Learning Objectives:

After reading this article you should be able to:

  1. define virulence, LD50 and ID50.
  2. describe the major stages of an infectious disease.
  3. list several factors that increase the chances of bacteria producing disease in a host.
  4. describe the major features of latent and chronic infections.
  5. describe the differences between normal flora, colonizing flora and pathogenic bacteria.
  6. explain the 2 general mechanisms by which bacteria produce disease and describe the major features of diseases produced in each way.
  7. compare and contrast the major features of exotoxins and endotoxins.
  8. list the major determinants of bacterial pathogenesis, including virulence factors that facilitate entry, invasion of cells, and evasion of host immune defenses.



Pathogenesis refers to the interaction of bacterial and host factors that leads to production of disease.  There are specific steps involved in bacterial pathogenesis:  to produce disease, bacteria must come into contact with a susceptible host, enter the host, overcome host defenses, grow, and produce cell and tissue damage.  It is important to remember:

  • Many, if not most, infections are subclinical-they do not produce disease.
  • The same disease may be produced by more than one bacterial species.
  • One bacterial species may produce a variety of diseases.
  • The outcome of an infection is determined by the interaction of the bacterium and the host.
  • Understanding the process of bacterial pathogenesis is critical for controlling the spread of infection, performing appropriate lab diagnostic tests, predicting disease outcomes, and developing effective treatments.



Definition of Virulence:

Virulence is a quantitative measure of pathogenicity:  the number of organisms necessary to produce disease.

The degree of pathogenicity of a given infectious agent (strain of a microbe or virus). Virulence depends both on the properties of the infectious agent and on the susceptibility (sensitivity) of the infected organism. The magnitude of virulence is judged by the severity of diseases caused by a microbe or a virus; in experiments on animals, by a lethal dose of an infectious agent. Virulence is determined not only by the ability of a microorganism to penetrate into the organism of a susceptible animal, multiply and spread within it, but also by the fact that the microbe (or virus) produces poisonous waste products — toxins. Virulence is not a species characteristic of a microbe (virus) and can vary widely in different strains. A change in virulence can be caused by artificial influences, for example, heating, radiation, chemical and vaccines.

Virulence Vs. pathogenicity

Pathogenicity is the ability of the causative agent of infectious diseases to cause pathological changes in tissues and organs and lead to the development of the disease.

Diseases are classified according to the level of pathogenicity, depending on the harm they can cause to the body. The diseases with the greatest known pathogenicity are the plague, Ebola and Marburg virus. These diseases pose a serious threat to both the sick person and society as a whole.

Unlike pathogenicity, virulence assesses precisely the ability of a microorganism to infect. This indicator takes into account not only the likelihood of developing a disease and dangerous consequences, but also being in the body without symptoms.

The danger to society is represented by those viruses or bacteria that are highly virulent. This means that even a minimal amount of particles can lead to an infectious process.


What is the virulence of the new coronavirus?

To date, experts are still continuing to study the new coronavirus. However, the World Health Organization (WHO) has already stated that the virulence of SARS-CoV-2 is much higher than that of the SARS virus, which led to the outbreak of SARS in 2002-2003, and the MERS coronavirus (Middle East respiratory syndrome, the outbreak was in 2015).

What is Lethal dose LD50 and LD100?

The lethal dose LD 50 and LD 100 represent the average dose of a substance in milligrams per 1 kilogram of weight that can cause the death of 50% or 100% of the experimental animals, respectively.  This indicator is used to characterize the acute toxicity of toxic substances, as well as to assess the degree of toxicity of chemical or medicinal products.

The average lethal dose of a substance varies depending on the route of administration. For example, when administered orally, the substances are less toxic than when administered intravenously. Therefore, when indicating the value of the average lethal dose, the route of administration is usually indicated.

The test was created by JW Trevan in 1927. Currently, LD50 is one of the most widely used hazard indicators for toxic and moderately toxic substances. At the same time, it is a somewhat unreliable criterion, since its results can differ significantly due to the genetic differences of the studied individuals, environmental factors, and others. Another drawback of the test is that it does not take into account serious toxic effects that do not lead to death, but are serious, for example, damage to internal organs.

In agriculture unlike medicine it is impossible to accurately determine the dose of a pesticide causing LD 50 and LD 100 effect on a single animal, insect or plant, since each biological species is characterized by different individual sensitivity to pesticides .

