GC100 Defense Against Microbes
The host defense against microbes encompasses the integrated system of innate and adaptive immune mechanisms—including physical barriers, phagocytes, complement, and lymphocyte-mediated responses—that collectively recognize, contain, and eliminate pathogenic microorganisms.
Defense Against Microbes
This lecture, delivered by Dr. Siddharth Sridhar (Microbiology, HKU), is the conceptual backbone for understanding why infections happen and how the body fights them. It sits at the intersection of immunology and infectious disease — the "holy grail" triad of Microbe ↔ Host ↔ Intervention [1]. Every other microbiology lecture in the General Clerkship (antimicrobial resistance, diagnosis of infections, fever after chemotherapy, medically important microbes, practical antibiotic use) builds on the framework laid here.
Core thesis of this lecture: Infections do not happen without reason. If you understand which arm of immunity is broken, you can predict which organisms will cause disease, how to investigate, and how to intervene — including manipulating the immune system itself as a therapeutic tool [1].
Learning Objectives (from Slide 53)
"Infections do not happen without reason — recognizing and reversing common predisposing factors can save your patients a lot of trouble. Vaccination: prevention is better than cure. Try to recognize infection patterns suggestive of rarer immunodeficiency syndromes. Antimicrobials are good, but immunomodulation may be a very necessary adjunct to ensure good patient outcomes." [1]
The outcome of any infection is determined by three interacting factors: the Microbe, the Host, and the Intervention. [1]
This is the conceptual framework. You cannot think about treating infection without simultaneously considering:
- Microbe factors: virulence, resistance, inoculum size
- Host factors: immune status, barriers, comorbidities
- Intervention: antimicrobials, surgery, immunomodulation, vaccination
The immune system provides: defense against microbes, defense against cancers. BUT it also mediates: allergic reactions, aberrant responses to infections, autoimmune disease, and malignancy. [1]
This is why immunology is not just about "killing bugs." The same machinery that protects you can harm you. Understanding this duality is crucial for appreciating why steroids are used in some infections (to dampen harmful inflammation) and why immunosuppression predisposes to specific infection patterns.
| Feature | Innate Immunity | Adaptive Immunity |
|---|---|---|
| Timing | Immediate; pre-existing before infection | Needs time; stimulated by antigen exposure |
| Specificity | Non-specific | Highly specific |
| Diversity | Limited | Very diverse |
| Memory | No memory | Memory (basis of vaccination) |
| Role | First line; stimulates adaptive response | Elimination of specific antigens |
| Components | Physical/chemical barriers, phagocytes (neutrophils, macrophages), NK cells, complement, cytokines, platelets | B lymphocytes (antibodies), T lymphocytes (CD4+, CD8+) |
Why does this matter clinically?
Innate immunity acts within minutes-hours. If it fails (e.g., neutropenia), infections are fulminant and often bacterial/fungal. Adaptive immunity takes days-weeks to mount but provides lasting protection. If it fails (e.g., HIV), you get opportunistic infections that immunocompetent people handle easily.
4. Innate Immune System — Detailed Breakdown
Skin, gastrointestinal, genitourinary, and respiratory tract epithelium form the first line of defense. [1]
Why this matters: Any break in these barriers (burns, wounds, IV lines, urinary catheters, intubation, mucositis from chemotherapy) immediately predisposes to infection. This is the single most common reason hospitalized patients get infected. The vaginal canal's acidic pH (maintained by Lactobacillus) is another example — conditions that raise vaginal pH (menstruation, pregnancy, antibiotics) increase infection risk [8].
e.g., cathelicidins, defensins [1]
These are small peptides produced by epithelial cells and phagocytes that directly kill microbes by disrupting their membranes. Think of them as the body's own antibiotics at mucosal surfaces.
