Infectious diseases: Pathology - General principles of microbial activity

Question 1

What are prions?

Answer 1

Abnormal forms of host protein, normally found in neurons
Do not contain RNA/DNA

Question 2

What is the pathophysiology of prion disease?

Answer 2

Prior protein undergoes conformational change that confers resistance to proteases and promotes conversion of normal protease-sensitive PrP to resistant form

Question 2

What kinds of disease are caused by prions?

Answer 2

Spongiform encephalopathies (e.g. kuru, Creutzfeldt-Jakob, bovine spongiform encephalopathy)
Neurodegenerative diseases (e.g. fatal familial insomnia)

Question 3

Describe the composition of viruses

Answer 3

Nucleic acid genome encased in (icosahedral or helical) protein capsid, with or without a lipid envelope

Question 4

What size are viruses?

Answer 4

20-300nm

Question 5

Give two examples of viruses which aggregate within cells to form larger inclusion bodies

Answer 5

CMV
HSV

Question 6

What kind of organism are bacteria?

Answer 6

Prokaryotes (have cell membrane but lack membrane-bound nuclei and other membrane-enclosed organelles)

Question 7

What is the difference between Gram positive and negative bacteria?

Answer 7

Gram positive: thick wall surrounding cell membrane which retains crystal-violet stain
Gram negative: thin wall sandwiched between two phospholipid bilayer membranes

Question 8

Do Gram positive or negative bacteria have capsules?

Answer 8

Both can be encapsulated

Question 9

Do Gram positive or negative bacteria express lipopolysaccharides?

Answer 9

Gram negative bacteria have LPS on their outer cell membranes

Question 10

How are bacteria based on whether they replicate inside or outside host cells?

Answer 10

Extracellular
Facultative intracellular: can survive and replicate inside or outside host cells
Obligate intracellular: can only grow inside cells

Question 11

Give three examples of obligate intracellular bacteria

Answer 11

1. Chlamydia
2. Rickettsiae
3. Coxiella burnetti

Question 12

Describe the replication of Chlamydia

Answer 12

Replicates inside membrane-bound vacuoles in epithelial cells
Cannot synthesise its own ATP (dependent on host cell)

Question 13

Three types of infection caused by Chlamydia

Answer 13

1. Genitourinary infections
2. Conjunctivitis
3. Respiratory infections

Question 14

Describe the replication of Rickettsiae

Answer 14

Replicates inside membrane-bound vacuoles in endothelial cells
Cannot synthesise its own ATP (dependent on host cell)

Question 15

What type of illness is caused by Rickettsiae?

Answer 15

Haemorrhagic vasculitis

Question 16

How are Rickettsial infections spread? Give three examples

Answer 16

Via arthropods:
- Lice: epidemic typhus
- Ticks: Rocky Mountain spotted fever
- Mites: scrub typhus

Question 17

How is Q fever spread?

Answer 17

Aerosol spread, often from domestic animals such as cattle

Question 18

What organism causes Q fever?

Answer 18

Coxiella burnetti

Question 19

Describe the structure of Mycoplasma

Answer 19

Unique extracellular bacteria that lacks a cell wall

Question 20

What are bacteriophages and plasmids?

Answer 20

Mobile genetic elements that encode bacterial virulence factors (e.g. adhesins, toxins, antibiotic resistance)

Question 21

What are fungi?

Answer 21

Eukaryotes with thick chitin-containing cell walls and ergosterol-containing cell membranes

Question 22

Describe the two possible structural arrangements of fungi

Answer 22

Rounded yeast cells
Filamentous hyphae (may be septate or aseptate)

Question 23

What is thermal dimorphism?

Answer 23

Refers to fungi that are in hyphal forms at room temperature but yeast form at body temperature

Question 24

What are fungal species confined to the superficial layers of human skin called?

Answer 24

Dermatophytes

Question 25

What three types of infections are caused by fungi in otherwise healthy people?

Answer 25

1. Superficial skin infections (e.g. tinea pedia) 2. Abscesses (e.g. sporotrichosis) 3. Granulomas (e.g. histoplasma)

Question 26

What types of infection are caused by fungi in immunodeficient populations? Give five examples of opportunistic fungal pathogens

Answer 26

In immunodeficiency patients, opportunistic fungal pathogens can cause life-threatening infection marked by tissue necrosis, haemorrhage, and vascular occlusion E.g. Pneumocystis jirovecii, Candida, Aspergillus, Mucor, Cryptococcus

Question 27

What are protozoa?

Answer 27

Single-celled eukaryotes with a nucleus, pliable plasma membrane, and complex cytoplasmic organelles

Question 28

How do protozoa replicate?

