance.
  3. Nonspecific resistance
    1. Mechanisms of nonspecific resistance:
      1. Nonspecific defenses represent the body's first lines of defenses against pathogens. Specific defenses represent the second.
      2. Mechanisms of nonspecific resistance may be divided into two general types:
        1. those that prevent microorganisms from gaining entrance to the body
        2. those that inhibit growth following entrance to the body
    2. Things that prevent pathogens from entering the body include:
      1. barriers
      2. microorganism removal by washing
      3. antimicrobials made by the body
    3. Things that inhibit pathogen population growth and survival given the occurrence of entrance into the body:
      1. leukocytosis
      2. phagocytosis
      3. inflammation
      4. fever
      5. complement
      6. interferon
  4. Barriers
    1. Barriers to the entrance of microorganisms into the body include:
      1. skin
      2. mucous membranes
      3. various one-way valves
  5. Skin barrier
    1. The skin represents a barrier to pathogens that must be breached in order for infection to occur.
    2. The skin also tends to be relatively dry which inhibits the growth of most bacteria.
    3. "The skin, which covers and protects the body, is the body's first line of defence against pathogens. Basically, the skin is an inhospitable place for most microorganisms because the secretions of the skin are acidic and most of the skin contains little moisture. Moreover, much of the skin is exposed to radiation, which discourages microbial life. Some parts of the body, however, such as the axilla (armpit), have enough moisture to support microbial growth. The axillary region can support relatively large bacterial populations, whereas other regions, such as the scalp, support rather small numbers of microorganisms. The skin is a physical as well as an ecological barrier, and it is almost impossible for pathogens to penetrate it. However, some can enter through openings that are not readily apparent, and the larval forms of a few parasites can penetrate intact skin." (p. 516, Tortora et al., 1995).
  6. Mucous membrane barrier
    1. Less robust than skin barriers:
      1. Mucous membranes form the external layer of much of the body which is not covered with skin.
      2. Mucous membranes are not as solid a barrier to microbes as is skin.
    2. Mucous trap:
      1. Because they secrete mucus, mucous membranes are not as dry as skin.
      2. Mucus does, however, play an important role in the prevention of pathogen entrance into the body by forming a viscous layer which traps pathogens.
      3. For example, microorganisms are trapped by mucus covered hairs in the nose.
  7. One-way valves
    1. Check valves:
      1. In certain circumstances a simple check valve can serve to separate a region of less likely sterility from one of higher sterility.
      2. An example of where a check (i.e., one-way) value is employed is between the urinary bladder and the kidneys, thus shielding the kidneys from any pathogen that may have made its way into the urinary bladder.
  8. Removal by washing
    1. In some locations microbes are removed from the body by washing. For example, as will be discussed below, microbes are washed from the:
      1. eyes
      2. mouth
      3. respiratory tract
      4. urogenital tract
      5. fresh wounds
    2. Mechanical removal:
      1. Various mucous membranes may be washed with substances other than or in addition to mucus.
      2. Mucus may also be actively moved across a surface thus further effecting microorganism removal. This counters the building up of microorganism numbers through their growth.