Pathogen-associated molecular patterns (PAMPs) on microbes are recognized by Pattern Recognition Receptors (PRRs) on host cell surfaces. Examples: Toll-like receptors (TLR), Nod-like receptors (NLR), RIG-I like receptors (RLR). [1]
Why from first principles: Microbes have conserved molecular structures (lipopolysaccharide in gram-negatives, peptidoglycan in gram-positives, flagellin, viral dsRNA) that human cells do not have. PRRs evolved to detect these foreign patterns without needing prior exposure. This is how the innate immune system "knows" something is foreign immediately.
| PRR Type | Location | Recognizes |
|---|---|---|
| TLRs | Cell surface + endosomal membranes | LPS (TLR4), flagellin (TLR5), dsRNA (TLR3), ssRNA (TLR7/8), CpG DNA (TLR9) |
| NLRs | Cytoplasm | Bacterial peptidoglycan fragments, danger signals → inflammasome activation |
| RLRs | Cytoplasm | Viral RNA (especially dsRNA) |
Neutrophils, Macrophages, Natural Killer cells [1]
- Neutrophils: First responders; recruited to sites of infection within hours. Kill by phagocytosis + respiratory burst (superoxide → hydrogen peroxide → hypochlorous acid). When neutrophils are deficient (quantitative = neutropenia; qualitative = CGD), bacterial and fungal infections dominate.
- Macrophages: Tissue-resident phagocytes; also serve as antigen-presenting cells bridging innate and adaptive immunity. Activated by IFN-γ from Th1 cells to kill intracellular organisms.
- NK cells: Kill virus-infected cells and tumor cells without prior sensitization. Also produce IFN-γ.
Plasma proteins activated by microbes. Promotes destruction and inflammation. [1]
Three activation pathways:
| Pathway | Trigger | Clinical Relevance |
|---|---|---|
| Classical | Antigen-antibody complex binds C1 | Deficiency → encapsulated bacterial infections; also associated with SLE |
| Lectin (MBL) | Mannose on microbial surfaces binds Mannose-Binding Lectin | Deficiency → sinopulmonary infections, Neisseria meningitidis |
| Alternative | Spontaneous C3b binding to microbial surfaces | Less common deficiency; also → Neisseria meningitidis |
Terminal components (C5-C9) — the Membrane Attack Complex (MAC):
Terminal component deficiency (C5-C9) → Neisseria meningitidis [1]
Why? Neisseria has a thin cell wall that is uniquely susceptible to complement-mediated lysis via the MAC. Without MAC, patients get recurrent meningococcal disease. Other bacteria have thicker walls or capsules that resist MAC, so complement deficiency tends to show up clinically with Neisseria specifically.
The innate immune system communicates using cytokines (e.g., IL-1, IL-6, TNF-α, IFN-γ, IFN-α/β). These recruit more immune cells, activate adaptive immunity, cause fever, and trigger the acute phase response.
5. Adaptive Immune System — Detailed Breakdown
B cells differentiate into plasma cells, which produce antibodies. [1]
Antibody Structure (Slide 9): Y-shaped molecule with two antigen-binding sites (Fab region) and an Fc region that determines the antibody class and interacts with immune cells/complement.
Antibody Key Features IgM First antibody produced; appears before IgG; pentameric → excellent at activating complement IgG Appears later; most abundant in serum; crosses placenta; provides neonatal passive immunity IgA Secreted at mucosal surfaces; key defense in GI and respiratory tracts IgE Bound to mast cells → allergic reactions; also important in helminth defense IgD Cell signaling in B cells; minor clinical role
IgM vs IgG — Exam Classic
IgM appears first in acute infection (diagnostic of recent/acute infection). IgG appears later and indicates past exposure or chronic infection. This distinction is the basis of serological diagnosis (GC 101).
T cells are divided into:
- Cytotoxic T cells (CD8+): Kill cells harboring intracellular microbes (viruses, intracellular bacteria)
- T helper cells (CD4+):
- Th1: Activate macrophages to kill intracellular microbes via IFN-γ. Key for Mycobacterium tuberculosis.
- Th2: Promote IgE production and eosinophil/mast cell responses via IL-4. Key for helminth infections.
- Th17: Protect against extracellular bacteria and fungi.
