These lecture notes will provide an outline of information from the lectures. They are not complete. They should be used to help follow the lecture and as a guideline for information I think is important. You will need to fill in the gaps.

These notes were updated February 24, 2001, and are ready for printing by Spring 2001 Med Micro. students.

Chapter 14

I.    Infection A.    The relationship between two organisms and the competition for supremacy that takes place between them 1.    This is a symbiotic relationship
2.    A host-parasite relationship
3.    Organism has invaded the host a)    It may even have colonized B.    Infection is not equal to disease II.   Disease A.    Any change from the general state of good health
B.    A change from the normal healthy status
C.    Some diseases are physiological in nature 1.    That is, they are due to a malfunctioning body organ or system D.    Other diseases are nutritional in nature 1.    That is, they are caused by a dietary insufficiency E.    Still other diseases are genetic in origin 1.    They are due to a defect in human genes F.    Infectious diseases are those caused by infectious organisms III.   Normal flora A.    Population of microorganisms that infect the body without causing disease
B.    This is a symbiotic relationship 1.    It is mutualism when the symbiosis is beneficial to both the host and the normal flora a)    Example is Lactobacillus in the vagina (1)   It derives nutrients from the vaginal environment
(2)   It produces acid that prevents the overgrowth of other organisms b)   E. coli is another example (despite the text book attempting to call it a commensal) (1)    It produces vitamins B and K for the host while deriving nourishment from the host 2.    Commensalism occurs when one organism derives benefit without benefiting or harming the host a)   Corynebacterium is a commensal of the surface of the eye C.    Under normal conditions, do not produce disease 1.    May be transient or permanent normal flora D.    Sometimes the flora are opportunistic 1.    Examples are normal flora that are found in other than their normal, expected location
2.    Or changes in the host that provide opportunities for a change in the health status of the host (disease) to occur (such as overgrowth of yeast after antibiotic therapy) E.    When disease occurs, the symbiosis is a parasitic one IV.   Pathogenicity A.    The ability of a parasite to gain entry to host tissues and cause disease to the host 1.    Portals of entry are important a)    Portal of entry is the site at which parasite enters the host
b)    Some organisms have multiple portals of entry (1)   Example is Mycobacterium tuberculosis bacillus, which can be breathed in, eaten, or acquired through an open wound c)    Other organisms have limited portals of entry (1)   Example is Clostridium tetani, which must enter through a skin puncture directly into tissue in order for endospores to germinate successfully B.    Virulence 1.    The degree of pathogenicity of a parasite V.    To Describe a Disease A.    Clinical Disease 1.    Disease in which symptoms are apparent B.    Subclinical 1.    Disease in which symptoms are not apparent C.    Communicable 1.    This means the diseases are transmissible among hosts
2.    Contagious diseases are highly communicable
3.    Portals of exit are important for communicability a)    Easy transmission occurs if pathogen can leave the host through some suitable portal of exit (1)   Droplets (coughing/sneezing)
(2)   Open lesions (contact)
(3)   Urine/feces (oral-fecal routes)
(4)   Blood (bloodborne)
(5)   Vectors (insect bites) D.    Noncommunicable diseases 1.    Causative agent is not easily transmitted to the next host from a host
2.    Rather, the causative agent may be acquired directly from the environment a)    An example is tetanus E.    Endemic, epidemic, or pandemic 1.    Endemic diseases occur at low levels all the time in certain geographic areas
2.    Epidemic diseases are outbreaks above the endemic levels
3.    Pandemics are worldwide outbreaks F.    Acute or chronic 1.    Acute diseases develop rapidly, climax, and fade quickly
2.    Chronic diseases develop slowly and linger G.    Primary or secondary 1.    Primary diseases occur in someone who is healthy and are caused by the initiating organism
2.    Secondary diseases develop as a result of the weakened status of the host after a primary disease has occurred a)    Quite often, secondary diseases are due to opportunistic infections H.    Local diseases are restricted to a single area of the body
I.    Systemic diseases have spread to the organs and organ systems 1.    Bacteremia is the presence of bacteria in the blood a)    Septicemia is the same 2.    Toxemia
3.    Fungemia
4.    Viremia
5.    Parasitemia VI.   The progress of disease A.    Period of incubation 1.    The time between the parasite's entry into the host and the appearance of symptoms a)    Varies from 1 day to 6 years or more 2.    Determined by number of invading parasites, their generation time, their virulence, and the level of the host's resistance a)    DOSE refers to the number of parasites taken in by the host (1)   The infectious dose is the number that must be takine into the body in order for disease to occur (a)   ID₅₀ is the number of microbes that will cause a demonstrable infection in 50% of inoculated test animals (2)   The lethal dose is the number required for death to occur (a)   LD₅₀ is the number of microbes that will kill 50% of inoculated test animals B.    Period of prodromal symptoms (the prodrome) 1.    Characetized by general symptoms, such as nausea, fever, headache, etc.
2.    These indicate the competition for supremacy has begun C.    Period of acme 1.    Acute stage of the disease
2.    Specific symptoms appear
3.    Examples are skin rashes, jaundice, vesicles, swollen lymph nodes D.    Period of decline (defervescence) 1.    Symptoms subside, often following a crisis period
2.    Recovery is often rapid E.    Period of convalescence 1.    Body's systems return to normal VII.   How We Make Others Sick (Transmission of disease) A.    Reservoirs of Infections 1.    Human a)    Carriers are a special type of reservoir (1)   Usually a person who has recovered from the disease but continues to shed the disease causing organism (through their feces, for example) 2.    Animal a)    They may show no symptoms of disease, but still transmit the causative agent 3.    Nonliving a)    Contaminated water and soil may be reservoirs B.    The Actual Transmission 1.    Direct transmission a)    Direct contact (1)   Includes droplet transmission and other direct contact b)    Indirect contact (1)   Includes fomites 2.    Vehicle transmission through a medium a)    Includes water, food, air 3.    Vector transmission a)    Mechanical vectors transport microbes on body parts
b)    Biological vectors are actual hosts to the microbes C.    The susceptible host 1.    Immune status (including vaccinations)
2.   Nutritional status
3.    Underlying disease status
4.    Miscellaneous (stress, medications, lifestyle choices) Wednesday's Test Material Up to Here
Below is Material That Will Be Covered on the Next test

