Host Defence Mechanisms and Immunocompromise 

Host Defence Mechanisms and Immunocompromise 

Non-Specific Defences

•    Physical barriers:

o    Skin: primary mechanical barrier; intact keratinised epithelium resists most pathogens.

o    Mucosal barriers: mucous traps pathogens; mucosal IgA important for neutralisation.

•    Chemical barriers:

o    Gastric acid: destroys ingested pathogens; reduced in achlorhydria (e.g., PPIs, pernicious anaemia).

o    Antimicrobial peptides: defensins, lysozyme in secretions.

•    Mechanical clearance:

o    Mucociliary escalator: clears inhaled particles; impaired in smoking, primary ciliary dyskinesia.

o    Tear flow, urine flow: prevent bacterial adhesion.

•    Phagocytes:

o    Neutrophils: first responders, important against bacteria and fungi.

o    Macrophages: derived from monocytes; phagocytose, produce cytokines (e.g., TNF-α, IL-1).

Humoral Immunity

•    B lymphocytes:

o    Differentiate into plasma cells → produce antibodies:

    IgM: first antibody produced; activates complement.

    IgG: most abundant; opsonisation, complement activation, neonatal immunity (crosses placenta).

    IgA: mucosal immunity (secretory IgA in gut, respiratory tract).

    IgE: allergic responses, parasitic infections.

    IgD: B cell receptor.

•    Complement system:

o    Three activation pathways: classical (antibody-mediated), alternative, lectin.

o    Functions:

    Opsonisation: C3b binds microbes → enhances phagocytosis.

    Chemotaxis: C5a recruits neutrophils.

    Membrane attack complex (MAC): C5b–C9 forms pore → lysis of Gram-negative bacteria.

o    Deficiencies:

    C5–C9 deficiencies → Neisseria infections.

    C1 esterase inhibitor deficiency → hereditary angioedema.

Cellular Immunity

•    CD4+ T helper cells:

o    Th1: intracellular pathogens (viruses, TB); activates macrophages (via IFN-γ).

o    Th2: humoral responses, parasites, allergic responses; activates B cells, eosinophils.

•    CD8+ cytotoxic T cells:

o    Destroy virus-infected and tumour cells via perforin and granzymes.

•    NK cells:

o    Kill cells lacking MHC I; important in early viral infections, tumour surveillance.

Immunocompromised States

Asplenia

•    Pathogens at risk: encapsulated organisms (SHiN)

o    S. pneumoniae: most common cause of sepsis post-splenectomy.

o    H. influenzae type b.

o    Neisseria meningitidis.

•    Vaccination:

o    Pneumococcal (both PCV13 and PPV23).

o    Meningococcal ACWY and B.

o    Hib.

•    Prophylactic antibiotics:

o    Long-term penicillin, especially in children.

•    Advice:

o    Seek urgent antibiotics at first sign of fever.

Neutropenia

•    Definition: neutrophils <1.5 × 10⁹/L; severe <0.5 × 10⁹/L.

•    Common pathogens:

o    Gram-negatives: Pseudomonas, E. coli, Klebsiella.

o    Fungi: Candida, Aspergillus.

•    Clinical pearl:

o    Neutropenic fever = medical emergency → immediate broad-spectrum antibiotics (e.g., piperacillin-tazobactam).

HIV/AIDS

•    CD4 thresholds:

o    <200: PCP (Pneumocystis jirovecii pneumonia), oral/esophageal candidiasis.

o    <100: Toxoplasma gondii encephalitis, cryptococcal meningitis.

o    <50: CMV retinitis, Mycobacterium avium complex (MAC).

•    Prophylaxis:

o    Co-trimoxazole (PCP ± toxoplasmosis).

o    Azithromycin (MAC).

Steroids / Chemotherapy

•    Risk factors:

o    Reduced T cell function → reactivation of latent infections.

•    Infections:

o    TB reactivation (granuloma breakdown).

o    HSV and VZV reactivation (herpes zoster).

o    CMV (colitis, retinitis).

o    Fungal infections: candidiasis, aspergillosis.

Extra Revision Pearls

•    Chronic granulomatous disease (CGD): defective NADPH oxidase → recurrent catalase-positive organism infections (e.g., Staph aureus, Aspergillus).

•    DiGeorge syndrome (22q11 deletion): T cell deficiency → viral/fungal infections, hypocalcaemia.

•    IgA deficiency: most common primary immunodeficiency → recurrent sinopulmonary infections, anaphylaxis with blood products containing IgA.