Immunodeficiency—Combined Cellular and Humoral Defects Combined T- and B-cell immune deficiencies can result from the absence of several components. Which of the following is the EXCEPTION (least likely to cause a combined deficiency)?

Introduction / Context:
Combined immunodeficiencies involve impaired cellular (T-cell) and humoral (B-cell) arms because B-cell responses depend on T-cell help for effective isotype switching, affinity maturation, and memory formation. This question asks you to identify which listed defect would NOT typically produce a combined deficiency pattern.

Given Data / Assumptions:

• Thymus absence → few/absent mature T cells → poor T-dependent antibody responses.
• Class II MHC deficiency → defective positive selection/activation of CD4+ T cells → profound help deficiency for B cells.
• HIV infection of CD4+ T cells → loss of T-cell help → impaired humoral immunity.
• TAP deficiency → low class I surface expression and poor CD8+ T-cell selection.

Concept / Approach:
Pick the defect that is primarily restricted to CD8+ T-cell development and cytotoxic responses (class I pathway) but leaves CD4+ T-cell help and B-cell function relatively intact. TAP deficiency fits this description, often presenting with recurrent infections but not a classic “combined” humoral defect pattern like class II deficiency or thymic aplasia.

Step-by-Step Solution:

Verification / Alternative check:
Clinical immunology texts describe class II deficiency and thymic aplasia as causing severe combined defects; TAP deficiency is categorized as a type of MHC class I deficiency with characteristic CD8 lymphopenia but often near-normal immunoglobulins.

Why Other Options Are Wrong:

• Thymus absence: eliminates T-cell education → combined defect.
• Class II absence: eliminates CD4+ T help → combined defect.
• HIV of CD4+ T cells: hallmark combined deficiency.
• Common γ chain absence (listed as E): causes X-linked SCID → classic combined defect.

Common Pitfalls:
Assuming any antigen-presentation defect automatically causes combined humoral failure; it is specifically lack of CD4+ T-cell help that collapses B-cell function.

Final Answer:
Transporter associated with antigen processing (TAP) is absent