- Regulatory T cells: Suppress immune responses; prevent autoimmunity.
Why Th1/Th2 distinction matters: If Th1 responses are impaired (e.g., HIV destroying CD4+ cells, anti-IFN-γ antibodies), intracellular pathogens like TB, non-tuberculous mycobacteria (NTM/MOTT), and fungi flourish. If Th2 responses dominate inappropriately, you get allergic disease.
6. Clinical Syndromes of Impaired INNATE Immunity
Pathway Deficiency Associated Infections Classical pathway Encapsulated bacteria (S. pneumoniae, H. influenzae, N. meningitidis) MBL pathway Sinopulmonary infections; Neisseria meningitidis Alternative pathway Less common; Neisseria meningitidis Terminal components (C5-C9) Neisseria meningitidis
High Yield
The take-home: Neisseria meningitidis is the hallmark organism of complement deficiency — especially terminal component deficiency. Early classical pathway deficiency also predisposes to SLE (immune complex clearance failure) [7].
6.2 Neutrophil Defects
Most common causes: hematological malignancy, drugs (chemotherapy, antibiotics) [1]
Problems in neutropenia:
- Bacterial infection:
- Gram-positive: Staphylococcus, Streptococcus, Enterococcus
- Gram-negative: E. coli, Pseudomonas aeruginosa (has > 50% mortality rate)
- Fungal infection:
- Candida
- Aspergillus, Fusarium, Zygomycetes
Why Pseudomonas is so deadly: It has intrinsic resistance to many antibiotics, forms biofilms, produces toxins (exotoxin A, elastase), and exploits the absence of neutrophils to cause rapidly progressive sepsis. The > 50% mortality stat from the lecture is exam-favorite.
Clinical images from lecture:
- Slide 17: Neutropenic patient with disseminated Candida skin nodules
- Slide 18: Aspergillosis in a post-liver transplant recipient
Exam Intelligence
Past paper 2021 Q12(a): "A 40-year-old man had bone marrow transplant for CML. He developed high fever on day 10 after conditioning with high dose chemotherapy. ANC < 0.1. List common microbes found in blood culture." Answer: Gram-positive (Staphylococcus, Streptococcus, Enterococcus), Gram-negative (E. coli, Pseudomonas, Klebsiella), Fungi (Candida, Aspergillus) [9].
Usually X-linked (66% gp91phox mutation). Defect in intracellular killing due to abnormal respiratory burst oxidase (NADPH oxidase) activity. Susceptible to catalase-positive organisms:
- Staphylococcus aureus
- Serratia marcescens
- Burkholderia cepacia
- Chromobacterium violaceum
- Nocardia
- Aspergillus
Why catalase-positive matters (first principles):
- Normal neutrophils kill bacteria using the respiratory burst: NADPH oxidase generates superoxide → hydrogen peroxide → hypochlorous acid (the actual killing agent)
- In CGD, this pathway is broken — neutrophils cannot generate reactive oxygen species (ROS)
- Some bacteria (catalase-negative ones like Streptococci) actually produce H₂O₂ themselves during their metabolism, and because they lack catalase, this H₂O₂ accumulates. The CGD neutrophil can "borrow" this bacterial H₂O₂ to still kill them
- Catalase-positive organisms (like S. aureus, Aspergillus) destroy their own H₂O₂ using catalase, so the CGD neutrophil has NO source of ROS to use → these organisms survive and cause disease
Inheritance: 66% X-linked (gp91phox), 30% autosomal recessive (p47phox), 5% other mutations [1]
Clinical presentation (Slide 21): 2.5-year-old boy with cervical lymphadenitis and retropharyngeal abscess [1]. Pediatric notes add: commonly presents with lymphadenitis, hepatosplenomegaly, skin/perianal abscess, TB/BCG dissemination [5].
Impaired adhesion of inflammatory cells within vasculature → inability to migrate into tissues. Recurrent infections with Staphylococcus and Pseudomonas aeruginosa. [1]
Why from first principles: Neutrophils need to adhere to vessel walls (using integrins like CD18) and then squeeze through (diapedesis) to reach infection sites. In LAD, neutrophils are trapped in the bloodstream → paradoxically, the blood neutrophil count is HIGH, but tissues are defenseless.