I.    Pathogenicity and Virulence (or What Makes a Microbe BAD?)

A.    Review of Previous Knowledge 1.    Principal Portals of Entry a)    Mucous membranes
b)    Respiratory tract lining
c)    GI tract
d)    GU tract
e)    Conjunctiva
f)    Skin
g)    Parenteral (1)   Beneath the skin or membranes 2.    Preferred Portal of Entry a)    Many pathogens have a preferred portal of entry that is a prerequisite to their causing disease 3.    Numbers of Invading Microbes a)    LD₅₀ is the number of microbes that will kill 50% of inoculated test animals
b)    ID₅₀ is the number of microbes that will cause a demonstrable infection in 50% of inoculated test animals II.   Tissue Penetration A.    Invasiveness is the ability of a parasite to penetrate tissues and cause structural damage 1.    This is a VIRULENCE factor
2.    BUT, it is not essential to infection and disease a)    For example, Bordetella pertussis (whooping cough) and Vibrio cholera (cholera) do not penetrate tissues (1)   However, both produce exotoxins that lead to disease B.    Adhesiveness is the ability of the parasite to adhere to tissue 1.    This enables the pathogen to become localized a)    This allows opportunities for colonization
b)    This allows for opportunities to enter the cells (1)    Either through phagocytosis
(2)   Or through bacterial induced endocytosis 2.    Adhesins are necessary for adhesion to occur a)    Adhesins are proteins
b)    They are usually found on the fimbriae (also called pili)
c)    BUT, they may not be associated with an external bacterial structure, but rather be found independently (1)   The M protein of the Streptococcus species is a very important example of an independent adhesin
(2)   It is contained within the cell wall of the Streptococcus organisms 3.    The host cell has receptor sites for the adhesins to bond to a)    Thus, it is an active participant in this process: (1)   Pathogen's adhesins + host's receptors 4.    Some pathogens produce substances allowing the bacteria to attach to host surfaces to form a biofilm a)    The glycocalyx, either in capsular or slime layer form, allows the bacteria to attach to the host (1)   For example, Streptococcus mutans forms a slime layer from the sucrose consumed by the host and attaches to form a biofilm upon the tooth surfaces 5.    Recall that viruses must also adhere and have spikes on their surfaces that act as adherence factors D.    Cell internalization is the process that allows the bacteria to be taken up by cells (either phagocytic or non-phagocytic) and move through the host in a safe setting 1.    Endocytosis occurs when a eukaryotic cell takes in material from the surrounding environment by surrounding and enclosing the material in a fluid-filled compartment a)    Endocytosis includes pinocytosis and phagocytosis 2.    Exocytosis is the opposite of endocytosis and allows the release of material
3.    This process allows pathogens to pass through impenetrable barriers in order to move to a protective niche where colonization can occur E.    Cell-to-cell transport involves the use of cadherin, a molecule that helps pathogens bridge the junction between two cells and move between cells 1.    This system allows bacterial invasion to occur without bacteria leaving the cellular environment F.    Summary 1.    Bacteria that have genes that code for any of the following invasive factors are more virulent than bacteria that do not a)    Adhesins
b)    M proteins
c)    Glycocalyx (1)    Capsules
(2)    Slime layers d)    Cell internalization through endocytosis
e)    Cell-to-cell transport through cadhesins 2.    All of the above help a bacterium penetrate host tissue III.   Enzymes Can Be Virulence Factors A.    The ability to produce certain enzymes is another important virulence factor
B.    Certain enzymes help the parasite resist host defenses 1.    Coagulases a)    Enzyme that catalyzes the formation of a blood clot from human fibrinogen
b)    This clot protects the bacteria from phagocytosis
c)    Produced by Staphylococcus aureus (1)    We are able to identify this group of bacteria in the lab using the coagulase test 2.    Streptokinase a)    Enzyme that dissolves fibrin clots that the host has formed as its defense against bacterial infection
b)    Many pathogenic streptococci can form this enzyme