What is Average Lethal Concentration LC50

The average lethal concentration is a standard indicator of the toxicity of the environment in which half of the studied group of organisms of a particular species will die within a certain period of time when inhaled. The exposure is usually 1 or 4 hours. Indicator is indicated by the symbol LC50 or CK50 and is measured in mg or μg of test material per liter, or parts per million (ppm – ppm) of water or air. The LC50 cannot be used directly to compare the toxicity of substances in terms of their effects on organisms.

What is Infectious dose ID50

Infectious dose (infectious dose, infection dose, dose-effect) is the smallest amount of a pathogen that can cause the development of an infection in an organism sensitive to the pathogen.

  • If a smaller amount of pathogen enters the body than ID, the disease may not occur at all, or it will be mild.
  • When a pathogen enters in an amount greater than ID, the likelihood of infection increases sharply and the course of the disease is usually more severe.

When making this measurement, the “50% infectious dose” (ID 50) is usually used – that is, 50% of the experimental individuals are infected. In this case, the method of administration (infection) is usually indicated.

General Principles & causes of Immune Deficiency

  1. The infectious dose of an organism necessary to produce disease varies, and depends on the presence of virulence factors.
  2. Infectious disease results from a sufficient infectious dose of an organism entering a host and evading host defense mechanisms. Hosts with compromised immune systems are more susceptible to infections:
    • Immunodeficiency due to a variety of factors increases the chances of disease:
    • Genetic immunodeficiencies should clinically be considered
    • B cell deficiencies are associated with recurring bacterial infections.
    • T cell deficiencies are associated with recurrent viral and fungal infections.
    • Combined B and T cell deficiencies are associated with recurrent viral, bacterial, fungal, and protozoal infections.
    • Phagocytic deficiencies.
    • AIDS, diabetes result in immune deficiencies
    • Drug-induced immunodeficiency associated with organ  transplant patients.
    • Immunosuppression associated with chemotherapy for cancer.
    • Autoimmune diseases.
    • Old age, poor nutrition, stress, pregnancy.
  3. Most infections are asymptomatic (inapparent, subclinical) because the host immune response is effective in clearing the organisms before disease is produced. How could you test someone to see if they have had an asymptomatic infection?
  4. Latent infections may occur in which the organism is maintained in a non-replicating state, but may be re-activated with recurrence of symptoms.
  5. Chronic infection of a host may occur in which organisms continue to replicate, with or without producing symptoms. Asymptomatic chronic carriers are an important source of infection.
  6. Diagnosis of a pathogenic bacterial infection involves distinguishing normal flora (which may or may not be acting as opportunistic pathogens), colonizing flora, and bacterial pathogen(s).

Bacteria cause disease by 2 Major Mechanisms:

  1. Toxin production
    • Exotoxins:  polypeptides secreted from the cell.
    • Endotoxins:  LPS of Gram-negative cell walls.
    • Both toxins can cause disease symptoms (fever, shock) in the absence of the organism!
  1. Invasion and Inflammation
    • Invasive bacteria can invade tissues (spread) and induce inflammation characterized by erythema, edema, warmth, and pain.


Typical Stages of an Infectious Disease

  1. Incubation period: the period between acquisition of the organism (or toxin) and the onset of symptoms.
  2. Prodrome:  period during which nonspecific symptoms occur, including fever, malaise, loss of appetite.  What causes these nonspecific symptoms?
  3. Specific Illness period: period during which the characteristic signs and symptoms occur and are observed.
  4. Recovery Period:  period during which the illness abates and patient returns to a healthy state.


Stages of Bacterial Pathogenesis

  1. Transmission from an external source into a portal of entry (except when members of normal flora involved).
  2. Evasion of primary host defenses (or not!).
  3. Adherence to mucous membranes, usually via pili or fimbriae.
  4. Colonization by growth at the site of adherence.
  5. Disease symptoms caused by toxin production or invasion/inflammation.
  6. Host immune responses (generally occur during previous 3 steps, C, D, E).
  7. Progression or resolution of disease.


