Lecture 12

Microbial Mechanisms of Disease

Normal Flora of Human Body

• Normal flora: population of microorganisms routinely found growing on the body of healthy individuals

• Many different species of microorganisms make up normal flora and they occur in large numbers

Figure 19.1

Importance of normal flora

• Protection against potentially harmful microorganisms

• Stimulate the immune system

• Flora of intestine stays stable- beneficial to both human and bacteria

Relationship between normal flora and host

Pioneers in discovering and studying disease caused by

microorganisms• Germ theory of disease: microorganisms

can cause disease and it can spread and reemerge

• Louis Pastuer (1822): proved yeast are living organisms, fermenting wine

• Robert Koch (1876): proved bacteria actually cause disease

Koch’s postulates

1. Microorganism must be present in every case of the disease

2. Organism must be grown in pure culture from the diseased host

3. Same disease must be produced when a pure culture of organism is injected into another host

4. Same organism must be recovered from the experimentally infected host

Classifying Infectious Diseases

• Symptoms: changes in body function

• Signs: physician can observe and measure

• Communicable disease vs. contagious disease vs. non-communicable disease

Occurrence of a disease

• Incidence: # of people in a population who develop the disease during a certain time period

• Prevalence: # of people in a population that have the disease at a specified time

Occurrence of a disease

• Sporadic disease: occurs only occasionally

• Endemic disease: constantly present in the population

• Epidemic disease: many people in a given area get disease in a short time period

• Pandemic disease: world-wide epidemic

Severity or duration of a disease

Primary Infection: initial infection, may leave person predisposed to get a Secondary Infection

• Acute Infection: characterized by symptoms that have rapid onset, last short time

• Chronic Infection: develops more slowly, lasts longer

• Latent Infection: remains inactive, then becomes active again to produce symptoms

Extent of host involvement

• Local infection: microbes limited to small area of body

• Systemic infection: microbes or products throughout the body

• Sepsis: toxic inflammatory condition

• Septecemia: systemic infection

Development of disease• Incubation period- time interval between

initial infection and the first appearance of any signs or symptoms

• Prodomal period- early mild symptoms• Period of illness- when disease is most

acute• Period of decline- signs and symptoms

decline• Period of convalescence- person regains

strength and body returns to prediseased state

Establishment of Disease

Microorganisms causing disease

• To cause disease microorganisms must:

1. Transmit disease to host

2. Enter the body

3. Adhere to host tissues

4. Penetrate or evade host defenses

5. Damage the host tissues

Transmission of disease

• Microorganisms can be transmitted from the reservoir of infection to a susceptible host by three principle routes– Contact– Vehicles– Vectors

Contact transmission

• Contact transmission=

• Direct contact transmission- physical contact between microorganisms source and susceptible host

• Indirect contact transmission- when microorganism transmitted from reservoir to susceptible host by means of nonliving object

• Droplet transmission- microorganisms spread by droplets that travel only short distance

Vehicle transmission

• Vehicle transmission=

• Waterborne transmission- water contaminated usually with untreated or poorly treated sewage

• Foodborne transmission- food that is usually incompletely cooked, poorly refrigerated, or prepared under unsanitary conditions

• Airborne transmission- transmission via droplets that travel more than 1 meter from reservoir to host

Vector

• Vector=

• Arthropods most important group

• Mechanical transmission- passive transport of the pathogens on insects feet or other body parts

• Biological transmission- active process

Enter the Body

• Portals of Entry:– Mucous membranes: often respiratory tract– Skin: must enter through openings– Parenteral Route: deposited directly into

tissues beneath the skin or mucous membranes

Adherence

• Adhesins or ligands on microbe bind to receptors on host cells

• Adhesions may be located on glycocallyx or other microbial surfaces such as pili, or flagella

How bacterial pathogens penetrate host defenses

• Several ways:

1. Capsules

2. Components of cell wall

3. Enzymes

4. Antigenic variation

5. Penetration into host cell cytoskeleton

Capsules

• Some bacteria make a glycocallyx that is outside of the cell wall

• This impairs phagocytosis

• Immune sytstem can overcome this

• Some strains of the same bacteria have glycocallyx others do not

Components of cell wall

• Some components of cell wall contribute to pathogenicity:– M protein– Fimbrae– Waxes

Enzymes

• Coagulases: form blood clot

• Kinases: break down fibrin and dissolve blood clots formed by the body to isolate infection

• Hyaluronidase: breaks down polysaccharide that holds together connective tissue

• Collagenase: breaks down collagen

Antigenic Variation

• Antigens=

• Antibodies=

• Some pathogens can alter surface antigens

• Makes it more difficult for immune system to fight against it

Penetration into host cell cytoskeleton

• Microbes attach by adhesions

• Triggers signals in host cell that activates factors that results in the entry of some bacteria

• Bacteria produce invasions, which rearrange actin

• Causes cytoskeleton disruption

• Allows bacteria to enter

How Bacterial Pathogens Damage Host Cells

• If pathogen overcomes host defenses then microorganism can damage host cells by:

1. Using host cell nutrients

2. Causing direct damage

3. Inducing hypersensitivity reactions

4. Producing toxins

Using Host Cell Nutrients

• Bacteria require iron

• Most iron in body tightly bound to iron-transport proteins

• Some bacteria produce siderophores- take iron away from iron-transport proteins

Direct Damage

• Use host cell for nutrients and produce waste products

• As pathogens metabolize and multiply in cells, cells usually rupture

• Then move onto other cells

Inducing hypersensitivity reactions

• Hypersensitivity=

• Occurs in people who have been sensitized by a previous encounter with an antigen

• When exposed to again, their immune system reacts to it in a damaging manner

Production of Toxins

• Toxins=

• Produce fever, cardiovascular disturbances, diarrhea, and shock

• Also inhibit protein synthesis, destroy red blood cells, disrupt nervous system

• Two types: Endotoxins and Exotoxins

Exotoxins

• Produced inside some bacteria as part of growth and metabolism and then secreted

• Diffuse easily within blood and rapidly travel throughout body

• Destroy parts of host cells or inhibit metabolic functions

Exotoxins

• Three principal types:

1. A-B toxins

2. Membrane-disrupting toxins

3. Superantigens

A-B toxins

Membrane-disrupting toxins

• Cause lysis of host cells by disrupting plasma membrane

• Two ways:

1. Form protein channels in plasma membrane

2. Disrupt phospholipid portion of plasma membrane

Superantigens

• Provoke very strong immune response

• Immune system produces too many immune cells

• Produce fever, vomiting, diarrhea, sometimes even shock and death

Most Notable Exotoxins

• Diphtheria toxin

• Botulinum toxin

• Tetanus toxin

Endotoxins

• Part of outer membrane of G- bacteria

• Endotoxins released when G- bacteria die

• Exert affect by stimulating macrophages to release cytokines at very high levels

Epidemiology

Descriptive Epidemiology

• Collecting all data that describe the occurrence of the disease under study

• Retrospective

Analytical Epidemiology

• Analyzes a particular disease to find it’s probable cause

• Case control method

• Cohort method

Experimental Epidemiology

• Hypothesis about disease

• Experiments to test hypothesis conducted on group of people

CDC

• Morbidity and Mortality Weekly Report

• Morbidity: incidence of specific notifiable diseases

• Mortality: number of deaths from these diseases

• Notifiable diseases: those physicians are required to report