Categories of infectious agents.
Host barriers to infection.
- IgA on mucosal membranes
- Mucus trapping – upper airways
- Cilliary action of trachea and large airways – disrupted by smoking, CF, trauma of intubation, viral infection.
- Alveolar macrophages
- Viscous mucosal layer
- Gastric acid secretions
- Lytic pancreatic enzymes
- Competition from comensals
- IgA antibodies
- Clearance by defecation
How micro-organisms cause disease.
- Cell death
- Cell dysfunction
- Weaken cell membrane
- Via toxins – to kill at distance
- Enzymes – for tissue breakdown/damage blood vessels –> necrosis
- Immune system response leading to collateral tissue damage
Viral – determined by trophism(viral receptors on tissues), presence of required intracellular enzymes, environmental conditions, –> cell death, death via antiviral response or malignant transformation.
Bacterial – ability of them to adhere, invade and release toxins. Plasmids. Quorom sensing in large colonies, biofilm
Spectrum of inflammatory responses to infection.
- Suppurative – inc vasc permeability, neutrophil predominance, liquifactive necrosis
- Mononuclear/granulomatous – mononuclear, can be chronic, usually for viruses, intracellular pathogens.
- Cytopathic-cytoproliferative – usually viral, sparse inflammatory cells.
- Necrosis- Eg necrosis in gangrene via toxins
- Chronic inflammation/scarring –
TB (Mycobacterium tuberculosis)
- Secondary TB – disease in a previously sensitised host (10% chance of latent converting to active TB)
- May occur shortly after primary infection, reactivation of latent organisms, or reinfection.
- Pathological Lung 2o TB – apical, caseous necrosis, cavitation, healing with fibrosis and calcification, area of inflammation/granuloma
- Multiply in alveolar macrophages. Primary focus is Gohn.
- Cx- erosion of blood vessels, miliary spread, pleural effusion, empyema, fibrous pleuritis. Brain, kidneys, LA.
- RIPE – rifampicin, isoniazid, Pyrazinamide, ethambutol for 2 mo then RI for next 4 mo.
- Compliance crucial.
- Tx – aerosol droplet 0.5 – 5 micrometer, latent TB is not infectious.
HSV (Herpes Simplex Virus)
- Ubiquitous and contagious
- HSV1 – cold sores
- HSV 2 – genital vesicles
- Spread via saliva, contact
- HSV-1 and -2 persist in the body by becoming latent and hiding in neurons
- After the initial infection–> episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron’s axon to the skin, where virus replication and shedding occur and cause new sores. Shedding can be asymptomatic.
- dsDNA in capsid cage inside lipid bilayer envelope.
- Treponema palidum is a GN spirochete and sexually transmitted.
- Asymptomatic incubation period 9-90d
- Primary stage
- A hard, usually painless, ulcer called a chancre develops at the site of infection, usually on the genitals. Untreated, the primary chancre usually goes away within four weeks.
- Secondary stage
- Two to four months after infection, lasts several weeks and often comes back in the following two years. The most common feature is a flat, red rash over the whole body. Syphilis is one of the few causes of this sort of rash on the palms and soles. Many other symptoms commonly occur and almost any part of the body may be involved.
- A latent period with no symptoms or obvious signs of disease usually lasts for the remainder of the person’s life.
- Tertiary stage
- May occur in up to 30% of untreated individuals. In some cases the disease may involve the brain and spinal cord (neurosyphilis), or the heart and blood vessels (cardiovascular syphilis), producing severe complications, disability and even death. Gumma.
- Pt is infectious during primary and secondary phase
- Rx – penicillin
- Herpes virus 4
- Infectious mononucleosis, hodgkins lymphoma, Burkitts lymphoma
- Tx via oral saliva or sexually
- Infects B cells and epithelial cells. Once lytic phase is under control it remains latent in B cells for life.
- DNA in capsid in envelope
- Opportunistic infections.
- Superficial mucosal, superficial cutaneous, chronic mucocutaneous, Invasive
- Virulence factors
- Phenotypic switching
- Adhesion to host cells
- Production of enzymes
- Secretion of adenosine – block neutrophil degranulation.