c)    These bacteria are able to overcome an important host defense (clotting) and penetrate further into the tissue 3.    Hyaluronidase a)    This enzyme is called the spreading factor because it catalyzes the breakdown of hyaluronic acid, the "glue" that holds cells together in a tissue
b)    A variety of bacteria have the ability to form this enzyme, including Streptococcus pneumoniae, Streptococcus pyogenes, Clostridium perfringens, and Staphylococcus aureus IV.   Certain Non-Enzymatic Proteins Can Contribute to Pathogenicity A.    Hemolysin 1.    This is a cytolytic protein that disrupts the cell membrane of the red blood cell by forming pores that allow water to enter and lysis to follow
2.   Clostridia perfringens, Staphylococcus aureus, and various Streptococci are examples of organisms having hemolytic capabilities a)    We can observe this virulence factor in the lab by looking for alpha or beta hemolysis in blood agar medium B.    Leukocidins 1.    These are cytolytic proteins that damage the cell membranes of the phagocytes, the host's defensive white blood cells
2.    The neutrophils, monocytes, and macrophages are the phagocytes
3.    Various bacteria, including S. aureus, have the ability to produce this proteins V.    Toxins A.    Toxins are poisons produced by certain bacteria
B.    There are two types of toxins 1.    Exotoxins a)    Produced by certain Gram positive OR Gram negative bacteria (note that this is a CORRECTION to what is stated in your book)
b)    These proteins are released by the bacteria into the surrounding tissues as they are produced by the bacteria
c)    They dissolve in the blood fluid and circulate to their site of activity and symptoms of disease follow
d)    Genes for the exotoxins are found on bacterial plasmids (phages) (1)   Thus, this is a new property conferred by lysogeny upon bacteria infected by an appropriate bacteriophage e)    These toxins are generally heat LABILE (an important exception is the exotoxin produced by S. aureus)
f)    Modus operandi is either cytotoxic, neurotoxic, or enterotoxic (1)   Examples of cytotoxins include the toxins produced by Bacillus anthracis, Staphylococcus aureus, Streptococcus pyogenes, Bordetella pertussis, and Pseudomonas aeruginosa
(2)   Examples of neurotoxins include the toxins produced by Clostridium botulinum and Clostridium tetani
(3)   Examples of enterotoxins include the toxins produced by Vibrio cholerae and Escherichia coli g)    Host can produce antibodies to exotoxins (1)   Called antitoxins h)    Most exotoxins formed by the Gram positive bacteria can be converted to toxoids (1)   Toxoids are effective immunizing agents (a)   Some vaccines contain toxoids, inactivated toxins that can still stimulate antibody production 2.    Endotoxins a)    Are a part of the outer portion of the cell wall of Gram negative bacteria (1)   RECALL outer membrane that surrounds the peptidoglycan layer is composed of LPS (lipopolysaccharides), lipoproteins, and phospholipids
(2)   BEWARE the LPS: it contains lipid A, the endotoxin b)    Are liberated AFTER the cell dies causing a worsening of symptoms, which improve as the endotoxin breaks down
c)    Cause chills, fever, weakness, aches, and in some cases, abortion, shock, and death
d)    Activate blood-clotting proteins, resulting in disseminated intravascular coagulation (DIC) C.    Summary 1.    Bacteria having genes that code for any of the following virulence factors are more virulent than those that do not a)    Enzymes such as coagulase, streptokinase, and hyaluronidase
b)    Non-enzymes such as hemolysins and leukocidins
c)    Exotoxins such as cytotoxic, neurotoxic, or enterotoxic toxins
d)    Endotoxins found in all Gram negative cell walls VI.   Pathogenic Properties of Non-Bacterial Microbes A.    Fungi 1.    May have capsules, toxins, or cause allergic responses B.    Protists and Helminths 1.    Cause damage to host tissue through invasion process or by metabolic waste products
2.    Some protists can change their surface antigens to evade detection C.   Viruses 1.    Avoid host's immune response by growing inside host cells
2.    Have attachment sites for host cell receptors
3.    Some are cytocidal; others noncytocidal
4.    Cytopathic effects (CPE) of a viral infection can be observed microscopically VII.    The Human Circulatory System: These notes will be covered with the next chapter, chapter 18, "Resistance and the Immune System"

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