Last revised: Monday, April 28, 2003
Topics: Microbiota. Pathogens and Host Defenses.
Text Reading: Chapter 26 and 27.
Overview:
- Chapter 26 introduces "microbiota", the many microbial partners that live inside our bodies or on our body surfaces. This chapter also introduces pathogens and the many factors needed to understand how successful pathogens manage to survive despite powerful host defense systems. Among these are the "fixed" defenses of the animal body, such as phagocytes, inflammation, complement, and specific tissue defenses.
- Chapter 27 discusses the enormously complex "adaptive" immune system, including B- and T-lymphocytes and their abilities to recognize potentially millions of different antigens, eliciting specific antibody or cellular responses. There is much more information in this chapter than we could cover in this course, so use the lecture notes as an example of where to focus your attention.
Chapter 26 and lecture notes.
- The term "microbial flora" has lost favor with the microbial community (after the 3 domains revelation, any lingering suspicions that bacteria are more "plant-like" than "animal-like" has evaporated.). The best term to describe microbial communities associated with animal tissues is microbiota.
- For each of the following environments, what are major constraints that limit microbial growth?
Skin, mouth, respiratory tract, stomach, small intestine, large intestine, urethra, vagina. - For each of the environments listed in the previous question, what is the dominant microbiota? Don't memorize this, but do spend some time examining Fig. 26.1 and associated text. Are any tissues devoid of microbiota in healthy individuals?
- Does the microbiota of the human body change over time, or is it stable? Explain.
- What microbe causes acne? Why is this disease usually limited to the adolescents, as opposed to children or older adults?
- For each of the following microorganisms, identify where they are typically found in/on the human body, and under what conditions their presence can lead to a disease: Staphylococcus epidermidis, Streptococcus mutansPropionobacterium acnes, Candida albicans, Helicobacter pylori, Clostridium botulinum.
- How does the incidence of microbiota in the stomach compare with other regions of the GI tract?
- How does the incidence of microbiota in the colon compare with other regions of the GI tract? What are the dominant types of colon microorganisms? How abundant is E. coli?
- About how many microorganisms are excreted daily by one adult human (see text p. 623)? ________ Considering that the mass of a single bacterial cell is approximately 10-12 gram, how many grams of microorganisms a day are you contributing to the UConn sewage plant?
- What microbiota is found in the upper reaches of the urinary tract? What are the major microbes present in the vagina? How do they affect pH?
- What microbiota are normally found in the urethra? kidney? Urinary bladder?
- What are gnotobiotic animal? What is an axenic animal? Are humans gnotobiotic at any stage of life? How do germfree animals compare to normal animals? How are such animals produced? How are they maintained? What benefits do a normal microbiota provide, based on the study of germfree animals?
- What is parasitism? Note that in ordinary usage the word "parasite" refers only to protist and helminth infections, although of course viruses, certain bacteria and fungi are also parasitic.
- What does the term "pathogen" refer to? Can an organism be parasitic and not pathogenic? If so, give an example.
- What factors determine the outcome of a host-parasite relation?
- What does the term "virulence" refer to? What are the major characteristics that promote virulence?
- Distinguish the following terms: obligate, accidental, opportunistic pathogens.
- What bacterial cell components promote specific adherence to host tissues? (see Table 26.2)
- How does each of the following enzymes contribute to virulence?
Collagenase, Coagulase, Leukocidin, Hemolysin. - To what class of molecules do exotoxins belong? What are typical properties of exotoxins? Of endotoxins? Be familiar with Table 26.6.
- Botulism is caused by a powerful exotoxin. Assume that a certain food has a small quantity of botulin toxin; if this food were boiled for 10 minutes, would it be theoretically safe to eat? Why or why not?
- What is an antitoxin? A toxoid?
- Table 26.7 lists some important bacterial toxins. For each of the following, be able to identify (a) the organism that produces this toxin, (b) where the toxin gene resides, (c) the type of enzymatic activity, and (d) the biological effect:
anthrax, botulinum, cholera, diphtheria, perfringens, tetanus. - What is the difference between neurotoxins, enterotoxins, and cytotoxins? For the toxins in the previous list, which of these terms applies?
- How do endotoxins cause disease?
- What are siderophores? How are they important in pathogenesis?