    3. Washing of the eyes:
      1. Tears and blinking:
        1. wash the eyes
        2. dilute microorganisms
        3. disrupt colonization on the surface of the eyeball
      2. Microorganisms are removed via the tear ducts.
    4. Washing of the mouth:
      1. Saliva and the chewing of foods:
        1. washes the mouth
        2. dilutes microorganisms
        3. disrupts colonization on the surface of the mouth
      2. Microorganisms are removed via spitting and swallowing.
    5. Washing of the respiratory tract (ciliary escalator):
      1. Mucus is moved by cilia (as well as by coughing and sneezing) lining the respiratory tract in the lungs.
      2. Removal occurs through the nose and the throat.
      3. Particles especially in range of 4 to 5 Ám (which includes many bacteria) are trapped.
      4. These microorganisms as well as trapped debris are thus removed from the body.
    6. Washing of the urogenital tract:
      1. The urethra is washed by the flow of urine.
      2. Mucus flow out of the vagina also serves to carry out microorganisms.
    7. The flow of blood out of a cut also represents a washing action, though one not occurring over a mucous membrane.
  9. Antimicrobials of the body
    1. Antimicrobials of the body differ from location to location. Below we will discuss:
      1. antimicrobials of the skin
      2. lysozyme made by the body
      3. gastric juices
    2. Inhospitable environments:
      1. A number of sites on the body provide an inhospitable environment for microorganisms for chemical (e.g., anti-microbial agents) and physical (e.g., dryness, pH) reasons.
      2. These environments include those found:
        1. on the skin
        2. within various secretions and fluids
        3. in the stomach
    3. Antimicrobials of the skin:
      1. Unsaturated fatty acids released onto the skin by various skin normal microbiota (e.g., Staphylococcus epidermidis, Propionibacterium acnes) are toxic to gram-negative bacteria.
      2. Skin also has a low pH, a consequence of skin lactobacilli, and this, too, inhibits bacterial growth. Sebum, too, is acidic.\
      3. Skin is also salty as a consequence of sweat evaporation.
    4. Many body secretions contain lysozyme including:
      1. saliva
      2. tears
      3. perspiration
    5. Gastric juices:
      1. The high acidity of the stomach (pH 1.2 to 3.0) is especially inhibiting of microorganism survival.
      2. Thus, gastrointestinal pathogens must survive the stomach in order to colonize the intestines.
      3. However, the heterogeneity and buffering of food can allow the passage of a fraction of the population of ingested pathogens through the stomach.
      4. Note that the ability of the stomach to kill pathogens cannot prevent food poisoning that is the result of toxins built up in food prior to ingestion.
  10. Inhibition within the body
    1. Things that inhibit pathogen population growth and survival given the occurrence of entrance into the body include:
      1. leukocytosis
      2. phagocytosis
      3. inflammation
      4. fever
      5. complement
      6. interferon
  11. Leukocytosis
    1. The increase in white blood cell number that occurs upon infection, especially bacterial infection.
    2. Paradoxical effect:
      1. Some diseases lead to a decline in while blood cell count.
      2. Unless understood otherwise, a decline in white blood count should be understood as an inappropriate (i.e., dysfunctional) response to infection.
  12. Phagocytosis [macrophage, neutrophil, phagocyte, pus, wandering macrophage]
    1. Eating pathogens:
      1. In response to an infection, white blood cells of certain types (collectively called phagocytes) concentrate about the site of infection.
      2. White blood cells called neutrophils predominate initially but are eventually replaced by wandering macrophages (macrophages for short).
      3. These cells actively engulf, kill, and digest most pathogens. This engulfing is called phagocytosis.
    2. Resistance to phagocytosis:
      1. Some pathogens however are resistant to phagocytosis and some of these can actually gain advantages by being temporarily ingested (e.g., escape from immune system control; Yersinia pestis, Mycobacterium leprae, Mycobacterium tuberculosis).
      2. Such microbial responses can make the phagocytosis an ineffective nonspecific response.
    3. Engulfment of microorganisms eventually leads to the death of phagocytes and their accumulation is one component of pus.
    4. The phagocytes involved in phagocytosis are also found within the lungs and play an active role in destroying pathogens which manage to find their way far into the lungs.
