Infection and Immunity: Concept Checklist

Concepts covered across the module lectures, grouped by lecture. Tick each once you can explain it from memory.

L1 Encephalitis (30 Mar) L1 Infection and Immunity Encephalitis

• Distinguish encephalopathy from acute brain inflammation by fever, headache, focal signs and pleocytosis
• Chronic traumatic encephalopathy: tau deposition and four clinical stages
• Distinguish meningitis from encephalitis by tissue involved and cerebral function; encephalitis as a clinical emergency
• Aetiology of viral encephalitis: common viruses, childhood viruses, arboviruses
• Arbovirus transmission cycles for Japanese encephalitis and West Nile virus, amplifying hosts and dead-end hosts
• HSV epidemiology and as the most common cause of encephalitis in NZ
• HSV latency: retrograde transport, episomal latency in sensory ganglia, anterograde reactivation; spread to the temporal lobe via trigeminal or olfactory nerves
• Clinical features of HSV encephalitis and their frequency
• Diagnosis of HSV encephalitis: temporal lobe MRI changes, CSF findings, PCR
• Untreated mortality, acyclovir dosing by age, and acyclovir mechanism (viral thymidine kinase activation, DNA chain termination)
• Cerebral venous sinus thrombosis as a rare complication of HSV encephalitis

L2 Urinary tract infection (5 Jun) L2 Infection and Immunity Urinary tract infection

• Upper vs lower urinary tract anatomy, the ascending route, and causative pathogens in community vs hospital UTI
• Stepwise pathogenesis of ascending UTI from periurethral colonisation to bacteraemia
• Clinical features of cystitis, pyelonephritis and urethritis
• Host defences of the urinary tract
• Epidemiology of UTI by age and sex, and predisposing conditions including BPH and catheterisation
• UTI in pregnancy: maternal and fetal risks, antibiotic safety
• Proteus mirabilis: urease-mediated struvite stone formation, staghorn calculi, catheter obstruction by crystalline biofilm
• Treatment of uncomplicated cystitis, complicated/upper tract UTI, catheter-associated UTI; when to treat asymptomatic bacteriuria
• ESBL-producing Enterobacteriaceae and antimicrobial resistance
• Distant effects of infection on the kidney: post-streptococcal glomerulonephritis, STEC and haemolytic uraemic syndrome
• Prevention measures for UTI
• Laboratory reasoning in UTI: identifying Staphylococcus saprophyticus; relapse vs reinfection; catheter-associated Pseudomonas pyelonephritis

L3 Environmental Pathogens (15 Jun) L3 Infection and Immunity Environmental Pathogens

• The six-link chain of infection and how breaking any link stops spread
• Burden of legionellosis, giardiasis and cryptosporidiosis in NZ by rate, sex and age
• Legionella: organism, amoebal reservoir, species in NZ including L. longbeachae in potting mix
• Legionnaires’ disease vs Pontiac fever: severity, incubation and clinical features; untreated mortality; no person-to-person spread
• Legionella transmission via aerosols and risk factors for disease
• Giardia duodenalis: life cycle, infective dose, clinical course, chain of infection, risk groups
• Breaking the chain for giardiasis: metronidazole/tinidazole, breastfeeding, water treatment and hygiene
• Cryptosporidium: apicomplexan classification, species, life cycle, severity in immunocompromised, risk factors
• Breaking the chain for cryptosporidiosis, including nitazoxanide

L4 Childhood infections (15 Jun) L4 Infection and Immunity Childhood infections

• TORCHeS congenital infections: organisms, organs affected and routes of transmission
• Common signs of congenital infection, and the effect of timing in pregnancy
• Organism-specific prevention of congenital infection, including GBS screening and intrapartum antibiotics
• Listeria monocytogenes: intracellular survival, mild maternal vs severe neonatal disease
• Vaccine-preventable disease notifications in NZ, and why pertussis dominates
• Pertussis epidemiology in NZ and worldwide
• Bordetella pertussis: organism, virulence factors, chain of infection
• Pathogenesis and clinical stages of pertussis
• Breaking the pertussis chain: education, azithromycin, vaccination; acellular vaccine components; immunisation schedule and the newborn window
• Herd immunity
• Otitis media: definitions and pathogenesis via Eustachian tube blockage and effusion
• Aetiology of otitis media, otoscopic appearances, and biofilms in recurrent and chronic disease
• Complications of otitis media, link to hearing loss and language delay, and treatment including tympanostomy tubes

