MECHANISMS of PATHOGENESIS
MECHANISMS of PATHOGENESIS
Part I
Host-Microbe Relationships
and Disease Processes
Chapter 14
Definitions
NORMAL FLORA or MICROBIOTA
HOST – any organism that harbors another organism
NORMAL FLORA - permanent and usually not pathogenic microorganisms
RESIDENT FLORA – always present on or in the human body
TRANSIENT FLORA - come & go
For a few hours to a few months
In utero - germ-free
Birth - microorganisms being to establish themselves
Lactobacilli from mother’s vagina
Feeding and breathing - colonization of URT and GIT
NORMAL FLORA
HOST & NORMAL FLORA exist together
The normal flora live in SYMBIOSIS with the human body
SYMBIOSIS – association between two or more species
COMMENSALISM = one organism benefits - the other is not affected
EX: Staphylococcus epidermidis - on our skin
The normal flora usually benefits the host by prevents pathogens from overgrowing
NORMAL FLORA - HOST INTERACTIONS
MUTUALISM = both organisms benefit
EX: E. coli in intestines produce vitamin K & some B vitamins
ANTAGONISM = competition between the microorganisms
Active competition ie between normal flora & pathogen
BACTERIOCINS = proteins secreted by E. coli in the large intestine to inhibit other bacteria
PARASITISM = one organism (microorganism) benefits - the other is harmed
EX: Any successful pathogenic microorganism
NORMAL FLORA INTERACTIONS
SYNERGISM = the effect of 2 organisms acting together is greater than the effect of either one acting alone
EX: Mycoplasma fermentans & HIV - if 1 cell is infected by both the cell will die much faster than when infected by either one alone
OPPORTUNISTS
OPPORTUNISTIC ORGANISMS = do not usually cause a disease but can become pathogenic under certain circumstances
OPPORTUNITY KNOCKS:
Normal flora disrupted /destroyed
Host defense mechanisms compromised
Normal protective barriers of host are disupted
EX: S. aureus - causes toxic shock syndrome (TSS)
EX: Pneumocystis carinii - causes pneumonia in AIDS patients
Evidence of Disease
Symptoms: changes in body functions such as pain and malaise
.Signs: changes that can be seen by an observer such as rash, fever, swelling
.Syndrome: specific symptoms and signs associated with a disease
TYPES of DISEASES
INFECTIOUS
Caused by bacteria, viruses, fungi, protozoa and helminths
COMMUNICABLE INFECTIOUS DISEASES
Contagious – can be spread from one host to another
NON-COMMUNICABLE INFECTIOUS DISEASES
Caused by: individual’s normal flora; ingestion of pre-formed toxins; organisms found in the environment
Not “caught” from another person
NON-INFECTIOUS
Caused by any other factor than infectious organisms
Occurrence of Diseases
Sporadic: occurs occasionally in a population
Endemic: a disease that is always found in the region
Epidemic: a disease that many people acquire in a very short period of time
Pandemic: is an epidemic that occurs worldwide
CLASSIFYING INFECTIOUS DISEASES: DURATION
ACUTE DISEASES = short duration (flu, cold)
CHRONIC DISEASES = longer duration (AIDS, leprosy)
SUBACUTE DISEASES = intermediate duration
LATENT DISEASES = causative agent becomes latent
Characterized by a period of time of no symptoms
VZV - chicken pox then shingles
SPREAD of INFECTION
THE INFECTIOUS AGENT:
WHERE DOES IT COME FROM?
HOW DOES IT GET INTO THE BODY?
HOW DOES IT GET OUT OF THE BODY?
HOW IS IT TRANSMITTED?
WHERE IS IT BETWEEN & DURING DISEASE?