Determinants of Bacterial Pathogenesis

  1. Transmission
  2. Adherence to Cell Surfaces
    • Bacteria use specialized structures (pili or fimbriae) or produce substances (capsules, glycocalyx) to adhere to cell (usually mucosal) surfaces. The molecules mediating adherence are called adhesins and are often important virulence factors.
    • Virulence factors are often identified as such when organisms without them are demonstrated to be nonpathogenic.
    • Bacteria adhere especially well to foreign bodies, like artificial heart valves and joints, but phagocytes do not.
  3. Invasion, Inflammation, and Intracellular Survival
    • Several enzymes secreted by invasive bacteria are considered virulence factors:
      • Collagenase and Hyaluronidase
        • degrade collagen and hyaluronic acid, respectively.
        • facilitate spread (invasion) of bacteria through subcutaneous tissue.
      • Coagulase
        • accelerates formation of fibrin clots from fibrinogen.
        • anti-phagocytic by coating organisms with fibrin.
      • Immunoglobulin A (IgA) protease
        • degrades IgA so organism can adhere to mucous membranes.
      • Leukocidins
        • destroy leukocytes and macrophages.
      • Anti-phagocytic factors
        • Capsules prevent phagocytes from adhering.
        • Antibodies to capsule antigens enhance phagocytosis by opsonization; basis of several effective vaccines.
    • M protein of Streptococcus pyogenes.
    • Protein A of Staphylococcus aureus binds to IgG and prevents activation of complement.

Bacteria can cause 2 types of inflammation:

  1. Pyogenic (pus-producing)
    • neutrophils predominate
  2. Granulomatous
    • macrophages and T cells predominate
  1. Some bacteria can grow intracellularly and commonly cause granulomatous lesions.
    • They are not obligate intracellular parasites.
    • Intracellular growth protects organisms from extracellular defense mechanisms.
    • Bacteria invade cells via specialized surface proteins, invasins, that bind to specific cellular receptors.
  2. Many virulence factors are encoded by genes clustered in pathogenicity islands.
  3. After bacteria have colonized and multiplied at the site of entry, invasion of the bloodstream and spread to other parts of the body may occur. The organs affected depend on the presence of specific receptors.
  4. Pseudomembranes are inflammatory lesions produced in diphtheria and pseudomembranous colitis.


Endotoxins and Exotoxins

Exotoxins Definition

Exotoxins  are substances produced by gram-positive and gram – negative bacteria and released into the environment by them; proteins with a molecular weight of 10–900 kDa. They have a toxic effect on the human body, disrupt processes in the cell, namely: increase the permeability of membranes, block protein synthesis, disrupt interactions between cells. Usually exotoxins are unstable, quickly lose their activity under the influence of heat, light and chemicals, but retain their immunogenic properties. It is the action of exotoxin that determines the clinical picture of many infectious diseases. Exotoxins are produced, for example, by the bacteria that cause botulism, diphtheria , gas gangrene , tetanus and other microorganisms of gram-positive microflora.

Exotoxins are more toxic than endotoxins. The minimum lethal dose of crude diphtheria toxin for guinea pig is 0.016 mg / kg , tetanus – 0.005 mg, botulinum – 0.0001 mg. The activity of the purified toxins is several times higher. Exotoxins are thermolabile: most of them are destroyed at a temperature of 60–80 ° C within 10–20 minutes. They are proteins. According to the action on cells, they are distinguished

Exotoxins explained

  • Secreted polypeptides produced by some Gram-positive and some Gram-negative organisms.
  • Often encoded by genes located on plasmids or lysogenic phages.
  • Some are extremely toxic with less than 1 μg in a fatal dose for a human.
  • Can produce disease in the absence of organism!
  • Are good antigens; induce protective antibodies (antitoxins).
  • Can be converted to toxoids, used in effective vaccines, when treated with formaldehyde, or other denaturing conditions.
  • Many have an A-B subunit structure:
    • A (active) subunit has the toxic activity.
    • B (binding) subunit mediates binding to specific cellular receptors.
  • Various exotoxins produce a variety of symptoms via different mechanisms of action.  Some examples:
    Main Location of Symptoms Organism/Disease Mode of Action of Exotoxin
    Gastrointestinal Tract
    1.  Gram-positive cocci Staphylococcus aureus/Food poisoning Enterotoxin is a superantigen
    2.  Gram-positive rods Clostridium difficile/Pseudomembrane colitis Depolymerizes actin filaments
    3.  Gram-negative rods Vibrio cholerae/Cholera Stimulates adenylate cyclase
    Escherichia coli O157:H7/Bloody diarrhea Inactivates protein synthesis
    Escherichia coli/Watery diarrhea Labile toxin stimulates adenylate cyclase; Stable toxin stimulates guanylate cyclase
    Nervous System
    1.  Gram-positive rods Clostridium botulinum/Botulism Neurotoxin inhibits acetylcholine release
    Respiratory Tract
    1.  Gram-positive rods Corynebacterium diphtheriae/Diphtheria Inactivates protein synthesis
    2.  Gram-negative rods Bordetella pertussis/Whooping cough Stimulates adenylate cyclase; inhibits chemokine receptor
    Skin, Soft Tissue, or Muscle
    1.  Gram-positive cocci Staphylococcus aureus/Scalded skin syndrome Protease cleaves desmosome in skin
    Streptococcus pyogenes/Scarlet fever Erythrogenic toxin is a superantigen
    2.  Gram-positive rods Clostridium perfringens/Gas gangrene Lecithinase cleaves cell membranes
    Bacillus anthracis/Anthrax Edema factor is an adenylate cyclase; lethal factor is a protease
    1.  Gram-positive cocci Staphylococcus aureus Toxic shock syndrome toxin is a superantigen