L5 Antimicrobials (19 Jun) L5 Infection and Immunity Antimicrobials

• Factors guiding empiric antimicrobial therapy: syndrome, host, severity, risk of resistance; when not to treat
• Typical causative organisms for cystitis, community-acquired pneumonia and skin/soft tissue infection
• SIRS, sepsis, severe sepsis and septic shock criteria; cost of inadequate initial therapy
• Local susceptibility patterns in empiric choice (e.g. MRSA rates)
• Spectrum of beta-lactams from penicillin to carbapenems, intrinsic resistance, and the ESCAPPM group
• Spectrum of non-beta-lactam antimicrobials
• Targeted therapy and principles of specimen collection
• Susceptibility testing: MIC, MBC, testing methods, S/I/R categories, breakpoints
• Antimicrobial pharmacokinetics: free drug, Cmax, half-life
• Pharmacodynamic classes: time-dependent, AUC/MIC and concentration-dependent killing; post-antibiotic effect
• Planktonic vs biofilm growth and implications for treatment
• Applying principles to a case of multidrug-resistant Klebsiella after overseas hospitalisation
• Antimicrobial stewardship: IV-to-oral switch criteria and shorter course durations

L6 Transmission of Infection (19 Jun) L6 Infection and Immunity Transmission of Infection

• The chain of infection: six components and what determines each
• Modes of transmission: direct and indirect contact, droplet vs airborne (particle size), common vehicle, vectorborne, with examples and controls
• Staphylococcus aureus and MRSA: diseases caused, infectious dose, SCCmec resistance, virulence factors
• Vertical vs horizontal gene transfer: conjugation, transformation, transduction
• MRSA carriage rates and sites, environmental survival and reservoirs
• Applying the chain of infection to MRSA; transient vs persistent carriage and hand carriage as the main hospital route
• Breaking the chain in hospitals: hand hygiene, glove use, screening and eradication, fomite disinfection
• Relative resistance of microorganisms to disinfectants
• Development of antibiotic resistance via vertical and horizontal routes, and the antibiotic discovery timeline
• Global burden of antimicrobial resistance, including carbapenem-resistant Gram-negative infections and inequity
• Actions to slow antimicrobial resistance

L7 Autoimmunity (31 Jul) L7 Infection and Immunity Autoimmunity

• History of the autoimmunity concept from horror autotoxicus to acceptance
• Autoimmunity as failure of central tolerance (negative selection, receptor editing) and peripheral tolerance (anergy, apoptosis, suppression)
• Prevalence of autoimmune disease, risk factors, and organ-specific vs systemic disease
• Rheumatoid arthritis: NZ epidemiology and ethnic differences, genetic and environmental risk factors
• RA immunopathology: ACPA and rheumatoid factor, stepwise pathway from pre-arthritis to manifest arthritis, joint destruction
• RA diagnosis, extra-articular features, and treatment with csDMARDs, bDMARDs and JAK inhibitors; vaccination precautions on biologics
• Multiple sclerosis: NZ epidemiology and higher South Island prevalence, genetic and environmental risk factors (vitamin D, EBV, smoking)
• MS immunopathology in early vs late lesions; clinical presentation, clinically isolated syndrome and diagnosis
• MS disease course (relapsing-remitting, secondary and primary progressive) and disease-modifying therapies, including natalizumab and PML risk
• SLE: epidemiology including higher rates in Māori and Pacific peoples, genetic (complement deficiency), epigenetic and environmental risk factors
• SLE pathogenesis: immune complexes, loss of B cell tolerance, antinuclear antibodies; clinical features
• SLICC classification criteria for SLE, and SLE treatment
• Why females are more susceptible to autoimmunity: immune vigour, pregnancy immune shift, oestrogen

