Human-Microbe Interactions

1. Chapter 21 Human-Microbe Interactions

2. Human-Microbe Interactions Normal flora: the hundreds of species/billions of individual microbes that live on or in the human body. Pathogens: microbial parasites (organisms that live on or in a host organism, causing damage to the host). Virulence: the quantitative measure of pathogenicity. Virulence vs. resistance of the host are constantly changing. Infection: microorganism is established and growing in a host (note that the host may or may not be harmed). Disease: damage or injury to the host that impairs host function. Infection ? disease.

3. Human-Microbe Interactions (cont.) Why would microorganisms want to live within an animal�s body? Is the animal body a uniform microbial environment? What areas of the body are normally colonized by microorganisms? Infections often begin at sites in the animal�s mucous membranes. Where are mucous membranes located in the body? What is mucus made of and what is its purpose? Why do mucosal surfaces have a larger variety of organisms associated than nonmuscosal surfaces?

4. Normal Flora of the Skin Avg. adult has 2 m2 of skin surface. Skin is not favorable to microbial growth since it is subject to drying. Most microbes are associated with the sweat glands. The flora of the skin consists of resident and transient populations of microbes. Resident microbes live and multiple on the skin, whereas transient flora almost always are unable to multiple and usually die. Resident flora remains fairly constant, although it can be affected by several factors. What are 3 of these factors?

5. Normal Flora of the Oral Cavity Saliva contains antibacterial enzymes: lysozyme and lactoperoxidase (also present in milk). Saliva (pervasive, although not the best nutrient source), food particles, and epithelial debris provide nutrients for microbes. Microbes colonize many surfaces in the mouth, including teeth and gingival crevices. The flora of the mouth changes with stages of growth, ex. acquisition of teeth. A thin organic film forms on the tooth surface, to which acidic glycoproteins from the saliva attach, enabling only a few species of Streptococcus (ex. S. mutans) to adhere. Dental caries = tooth decay = infectious disease caused by microbes. High sugar diets promote tooth decay because lactic acid bacteria ferment the sugars to lactic acid ? decalcification of the enamel ? proteolysis of the matrix of tooth enamel ? further infection/decay. Fluoride prevents the decalcification step. Microorganisms in the mouth can also cause other infections.

6. Normal Flora of the Gastrointestinal Tract The stomach is not hospitable to microbes due to its low pH (pH 2), except Helicobacter pylori, which causes ulcers.

7. Normal Flora of the Respiratory Tract Upper respiratory tract = nasopharynx, oral cavity, and throat. Staphylococci, streptococci, diphtheroid bacillia, and gram-neg. cocci, as well as potentially harmful bacteria (ex. Staph. aureus and Strep. Pneumoniae) are often part of the normal flora of the nasopharynx of healthy individuals. Lower respiratory tract = trachea, bronchi, and lungs. The lower respiratory tract is essentially sterile. Ciliated epithelium beat contaminants upward.

8. Normal Flora of the Urogenital Tract The bladder itself is usually sterile, but the epithelial cells lining the urethra are colonized by facultatively aerobic gram-neg. rods and cocci, including E. coli, Proteus mirabilis, etc. Occasionally, these organisms become opportunistic pathogens. Factors such as local pH changes allow organisms to multiply and become pathogenic. The vagina of the adult female is generally weakly acidic and contains significant amounts of the polysaccharide glycogen. Lactobacillus acidophilus, yeasts such as Candida, streptococci, and E. coli may also be present. Before puberty, the vagina is alkaline and does not produce glycogen. L. acidophilus is absent at this time. After menopause, the flora resembles that before puberty.

9. Entry of the Pathogen into the Host Virulence: the relative ability of a pathogen to cause disease. Organisms must penetrate the skin, mucous membranes, or intestinal epithelium, which normally act as barriers. Most microbial infections begin at breaks or wounds in the skin, etc. Bacteria or viruses adhere specifically to epithelial cells through protein-protein interactions on the surfaces of the host and pathogen cells. These interactions are often cell and species specific. Bacterial adherence not dependent on this type of attachment include structures such as a capsule, glycocalyx, and slime layer. Fimbriae and pili are also used for attachment of the pathogen to the host. Most pathogens penetrate the epithelium to initiate pathogenicity = invasion, although some produce toxins that may eliminate normal flora or cause breaks in the epithelium, allowing access of the pathogen to the underlying tissues.