Endotoxins Definition

  • Endotoxins are bacterial toxic substances that are structural components of certain bacteria and are released only during lysis (decay) of a bacterial cell. This distinguishes endotoxins from exotoxins , soluble compounds secreted by a living bacterial cell.A prime example of endotoxins is lipopolysaccharide or lipooligosaccharide. The lipopolysaccharide of gram-negative bacteria is so deeply researched and so widely used as an endotoxin that the terms endotoxin and lipopolysaccharide are often used interchangeably.

The structure of bacterial endotoxins

Bacterial endotoxins are composed of polysaccharide and lipid fragments. The polysaccharide fragment contains an O-specific chain (O-antigen), which includes a repeating sequence of oligosaccharide units based on glycosyl residues (up to 50), as well as a nucleus. Lipid A and the inner core of the polysaccharide component of endotoxins are partially phosphorylated. This leads to the fact that in solutions with neutral or basic pH, endotoxins will have a pronounced negative charge (pKa 1.3).

The molecular weight of the monomers of various lipopolysaccharides can vary within fairly wide ranges, which is explained by the variability of the O-specific chain. Endotoxins with molecular weights from 2.5 kDa (with a shortened O-specific chain) to 70 kDa (with a very long O-specific chain) are known. Most of the lipopolysaccharides have a molecular weight of 10 to 20 kDa.

However, it should be noted that monomeric lipopolysaccharides can form supramolecular structures due to non-polar interactions between lipid “tails”, as well as due to the formation of “crosslinks” of phosphate groups by bivalent cations. Thus, in aqueous solutions, endotoxins can aggregate into lamellar, cubic or inverted hexagonal structures such as micelles or vesicles. The diameter of such structures reaches 0.1 μm, and the molecular weight is 1000 kDa. Bivalent cations, such as Ca 2+ and Mg 2+ , promote the formation of supramolecular structures, while detergents, EDTA, and proteins, on the contrary, shift the equilibrium towards the formation of monomeric forms.


The O-specific chain is unique to each prokaryotic strain; it makes a significant contribution to serological specificity by inducing an immune response in human and animal organisms.


The main constituents of the core are heptose residues (hexapyranose in the outer part of the nucleus and L-glycero-D-mannoheptose in the inner part), as well as the 2-keto-3-deoxyoctonic acid group.

Lipid A

The lipid moiety of endotoxins or lipid A is the least variable and most conserved part. Lipid A is responsible for endotoxic activity. It manifests itself in stimulating the production and release of endogenous mediators by granulocytes and macrophages, such as bioactive lipids, NO, cytokines (for example, interleukin-1). Large concentrations of such mediators in the body can lead to many different pathophysiological reactions, such as an increase in body temperature, leukopenia, tachycardia, hypotension, diffuse intravascular coagulation, etc.

Endotoxin Mechanism

Scheme of recognition of lipopolysaccharide (LPS) by immune cells and transmission of a signal that induces an immune response.

The presence of a glycolipid in a molecule of endotoxins of different origin determines the commonality of their biological properties. Physiological concentrations of endotoxin fluctuate in a very wide range (from close to zero to 1.0 EU / ml) and have a steady tendency to increase with age. Under physiological conditions, 5-7% of circulating leukocytes carry LPS on their surface. The receptor complex CD14 / TLR4 / MD2, which is present on macrophages and many other cells in the body, binds LPS.

