Pathology of Infection

Question 1

What are Koch’s Postulates?

Answer 1

Criteria for whether an organism causes disease - some exceptions and limitations, but in general are useful in establishing origin of infectious disease.
States that the organism:
1. Must be found in lesions of the disease
2. Must be isolated and cultured in vitro
3. Must be able to transmit the disease to another animal
4. Must be recovered from lesions in that animal

Question 2

What are some different ways that an organism can be observed?

Answer 2

• directly observed in microscopic sections (CMV, herpes)
• require special stains to be visualized based on particular characteristics in their cell walls (gram +/-, acid fast or silver stains)
• lab studies (isolation and growth of organisms from sputum, blood, stool or urine sample)
• radiographic examination (chest x-ray)
• DNA sequence analysis and PCR-based methods
  -identify a host response to the organism (serology, IgM - acute infection or IgG - acute or previously exposed)

Question 3

What are Prions?

Answer 3

-infectious proteins (or proteinaceous infectious particles), lack DNA or RNA
-represent an abnormal form of a normal host prion protein (PrP)
-modify the host protein to undergo a conformation change conferring resistance to degradation.
-cause spongiform encephalitis (CJD), mad cows disease (new variant CJD), Creutzfeld-Jakob disease (CJD), bovine spongiform encephalopathy (BSE)

Question 4

What are viruses?

Answer 4

-obligate intracellular organisms, take over genetic apparatus of host cell for their own replication (depend on host cell for replication)
-cell specific (e.g. COVID19 only affects lung or respiratory cells)
-the viral genome may be DNA or RNA (not both) surrounded by a protein coat (capsid)
-illnesses may be acute (colds, influenza), chronic - lasting more than 6 months (hepatitis B/C) or latent (herpes zoster)
-some viruses have the capacity to transform host cells into neoplastic cells (HPV)

Question 5

What are Bacteria?

Answer 5

-intracellular or extracellular
-have a cell membrane but lack membrane-bound nuclei or organelles; also bound by a cell wall
-can synthesize own DNA, RNA and proteins
-depend on the host for favorable growth conditions
-often classified by shape (round= cocci, rods= bacilli, spirochetes); reaction on gram staining, gram+ (have a thick wall that retains stain) or gram- (do not stain) or oxygen requirement for growth (aerobic or anaerobic)
-pathogenic strains “in the wild” but normal flora may infect if defenses are down (opportunistic)
-e.g pneumonia

Question 6

What are atypical bacteria?

Answer 6

-lack specific features of typical bacteria
-Chlamydia, mycoplasma, rickettsia

Question 7

What are bacteriophages, plasmids and transposons?

Answer 7

Mobile genetic elements that infect bacteria and may impart bacterial virulence factors. Just genetic elements. Infect bacteria and provide them with virulence factors.

Question 8

What are fungi?

Answer 8

-have thick cell walls and cell membranes - rigid cell walls
-many are normal flora but are common opportunistic infections (e.g. Candida albicans)
-exist as yeast cells and hyphae
-only depend on host for favorable conditions
-extracellular

Question 9

What are Protozoa?

Answer 9

-single celled organisms that may have complex life cycles (may cycle in multiple hosts and be transmitted from one host to another) e.g. plasmodium falciparum - malaria - replicate in insect vector before transmission to human host; giardia toxoplasma
-parasites
can be:
-blood borne (plasmodium sp - malaria_
-intestinal (giardia lamblia, toxoplasma)
-sexually transmitted (trichomonas)

Question 10

What are helminths?

Answer 10

-parasitic worms, find 3 classes of Roundworms (nematodes=ascaris, hookworms =trichinella spiralis), and flatworms (cestodes- pork, beer or fish tapeworms - taenia solium), flukes (trematodes - schistosoma sp - burr through the skin)
-multicellular organism

Question 11

What are ectoparasites?

Answer 11

-arthropods: ticks, fleas, lice - attach to and live on the skin
-may cause disease directly or be vectors for other organisms (e.g. deer tick transmits Lyme disease spirochete -infectious organism)
-e.g. bed bug

Question 12

What is virulence?

Answer 12

Factors that are characteristic of the organism that allows it to colonize, proliferate, invade and destroy host tissues - pathogenetic potential.

