Infectious diseases: Pathology - General principles of microbial activity Flashcards
What are prions?
Abnormal forms of host protein, normally found in neurons
Do not contain RNA/DNA
What is the pathophysiology of prion disease?
Prior protein undergoes conformational change that confers resistance to proteases and promotes conversion of normal protease-sensitive PrP to resistant form
What kinds of disease are caused by prions?
Spongiform encephalopathies (e.g. kuru, Creutzfeldt-Jakob, bovine spongiform encephalopathy)
Neurodegenerative diseases (e.g. fatal familial insomnia)
Describe the composition of viruses
Nucleic acid genome encased in (icosahedral or helical) protein capsid, with or without a lipid envelope
What size are viruses?
20-300nm
Give two examples of viruses which aggregate within cells to form larger inclusion bodies
CMV
HSV
What kind of organism are bacteria?
Prokaryotes (have cell membrane but lack membrane-bound nuclei and other membrane-enclosed organelles)
What is the difference between Gram positive and negative bacteria?
Gram positive: thick wall surrounding cell membrane which retains crystal-violet stain
Gram negative: thin wall sandwiched between two phospholipid bilayer membranes
Do Gram positive or negative bacteria have capsules?
Both can be encapsulated
Do Gram positive or negative bacteria express lipopolysaccharides?
Gram negative bacteria have LPS on their outer cell membranes
How are bacteria based on whether they replicate inside or outside host cells?
Extracellular
Facultative intracellular: can survive and replicate inside or outside host cells
Obligate intracellular: can only grow inside cells
Give three examples of obligate intracellular bacteria
- Chlamydia
- Rickettsiae
- Coxiella burnetti
Describe the replication of Chlamydia
Replicates inside membrane-bound vacuoles in epithelial cells
Cannot synthesise its own ATP (dependent on host cell)
Three types of infection caused by Chlamydia
- Genitourinary infections
- Conjunctivitis
- Respiratory infections
Describe the replication of Rickettsiae
Replicates inside membrane-bound vacuoles in endothelial cells
Cannot synthesise its own ATP (dependent on host cell)
What type of illness is caused by Rickettsiae?
Haemorrhagic vasculitis
How are Rickettsial infections spread? Give three examples
Via arthropods:
- Lice: epidemic typhus
- Ticks: Rocky Mountain spotted fever
- Mites: scrub typhus
How is Q fever spread?
Aerosol spread, often from domestic animals such as cattle
What organism causes Q fever?
Coxiella burnetti
Describe the structure of Mycoplasma
Unique extracellular bacteria that lacks a cell wall
What are bacteriophages and plasmids?
Mobile genetic elements that encode bacterial virulence factors (e.g. adhesins, toxins, antibiotic resistance)
What are fungi?
Eukaryotes with thick chitin-containing cell walls and ergosterol-containing cell membranes
Describe the two possible structural arrangements of fungi
Rounded yeast cells
Filamentous hyphae (may be septate or aseptate)
What is thermal dimorphism?
Refers to fungi that are in hyphal forms at room temperature but yeast form at body temperature
What are fungal species confined to the superficial layers of human skin called?
Dermatophytes
What three types of infections are caused by fungi in otherwise healthy people?
- Superficial skin infections (e.g. tinea pedia)
- Abscesses (e.g. sporotrichosis)
- Granulomas (e.g. histoplasma)
What types of infection are caused by fungi in immunodeficient populations? Give five examples of opportunistic fungal pathogens
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
What are protozoa?
Single-celled eukaryotes with a nucleus, pliable plasma membrane, and complex cytoplasmic organelles
How do protozoa replicate?
Intracellularly within a variety of cells (e.g. Plasmodium within RBCs, Leishmania in macrophages)
Extracellularly in genitourinary system, intestine or blood
How are bloodborne protozoa spread? How are intestinal protozoa spread?
Bloodborne: insect vectors
Intestinal: ingestion of cysts in contaminated food/water
Give three examples of protozoa and explain how each is transmitted
- Trichomonas vaginalis: sexually transmitted, colonises vagina and male urethra
- Entamoeba histolytica, Giardia lambia: inform of mobile trophozoites that attach to intestinal wall, or immobile stomach acid-resistant cysts
- Toxoplasma gondii: from cats
What are helminths?
Highly differentiated multicellular organisms with complex life cycles
Describe the life cycles of helminths
Alternate between sexual reproduction in the definitive host and asexual multiplication in the intermediary host
What are ectoparasites?
Insects or arachnoids that attach to or live on skin
E.g. lice, ticks, mites, bedbugs
Five immune factors that form part of the host barrier to infection
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
Three skin factors that form part of the host barrier to infection
- Physical barrier (dense keratinised epithelium)
- Low pH 5.5*
- Presence of fatty acids*
- prevents growth of microorganisms other than normal flora
Six GIT factors that form part of the host barrier to infection
- Acidic gastric secretions
- Viscous mucus layer covering intestinal epithelium
- Lytic pancreatic enzymes and bile detergents
- Defensins (mucosal antimicrobial peptides)
- Normal flora
- IgA antibodies (secreted by B cells in mucosa-associated lymphoid tissue, MALT)
Two respiratory tract factors that form part of the host barrier to infection
- Mucociliary action:
- Mucus secreted by goblet cells is transported by ciliary action to the back of the throat, where it’s swallowed and cleared - Alveolar macrophages and neutrophils
Three genitourinary system factors that form part of the host barrier to infection
- Regular flushing of urethra with urine
- Lactobacilli in vagina maintain low pH
- Anatomy (e.g. longer urethra in men protective against UTI)
Give four examples of bacteria which impair mucociliary activity
- H. influenzae
- B. pertussis
- P. aeruginosa
- M. pneumoniae
What is tropism?