Answer 28

Intracellularly within a variety of cells (e.g. Plasmodium within RBCs, Leishmania in macrophages) Extracellularly in genitourinary system, intestine or blood

Question 29

How are bloodborne protozoa spread? How are intestinal protozoa spread?

Answer 29

Bloodborne: insect vectors Intestinal: ingestion of cysts in contaminated food/water

Question 30

Give three examples of protozoa and explain how each is transmitted

Answer 30

1. Trichomonas vaginalis: sexually transmitted, colonises vagina and male urethra 2. Entamoeba histolytica, Giardia lambia: inform of mobile trophozoites that attach to intestinal wall, or immobile stomach acid-resistant cysts 3. Toxoplasma gondii: from cats

Question 31

What are helminths?

Answer 31

Highly differentiated multicellular organisms with complex life cycles

Question 32

Describe the life cycles of helminths

Answer 32

Alternate between sexual reproduction in the definitive host and asexual multiplication in the intermediary host

Question 33

What are ectoparasites?

Answer 33

Insects or arachnoids that attach to or live on skin E.g. lice, ticks, mites, bedbugs

Question 34

Five immune factors that form part of the host barrier to infection

Answer 34

Innate immunity: 1. Physical barriers (e.g. skin epithelium) 2. Phagocytes and natural killer cells 3. Plasma proteins (complement, cytokines, collectins, acute phase proteins) Adaptive immunity (stimulated by exposure to microbes, and increase in magnitude, speed, and effectiveness with successive exposures): 1. B lymphocytes 2. T lymphocytes

Question 35

Three skin factors that form part of the host barrier to infection

Answer 35

1. Physical barrier (dense keratinised epithelium) 2. Low pH 5.5* 3. Presence of fatty acids* * prevents growth of microorganisms other than normal flora

Question 36

Six GIT factors that form part of the host barrier to infection

Answer 36

1. Acidic gastric secretions 2. Viscous mucus layer covering intestinal epithelium 3. Lytic pancreatic enzymes and bile detergents 4. Defensins (mucosal antimicrobial peptides) 5. Normal flora 6. IgA antibodies (secreted by B cells in mucosa-associated lymphoid tissue, MALT)

Question 37

Two respiratory tract factors that form part of the host barrier to infection

Answer 37

1. Mucociliary action: - Mucus secreted by goblet cells is transported by ciliary action to the back of the throat, where it's swallowed and cleared 2. Alveolar macrophages and neutrophils

Question 38

Three genitourinary system factors that form part of the host barrier to infection

Answer 38

1. Regular flushing of urethra with urine 2. Lactobacilli in vagina maintain low pH 3. Anatomy (e.g. longer urethra in men protective against UTI)

Question 39

Give four examples of bacteria which impair mucociliary activity

Answer 39

1. H. influenzae 2. B. pertussis 3. P. aeruginosa 4. M. pneumoniae

Question 40

What is tropism?

Answer 40

Describes the predilection of viruses to infect certain cell types

Question 41

Outline four factors which determine viral tropism, giving an example of each

Answer 41

1. Expression of host cell receptors for virus (e.g. HIV glycoprotein gp120 binds CD4, CXCR4, CCR5) 2. Presence of cellular transcription factors that recognise viral enhancer and promoter sequences (e.g. JC virus limited to oligodendrocytes for this reason) 3. Anatomic barriers (e.g. enteroviruses replicate in GIT due to inherent resistance to acids, bile, digestive enzymes) 4. Local temperature, pH and host defences (e.g. rhinoviruses replicate optimally in lower temperatures of the upper respiratory tract)

Question 42

What are the three mechanisms by which viruses damage host cells? Give examples where relevant

Answer 42

1. Direct cytopathic effects: - Prevent synthesis of host DNA, RNA and proteins (e.g. poliovirus) - Produce degradative enzymes (e.g. HSV) - Induce apoptosis (e.g. HIV) 2. Antiviral immune responses (especially cytotoxic T lymphocytes) 3. Transformation of infected cells into benign or malignant tumour cells

Question 43

Describe three factors which determine bacteria's ability to damage host cells

Answer 43

1. Adherence to host cells 2. Invasion of cells and tissues 3. Toxin production

Question 44

How do bacteria adhere to cells? Give an example

Answer 44

Via adhesins (including filamentous bacterial surface proteins called pili) E.g. protein F and tecichoic acid on Streptococcus pyogenes bind to fibronectin

Question 45

Give two examples of bacteria which have pili

Answer 45

E. coli N. gonorrhoeae

Question 46

Give three examples of mechanisms by which bacteria invade cells and tissues

Answer 46

1. Opsonisation (e.g. M tuberculosis activates the alternative complement pathway) 2. Gram negative bacteria have a complex secretion system which involves creating pores in host cell membranes to gain entry 3. Direct cell-to-cell entry via manipulation of the cytoskeleton (e.g. Listeria)

Question 47

Define endotoxin vs exotoxin

Answer 47

Endotoxin: lipopolysaccharide (LPS) from outer cell membrane of Gram negative bacteria Exotoxin: secreted bacterial proteins

Question 48

What is the mechanism of action of endotoxin?