Many pathogens can not survive outside the host long enough to serve as a source of infection
There must be sites where the pathogen can persist and maintain infectivity
RESERVOIR = a continual source of the disease causing organisms, it can be living or inanimate objects
LIVING RESERVOIRS of INFECTION
HUMAN RESERVOIRS:
May transmit M/O directly or indirectly
Carriers (asymptomatic people)
AIDS, diptheria, typhoid fever, hepatitis, gonorrhea
Convalescing patients
ANIMAL RESERVOIRS:
Wild and/or domestic
ZOONOSES = a disease that occurs PRIMARILY in animals but that CAN BE TRANSMITTED to HUMANS
~150 are known: anthrax, bubonic plaque, Lyme disease
Transmitted: bites, contaminated hides/feathers, food, insect vectors
NONLIVING RESERVOIRS of INFECTION
SOIL
Many fungal diseases
Clostridium tetani, Bacillus anthracis
WATER
HAV, pathogenic E. coli, polio and various gastrointestinal diseases, typhoid fever
MODES of DISEASE TRANSMISSION
New cases of infectious diseases
Pathogen must leave reservoir or portal of exit ( portal of entry in the new host
Three categories:
Contact transmission
Vehicle transmission
Vector transmission
CONTACT TRANSMISSION
DIRECT: person-to-person
HORIZONTAL transmission = from one person to another OR from one part of the host to another part of the host
Kissing, sexual contact, touching sores, shaking hands; direct fecal-oral transmission
VERTICAL transmission = from parent to offspring
In egg or sperm; placenta; breast milk; birth canal
INDIRECT TRANSMISSION:
FOMITES ie nonliving object
Syringe, drinking glass, contaminated linens, toys
DROPLET TRANSMISSION:
Coughing, sneezing, talking
VEHICLE TRANSMISSION
Is transmission through a medium
A non-living carrier of an infectious agent from its reservoir to a susceptible host
WATER
Often due to fecal contamination
Ex: Cholera, shigellosis, leptospirosis
FOOD
Often due to incompletely cooked food or improperly refrigerated foods ( food poisoning
Ex: Botulism, typhoid fever
AIR
Mucus droplets – can travel a long distance
Ex: Histoplasmosis, the flu, measles, tuberculosis
BODY FLUIDS
VECTOR TRANSMISSION
Usually an arthropod (insect)
Transfer of M/O from feet or other body parts of insects to food or skin of person
Or person can be bitten by insects that are harboring these M/O and thus introduce them to the body
BIOLOGICAL transmission
M/O replicates in vector (or at least part of the M/Os replicative cycle occurs in the vector)
Ex: Lyme disease, malaria
MECHANICAL transmission
Passive – no replication of M/O within vector
Ex: shigellosis, typhoid fever
Emerging Infectious Diseases
Diseases that are either new or changing
Many different factors
A new strain of pathogen that is more virulent
Overuse of antibiotics promotes resistant strains
Global warming increases survival of reservoirs and vectors
Modern transportation
Natural disasters
Animal control measures increase # of animals that carry microbes
Failure to comply with public health measures
AGE OF ANTIBIOTICS = NO DISEASE?
EMERGING INFECTIOUS DISEASES
New or changing diseases
E. coli O157:H7
HIV
Ebola virus
Hepatitis C Virus
Drug resistant T.B.
NOSOCOMIAL INFECTIONS
Hospital or other medical facility acquired
5-15% of patients affected
~2 million (10%) in American Hospitals
20,000 or more patients die/year
THREE FACTORS:
M/O in hospital
Patient’s general health
Chain of transmission
NOSOCOMIAL MICROORGANISMS
Often the most pathogenic will be in the hospital
S. aureus - urinary & respiratory infections
Pseudomonas aeruginosa - burns & surgical wounds
E. coli - urinary tract, neonatal meningitis
Enterococcus - urinary tract & wound
Many M/O contain R plasmids = antibiotic resistance
Endogenous infections
Caused by opportunistic M/O among patient’s own normal flora
Exogenous infections
Caused by M/O that enter the patient through the environment
HOSPITAL PATIENTS
Host is usually immunocompromised
Resistance to infection is reduced
Broken skin or mucous membranes
Surgery, burns, catheters
Suppressed immune system
Drugs, diabetes, stress, HIV etc
CHAIN of TRANSMISSION
Hospital staff ---> patient
Patient ---> patient
Fomites ---> patient
Ventilation system ---> patient
CONTROL:
Educate personnel
Practice good techniques
Monitor for drug resistance
HOW VIRUSES CAUSE DISEASE
Evade host immune system
Sometimes can destroy cells of the immune system (cytocidal)
CPE: Cytopathic Effects
Abnormalities in the host cell induced by virus
Inhibition of DNA, RNA and protein synthesis
Inclusion bodies
Small granules containing viral nucleic acids & proteins; found in nucleus and cytoplasm
Syncytia formation (giant cells)
Cause several host cells to fuse together
EXTENT of HOST INVOLVEMENT
SEPTICEMIA – “blood poisoning”
Pathogens are present and multiplying in the blood
BACTEREMIA - presence of bacteria in the blood
Bacteria are being transported but are NOT multiplying in the blood
VIREMIA - presence of viruses in the blood
Viruses are being transported but are NOT multiplying in the blood
TOXEMIA - presence of toxins in the blood causing symptoms
Definitions
PATHOGENICITY: Is the ability of an organism to cause disease
VIRULENCE: Is the degree of pathogenicity
PORTALS of ENTRY
Organisms need to ENTER to establish disease
These portals of entry differ for different M/O
Some M/O have only 1 portal and some have several portals
MUCOUS MEMBRANES
Respiratory, GI, & genitourinary tracts, conjunctiva (eyes)
SKIN
Largest organ & outermost protective layer
PARENTERAL ROUTE
Deposition directly under the skin into the tissues beneath skin or mucous membranes
Bites, burns, injections etc.