- Plasmodium Falciparum – commonest, affects all RBC ages, clumping and rosetting –> iscahemia. High levels of parasites and cytokines–> severe anaemia, cerebral symptoms, renal failure, pulmonary oedema, death
- Plasmodium Ovale – latent hypnozoites
- Plasmodium vivax – latent hypnozoites
- Plasmodium malariae
- Life cycle: anopheles mosquito – sporozoite–> enter blood–> liver–> merozoites formed–> released into blood again–> bind to RBC–> Hb hydrolysed–> trophozoites–> schizont–> merozoite/gametocyte –> anopheles again where sexual reproduction occurs
- Bacterial – ecoli, salmonella, cholera, Shigella, campylobacter, yersinia, mycobacteria
- Viral – norovirus, rotavirus, adenovirus
- Parasites – giardia, amoeba, cryptopsporidium
- Vibrio cholerae – GN comma shaped
- Non invasive, flagella protein for adherence and colonization of duodenum and jejunum
- Enterotoxin – 1 Alpha and 5 B sub unit
- B taken up by retrograde transport into cell
- A goes into cytoplasm and activates G protein –> adenyl cyclase –> c-amp–> CFTR –> Chloride channel –> Hypersecretion of Cl into lumen leads to osmotic shift of water and HCO3, Na –> profuse watery diarrhoea(overwhelms colonic reabsorption)
- GN bacillus
- Typhoid fever – salmonella typhi and paratyphi causes it. Taken up by mononuclear cells in lymphoid tissues in gut –> invades M cells –> reactive hyperplasia in lymph tissue–> disseminated by blood.
- Sx – fever, anorexia, vomiting, and bloody diarrhoea, BC+ in 90% with fevers. Can have asymptomatic carriers who can spread by faecal oral route.
- GN bacilli
- Enterotoxic – food and water, LT heat labile(cAMP–>Cl, cholera like) and ST heat stable toxins(increase guanylate cyclase –> inc cGMP)
- Enterohaemorrhagic – ground beef, shigella like toxin, bloody diarrhoea, haemolytic uraemic syndrome, TTP(2%)
- Enteroinvasive – food, water, invades mucosa for colitis
- Entero aggregative – adherence fimbriae, shigella like and ST toxins, no bloody diarrhoea, prolonged in aids.
- Clostridium difficile –> Disruption of epithelial cytoskeleton–> tight junction barrier loss–> cytokine release,–> apoptosis –> denuded surface epithelium–> damaged crypts distended by mucopurulent exudates–>adherent layer of inflammatory cells and debris.
- RF- advanced age, hospitalisation, antibiotic use.
- Features – fever, leukocytosis, bloody diarrhoea, but usually watery, abdo pain, cramps, dehydration.
- Mx –> detect toxin and treat with metronidazole or vancomycin
- S Aureus – pneumonia, skin, osteomyelitis
- S epidermidis – opportunistic eg prosthetic valves
- S saprophyticus – UTI
- Virulence factors
- Surface proteins adhere well to endothelial cells
- Secrete enzymes to degrade proteins
- Toxins to damage host – alpha – membrane damage, beta – sphingomyelinase, exfoliative A and B, Superantigens – TSS and food poisoning.
- Gram positive Cocci – pairs or chains
- Facultative or obligate anaerobes
- Alpha haemolytic
- S pneumoniae – pneumonia, meningitis
- S viridans – endocarditis
- Beta haemolytic
- Group A
- Pyogenes – pharyngitis, scarlet fever, impetigo, rh fever, Toxic shock,
- Post strep GN(1-4wks after pharyngeal/skin infection, ?T2 or T3 hypersensitivity. Immune deposits in Gomeruli–>complement activation, Sx – malaise, fever, haematuria, red cell casts, proteinuria, oedema, hypertension, 95% recover, 4% chronic, 1% fulminant renal failure. Adult is worse. High strep antigen and Ab, depleted C3. )
- Group B
- Agalactiae – neonatal sepsis, meningitis, chorioamnionitis
- Mutans – dental caries
- Group A
- Virulence factors
- M protein(prevents phagocytosis),
- C5a peptidase, pneumolysin(lyses target cells),
- GP bacilli, anaerobic, spore forming.
- Clostridia difficile – described above
- Clostridia tetani – tetanic contractions
- Clostridia botuli – flacid paralysis
- Clostridia perfringens – gas gangrene