Clinical hallmarks (from Pediatric notes): Poor wound healing, absent pus formation, omphalitis with delayed umbilical cord separation [5].
Clinical image (Slide 23): Baby with LAD showing ecthyma gangrenosum due to Pseudomonas aeruginosa [1].
Adult-onset; Asians. IFN-γ activates macrophages to kill intracellular microbes. Anti-IFN-γ autoantibodies → susceptibility to:
- MOTT (Mycobacteria other than TB, including M. chelonae, M. abscessus)
- Non-typhoidal Salmonella
- Burkholderia pseudomallei
- Penicillium marneffei (Talaromyces marneffei)
- VZV
- (Cryptococcosis, histoplasmosis)
Why this condition is important: It's a newly recognized phenocopy of primary immunodeficiency. It predominantly affects Asian adults with previously good health, who present with disseminated infections by organisms that are normally controlled by cell-mediated immunity. The lecture shows a case of a 55-year-old female with M. chelonae skin infection (Slide 25) [1].
Anti-IFN-γ Autoantibodies vs. HIV
Both cause susceptibility to intracellular organisms. Key difference: Anti-IFN-γ autoantibody disease is adult-onset, typically in Asians, and the CD4 count is normal. HIV patients have low CD4 counts. Both get NTM, but the organism spectrum differs slightly (anti-IFN-γ patients get more M. abscessus-type organisms).
The lecture references Bastard et al, Science 2020 [1] — this landmark study showed that autoantibodies against type I interferons (IFN-α, IFN-ω) were found in patients with severe COVID-19, particularly elderly males. This is an example of how innate immune defects can determine disease severity.
7. Clinical Syndromes of Impaired ADAPTIVE Immunity
7.1 Impaired Humoral Immunity (Antibody Deficiency)
Key organisms: Streptococcus pneumoniae, Haemophilus influenzae [1]
Presents with:
- Sinusitis, otitis media, pneumonia (S. pneumoniae, H. influenzae, Meningococci, Mycoplasma)
- Intestinal infections (Salmonella, Shigella, Campylobacter, Giardia, Rotavirus)
Why these organisms? Antibodies opsonize encapsulated bacteria for phagocytosis and activate complement via the classical pathway. Without antibodies, encapsulated organisms (which resist phagocytosis due to their polysaccharide capsule) thrive. At mucosal surfaces (sinopulmonary, GI), secretory IgA normally neutralizes pathogens — without it, mucosal infections predominate.
Recurrent sinopulmonary infection. Important: anaphylactic reaction if given IVIG [1]
Why anaphylaxis with IVIG? Patients with IgA deficiency can develop anti-IgA antibodies (typically IgE class). IVIG preparations contain trace amounts of IgA. When these patients receive IVIG, the anti-IgA IgE triggers mast cell degranulation → anaphylaxis. This is a classic exam trap.
Exam Trap — IgA Deficiency + IVIG
If asked about contraindications or complications of IVIG, always mention anaphylaxis in IgA-deficient patients. This is a direct lecture point and commonly tested.