ENTRY of M/O into HOST
PREFERRED PORTALS of ENTRY
Route of entry that is required for establishment of disesase
NUMBERS of INVADING M/O
Number required for disease may vary from person to person
ADHERENCE
To tissue surfaces to establish infection
ADHESINS = surface molecules on the pathogen that bind to RECEPTORS on the surface of the host cell/tissues
Can be found on capsules, fimbriae, capsid, or envelope of a virus
PORTALS of EXIT
Usually pathogens leave host with body fluids or feces
Gastrointestinal tract
Diarrhea, vomitting
Urogenital tract
Sexual contact, urine
Blood
Insects, needles
Wounds
Respiratory tract
Coughing, sneezing, speaking
ESTABLISHMENT of DISEASE
To cause an infection or disease, microorganisms need to:
ENTER the organism (Portal of Entry – Chpt 15)
ADHERE to tissues
PENETRATE the tissues
DAMAGE CELLS to establish disease
HOW BACTERIA CAUSE DISEASE
VIRULENCE FACTORS – characteristics that help M/O cause infection and disease
Structural: pili for adhesion
Physiological: enzymes help to evade host defenses; toxins
DIRECT ACTIONS by BACTERIA
Adhesins – proteins/glycoproteins allow M/O to adhere to host cells
Colonization – growth of M/O on epithelial cell surfaces (skin, mucous membranes)
Invasiveness – degree to which a M/O can invade and grow in host tissues – related to virulence factors
Toxins – any substance poisonous to other organisms
HOW BACTERIA CAUSE DISEASE
VIRULENCE FACTORS – characteristics that help M/O cause infection and disease
Structural: pili for adhesion
Physiological: enzymes help to evade host defenses; toxins
DIRECT ACTIONS by BACTERIA
Adhesins – proteins/glycoproteins allow M/O to adhere to host cells
Colonization – growth of M/O on epithelial cell surfaces (skin, mucous membranes)
Invasiveness – degree to which a M/O can invade and grow in host tissues – related to virulence factors
Toxins – any substance poisonous to other organisms
BACTERIAL VIRULENCE FACTORS
CAPSULES – resist host defenses
Phagocytosis and complement
CELL WALL COMPONENTS – some may help
Streptococcus pyogenes - protein M
Mycobacteria – waxes (mycolic acid)
ENZYMES – extracellular enzymes
Help to breakdown and dissolve material found between/around cells
Hyaluronidase – “spreading factor”
Streptococci produce - digests hyaluronic acid
Coagulase – increases clotting (coagulation)
Staphylococcus aureus produces – keeps organism from spreading BUT also walls off M/O from immune system
BACTERIAL VIRULENCE FACTORS cont’d
Streptokinase – dissolves clots (digests fibrin)
Streptococcus pyogenes- pathogens trapped in clots free themselves to spread to other tissues
Collagenases – breaks down collagen
Produced by some Clostridia
Hemolysins – hemolyze RBCs
Alpha – partially digests hemoglobin ( greenish color
Beta – completely digests hemoglobin ( clear area
Staphylococci, Streptococci, Clostridium perfringes
Streptolysin O (SLO) is sensitive to oxygen
Streptolysin S (SLS) is not sensitive to oxygen
Leukocidins – destroys neutrophils
A type of WBC important for phagocytosis
Produced by Staphylococci and Streptococci
BACTERIAL TOXINS
TOXINS: poisonous substances produced by some M/O
Some produce fever, cardiovascular disturbances; neurological disturbances; diarrhea, shock
INTOXICATION
Diseases due to ingestion of the toxin (vs the M/O)
EXOTOXINS
Produced by bacterial and released into the surrounding medium
ENDOTOXIN
Lipid A portion of LPS released from cell wall of Gram –ve bacteria
BACTERIAL ENDOTOXIN
ENDOTOXIN -
Causes chills, fever, weakness, aches & sometimes shock and death
