HIV infection primarily leads to immunodeficiency by which mechanism?

• A. Depletion of B cells due to direct infection of B lymphocytes
• B. Loss of innate immune signaling due to macrophage dysfunction
• C. Depletion of CD4+ T helper cells via infection of CD4-expressing cells, leading to impaired adaptive immunity
• D. Deficiency of complement components leading to reduced opsonization

Answer: (C)

HIV immunodeficiency primarily comes from loss of CD4+ T helper cells, the cells that coordinate the entire adaptive immune response. The virus infects cells that express CD4, using coreceptors to enter them; this leads to death of these helper T cells and a progressive drop in their numbers. When CD4+ T cells are depleted, B cells receive less help to produce high-affinity antibodies and class-switched responses, and cytotoxic T cell responses are less effectively primed. The result is a broad failure of adaptive immunity, paving the way for opportunistic infections and malignancies associated with AIDS. Other ideas—such as direct depletion of B cells, major loss of innate signaling from macrophages, or a primary deficiency in complement—don’t account for the central, coordinated role of CD4+ T cells in orchestrating immune responses, which is why this mechanism best explains HIV-related immunodeficiency.