AIDS caused by HIV. Main problem: reduced CD4+ T cells. Also affects other parts of immune system. [1]
Opportunistic Infections in Advanced HIV (Slide 32)
This is an extremely comprehensive list from the lecture. The examiners expect you to know the categories and the most important examples:
| Category | Organisms |
|---|---|
| Bacteria | MAC/M. kansasii (disseminated), MTB (disseminated/extrapulmonary), Salmonella septicemia (recurrent) |
| Virus | CMV (retinitis, other organs), HSV (chronic ulcers, esophagitis), PML (JC virus) |
| Fungal | Candida (esophageal, bronchial), Cryptococcosis (meningitis), PCP (Pneumocystis jirovecii pneumonia), Histoplasmosis, Coccidioidomycosis |
| Parasite | Cryptosporidium (chronic diarrhea), Toxoplasma (brain abscess), Isospora |
| Cancer | Kaposi sarcoma (HHV-8), Burkitt's lymphoma, Primary CNS lymphoma, Invasive cervical cancer |
| HIV-related | Encephalopathy, Wasting syndrome |
Hong Kong-specific additions:
- MTB: only extrapulmonary or if CD4 < 200, pulmonary/LN
- Penicilliosis (Talaromyces marneffei) — disseminated
Penicillium marneffei (Talaromyces marneffei): This is a dimorphic fungus endemic to Southeast Asia. It is THE hallmark opportunistic infection of advanced HIV in Hong Kong/Southern China. The lecture shows it growing as a mold at 25°C and as yeast at 37°C (Slide 33) [1]. On blood agar at 25°C, it produces a distinctive red pigment.
Systemic diseases/conditions that affect immune functions:
- Breaks in physical barriers (skin, mucosa)
- Diabetes mellitus
- Cirrhosis
- Autoimmune disease (e.g., SLE)
- Malignancy
- Transplantation
- Iron overload
- Splenectomy
- Drugs (e.g., steroids)
- Malnutrition
- Pregnancy
- Extremes of age
Clinical examples from lecture:
- Slide 36: S. aureus bacteremia with pacemaker infection in an eczema patient (broken skin barrier) [1]
- Slide 37: Norwegian (crusted) scabies in a post-renal transplant recipient (immunosuppression allows massive mite proliferation) [1]
- Slide 38: Necrotizing fasciitis due to Aeromonas in a patient with DM and cirrhosis (DM impairs neutrophil function; cirrhosis impairs complement and humoral immunity; Aeromonas is associated with water/seafood exposure) [1]
8.1 Post-Splenectomy Sepsis — HIGH YIELD
Splenectomy or functional hyposplenism
Major functions of spleen in immunity:
- Production of antibody (especially against polysaccharide antigens)
- Clearance of encapsulated bacteria
Organisms (mainly bacteria with polysaccharide capsule):
- Streptococcus pneumoniae
- Haemophilus influenzae type B
- N. meningitidis
- Capnocytophaga canimorsus
Rapid progression → need urgent antibiotic treatment
Vaccination:
- Streptococcus pneumoniae
- Influenza
- (Haemophilus influenzae type B)
- (Neisseria meningitidis)
Why the spleen is so critical: The spleen is the primary site where blood-borne pathogens are filtered and presented to B cells in the marginal zone. It is especially important for generating IgM antibodies against polysaccharide antigens (the capsules of encapsulated bacteria). Without a spleen, the initial antibody response to these organisms is severely impaired → overwhelming sepsis can develop within hours.
Capnocytophaga canimorsus is transmitted by dog/cat bites and is especially dangerous in asplenic patients — a classic exam question stem.
Past Paper Link — 2021 SAQ Q12(c)
"He did not come back for routine vaccination after transplant for 1 year. Four years after transplant, sudden high fever, hypotension, purpuric rash, died within 24 hours. Peripheral blood smear showed Howell-Jolly bodies. List organisms found in blood cultures." Answer: S. pneumoniae, H. influenzae, N. meningitidis. Howell-Jolly bodies = functional asplenia (RBC inclusions normally removed by the spleen) [9].
Functional asplenia (e.g., sickle cell disease, post-radiation) carries the same risk as surgical splenectomy.