Describes the predilection of viruses to infect certain cell types
Outline four factors which determine viral tropism, giving an example of each
- Expression of host cell receptors for virus (e.g. HIV glycoprotein gp120 binds CD4, CXCR4, CCR5)
- Presence of cellular transcription factors that recognise viral enhancer and promoter sequences (e.g. JC virus limited to oligodendrocytes for this reason)
- Anatomic barriers (e.g. enteroviruses replicate in GIT due to inherent resistance to acids, bile, digestive enzymes)
- Local temperature, pH and host defences (e.g. rhinoviruses replicate optimally in lower temperatures of the upper respiratory tract)
What are the three mechanisms by which viruses damage host cells? Give examples where relevant
- 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) - Antiviral immune responses (especially cytotoxic T lymphocytes)
- Transformation of infected cells into benign or malignant tumour cells
Describe three factors which determine bacteria’s ability to damage host cells
- Adherence to host cells
- Invasion of cells and tissues
- Toxin production
How do bacteria adhere to cells? Give an example
Via adhesins (including filamentous bacterial surface proteins called pili)
E.g. protein F and tecichoic acid on Streptococcus pyogenes bind to fibronectin
Give two examples of bacteria which have pili
E. coli
N. gonorrhoeae
Give three examples of mechanisms by which bacteria invade cells and tissues
- Opsonisation (e.g. M tuberculosis activates the alternative complement pathway)
- Gram negative bacteria have a complex secretion system which involves creating pores in host cell membranes to gain entry
- Direct cell-to-cell entry via manipulation of the cytoskeleton (e.g. Listeria)
Define endotoxin vs exotoxin
Endotoxin: lipopolysaccharide (LPS) from outer cell membrane of Gram negative bacteria
Exotoxin: secreted bacterial proteins
What is the mechanism of action of endotoxin?
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)
Which receptor does endotoxin bind?
Complexes with CD14 and then binds TLR4
What are the four types of bacterial exotoxins? Give an example of each
- Enzymes (e.g. proteases secreted by S. aureus)
- 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)
- Neurotoxins (e.g. Clostridium botulinum and tetani produce toxins which impair neurotransmitter release and cause paralysis)
- Superantigens: stimulate very large numbers of T cell lymphocytes (e.g. S. aureus and S. pyogenes cause toxic shock syndrome)
Describe four mechanisms by which microbes evade the host immune system
- Growth in niches inaccessible to host immune system
- Antigenic variation
- Resistance to innate immune defences
- Impairment of T cell response
Give four examples of ways in which microbes grow in niches inaccessible to the host immune system, to evade the immune response
- Propagate in intestinal lumen (e.g. Clostridium difficile) or gallbladder (e.g. S. typhi)
- Rapid invasion of hostel cell before effective humoral response is mounted (e.g. malaria sporozoites entering hepatocytes)
- Forming cysts with dense capsule (e.g. tapeworm larvae)
- Viral latency
Give two examples of mechanisms of antigenic variation
- Inherent genomic instability (e.g. HIV, influenza)
- Variable expression of surface proteins (e.g. Trypanosoma, pneumococcus)
Give four examples of ways in which microbes exhibit resistance to innate immune defences
- Produce capsule which shields bacterial antigens from phagocytosis (e.g. pneumococcus, meningococcus)
- Secrete proteases that degrade antibodies (e.g. Neisseria, Haemophilus, Streptococcus)
- Replicate inside phagocytes (e.g. mycobacteria, Listeria, Legionella, Cryptococcus, toxoplasmosis)
- Produce proteins that block complement activation (e.g. many viruses including HIV)
Give two examples of ways in which microbes may impair T cell responses
- Binding or altering expression of MHC class I (e.g. HSV, CMV, EBV)
- Direct infection of lymphocytes (e.g. HIV, EBV)
What are the five histological patterns of tissue reaction seen in infection? What types of microbes typically produce each?
- Suppurative/purulent: pyogenic bacteria (mostly extracellular Gram positive cocci and Gram negative rods)
- Mononuclear/granulomatous: viruses, intracellular bacteria, spirochetes, intracellular parasites, helminths
- Cytopathic-cytoproliferative: viruses
- Tissue necrosis: Clostridium perfringens, E. histolytica
- Chronic inflammation: chronic HBV, schistosomiasis
Describe the histological features of suppurative infection
Increased vascular permeability
Leukocyte infiltration (predominantly neutrophils)
Liquefactive necrosis -> pus
Describe the histological features of mononuclear infection
Diffuse mononuclear interstitial infiltrate
Mononuclear cell type dependent on host response
Granulomas stimulated by M. tuberculosis, Histoplasma (characterised by epithelioid/giant cells +/- caseous necrosis)
Describe the histological features of cytopathic-cytoproliferative infection
Cell necrosis or proliferation, usually with sparse inflammatory cells
Inclusion bodies, polykarons, benign/malignant masses
Describe the histological features of tissue necrosis infection
Gangrenous necrosis
Few inflammatory cells -> resemble infarcts
