Two subsets, two jobs
CD4 helper T cells recognize peptide on MHC class II, which is displayed mainly by professional antigen-presenting cells. When activated, they secrete cytokines and express surface molecules that instruct other cells: they help B cells produce antibody, they activate macrophages to kill ingested organisms, and they license dendritic cells. CD8 cytotoxic T cells recognize peptide on MHC class I, which is displayed by nearly every nucleated cell, and kill the cell displaying it. Because MHC class I presents peptides from the cell's own cytosol, CD8 cells are the defense against pathogens that live inside cells.
Loss of CD4 help disables several arms at once
Without CD4 help, macrophages that have ingested organisms such as mycobacteria are not activated and the organisms survive inside them. B cells receive weak or no help, so antibody responses are poor even though the B cells are normal. Cytotoxic T cells are also less efficiently primed. A single CD4 defect therefore produces a broad collapse rather than one narrow failure, which is why CD4 loss is the most devastating form of cellular immunodeficiency.
Loss of CD8 killing permits unchecked replication
When cytotoxic T cells are absent, virus-infected cells are not destroyed. Viruses continue to replicate and spread from cell to cell, and the infections that follow are persistent and progressive rather than self-limited. The same applies to intracellular bacteria and protozoa that escape into the cytosol.
Cellular versus humoral failure
Cellular (T-cell) failure
- Viruses, including persistent and progressive infections
- Fungi such as Candida and Pneumocystis
- Protozoa such as Toxoplasma
- Intracellular bacteria such as mycobacteria
- Live attenuated vaccines can cause disseminated disease
Humoral (B-cell) failure
- Encapsulated bacteria: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis
- Recurrent sinopulmonary infection
- Enteroviral meningoencephalitis
- Live attenuated vaccines are generally tolerated
Why these are called opportunistic
The organisms that dominate cellular immunodeficiency are ones a healthy immune system controls easily. They are not intrinsically highly virulent; they take advantage of the specific gap left by missing T-cell function. This is why the infection pattern itself is diagnostic evidence about which layer has failed.