Question 13

Describe colonization

Answer 13

-the organism must be able to colonize the site it was introduced to
-dependent on:
size of inoculum
ability to adhere to the tissues - viruses: binds to cell surface receptors (very specific receptors, HIV is CD4 receptor - bacteria: express adhesion gene products to enhance binding to cell surfaces

Question 14

Describe proliferation

Answer 14

-dependent upon local conditions - moisture, oxygen content, pH, and availability of nutrients
-must be able to evade host defenses (e.g. difficult to digest B encapsulated viruses and bacteria reproduce quickly and covertly- overwhelm the immune system)
-evade host defenses via:
difficult to digest (encapsulated
reproduce quickly and covertly
overwhelm the immune system
develop antibiotic resistance
varying the antigens they express (e.g. influenza)
-must compete with normal flora

Question 15

Describe tissue injury

Answer 15

infectious agents can establish infection and damage tissue via:
-directly causing cell death
-release of toxins (endotoxin/exotoxin) and enzymes
-induce host cellular responses

Question 16

How to viruses damage host cells?

Answer 16

Damage host cells by entering the cell and replicating at the hosts expense - viral tropism B specific cells for specific viruses
Kill the host in a number of ways:
-inhibit host cell metabolic function
-affect integrity of host cells plasma membrane
-lyse the cell
-host immune response destroys the host cell, leads to secondary infections
-induce cell proliferation and transformation - cancer (altered cells genetic profile)

Question 17

How do bacteria damage host cells?

Answer 17

1. Enzymes: facilitate the penetration of anatomic barriers (e.g. collagenase, hyaluronidase, phospholipases, proteases - degrade things like collagen to allow bacteria into the cell
2. Release toxins:
   -Endotoxin: a structural component of the cell wall of gram negative bacteria. Lipopolysaccharide. Exposure induces production of cytokines by host cells - fever, leukocyte proliferation, circulatory disturbances and organ dysfunction
   -Exotoxin (gram positive): a secreted toxin which disrupts cell metabolism or plasma membranes. Causes disease without antecedent infection (e.g. S. aureus food poisoning). causes disease without invasion

Question 18

Describe Dissemination

Answer 18

Spreading
Occurs via:
-tissues planes of least resistance (easiest route)
-lymphatics to regional lymph nodes - bloodstream
-axonal transport (Varicella-Zoster virus causes chicken pox in children. Resides in dorsal spinal ganglion where it may lie dormant for many years. Can be activated and spread from ganglia along the sensory nerves to the peripheral nerves of sensory dermatomes to cause shingles in the elderly adult)
-the cells the organisms infect get carried to distant sites

Question 19

Describe transmission

Answer 19

-inhalation, ingestion, sexual transmission, insect or animal bites and injection
-the infectious organism must be able to leave the host organism. this can occur via direct contact, airborne, animal or arthropod vector
-knowledge of means of transmission is important in understanding how a disease develops and controlling outbreaks or preventing further illness by disrupting routes of transmission or removing sources of infection.

Question 20

Describe mononucleosis (virus)

Answer 20

-fever, lymphadenopathy (big lymph nodes), sore throat, large spleen
-organism: EBV - DNA virus, B cells (via CD21: surface receptor)
-tonsils contain lots of B cells
-proliferate in the B cells
-tissue injury: lysis of infected B cells and release of virus, latent infection - does not kill the infected cell - smaller viral load in the infected cell - stimulate the B cells to proliferate - gain access to the general circulation (disseminate), transmission - close human contact with saliva

Question 21

Describe meningitis (bacteria)

Answer 21

-inflammation of the leptomeninges and cerebrospinal fluid
-headache, irritability, clouding of conciousness, neck stiffness
-organisms: Neisseria meningitidis - gram negative bacterial organism - inhalation via respiratory route into mouth
-colonization: pili: adhere to epithelial cells
-proliferation: evade host defenses by: altering the antigen expression (13 types), capsule (difficult to phagocytose)
-tissue injury: endotoxin
-dissemination: via blood stream -leptomeninges - adrenal gland - skin
-transmission: inhalation

Question 22

Describe malaria (parasite)

Answer 22

-life threatening parasitic disease
-initially believed that the disease came from fetid marshes - “mal aria” (bad air)
-affects 40% of the world’s population: 300 million acute illnesses per year, 1 million deaths annually, kill one african child every 30 seconds, 418 cases in Canada
-Organism: plasmodium sp. intracellular parasite - protozoa
-proliferation: evade host defences - replicate covertly in hepatocytes and red blood cells, alter antigen profile
-tissue injury: lysis of cells, and alter the cell (makes the RBC sticky - clump, stick to vessel wall - narrow vessel lumen and decrease blood flow
-dissemination: infected RBC
-transmission: insect vector, blood transfusion

Question 23

List some of the host defences to infection

Answer 23

-Epithelial (mucosal) and epidermal (skin) barrier
-immune system B humoral or cellular
-exogenous factors (external defences) including antiviral agents, antibiotics, etc.