L8 Vaccination and cancer (14 Sep) L8 Infection and Immunity Vaccination and cancer

• Immunological memory: quantity and quality of responding cells; Faroe Islands measles evidence
• B cell memory: memory B cells, long-lived plasma cells, primary vs secondary antibody response
• T cell memory: requirements for effective memory T cells
• Five antibody effector functions
• What vaccines do, and herd immunity protecting those who cannot be vaccinated
• Types of vaccine: live attenuated, inactivated, subunit/toxoid, vector, RNA/DNA
• Features of an effective vaccine, including neutralising antibody vs protective T cells
• Routes of vaccination and their trade-offs
• Why boosters are needed for inactivated/subunit vaccines but not live vaccines
• HPV and cancer: oncogenic types, cancers caused, type 16 and 18 contribution, rising HPV-related oropharyngeal cancer
• Mechanism of HPV oncogenesis: genome integration, E2 loss, E6 and E7 upregulation disrupting tumour suppressors; CIN progression
• Gardasil: virus-like particle composition, types covered, aluminium adjuvant
• HPV vaccination programme in NZ: timing before onset of sexual activity, eligibility, coverage, continued need for screening; efficacy and herd effects
• Impact of vaccines on disease burden, and diseases still lacking effective vaccines

L9 Sexually transmitted infections (21 Sep) L9 Infection and Immunity Sexually transmitted infections

• Epidemiology of chlamydia, gonorrhoea and syphilis in the US and NZ
• Chlamydia trachomatis: obligate intracellular biology and the elementary body/reticulate body cycle
• Chlamydia: symptoms in men and women, high rate of asymptomatic infection, PID and infertility
• Chlamydia diagnosis by NAAT (specimen choice by sex) and treatment
• Neisseria gonorrhoeae: organism and pathogenesis; symptoms in men and women
• Sex differences in gonorrhoea: transmission risk, asymptomatic female reservoir, ascending and disseminated infection
• Gonorrhoea diagnosis (NAAT vs culture for resistance testing, microscopy), treatment, and rising azithromycin resistance; pharynx as reservoir
• Neonatal chlamydia and gonococcal infection
• Treponema pallidum: biology, transmission, NZ trends
• Stages of untreated syphilis: primary, secondary, latent, tertiary, neurosyphilis; congenital syphilis
• Syphilis serology: treponemal (CLIA/EIA, TPPA) vs non-treponemal (RPR) tests and their uses
• Treatment of syphilis by stage with benzathine or aqueous penicillin

L10 Immunity through life (24 Sep) L10 Infection and Immunity Immunity through life

• Maternal antibody transfer via placental IgG and breast milk IgA, and the kinetics of waning; agammaglobulinaemia and rotavirus timing as evidence
• Muted neonatal innate immunity: neutrophils, monocytes/macrophages, dendritic cells, complement
• Neonatal adaptive immunity: Treg and Th2 skewing, blunted B cell responses with B1 predominance
• Gut microbiota in early life: factors shaping it and effects on immune development and later disease
• Infant vaccination and the NZ childhood schedule
• Pregnancy immune adaptation: decidual NK cells, macrophages and DCs in placentation; fetal-specific Tregs and progesterone
• Consequences of pregnancy immune changes: infection susceptibility (influenza) and autoimmune remission
• Immunology of preeclampsia: shallow vs deep trophoblast invasion
• Vaccination in pregnancy: inactivated vaccines, influenza, pertussis booster timing
• Immunosenescence: B cell decline and its consequences
• T cell decline with age: declining thymic output, reduced naive T cells and TCR repertoire, CMV-associated CD8 expansion; link to cancer
• Vaccination in older adults: shingles risk by age and zoster vaccine considerations; influenza vaccination
• U-shaped age distribution of infectious disease incidence and mortality; bimodal TB mortality; COVID-19 deaths by age
• Strength of different immune response components across the lifespan