Answer 48

Induces cytokines, chemokines and costimulatory molecules for T cell activation Plays a role in shock, DIC and ARDS due to excess cytokine production (particularly TNF-a, IL-1 and IL-12)

Question 49

Which receptor does endotoxin bind?

Answer 49

Complexes with CD14 and then binds TLR4

Question 50

What are the four types of bacterial exotoxins? Give an example of each

Answer 50

1. Enzymes (e.g. proteases secreted by S. aureus) 2. Toxins altering intracellular signalling and regulatory pathways: have B (Binding) subunits and A (enzymatically Active) subunits (e.g. Vibrio cholerae, Bacillus anthracis, some E. coli strains) 3. Neurotoxins (e.g. Clostridium botulinum and tetani produce toxins which impair neurotransmitter release and cause paralysis) 4. Superantigens: stimulate very large numbers of T cell lymphocytes (e.g. S. aureus and S. pyogenes cause toxic shock syndrome)

Question 51

Describe four mechanisms by which microbes evade the host immune system

Answer 51

1. Growth in niches inaccessible to host immune system 2. Antigenic variation 3. Resistance to innate immune defences 4. Impairment of T cell response

Question 52

Give four examples of ways in which microbes grow in niches inaccessible to the host immune system, to evade the immune response

Answer 52

1. Propagate in intestinal lumen (e.g. Clostridium difficile) or gallbladder (e.g. S. typhi) 2. Rapid invasion of hostel cell before effective humoral response is mounted (e.g. malaria sporozoites entering hepatocytes) 3. Forming cysts with dense capsule (e.g. tapeworm larvae) 4. Viral latency

Question 53

Give two examples of mechanisms of antigenic variation

Answer 53

1. Inherent genomic instability (e.g. HIV, influenza) 2. Variable expression of surface proteins (e.g. Trypanosoma, pneumococcus)

Question 54

Give four examples of ways in which microbes exhibit resistance to innate immune defences

Answer 54

1. Produce capsule which shields bacterial antigens from phagocytosis (e.g. pneumococcus, meningococcus) 2. Secrete proteases that degrade antibodies (e.g. Neisseria, Haemophilus, Streptococcus) 3. Replicate inside phagocytes (e.g. mycobacteria, Listeria, Legionella, Cryptococcus, toxoplasmosis) 4. Produce proteins that block complement activation (e.g. many viruses including HIV)

Question 55

Give two examples of ways in which microbes may impair T cell responses

Answer 55

1. Binding or altering expression of MHC class I (e.g. HSV, CMV, EBV) 2. Direct infection of lymphocytes (e.g. HIV, EBV)

Question 56

What are the five histological patterns of tissue reaction seen in infection? What types of microbes typically produce each?

Answer 56

1. Suppurative/purulent: pyogenic bacteria (mostly extracellular Gram positive cocci and Gram negative rods) 2. Mononuclear/granulomatous: viruses, intracellular bacteria, spirochetes, intracellular parasites, helminths 3. Cytopathic-cytoproliferative: viruses 4. Tissue necrosis: Clostridium perfringens, E. histolytica 5. Chronic inflammation: chronic HBV, schistosomiasis

Question 57

Describe the histological features of suppurative infection

Answer 57

Increased vascular permeability Leukocyte infiltration (predominantly neutrophils) Liquefactive necrosis -> pus

Question 58

Describe the histological features of mononuclear infection

Answer 58

Diffuse mononuclear interstitial infiltrate Mononuclear cell type dependent on host response Granulomas stimulated by M. tuberculosis, Histoplasma (characterised by epithelioid/giant cells +/- caseous necrosis)

Question 59

Describe the histological features of cytopathic-cytoproliferative infection

Answer 59

Cell necrosis or proliferation, usually with sparse inflammatory cells Inclusion bodies, polykarons, benign/malignant masses

Question 60

Describe the histological features of tissue necrosis infection

Answer 60

Gangrenous necrosis Few inflammatory cells -> resemble infarcts