Two outcomes possible:
Fever or pyrogenic response
Septic shock
ENDOTOXIN & the PYROGENIC RESPONSE
Pyrogenic or Fever Response
Macrophage phagocytosis Gram -ve cell
Cell degraded releasing endotoxin
Endotoxin stimulates macrophage to secrete IL-1
IL-1 = INTERLEUKIN 1 (Endogenous pyrogen)
IL-1 causes the hypothalamus of brain to produce prostaglandins
PGs causes the body temperature to rise
ENDOTOXIC (SEPTIC) SHOCK #1
Reaction is due to a cascade of events
Fairly high fatality rate
100,000 die / year (USA)
13th leading cause of death in the USA
Macrophage may also secrete tumor necrosis factor (TNF) or cachetin in response to endotoxin
TNF + IL-1 activate other cells in the immune system which release MEDIATORS
Constriction of small blood vessels & increased permeability of capillaries
Rapid decrease in blood pressure (HYPOTENSION)
Impaired blood flow to the kidneys
ENDOTOXIC (SEPTIC) SHOCK #2
RESULTS: Chills, fever, vomitting, diarrhea, rapid decrease in b.p., convulsions, shock ± death
NORMAL? - a low level response allows for cells of the immune system to leave the blood and enter the site of infection
MAJOR PRODUCERS
P. aeruginosa
E. coli
Klebsiella
Proteus
Enterobacter
Salmonella typhi
BACTERIAL EXOTOXINS #1
EXOTOXINS –
Usually proteins and enzymes, mainly produced by Gram +ve bacteria
Genes often carried on plasmids or bacteriophages
Easily diffuse to blood & lymph
Exotoxins can be destroyed by heat or chemicals to become TOXOIDS.used as vaccines
Three categories of exotoxins based on effect:
CYTOTOXINS - Kill cells & affect their function
NEUROTOXINS - Interfere with normal nerve impulses
ENTEROTOXINS - Affect the GI tract
BACTERIAL EXOTOXINS #2
DIPTHERIA Toxin - Corynebacterium diptheria
Infected with a lysogenic phage
Cytotoxin that inhibits protein synthesis, AB toxin
Polypeptide B binds to cells; Polypeptide A inhibits protein synthesis
ERYTHROGENIC Toxin – Streptococcus pyogenes
3 types: A, B and C
Damages blood capillaries under the skin ( rash of Scarlet Fever
BOTULINUM Toxin – Clostridium botulinum
Neurotoxin acts at neuromuscular junction
Prevents impulses from nerve ( muscle and inhibits release of acetylcholine ( flaccid paralysis
BACTERIAL EXOTOXINS #3
TETANUS Toxin – Clostridium tetani
Neurotoxin (tetanospasmin) – inhibits nerve cell impulses for muscle relaxtion ( uncontrollable muscle contractions
VIBRIO Enterotoxin (Cholera Toxin)
Vibrio cholerae – AB toxin
Polypeptide B binds to cells; Polypeptide A induces formation of cAMP ( release of large amounts of fluid & electrolytes ( “rice water stools”
STAPHYLOCOCCAL Enterotoxin
Affects intestinal tract similar manner to cholera toxin
STAPHYLOCOCCAL TSS Toxin
Toxic Shock Syndrome Toxin
EXOTOXINS vs. ENDOTOXINS
Gram positive and gram negative bacteria
Protein
Neurotoxin, cytotoxin, enterotoxin
Destroyed by heat
Can be made into TOXOID, neutralized by antitoxin
Only gram negative bacteria
Lipid
Found in LPS of gram negative cells, LIPID A
Fever, toxic shock
Cannot be destroyed by heat
Cannot be made into toxoid, no neutralizing Ab.
PLASMIDS, LYSOGENY & PATHOGENICITY
R factors - antibiotic resistance increases pathogenicity
Plasmids that code for virulence factors
Staph enterotoxin
Certain fimbriae of E. coli
Tetanus toxin
LYSOGENY = incorporation of a phage into a bacterial chromosome often containing gene for toxins
C. diptheriae - prophage beta codes for diptheria toxin
Streptococcus pneumoniae - phage codes for capsule
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