INFECTIONS VIVAS
General Principals
2009-2
What are the normal barriers to infection by ingested pathogens in the gastrointestinal tract?
- Acid gastric secretions
- Viscous mucosal layer
- Lytic pancreatic enzymes
- Defensins (mucosal antimicrobial peptides)
- Bile detergents
- Secreted IgA antibodies
- Competition for nutrients with commensal bacteria
- Clearance by defaecation
These barriers are lost with loss of gastric acidity, disruption of normal flora (antibiotics), loss of
pancreatic function, diminished bowel motility.
Describe the barriers to infection that exist within the respiratory tract
- Mucociliary blanket within upper airways for trapping large microbes
- Coughing (clears microbes from trachea)
- Ciliary action within trachea and large airways (moves them up to be swallowed)
- Alveolar macrophages or neutrophils attack and destroy microbes
- Secreted IgA
- Defensins
What processes can disrupt the normal protective mucociliary action?
Smoking, cystic fibrosis (viscous secretions), aspiration of stomach contents, trauma of intubation,
viral infection, bacterial infection.
Additional:
Skin defences
- Keratinised outer layer
- Fatty Acids
- Low pH
Can be breached directly, or by damage (e.g. burns, trauma, IV lines)
Urogenital tract defenses
- Frequent bladder flushing
- Catabolism of glycogen by normal lactobacilli (in vagina) – lowers pH reducing fungal growth
Barriers lost with atonia, flow obstruction, reflux, antibiotics kill lactobacilli (-> candidal infection)
Viral Infections
2011-1, 2007-1
Describe the pathogenesis of measles
- Paramyxovirus (single stranded RNA)
- Respiratory droplet spread
- Multiplies in upper respiratory tract epithelial cells
- Spreads to lymphoid tissue where it replicates in mononuclear cells
- Haematogenous spread
- Preventable by vaccination as only single strain
- Epidemics amongst un-vaccinated individuals
What type of immune responses occur in measles?
- T cell mediated immunity controls infection and causes rash (hypersensitivity to infected
cutaneous cells)
- Antibody mediated protects against re-infection
- Epidemics in unvaccinated hosts
Describe some of the systemic features of measles virus infection
- Rash–blotchy, red/brown. Skin hypersensitivity reaction
- Oral mucosal ulceration – Koplik’s spots (pathomonic)
- Croup
- Interstitial pneumonia
- Conjunctivitis and Keratitis, with scarring and visual loss
- Encephalitis; - plus SSPE, measles inclusion-body encephalitis
- Diarrhoea with protein losing enteropathy
- Immunosuppression
- Secondary bacterial infection
What are the cell-surface receptors for the measles virus 2007-1
1. CD 46 (complement regulatory protein): inactivates C3 convertases; present on all nucleated
cells; binds viral haemagglutinin protein
2. SLAM (Signalling Lymphocytic Activation Molecule): involved in T cell activation; only present on
cells of the immune system; binds viral haemagglutinin protein
2007-1
Please give some examples of clinical Herpes Simplex Infection?
- Cold sores and Gingivostomatitis (HSV-1)
- Genital herpes (HSV-2)
- Keratitis (epithelial & stromal) – HSV-1 major infectious cause of corneal blindness
- Encephalitis - HSV-1 major cause of fatal encephalitis in US
- Disseminated visceral herpes (esp in compromised cellular immunity e.g. HIV) - esophagitis,
bronchopneumonia, hepatitis, Kaposi varicelliform eruption, eczema herpeticum)
After primary herpes simplex infection, how does reactivation occur?
- Viral nucleocapsids travel from the skin/ oropharynx/genitalia to the nucleus in the sensory
neuron.