9. Immunization
Artificially induce immunity. Active vs Passive. [1]
| Type | Mechanism | Duration | Examples |
|---|---|---|---|
| Active (Vaccination) | Stimulate host's own immune response | Long-lasting; memory | All vaccines |
| Passive (Immunoglobulin) | Provide pre-formed antibodies | Temporary (weeks-months) | IVIG, anti-D, post-exposure prophylaxis |
Vaccine Type Principle Examples Live attenuated Weakened organism; replicates but doesn't cause disease; strong immune response MMR, BCG, oral polio, yellow fever, varicella Inactivated (killed) Whole killed organism; weaker immune response; needs boosters Rabies, some COVID-19 vaccines, Hepatitis A Toxoid Inactivated toxin; generates antitoxin antibodies Tetanus, Diphtheria Soluble capsular material Purified polysaccharide capsule Pneumococcal vaccine (PPSV23) Recombinant protein Genetically engineered protein subunit HBV, HPV Vector vaccines Harmless virus delivers antigen gene Some COVID-19 vaccines (AstraZeneca) mRNA vaccines mRNA encodes antigen; host cells produce it Pfizer/BioNTech, Moderna COVID-19 vaccines
Live Attenuated Vaccines — Contraindicated in Immunocompromised
Live vaccines (MMR, BCG, varicella, oral polio) can cause disease in immunocompromised patients because the attenuated organism can revert to virulence. This is why CGD patients can get disseminated BCG and why HIV patients with very low CD4 counts should not receive live vaccines.
Humoral immunity (elicit antibody response): e.g., Influenza vaccine, Pneumococcal vaccine Cell-mediated immunity: e.g., BCG Some combination of both — poorly understood [1]
10. Treatment of Infectious Disease by Manipulating the Immune System
Examples:
- Glucose control in DM
- HAART for HIV
- G-CSF in patients with neutropenia
- IVIG in patients with CVID (Common Variable Immunodeficiency)
Why each matters:
- Glucose control in DM: Hyperglycemia impairs neutrophil chemotaxis, phagocytosis, and intracellular killing. Good glycemic control directly improves immune function.
- HAART for HIV: Restoring CD4 count restores cell-mediated immunity → opportunistic infections resolve. However, rapid immune recovery can cause IRIS (Immune Reconstitution Inflammatory Syndrome) [3].
- G-CSF: Granulocyte colony-stimulating factor stimulates bone marrow to produce more neutrophils. Used during chemotherapy-induced neutropenia to shorten the duration of neutropenia.
- IVIG for CVID: Replaces the deficient immunoglobulins; reduces frequency of sinopulmonary infections.
10.2 Immunomodulators
Types: Naturally occurring cytokines, Immunoglobulins, Glucocorticoids, Biologics, Synthetic immunomodulatory compounds [1]
Rationale: Antiviral activity. Treatment of:
- HCV (pegylated interferon — now obsolete, replaced by DAAs)
- HBV (pegylated interferon — now considered second-line to nucleos(t)ide analogues)
- (Kaposi sarcoma)
- (Condyloma acuminatum)
Rationale: Reduce detrimental effects of inflammation. Used in:
- Pneumocystis pneumonia (PCP) — reduces mortality when PaO₂ < 70 mmHg
- TB meningitis — reduces mortality and neurological sequelae by decreasing meningeal inflammation
- COVID-19 patients requiring supplemental oxygen — dexamethasone (RECOVERY trial)
- Bacterial meningitis — dexamethasone before/with first dose of antibiotics reduces hearing loss (especially in pneumococcal meningitis)
Steroids in Infection — Paradox Explained
Why would you give an immunosuppressant during an infection? In these specific conditions, the host's inflammatory response causes MORE damage than the pathogen itself. Steroids dampen this excessive inflammation while antimicrobials handle the pathogen. This only works when effective antimicrobial therapy is given simultaneously.
Mechanism: Bind to pathogens/toxins + Immunomodulation
Treatment:
- Toxic shock syndrome due to Group A Streptococcus / Staphylococcus (controversial)
- Parvovirus B19 infection in immunocompromised patients
Prophylaxis:
- Post-exposure prophylaxis: VZV, measles, hepatitis A
- Prophylaxis in patients with humoral immunodeficiencies
Why IVIG for toxic shock: Toxic shock syndrome is driven by superantigens. IVIG contains antibodies that can neutralize these superantigens and also modulates the overactive immune response. The evidence is mixed (hence "controversial"), but it's used in severe cases.