  13. Inflammation
    1. Localized tissue response:
      1. Inflammation is a localized tissue response to infection or injury.
      2. Inflammation is characterized by localized:
        1. redness
        2. pain
        3. heat
        4. swelling
      3. Inflammation has three purposes:
        1. pathogen destruction
        2. pathogen confinement (walling off)
        3. repair or replacement of damaged tissue
    2. Inflammation involves:
      1. an increase in blood flow to the site of infection or injury
      2. increased permeability of tissues at that site
      3. formation of blood clots
      4. migration of phagocytes to the site
  14. Fever
    1. Systemic response:
      1. Fever is an abnormally high body temperature that occurs in response to disease.
      2. Particularly, it is a systemic (as opposed to local) response to infection.
      3. The adaptive advantage of a fever is not completely understood. However, there is reasonable agreement that, except for very high fevers, having a fever in response to an infection is better than not having a fever in response to an infection.
    2. Fevers have three stages:
      1. chill
      2. fever
      3. crisis
    3. Chill is the rising of body temperature (the environment appears to become colder relative to body temperature as, indeed, it is).
    4. Crisis is the cooling of the body temperature through a warming of the skin and perspiration.
  15. Complement
    1. Non-specific distinguisher of self from non-self:
      1. Complement is a series of proteins which are used to distinguish between self and non-self in a manner unlike that employed by the body's immune system.
      2. Specifically, complement proteins are found in the blood and act by glomming onto cell surface components fairly indiscriminately, and binding especially to the surfaces of pathogens.
      3. These proteins are also actively removed by cell surface components. However, pathogens are not necessarily able to remove complement components so this tags them as non-self.
      4. Complement components can also adhere to antibodies bound to the surface of pathogens.
    2. Complement binding sets off a cascade of complement protein binding that results in local effects such as:
      1. active lysis of the pathogen
      2. active lysis of the pathogen infected cell
      3. marking the pathogen for phagocytosis
      4. contributing to the development of inflammation
  16. Interferon
    1. Essentially hormones:
      1. Interferons are small proteins that are released by virus infected cells in very small quantities.
      2. A number of different kinds of interferons have been identified.
    2. Interferons act to reversibly inhibit normal cell function in neighboring cells thus potentially interfering with viral replication should neighboring cells also become infected.
  17. Conjunctiva
    1. The conjunctiva is the mucous membrane lining the inner surface of the eyelids a part of the eyeball.
  18. Skin
    1. Skin consists of dermis and epidermis.
    2. See skin as barrier to pathogen entry.
  19. Dermis
    1. The dermis is the thicker, inner layers of skin cells.
    2. The dermis is punctuated by a number of structures which form passageways through which microorganisms can pass:
      1. hair follicles
      2. sweat-gland ducts
      3. oil-gland ducts
  20. Epidermis
    1. The epidermis is the thin, outer layers of skin cells.
    2. An unbroken epidermis is an effective physical barrier against microbes.
  21. Perspiration
    1. Perspiration provides moisture and nutrients to some microorganisms living on the skin.
    2. However, perspiration keeps the skin salty and consequently an inhospitable site for most microbial growth.
    3. Perspiration also contains lysozyme, an antimicrobial (esp. gram-positive) enzyme.
  22. Sebum
    1. Sebum is the lipids, salts, and proteins secreted onto the skin by oil glands.
    2. Sebum moisturizes skin and hair and simultaneously provides some chemical antimicrobial protection and a nutritional basis for the growth of other skin normal flora such as corynebacterium.
