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experience: over time, the body simply stops responding to
the drug. The therapeutic effect fades. The disease
resurfaces. What now?
How It Works: The Biology of Betrayal
Most biologics are large, complex proteins—monoclonal
antibodies, enzymes, or receptor antagonists—
manufactured in living cells and delivered by injection or
infusion. While they’re engineered to be as human-like as
possible, they are still foreign to the immune system,
especially when delivered without the usual immunological
context (e.g., via the gut, skin, or mucosa).
Most biologics tread a fine line in our immune system.
They avoid detection by our innate immune system, a
collection of white blood cells which seek out large
irregularities known as PAMPs. This front line of defense
is where our allergic and initial inflammatory responses
come from.
The problem comes with adaptive immunity. Where innate
responses are fast, adaptive responses take a significant
amount of time. This response includes the B and T white
blood cells that receive the majority of the attention when
our immune system is described. Biologic drugs that are
identified as “foreign” are seen as the body as “antigens.”
As the body begins to identify these antigens, whether they
belong to a virus, a bacterium, or in our a case a biologic
drug, they create plasma cells specific to that molecule. At
this point, weeks or potentially months after treatment has
begun these plasma cells begin producing antibodies.
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