- What typical role(s) does each of the following systems play in host defense? Skin, mucosal membranes, inflammation, phagocytes, complement, cytokines.
- To what do the acronyms SALT and MALT refer? Where are these cells found? What do they do?
- What is mucin (mucus)? What antimicrobial properties does it possess? Where is it found?
- Describe the sequence of events in phagocytosis. What steps do intracellular pathogens often inhibit or alter? What enzymes are found in lysosomes? What is a phagolysosome? What is a "respiratory burst"?
- What are some stratagems by which bacteria can avoid phagocytosis?
- What chemical signals trigger inflammation? What events are typically involved? (see text pp. 641-642 and lecture notes)
- What is complement? How is it activated?
- What is a complement cascade?
- How does complement facilitate in the destruction of bacteria? (Name at least two ways)
- What is opsonization?
- The terminology for cells of the immune system is complex. Note that all immune cells derive from stem cells found in bone marrow. As these cells mature, they take different routes. Some become phagocytic cells (e.g. macrophages or neutrophils) or other components (e.g. platelets). Others become lymphocytes. Although all lymphocytes look alike in the microscope, they are very different functionally. T cells mature in the thymus gland, and differentiate further into several varieties which can be distinguished based on whether they carry surface proteins of type CD4 or CD8. By contrast, B cells mature in the bone marrow, and have the capacity to differentiate further (if stimulated) into memory and plasma cells. T cells are involved in regulating B cells, in recruiting macrophages, and in killing cells with detectable "foreign" antigens. Some lymphocytes, called natural killer cells, are distinct from both T and B cells.
- What is an antibody? What is an antigen?
- (a) What properties do IgG, IgM, and IgA antibodies have in common? What properties distinguish them?
(b) Which type of antibody binds antigen most avidly? Which type is most abundant in blood and lymph?
(c) Where would you find IgA?
(d) Where are the antigen binding sites located on a Y-shaped unit?
(e) Where are variable and constant regions located? How do they differ?
(f) If you compare IgG antibodies directed against influenza virus and against poliovirus, where and how do they differ?
- What is an epitope? How does it differ from an antigen? (Hint: Only large molecules, such as proteins or polysaccharides, function as antigens.)
- Once an antigen has bound to an antibody, what happens? (Hint: it depends on the size and nature of the antigen. A toxin molecule consisting of a single protein will have a different fate than a whole cell.)
- How does the immune system deal with capsulated bacteria?
- What is serum? How does it differ from blood and from plasma?
- What is "antigen presentation?" What cells are involved? In what molecule are antigens "presented"?
- What is the clonal selection theory? Which class of cells actually produce circulating antibodies? Where do these cells come from?
- What is meant by "somatic recombination"? How does this process generate antibody diversity? (Hint: remember the animation we demonstrated in class).
- T-cells carry T-cell antigen receptors (TCRs) on their cell surface. These are not antibodies, but they have certain antibody-like properties; variable and constant regions, specific binding to antigen. TCRs must recognize antigen in order to produce cytokines necessary for stimulating B-cells.
- B-cells contain antibody-like molecules attached to their cell membranes, called B-cell antigen receptors (BCRs). How many BCRs are found on one B-cell? How many different antigens can these BCRs recognize?
- What are the steps that activate a B-cell? Is it necessary that antigen binds to a B-cell? Is this sufficient? Study Fig. 27.10-A, which illustrates this process.
- How do primary and secondary antibody responses differ? How long does it take for the body to mount an effective response in each case? Which kind of antibody is involved in each?
- What role do cytotoxic T cells play? What kind of microbial infection would they be most useful for?
- What is an autoimmune disease? Give an example.
- What is a superantigen? Identify a pathogen that secretes superantigens. What effect do they have on their hosts?
- What contribution did Jenner make to vaccination? How about Pasteur?
- What is a vaccine? Compare the advantages and disadvantages of the following: killed whole vaccine, attenuated live vaccine, subunit vaccine, toxoid.
- What two microbes have been virtually annihilated due to effective vaccines?
- What does "DPT" stand for, and what type of antigen is used to produce each of the components of this multiple vaccine?
- What is an "adjuvant"?
- What is(are) the problem(s) with each of the following vaccines: Strep pneumoniae vaccine, BCG vaccine.
- What is a recombinant vaccine? How do you in principle construct one?