Why IVIG for Parvovirus B19: This virus causes pure red cell aplasia in immunocompromised patients who cannot mount an adequate antibody response. IVIG provides the anti-Parvovirus antibodies they cannot make.
Tocilizumab: IL-6 antagonist Sarilumab: IL-6 antagonist Baricitinib: JAK inhibitor Tofacitinib: JAK inhibitor
Rationale: Severe COVID-19 is characterized by a "cytokine storm" with markedly elevated IL-6. These agents dampen this hyperinflammatory response. They are used in hospitalized patients requiring supplemental oxygen, in addition to dexamethasone.
| Related GC Lecture | Connection to This Lecture |
|---|---|
| GC 096 — Why do I always get sick | Primary immunodeficiencies in detail; SPUR criteria (Serious, Persistent, Unusual, Recurring) |
| GC 099 — Antimicrobial resistance | The "host-microbe-antibiotic" triad directly parallels the "host-microbe-intervention" triad here |
| GC 101 — Diagnosis of infections | IgM vs IgG serology; using immune markers to diagnose infection |
| GC 102 — Fever after chemotherapy | Direct clinical application of neutropenia concepts; empirical antibiotics in febrile neutropenia |
| GC 104 — Infection outbreak/control | Barrier defenses (hand hygiene = protecting epithelial barriers at population level) |
| GC 105 — Medically important microbes | The organisms listed here (encapsulated bacteria, catalase-positive organisms, intracellular pathogens) are classified systematically in GC 105 |
| GC 106 — Practical antibiotic use | Why empirical coverage must be broad in neutropenic patients (Pseudomonas coverage mandatory) |
12. Exam Intelligence
- "List organisms causing infection in a patient with [specific immune defect]" — Must match defect to organism pattern (see tables above)
- "What is the mechanism of increased susceptibility in [condition]?" — Expect you to explain the immunology, not just name organisms
- "Name vaccines recommended for a splenectomised patient" — Pneumococcal, influenza, Hib, meningococcal
- "Why are steroids used in PCP / TB meningitis / bacterial meningitis?" — Reduce detrimental inflammatory response
- "What is CGD? Why are catalase-positive organisms problematic?" — NADPH oxidase deficiency; catalase destroys H₂O₂ that would otherwise compensate
- Mini-case: Immunocompromised patient with specific organism — Reverse-engineer which immune defect allows that organism
| Trap | Correct Approach |
|---|---|
| Confusing neutropenia organisms with splenectomy organisms | Neutropenia → broad spectrum (GP + GN bacteria + fungi). Splenectomy → specifically encapsulated bacteria |
| Forgetting Capnocytophaga in post-splenectomy | It's in the lecture slide — always include it |
| Saying "IVIG is safe in all patients" | Anaphylaxis risk in IgA deficiency |
| Listing only bacteria for neutropenic patients | Must include fungi (Candida, Aspergillus) |
| Not specifying catalase-positive for CGD | The concept of catalase positivity IS the answer — not just listing random organisms |
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Q: A 3-year-old boy presents with recurrent liver abscesses growing Staphylococcus aureus and a recent episode of invasive Aspergillus infection. What is the most likely diagnosis and explain the mechanism? A: Chronic granulomatous disease. X-linked deficiency of NADPH oxidase (gp91phox). Neutrophils cannot generate superoxide → no respiratory burst → cannot kill catalase-positive organisms. Catalase-positive organisms destroy H₂O₂, removing the compensatory source of ROS.
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Q: A 50-year-old previously healthy Chinese woman presents with disseminated Mycobacterium abscessus infection. What acquired immunodeficiency should be investigated? A: Anti-IFN-γ autoantibodies. Adult-onset, Asian predilection. IFN-γ activates macrophages to kill intracellular pathogens. Autoantibodies neutralize IFN-γ → susceptibility to NTM, non-typhoidal Salmonella, Burkholderia pseudomallei, Talaromyces marneffei.
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Q: What vaccinations should be given to a patient undergoing elective splenectomy? A: Pneumococcal (PCV13 + PPSV23), Haemophilus influenzae type B, Meningococcal ACWY, Influenza. Ideally ≥ 2 weeks pre-operatively.