Question 24

What are opportunistic infections?

Answer 24

Infections caused by organisms which would not typically occur in healthy individuals with an intact immune system, but because it has been suppressed or affected they can. These infectious organisms are usually of low virulence and include viruses (CMV, herpes virus), bacteria (pneumococcus), fungal (candida, aspergillus), and protozoa (toxoplasma, pneumocystis).

Question 25

What are the symptoms and signs (clinical features) of infection?

Answer 25

-Leukocytosis (increase in number of white blood cells)
-Erythema, pain and swelling
-Fever
-Hypotension and shock

Question 26

What are the five major patterns of tissue reaction?

Answer 26

1. Suppurative (PMN) inflammation: neutrophils are attracted to a site of infection by chemoattractants released from bacteria. Pus
2. Mononuclear and granulomatous inflammation: lymphocytes will respond to viruses intracellular bacteria or parasites. Granulomatous inflammation B characterized by aggregates of epitheliod histiocytes (altered macrophages). Occur with fungal infections or tuberculosis.
3. Cytopathic-cytoproliferative inflammation: virus-mediated damage to host cells will lead to:
   -viral aggregates (inclusion bodies) - CMV - can be present in the nuclei - HSV I or II
   -cell fusion - virus alters the cell - they start to fuse together to form gian cell - associated with measles
   -Discohesion B blisters - no longer cohesion together, associated with herpes
   -cell proliferation - tumors, carcinoma - condyloma accuminatum
4. Necrotizing inflammation: tissue damage (necrosis) is the dominant feature - flesh eating
5. Chronic inflammations and scarring: fibrosis

Question 27

What are the barriers to infection (host)?

Answer 27

-anatomic barriers (skin, filtration system of the upper airways)
-enzymes (lysozyme), acids (secreted by stomach), detergents (bile)
-mucous secretions (contain IgA)
-the mucociliary blanket of the respiratory system (traps organisms which are expelled by coughing)
-macrophages (those present in airways ingest inhaled particles)
-“good” bacteria (the microbial flora normally present in the gastrointestinal tract compete with pathogenic bacteria to keep them from establishing a hold in the host

Question 28

What are the outcomes of infection?

Answer 28

Once a microorganism invades a tissue one of these things may happen:
- Organism may die and no disease is produced
- The host may mount a successful immune reaction which results in no symptoms or mild symptoms of disease and subsequent immunity which will abbreviate further infections. (resolution)
- The host defences contain, but do not eliminate, the organism and chronic infection results (e.g. latent shingles from the chicken pox)
- The host defences are unsuccessful and severe disease (chronic disease secondary to chronic infection e.g. oncogenesis like HPV which leads to cervical cancer) or death results

Question 29

How does skin protect from infection?

Answer 29

-outer skin layer is constantly shed
-low pH of the skin 5.5
-presence of fatty acids inhibit microbial growth

Question 30

How might organisms get through this skin layer?

Answer 30

-wet skin is more permeable to organisms, and organisms may penetrate warm, moist skin of the genital tract during intercourse
-may penetrate through lesions in the skin: injuries to skin or mucosa (burns, trauma, catheterization, surgery), direct inoculation (bites by fleas, ticks, mosquitoes, etc.), and IV drug use (HIV).

Question 31

Describe the correlation of the urinary tract with infection

Answer 31

Defences: regular flushing by the kidneys (several times a day)
Compromised by: obstruction, anatomy (women - urethra is shorter than in men - shorter distance between the bladder and bacteria-ladden skin, easier to get infection) and sexual intercourse.

Question 32

Describe the correlation of the respiratory system with infection

Answer 32

Defences: mucociliary blanket and macrophages
Compromised by: smoking and alcohol (ciliary dysfunction) and intubation

Question 33

Describe the correlation of the gastrointestinal system with infection

Answer 33

Defences: acidic stomach contents, viscous mucous layer of the gut, lytic pancreatic enzymes and bile detergents, secreted IgA antibodies, and normal microbial flora of the gut
Compromised by: low stomach acidity, antibiotics which kill the normal flora, and mechanical obstruction of the bowel
*most gastrointestinal pathogens are ingested in food or water contaminated with fecal matter. Safe food handling practices, hand washing and thorough cooking can reduce exposure.