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When the Immune System Fails: Mechanisms of Immune Dysfunction

1Normal Immune Defense as a Layered System2Barrier and Innate Failure: When the First Lines Collapse3B-Cell and Antibody Failure4T-Cell and Thymic Failure5Regulatory Failure: Autoimmunity and Allergy
Barrier and Innate Failure: When the First Lines Collapse

When the Surface Stops Holding

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Think of the barrier as doing two separate jobs. One is to seal the surface so nothing gets through. The other is to clear whatever lands there before it can settle. Mucus traps organisms, cilia sweep the mucus out, urine flow washes the urethra, and tears and saliva dilute and remove microbes. If either job fails, bacteria stay in place and multiply. In cystic fibrosis the mucus is too thick for cilia to move, so Pseudomonas and Staphylococcus colonize the airway. In primary ciliary dyskinesia the cilia do not beat at all, and the same organisms cause repeated sinus and ear infections. Notice that these are local problems: the person's antibodies and T cells are fine, so a bloodstream infection would still be handled normally. The defect is that the surface never clears the bacteria in the first place.
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Two jobs: block and clear

A barrier does two things at once. It blocks entry with a physical seal and chemical defenses, and it clears whatever lands on the surface before it can establish itself. Mucus traps organisms, cilia move the mucus out, urine flow washes the urethra, and tears and saliva dilute and remove microbes. Losing either job opens the door.

Where the failure shows

In cystic fibrosis, thick dehydrated mucus cannot be cleared by cilia, so Pseudomonas aeruginosa and Staphylococcus aureus colonize the airway and cause chronic infection. In primary ciliary dyskinesia, the cilia themselves do not beat, and the same organisms plus Haemophilus influenzae cause recurrent sinusitis, otitis media, and bronchiectasis. A burn destroys the skin barrier over a large area, and the wound becomes a portal for Pseudomonas and other gram-negative bacteria.

Local, not systemic

These defects are localized to the affected surface. A person with immotile cilia has normal antibodies and T cells and can fight a bloodstream infection normally; the problem is that the airway never clears the bacteria in the first place.

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