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Q: Name four infections where adjunctive steroids improve outcomes and explain why. A: PCP (reduces mortality when hypoxic), TB meningitis (reduces meningeal inflammation and neurological sequelae), COVID-19 requiring O₂ (dampens cytokine storm), Bacterial meningitis (reduces hearing loss). In all cases, the host inflammatory response causes more damage than the infection itself; steroids modulate this while antimicrobials treat the pathogen.
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Q: A patient with IgA deficiency requires IVIG. What complication should you warn about? A: Anaphylaxis. Anti-IgA antibodies (IgE class) react with trace IgA in IVIG preparations → mast cell degranulation → anaphylaxis.
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Q: Compare innate and adaptive immunity with respect to timing, specificity, memory, and key cellular components. A: See table in Section 3 above. Innate = immediate, non-specific, no memory, uses neutrophils/macrophages/NK/complement. Adaptive = delayed, specific, has memory, uses B cells (antibodies) and T cells (CD4+ helper, CD8+ cytotoxic).
High Yield Summary
- The outcome of infection = Microbe × Host × Intervention. 2. Innate immunity (barriers, neutrophils, complement, NK cells) acts immediately and non-specifically; adaptive immunity (B cells/antibodies, T cells) is specific with memory. 3. Complement deficiency (especially terminal C5-C9) → Neisseria meningitidis. 4. Neutropenia → GP bacteria + GN bacteria (especially Pseudomonas, > 50% mortality) + fungi (Candida, Aspergillus). 5. CGD = NADPH oxidase defect → catalase-positive organisms (S. aureus, Serratia, Burkholderia, Aspergillus). 6. Anti-IFN-γ autoantibodies (adult-onset, Asian) → MOTT, NTS, Burkholderia, Talaromyces marneffei. 7. Antibody deficiency → encapsulated bacteria (S. pneumoniae, H. influenzae). IgA deficiency → anaphylaxis with IVIG. 8. HIV/AIDS = CD4+ T cell depletion → wide range of opportunistic infections; HK-specific = Talaromyces marneffei. 9. Splenectomy → encapsulated bacteria (S. pneumoniae, H. influenzae, N. meningitidis, Capnocytophaga) → VACCINATE. 10. Immunomodulation in infection: steroids (PCP, TB meningitis, COVID-19, bacterial meningitis), IVIG (toxic shock, Parvovirus, post-exposure prophylaxis), G-CSF (neutropenia), HAART (HIV).
Active Recall - Defense Against Microbes
[1] Lecture slides: GC 100. Defense against microbes.pdf (all slides 1–54) [2] Lecture slides: GC 105. Medically important microbes what every doctor should know.pdf [3] Lecture slides: GC 102. Fever after chemotherapy infections in immunocompromised hosts [Handout].pdf (p4, p6) [4] Senior notes: Gen Clerk Anaes + Microbiology Summary.pdf (p19) [5] Senior notes: Adrian Lui Pediatrics Notes.pdf (p411) [6] Senior notes: Jerry's immunodeficiencies.pdf (p1, p3, p4) [7] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p637) [8] Lecture slides: Block C - Vaginal discharge_ obstetric and gynaecological infections.pdf (p2–3) [9] Past papers: 2021 Fourth Summative SAQ.pdf (p14, Q12) [10] Past papers: 2024 Fourth Summative SAQ.pdf (p13, Q12) [11] Senior notes: Maksim Surgery Notes.pdf (p153) [12] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p1329)
GC099 Antimicrobial Resistance
Antimicrobial resistance is the ability of microorganisms to survive and proliferate despite exposure to antimicrobial agents that would normally inhibit or kill them, rendering standard treatments ineffective.
GC101 Diagnosis Of Infections
Diagnosis of infections is the systematic process of identifying causative pathogens through clinical assessment, microbiological techniques (culture, microscopy, serology, molecular methods), and laboratory markers to guide appropriate antimicrobial therapy.