The outcome of the LPS reaction with the cells of the macroorganism depends on its concentration. Moderate activation of cells and systems at low doses of endotoxin with increasing dose turns into hyperactivation, which is accompanied by increased production of inflammatory cytokines, enhanced activation of the complement system and blood coagulation factors, which can end in the development of such formidable complications as disseminated intravascular coagulation (DIC), endotoxin shock and acute multiple organ failure. With an excessive intake of endotoxin into the systemic circulation under conditions of relative deficiency of LPS-binding factors, as well as with insufficient LPS of the excretory systems (primarily of the kidneys), endotoxin can exhibit its numerous pathogenic properties. The fact that an excess of LPS participates in the pathogenesis of various diseases is called “endotoxin aggression”. The reasons for the development of endotoxin aggression are very diverse: the most common is stress, as well as any pathological processes leading to an increase in the permeability of the intestinal barrier (food poisoning and acute intestinal infections, alcohol excess and dysbiosis , unusually fatty and spicy foods, acute viral infections, shock, etc.), portal hypertension and liver diseases, chronic and acute renal failure (since it is the kidneys that serve as the main LPS-excreting organ).

Enterosorption is an affordable and safe method for normalizing blood endotoxin levels. Enterosorbent in the intestine binds endotoxin and reduces its entry through the enterohematic barrier.


Endotoxins and their role

Endotoxin, or, to use a more precise term, bacterial lipopolysaccharide (LPS), is considered the most potent microbial mediator involved in the pathogenesis of sepsis and septic shock. Despite the fact that this factor was discovered more than a hundred years ago, the main role of endotoxin, which is present in the systemic circulation of most patients with septic shock, has not yet been established and is the subject of intense controversy. LPS is the most essential “signaling molecule” that is perceived by the early warning system of natural host immunity, as a harbinger of the introduction of gram-negative microorganisms into the internal environment of the body. Small doses of LPS in a limited tissue space help the host’s body organize effective antimicrobial protection and the removal of pathogens into the external environment. At the same time, the sudden release of a large amount of LPS, on the contrary, has a detrimental effect on the host organism, since in this case, an uncontrollable and life-threatening release of numerous inflammatory mediators and procoagulants into the systemic circulation is triggered. A pronounced host response to this molecule, which recognizes the introduction of bacteria into the internal environment of the body, is sufficient to cause diffuse endothelial damage, tissue hypoperfusion, disseminated intravascular coagulation, and refractory shock. Numerous attempts to block the activity of endotoxin, undertaken in the framework of clinical studies carried out in a population of patients with sepsis, are characterized by conflicting and, mainly, negative results. However, during the previous decade, significant discoveries were made in the molecular basis of LPS-mediated cellular activation and tissue damage, which revived optimism associated with the possible success of a new generation of therapy aimed at specifically blocking the LPS signaling system.

It is now believed that other microbial mediators, which are part of the structure of gram-positive bacteria, viruses and fungi, are also capable of activating numerous host defense systems that are affected by LPS.

Endotoxin is distributed in the blood stream and promotes the activation of monocytes and macrophages. As a result, mediators, including cytokines, are released, and favorable conditions for infection-induced systemic inflammation are created. Endotoxin is the trigger for the release of cytokines and mediators. The presence of endotoxins in the blood is called endotoxemia . With a strong immune response, endotoxemia can lead to septic shock . It is believed that the impact on endotoxin and its early elimination from the body are the most important tasks in the treatment of sepsis.

Endotoxins Summary

  • Integral parts of cell walls of both Gram-negative rods and cocci; lipopolysaccharides (LPS).
  • Encoded by genes located on the bacterial chromosome.
  • Lower toxicity than exotoxins.
  • Can produce disease (fever and shock) in the absence of organism!
  • Are weak antigens; do not effectively induce protective antibodies.  What is the consequence(s) of this?
  • No endotoxin toxoids or vaccines.
  • Are the best-established cause of septic shock.


Definition of Septic shock

Septic shock is a life-threatening complication of severe infectious diseases, characterized by a decrease in tissue perfusion , which disrupts the delivery of oxygen and other substances to tissues and leads to the development of multiple organ failure syndrome . Septic shock is most common in children, immunocompromised people, the elderly, and abortion. The probability of a fatal outcome is 25-50%

Criteria for the diagnosis of septic shock

Septic shock is a subclass of distributive (distributive) shock , a condition in which the pathological distribution of blood flow through the microvasculature leads to inadequate blood supply to body tissues, ischemia and multiple organ failure .

Septic shock can be defined as persistent septic-induced hypotension that does not resolve despite infusion therapy .

