ImmunologyTier 2Medical Sciences concept

Infection patterns by immunodeficiency type (T-cell/B-cell/complement/neutrophil)

Core concept

Arm	Organisms	Clinical pattern
Antibody / B cell	Encapsulated pyogenic - S. pneumoniae, H. influenzae, S. pyogenes, Moraxella, S. aureus, Neisseria; enterovirus (chronic meningoencephalitis); **Giardia, Campylobacter, mycoplasma/ureaplasma**	Recurrent sinopulmonary - sinusitis, otitis, bronchitis, pneumonia -> bronchiectasis; chronic diarrhoea; onset after 6 months
T cell / combined	Intracellular and opportunistic - CMV, EBV, VZV, HSV, adenovirus, JC virus; PJP, Candida, Cryptococcus, endemic fungi; mycobacteria and disseminated BCG, Listeria, Salmonella, Toxoplasma, Cryptosporidium	Failure to thrive, persistent thrush, chronic diarrhoea, opportunistic infection in infancy; live vaccines cause disease
Phagocyte (number or function)	High-grade bacterial - S. aureus, Gram-negatives (E. coli, Klebsiella, Proteus, Serratia, Pseudomonas, Burkholderia), Nocardia; *fungi - invasive Aspergillus, Candida, mucorales*	Deep and recurrent abscess, cellulitis, gingivitis, perirectal abscess, osteomyelitis, poor wound healing; pus may be absent in adhesion defects
Complement - early classical (C1-C4)	Encapsulated pyogenic	Plus SLE-like immune complex disease
Complement - terminal (C5-C9), properdin	**Neisseria almost exclusively**	Recurrent meningococcal and disseminated gonococcal infection
Spleen (asplenia/hyposplenism)	Encapsulated - pneumococcus above all; Capnocytophaga (dog bite), Babesia, severe malaria	Overwhelming post-splenectomy infection - fulminant over hours
Barrier / anatomical	Skin and mucosal flora; line-related organisms	Localised, recurrent at one site

The organism is the diagnosis - disseminated NTM points to the IL-12/IFN-gamma axis; recurrent Neisseria to terminal complement; Serratia and Aspergillus to CGD; Giardia to antibody deficiency

Key detail

Age of onset is the second discriminator

Birth to 3 months - phagocyte defects, complement, maternal-fetal transmission
After 6 months - antibody deficiency (maternal IgG has waned)
First year with opportunistic infection - SCID/combined defect
Childhood, recurrent abscess - CGD, hyper-IgE
Adolescent/adult, second meningococcal episode - complement
Adult onset with bronchiectasis or autoimmunity - CVID, or a secondary cause

Secondary immunodeficiency is far commoner and has the same patterns

Cause	Arm lost
HIV	T cell (CD4)
Corticosteroids	T cell / phagocyte -> PJP, TB, strongyloides hyperinfection
Rituximab, anti-CD20	Antibody -> hypogammaglobulinaemia, hepatitis B reactivation, PML, enteroviral disease
Anti-TNF	Granuloma maintenance -> reactivation TB, histoplasmosis, listeria
Complement inhibitors (eculizumab etc)	Terminal complement -> Neisseria
Chemotherapy / neutropenia	Phagocyte -> Gram-negative sepsis, invasive fungal
CLL, myeloma, lymphoma	Antibody
Splenectomy, coeliac, sickle cell, portal hypertension	Spleen
Nephrotic syndrome, protein-losing enteropathy, burns, malnutrition, diabetes, CKD, cirrhosis	Mixed
Ibrutinib/BTK inhibitors	Aspergillus, PJP
Alemtuzumab, CAR-T, HSCT	Profound combined

Timing after transplant predicts the organism: <1 month nosocomial/surgical; 1-6 months CMV, PJP, EBV, aspergillus, BK, reactivation TB; >6 months community-acquired plus late CMV/PTLD

Clinical relevance

Prophylaxis follows the deficit, not the drug name
- T-cell / high-dose steroid (>=20 mg prednisolone for >=4 weeks) / purine analogue -> cotrimoxazole for PJP
- Anti-TNF, JAK inhibitor -> screen and treat latent TB and hepatitis B before starting
- Antibody deficiency -> immunoglobulin replacement +/- azithromycin
- Complement deficiency or inhibitor -> meningococcal ACWY + B vaccine and penicillin prophylaxis
- Asplenia -> pneumococcal, Hib, meningococcal, annual influenza + standby antibiotics + medical alert
- CGD -> cotrimoxazole + itraconazole (+/- interferon-gamma)
Strongyloides serology before steroids or HTLV-1-associated immunosuppression in anyone from an endemic area - hyperinfection is fatal
Live vaccines are contraindicated in significant T-cell deficiency, high-dose steroids, biologics and after transplant
Irradiated, CMV-negative, leucodepleted cellular blood products where T-cell function is impaired
*An unusual organism in an apparently well host is itself the presenting sign of immunodeficiency - disseminated NTM, Nocardia, recurrent Neisseria, invasive Aspergillus* or PJP without HIV should each trigger an immune workup

Correlations

Primary immunodeficiency syndromes
Screening tests for primary immunodeficiency
Complement deficiencies and infection risk
Asplenia and encapsulated organisms
HIV and opportunistic infection by CD4 count
Febrile neutropenia; transplant infection timelines
Immunosuppressant mechanisms and their infection profiles

3 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.

Get premium access