- During latent period, only viral mRNA is produced, no viral proteins are made to escape immune
recognition
- Reactivation from latency occurs by avoiding immune recognition, inhibiting the MHC class I
recognition pathway, and elude humoral immune defences by producing receptors for the Fc
domain of immunoglobulin and inhibitors of complement
- Antidromically along sensory nerve
2006-1, 2005-2
Describe the illness caused by acute varicella infection
-
Transmitted in epidemic fashion by aerosols -> respiratory infection -> haemtogenous spread
Rash occurs 2 weeks after exposure
Rash begins centrally and spread centrifugally in waves
Initially macular with rapid progression to a vesicle “like a dewdrop on a rose petal”
After a few days the vesicle ruptures and crusts – most heal with no scarring unless bacterial
superinfection (disruption of the basal epidermal layer)
Involves skin, mucous membranes and neurones
Milder illness in children vs adults and the immunocompromised
What are the complications of acute vaicella infection
- Secondary bacterial skin infection
- Encephalitis/cerebellitis
- Interstitial pneumonitis
- Transverse myelitis
- Necrotising visceral lesions (esp. in the immunosuppressed)
Describe the relationship between varicella infection and subsequent zoster eruption
- VZV evades immune defences and infects neurons in and round the dorsal root gnglia
- Able to remain latent for years
- Usually a single episode of recurrence in the form of zoster
- Reactivation often in the elderly or otherwise immuno-compromised
- Infection of sensory nerve to keratinocytes (dermatomal vesicular eruptions)
- Often very painful due to radiculoneuritis, especially if trigeminal
- If the geniculate nucleus is involved may cause facial paralysis (Ramsay Hunt Syndrome)
Additional:
Cytomegalovirus (CMV)
- Causes marked cellular enlargement
- Infections are usually asymptomatic, but can manifest as a mononucleosis-like syndrome (e.g.
fever, lymphocytosis, lymphadenopathy, hepatosplenomegaly)
- Infects dendritic cells, and can be latent in leukocytes
- In the immunocompromised can cause colitis, pneumonitis, hepatitis, chorioretinitis,
meningoencephalitis
- Most common opportunistic viral pathogen in AIDS
- In 5% of congenitally infected infants and cause cytomegalic inclusion disease (CID) similar to
erythroblastosis fetalis (IUGR, haemolytic anaemia, jaundice, encephalitis)
Epstein-Barr Virus
- Causes infectious mononucleosis
- By saliva, blood or venereal
- Infects B cells – most latently, by some lytic and release more virons
- CD8+ T cells (CTLs) kill infected B cells – the prolifereaion of these T cells -> lymphadeopthy and
splenomegaly
- Other symptoms: fever, fatigue, sore throat, lymphocytosis, hepatitis and rash
- Roll in B cell lymphoma and Burkitt lymphoma
Bacterial Infections
2009-2
What are streptococci?
- Gram-positive cocci growing in pairs or chains.
- Facultative or obligate anaerobes.
- Cause variety of suppurative infections and immunologically mediated post-streptococcal
syndromes
Name some of the different types of streptococci and give examples of diseases they cause
Alpha haemolytic
- S. pneumonia: pneumonia, meningitis
- S viridans: endocarditis
β Haemolytic
Group A. (Pyogenes)
- pharyngitis, scarlet fever, erysipelas, impetigo
- Rheumatic fever, Toxic Shock Syndrome, Glomerulonephritis
Group B. (Agalactiae)
- neonatal sepsis and meningitis, chorioamnionitis
- Strept. mutans: dental caries
What factors in streptococci contribute to their virulence?
- Capsules: pyogenes, pneumoniae
- M Protein: prevents phagocytosis
- Complement C5a peptidase
- Pneumolysin: lyses target cells (S pneumoniae) activates complement
- Pyrogenic exotoxin- rash and fever
- High MW glucans: plaque formation, aggregation of platelets
- Sucrose => lactic acid (S. mutans, plaque and tooth decay)
2009-1
What are the two clinically significant Neisseria
1. N. meningitidis
2. N. gonorrhoeae
Describe the pathogenesis of a N. meningitidis infection
1. Respiratory spread
2. Common coloniser of the oropharynx (10% of the population at any one time)
3. Colonisation lasts for months
4. Immune response leads to protection against that strain
5. Invasive disease crosses respiratory epithelium to enter blood
6. Capsule of Neisseria reduces opsonisation & protects against destruction by complement proteins
Outbreaks in young people living in crowded quarters who encounter new strains
What are the microbiological features of Neisseria
- Aerobic
- Gram –ve diplococci
- Coffee bean shaped
- Require chocolate blood agar
- 13 serotypes of N. meningitides
2011-1, 2005-1
What is secondary tuberculosis?
- Pattern of disease that arises in a previously sensitised host
How may infection occur in secondary tuberculosis?