Septic shock is a stage of the systemic inflammatory response syndrome (SIRS), which develops when the body is unable to stop a local infection. The massive release of inflammatory response mediators during the generalization of the inflammatory response causes pronounced vasodilation, a decrease in blood pressure, and, as a consequence, tissue perfusion pressure, which leads to tissue hypoxia and multiple organ failure.

According to current guidelines, sepsis is defined as an infectious disease (suspected or confirmed) associated with systemic manifestations. These manifestations include:

  • Tachypnea > 20 per minute or PaCO2 level below 32 mmHg. Art.
  • The number of leukocytes is increased by more than 12 × 10 9 / l or decreased below 4 × 10 9 / l;
  • Tachycardia > 90 beats per minute;
  • Body temperature > 38.0 ° C or <36.0 ° C;

Systemic shock is diagnosed in the presence of the above symptoms and persistent intractable sepsis-induced hypotension  – systolic pressure below 90 mm Hg. Art., mean arterial pressure below 70 mm Hg, or due to sepsis, a decrease in blood pressure by 40 mm Hg. Art. and more .

 Septic Shock Summary:

  1. Septic shock is characterized by fever and hypotension
  2. Septic shock is a leading cause of death in ICUs and has a mortality rate of 30-50%.
  3. Also cause disseminated intravascular coagulation (DIC) due to activation of the coagulation system, resulting in thrombosis, tissue ischemia and ultimately multiple organ failure.
  4. Endotoxin effects are due to induction of the production of cytokines, including interleukin-1 (IL-1) and tumor necrosis factor (TNF).
  5. Intravenous fluids are sterilized by filtration to eliminate LPS, since it cannot be inactivated by heat.
  6. Endotoxin-like effects can be also caused by teichoic or lipoteichoic acids of Gram-positive organisms, like S. aureus



  1. Molecular mimicry can result in the production of antibodies that cross react with bacterial antigens and host antigens.
  2. Ex. M protein of Streptococcus pyogenes induces production of antibodies that cross react with joint, heart, and brain tissue.  The resulting inflammation produces arthritis, carditis, and chorea associated with rheumatic fever.


Study Questions

  1. What is the difference between the LD50 and the ID50? Why are these measures of virulence measured in terms of 50% of an experimental population?
  2. What does the term “virulence” mean? If I tell you that Shigella species are more virulent than Salmonella species, and that Bob ate 1 cup of salad contaminated with Salmonella and Barb ate 1 cup of salad contaminated with Shigella, who would you predict will get sick or get sick first?  Why?
  3. If Barb didn’t get sick from eating the Salmonella-contaminated salad, what 2 basic requirements for the production of infectious disease were not likely met?
  4. What host factors can increase the likelihood that exposure to an infectious agent will result in disease?
  5. People with defective or deficient humoral immune responses are more susceptible to infections with ____________________.
  6. List at least 4 ways in which one can become immunocompromised.
  7. For an immunocompetent person, the most likely outcome of an exposure to an infectious agent is ___________________________.
  8. What is the difference between a chronic and a latent infection?
  9. What are the 2 general mechanisms by which bacteria cause disease and how do they differ? What are the clinical manifestations of these 2 different mechanisms?
  10. What are the 4 typical stages of an infectious disease?
  11. What are the clinical signs of the prodrome and why are they the same regardless of the infectious agent?
  12. What are 3 bacterial structures that mediate adherence and why are they considered virulence factors? What types of surfaces do bacteria adhere to?
  13. List 5 bacterial virulence factors that enable bacteria to invade (or spread through) tissues of the body and how they do this. Which ones function to evade the immune response?
  14. What is the difference between pyogenic and granulomatous inflammation? What is pus composed of?
  15. Why is the ability of a bacterium to invade and survive inside a cell considered a virulence factor?
  16. What is the definition of an exotoxin? Of an endotoxin? Which one would you guess might be listed on the Homeland Security’s list of potential biowarfare agents?  Why?
  17. Do endotoxins or exotoxins make the best vaccines? Do they have to be in their active form to elicit an immune response? Do they need to be associated with the bacterial cell that produces them to be effective?
  18. Do all exotoxins have the same mode of action?
  19. What is the main endotoxin found in Gram-negative cells and what are the 2 most serious clinical syndromes it causes? How does endotoxin produce these syndromes?
  20. What is the main endotoxin found in Gram-positive cells?
  21. Where are the genes for exotoxins and endotoxins usually located? What are the consequences of this?
  22. Describe 2 examples of immunopathogenesis.
  23. How can some bacteria be pathogenic even when they are no longer viable?