Hyperglycaemia impairs immune function through multiple simultaneous mechanisms: neutrophil chemotaxis and phagocytosis are reduced — white cells can still find bacteria but cannot kill them efficiently; complement activation is impaired; glucose-rich tissues provide ideal bacterial growth conditions; and vascular disease reduces blood supply to peripheral tissues (feet, skin), reducing antibiotic and immune cell delivery. HbA1c above 9–10% produces clinically significant immune impairment.

HIV destroys CD4 T-helper cells — the coordinators of both cell-mediated and antibody-mediated immune responses. As CD4 falls, susceptibility to an increasingly wide range of pathogens grows. Recurrent bacterial infections occur at CD4 200–500; opportunistic infections appear below 200. Recurrent herpes zoster in a person under 50 is a specific signal for HIV — shingles at young age is unusual without immune impairment.

Long-term corticosteroids (prednisolone ×2 weeks or more) impair every arm of immune defence. TNF inhibitors (adalimumab, etanercept, infliximab) dramatically increase risk of TB reactivation and opportunistic infections — TB screening is mandatory before starting these drugs. Chemotherapy causes neutropenia (low neutrophil count), making patients vulnerable to rapidly fatal bacterial and fungal infections. Calcineurin inhibitors (tacrolimus, cyclosporine) cause profound T-cell suppression post-transplant. Note: some Ayurvedic preparations in India contain unlabelled corticosteroids.

Multiple myeloma crowds out normal antibody-producing plasma cells, causing hypogammaglobulinaemia and recurrent bacterial pneumonia — often the presenting complaint. CLL similarly impairs antibody production. Lymphoma impairs cell-mediated immunity. Acute leukaemia causes neutropenia and rapidly life-threatening bacterial and fungal infections. Serum protein electrophoresis (M-band in myeloma), serum immunoglobulins, and full blood count differential are screening tests.

Common Variable Immunodeficiency (CVID) — most common adult PID; low IgG, IgA, IgM with recurrent sinopulmonary bacterial infections. Often diagnosed in the 2nd–4th decade after years of recurrent infections. IgA deficiency — most common specific antibody deficiency; recurrent respiratory and GI infections. Complement deficiencies — particularly C5–C9 deficiency predisposes to recurrent Neisseria meningitidis and Neisseria gonorrhoeae infections. Serum immunoglobulins (IgG, IgA, IgM) are the first-line test for humoral PID.

Structural causes produce recurrent infections at a specific site rather than systemic immune failure. Urinary stones — calculi harbour bacteria that seed recurrent UTIs; never fully cleared by antibiotics alone. Prostatic hypertrophy — residual urine pools and becomes infected repeatedly. Bronchiectasis — dilated airways harbour bacterial biofilm; recurrent chest infections until the underlying bronchiectasis is diagnosed and managed. Nasal polyps and deviated septum — impaired sinus drainage leads to recurrent sinusitis. These are identified with imaging — renal ultrasound, HRCT chest, CT sinuses.