- May follow shortly after primary infection, but more commonly years later
- Reactivation of latent organisms – typically in areas of low disease prevalence
- Reinfection - typical in regions of high prevalence
Describe the pathological features in the lung of secondary infection with TB
- Locale - apical UL in secondary
- Area of inflammation / granuloma / multinucleate giant cells
- Central caseous necrosis
- Cavitation
- Healing with fibrosis and calcification
- Complications include: tissue destruction, erosion of blood vessels, miliary spread, pleural
effusion, empyema, fibrous pleuritis
2008-2, 2003-2
Describe the pathogenesis of TB in a previously unexposed immunocompetent person
- Infection by M. tuberculosis airborne, usually person to person airborne droplet spread
- M. tuberculosis enters alveolar macrophages and replicates by blocking
phagosome/lysosome fusion leading to bacteraemia (person generally (95%) asymptomatic or
mild flu like illness)
- Immunity through T cell mediated delayed type hypersensitivity reaction that also causes
hypersensitivity and tissue destruction - in particular granuloma formation and caseation
- About 3 weeks later T cell activation via MHC antigens on macrophages and IL-2 leading
to macrophage becoming bactericidal (thru IFN-γ)
- This macrophage response also causes tuberculin positivity and formation of granuloma
and caseation by recruiting monocytes (“epithelioid histiocytes”)
- Granulomas formed usually at the lower part of upper lobe or upper part of lower lobe and
the parenchymal lesion and draining lymph node is termed the Ghon complex
- Eventual control leaves behind a tiny fibrocalcifc nodule where viable organisms may
remain dormant for decades
- 5% of primary infections are symptomatic with lobar consolidation, hilar adenopathy and pleural
effusions
- Rarely haematogenous spread leads to TB meningitis and military TB
- Re- exposure or reactivation causes heightened immune reaction as well as tissue
destruction
2011-2, 2008-1
What type of organisms are the Clostridia?
- Gram +ve anaerobic spore-forming bacilli
Name the organisms and the diseases they cause in humans?
- Tetanus (lockjaw) – Clostridium tetani
- Botulism (paralytic food poisoning) – Clostridium botulinum
- Gas gangrene, necrotizing cellulitis – Clostridium perfringens, C. septicum
- Pseudomembranous colitis – Clostridium difficile
How does botulism toxin cause disease? 2011-2
- Normally ingested
- In the cytoplasm, the “A” fragment cleaves the protein “synactobrevin”
- Synactobrevin is needed for fusion of neurotransmitter vesicles
- Results in flaccid paralysis
What is the pathogenesis of gas gangrene (C. perfringens, C. septicum)? 2008-1
- Release enzymes – hyaluronidase; collagenase
- Virulence factors – 14 toxins, multiple actions
- α-toxin most important
- Phospholipase C: degrades membranes; muscle; RBC
- Release phospholipid derivatives: ITP; prostaglandins
- These cause derangement in cell metabolism and cell death
- Marked oedema, enzymatic necrosis, fermentation gas bubbles, haemolysis and thrombosis
Additional: C. tetani produces a neurotoxin that blocks the release of GABA (inhibitory) leading to the
convulsive contraction of muscle
Fungal Infections
2008-2
What is the clinical spectrum of candida infection?
- Benign commensal
- Superficial mucosal infection: mouth, vagina, oesophagus
- Superficial cutaneous infection: intertrigo, nappy rash, balanitis, folliculitis, paronychia,
onychomycosis
- Chronic mucocutaneous (T-cell defects, endocrinopathy)
- Invasive (disseminated): myocardial/ abscess/endocarditis, cerebral abscess/meningitis,
renal/hepatic abscess, endophthalmitis, pneumonia
What mechanisms enable candida to cause disease?
1. Phenotypic switching to adapt rapidly to changes in host environment
2. Adhesion to host cells - imp. determ. of virulence –via adhesins (several types)
3. Production of enzymes (aspartyl proteases and catalases) degrade extracellular matrix proteins
and may aid intracellular survival secretion of adenosine – blocks neutrophil degranulation
Parasitic Infections
2008-2, 2003-2
What micro-organisms cause malaria?
- Parasitic protozoa: Plasmodium falciparum, vivax, ovale, malarie
- Transmitted by the female Anopheles genus mosquito
How does Plasmodium falciparum infection differ from other forms of malaria?
All do: sporozoite→liver→merozoites formed → release & bind to RBC→ Hb hydrolysed →
trophozoite→ schizont → merozoite/gametocyte
P. falciparum: infects RBCs of any age, causing clumping/rosetting so ischemia, high cytokine
production, high level parasitemia, severe anemia, HSM, splenic rupture, cerebral symptoms, renal
failure, pulmonary oedema, DIC, death
Others: infect only new or old RBCs, P vivax & ovale form latent hynpnozoites (relapses), low
parasitemia, mild anemia, rarely splenic rupture, nephrotic syndrome
What factors can make people less susceptible to malaria?
- Inherited alterations in RBCs: HbS trait, HbC
- Absence of Duffy group Ag prevents P. vivax binding to erythrocytes
- Repeated exposure stimulates immune response: Ab and T lymphocytes (P falc avoids this)