# T Cell and Combined Immunodeficiencies

> T cell and combined immunodeficiencies for NEET-PG Microbiology, with DiGeorge, SCID, Wiskott-Aldrich, hyper-IgM and phagocyte defects and key tests.

- Canonical URL: https://prepelephant.com/topics/neet-pg/microbiology/t-cell-and-combined-immunodeficiencies
- Exam / course: NEET-PG · Subject: Microbiology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-14
- Last updated: 2026-10-14
- Reference basis: Janeway's Immunobiology; Abbas, Lichtman and Pillai Cellular and Molecular Immunology; Harrison's Principles of Internal Medicine
- How to cite: "T Cell and Combined Immunodeficiencies", PrepElephant, https://prepelephant.com/topics/neet-pg/microbiology/t-cell-and-combined-immunodeficiencies

## Direct answer

T cell and combined immunodeficiencies are inherited defects that impair T cell function, often with secondary loss of B cell help, leaving infants prone to severe opportunistic infection. Severe combined immunodeficiency is the most urgent form, presenting in infancy with failure to thrive and Pneumocystis pneumonia. DiGeorge syndrome, caused by a 22q11.2 deletion, is the commonest thymic defect, and its T cell deficiency is often partial.

## What you must remember

- **DiGeorge syndrome:** 22q11.2 deletion disrupting the third and fourth pharyngeal pouches, causing thymic hypoplasia, hypocalcaemia and conotruncal heart defects.
- **CATCH-22:** the mnemonic for cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcaemia linked to 22q11.2 deletion.
- **SCID:** absent or severely impaired T cell function, with B cell defects in many forms, most commonly X-linked and caused by the IL2RG gene.
- **ADA deficiency:** autosomal recessive SCID in which toxic metabolites accumulate and kill lymphocytes, treatable with enzyme replacement or transplant.
- **SCID presentation:** failure to thrive, chronic diarrhoea, oral thrush and Pneumocystis pneumonia in infancy, with risk from live vaccines such as BCG.
- **Wiskott-Aldrich syndrome:** X-linked WASP defect with eczema, small platelets and recurrent infections, plus a risk of autoimmunity and lymphoma.
- **X-linked hyper-IgM:** CD40L defect on T cells prevents class switching, giving high IgM with low IgG, IgA and IgE.
- **Chronic granulomatous disease:** NADPH oxidase defect causing failure of the respiratory burst and infection with catalase-positive organisms such as Staphylococcus aureus and Aspergillus.

## Narrowing down a combined immunodeficiency

Combined defects are easier to sort when the clinical pattern is matched to a laboratory result, so each step below eliminates one group of diagnoses. The order mirrors how an immunology clinic typically works through a suspected case.

1. **Age and pattern:** failure to thrive with opportunistic infection in an infant suggests SCID, whereas eczema with bleeding in an older boy suggests Wiskott-Aldrich syndrome.
2. **Lymphocyte count:** lymphopenia with absent T cells on flow cytometry points to SCID or severe DiGeorge syndrome, while normal T cells direct attention elsewhere.
3. **Calcium and facies:** hypocalcaemia with a cardiac murmur and dysmorphic features prompts a 22q11.2 deletion test, usually by FISH.
4. **Immunoglobulin profile:** raised IgM with low IgG, IgA and IgE points to the hyper-IgM pattern caused by a CD40L defect.
5. **Neutrophil function:** the NBT or DHR123 test distinguishes chronic granulomatous disease, and a normal result rules it out.
6. **Definitive test:** genetic sequencing identifies the mutation and guides decisions on transplant or gene therapy.

## Where the exam tries to catch you

Combined immunodeficiency questions often test which cell line is affected, so tracing the defect to its cell type prevents most errors.

- **Trap:** labelling DiGeorge syndrome as a B cell defect — **Correct:** DiGeorge is a T cell defect from thymic hypoplasia, and B cells are usually normal, so antibody levels are often normal too.
- **Trap:** giving live BCG to an infant with suspected SCID — **Correct:** live vaccines are contraindicated in SCID, because the vaccine strain can cause disseminated disease in a child who cannot clear it.
- **Trap:** choosing chronic granulomatous disease for a patient with raised IgM — **Correct:** raised IgM with low IgG and IgA points to hyper-IgM from CD40L deficiency, whereas chronic granulomatous disease is a phagocyte defect with normal immunoglobulins.

## Frequently asked questions

### What genetic change causes DiGeorge syndrome?
DiGeorge syndrome is caused by a deletion of chromosome 22q11.2, which disrupts development of the third and fourth pharyngeal pouches. The resulting thymic hypoplasia causes variable T cell deficiency, and the same deletion accounts for the parathyroid and cardiac defects.

### Why is live BCG vaccine contraindicated in severe combined immunodeficiency?
Live BCG vaccine is contraindicated in severe combined immunodeficiency because the attenuated bacteria can cause disseminated infection in a child who cannot clear them. Such children need a full immunological assessment before any live vaccine is considered.

### Which test distinguishes chronic granulomatous disease from normal neutrophil function?
The nitroblue tetrazolium test and the dihydrorhodamine flow cytometry test distinguish chronic granulomatous disease from normal neutrophil function. Neutrophils from patients with this condition fail to generate a respiratory burst, so the dye is not reduced.

### Which features point to Wiskott-Aldrich syndrome in a boy?
Eczema, small platelets causing bleeding and recurrent infections together point to Wiskott-Aldrich syndrome in a boy. The condition is X-linked and caused by a defect in the WASP protein, and it carries a risk of autoimmunity and lymphoma.