  23. Stratum corneum
    1. The stratum corneum is the very outermost layer of the epidermis consisting of dead cells and keratin.
  24. Vocabulary
    1. Antimicrobials of the skin
    2. Barriers to entrance to the body
    3. Complement
    4. Fever
    5. Gastric juices
    6. Inflammation
    7. Interferon
    8. Leukocytosis
    9. Lysozyme made by the body
    10. Mucous membrane barrier
    11. Nonspecific resistance
    12. Phagocytosis
    13. Removal by washing
    14. Resistance
    15. Skin barrier
    16. Susceptibility
    17. Washing of the eyes
    18. Washing of the mouth
    19. Washing of the respiratory tract
    20. Washing of the urogenital tract
  25. Practice questions
    1. An increase in white blood cell number that occurs upon infection, especially bacterial infection, is called? (choose best answer) [PEEK]
      1. leukocytosis
      2. phagocytosis
      3. inflammation
      4. lymphangitis
      5. all of the above
      6. none of the above
    2. The nonspecific host defences including lysozyme found in tears, saliva, and on the skin, unsaturated fatty acids found on the skin, and the high acidity of the stomach are all examples of __________? [PEEK]
    3. What are the three stages of a fever? [PEEK]
    4. Name three attributes of skin (or substances found on the skin's surface) which contribute to the skin's ability to prevent most pathogens from infecting the body. [PEEK]
    5. __________ is a nonspecific host defence (i.e., not antibodies) which (i) tags pathogens for phagocytosis, (ii) induces inflammation, and (iii) actively lyses pathogens. [PEEK]
    6. __________ is an antimicrobial protein found in saliva, tears, and perspiration. [PEEK]
    7. Fundamentally, what distinguishes nonspecific defences from specific defences? [PEEK]
    8. Describe two antimicrobials produced by the body or its flora. Indicate their site of action and, if possible, their specificity. [PEEK]
    9. Name the three positive functions of inflammation (i.e., why the body has this response). [PEEK]
    10. _________ is a body fluid involved in washing an external portion of your body, is removed via a duct, and which contains lysozyme. [PEEK]
    11. Leukocytosis is _________. [PEEK]
    12. What non-specific host defense involves pathogen killing, walling off of infections, and subsequent repair of damaged tissue? [PEEK]
    13. One-way valves in the body serve as nonspecific host defenses to _________. (multi-word answer) [PEEK]
    14. _________ forms a viscous layer that traps microorganisms. [PEEK]
    15. Removal of pathogens from the lungs occurs via coughing, sneezing, and _________. [PEEK]
    16. _________ is a category of proteins involved in pathogen lysis, phagocytosis, and inflammation. [PEEK]
    17. Name two lysozyme-containing substances which serve as non-specific defenses of the host and which are involved in the washing and diluting of microorganisms, as well as the disruption of the colonization of surfaces by microorganisms. [PEEK]
  26. Practice question answers
    1. i, leukocytosis
    2. antimicrobials of the body
    3. chill, fever, and crisis
    4. The skin (i) is a barrier, (ii) is dry, (iii) has a low pH, (iv) has high salt concentrations, and (v) possesses lysozyme (in sweat).
    5. complement.
    6. lysozyme.
    7. nonspecific defenses do not adapt to the presence of specific pathogens and consequently are not capable of memorizing an immune response against a specific pathogen. Put slightly differently, nonspecific immunity is innate and specific immunity is acquired.
    8. lysozyme, tears, saliva, perspiration, anti-gram-positive; low pH, skin, vagina, stomach (gastric juices), no specificity except against organism less well adapted to low pH; free, unsaturated fatty acids, produced by normal flora on the skin, anti-gram-negative bacteria
    9. (i) pathogen destruction, (ii) walling off of injured local (pathogen confinement), (iii) repair or replacement of host tissue
    10. tears
    11. an elevated white blood cell count which typically coincides with infection
    12. inflammation
    13. separate regions that are less aseptic from regions that are more aseptic (such as the bladder, an infection in which is uncomfortable, from ureters/kidneys, an infection of which can kill you)
    14. mucous
    15. the ciliary escalator, i.e., movement of mucous from within the lungs out of the lungs via the beating of cilia along lung passages
    16. complement
    17. tears and sweat
  27. References
    1. Black, J.G. (1996). Microbiology. Principles and Applications. Third Edition. Prentice Hall. Upper Saddle River, New Jersey. pp. 448-475.
    2. Tortora, G.J., Funke, B.R., Case, C.L. (1995). Microbiology. An Introduction. Fifth Edition. The Benjamin/Cummings Publishing, Co., Inc., Redwood City, CA, pp. 406-424.