10. Colonization and Growth Colonization: multiplication of a pathogen after it has gained access to the host�s tissues. The initial inoculum of a pathogen is rarely sufficient to cause damage, so it must find appropriate nutrients and environmental cond. in order to grow � which is most imporant? Vitamins, growth factors, trace elements may be in short supply. Pathogens usually remain localized at the site of entry, but can pass through the lymphatic vessels, and eventually to the blood, where it can travel around the body ? bacteremia.

11. Virulence Measuring virulence: calculated as LD50 (lethal dose50) = dose of an agent that kills 50% of the animals in a test group. Highly virulent pathogens show little difference between # cells required for LD50 and # required for LD100. This can be as little as a few cells. When pathogens are kept in lab culture and not passed through animals, their virulence is often decreased or lost = attenuated. Why does this occur? Toxicity: the ability of an organism to cause disease by means of a preformed toxin that inhibits host cell function or kills host cells, ex. Clostridium tetani ? tetanus exotoxin. Invasiveness: ability of an organism to grow in host tissue in such large #�s that the pathogen inhibits host function. Virulence factor allowing invasiveness may not be a toxin, but may be something such as a capsule, ex. Streptococcus pneumoniae.

12. Virulence Factors Virulence factors: pathogen-produced extracellular proteins that aid in the establishment and maintenance of disease. Most are enzymes that help the pathogens colonize and grow, ex. enzymes that help the pathogen to spread within the tissues. Fibrin clots form at the site of microbial invasion to limit infection, but some organisms can dissolve these clots. Other organisms promote the formation of clots in order to protect themselves � from what?

13. Virulence Factors

14. Exotoxins Exotoxins: proteins released extracellularly as the organism grows. 3 classes: 1. Cytolytic toxins: attacking cell constituents causing lysis, ex. hemolysins. 2. A-B toxins: consists of 2 subunits - one binds to cell surface receptor and the other is transferred into the cell to damage the cell, ex. diphtheria toxin, botulism toxin, and tetanus toxin. 3. SuperAg toxins: stimulate large #�s of immune response cells.

15. Enterotoxins Enterotoxins: exotoxins that act on the small intestine, generally causing massive secretion of fluid into the intestinal lumen, leading to vomiting and diarrhea. Ex. cholera toxin, E. coli O157:H7 toxin.

16. Endotoxins Endotoxins: generally cell-bound toxins that are released in large amounts only when cells are lysed. e.x. LPS of gram-neg. bacteria. Fever is an almost universal symptom because host cells are stimulated to release endogenous pyrogens, affecting the temp.-controlling center of the brain.

17. Nonspecific Innate Resistance to Infection Natural host resistance varies. Age: Newborns haven�t acquire adequate normal flora, the elderly suffer from declining ability to make an effective immune response to respiratory pathogens, for ex. Stress: such as fatigue, exertion, poor diet, dehydration, drastic climatic changes, increase the incidence and severity of infectious diseases. Hormones produced under stress influence the immune system, for ex. by suppressing it. Diet: can alter the composition of the normal flora, ex. either lack of a nutrient can put the host at a disadvantage or deprive a pathogen of an essential nutrient.

18. Nonspecific Innate Resistance to Infection (cont.) Physical and Chemical Defenses: include structural integrity of tissue surfaces (skin, mucosum), cilia, secretions (ex. fatty acids and lactic acid produced by sebaceous glands), stomach acid, lysozyme. Most pathogens must first adhere and colonize at the site of exposure and this interaction is very specific for the type of cells/tissue. Pathogens might not survive interactions in other locations in the body besides the target tissue. Compromised host: host in which one or more resistance mechanisms are inactive and in which the probability of infection is increased, ex. hospital patients (cancer, heart disease, transplants, AIDS, surgery, routine lab tests), people outside the hospital (smokers, drinkers, IV drug users, sleep-deprived, malnourished), or people with certain genetic diseases.

19. Inflammation Inflammation: nonspecific reaction to noxious stimuli such as toxins and pathogens. Inflammatory response: redness, swelling, pain, and heat. Cytokines produced by leukocytes mediate inflammation. Septic shock: systemic inflammation results in severe swelling (edema) and uncontrollable fever. Inflammation spreads throughout the body via the circulatory or lymphatic systems.

20. Fever Normal body temp. = ~37�C. Fever = abnormal increase in body temp., usually caused by infection. Pyrogenic = fever-inducing. Fevers 40�C (104�F) + benefit the pathogen because host tissues are further damaged. Types of fever: 1. Continuous: body temp. is remains elevated over at 24-hr. period, but does not vary by more than 1�C. 2. Remittant: temp. is abnormal over a 24-hr. period, but varies by more than 1�C. 3. Intermittant: temp. is normal for part of the day and elevated for part of the day. Most infectious diseases elicit some intermittant fever.