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When the Immune System Turns on the Body: Mechanisms of Overreaction

1The Logic of Immune Activation: Why Restraint Is the Default2Breaking Tolerance: How Self-Reactive Responses Escape Control3Effector Mechanisms of Self-Damage: How Immune Attack Injures Tissue4Allergy: Overreaction to a Harmless Target5Cytokine Storm: When Amplification Replaces Control6Connecting the Mechanisms: Shared Principles and Points of Intervention
Breaking Tolerance: How Self-Reactive Responses Escape Control

Molecular Mimicry: When a Pathogen Looks Like Self

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Watch the sequence. A pathogen peptide is presented, and a T cell recognizes it and expands. That clone was selected against the pathogen, not against self. But the pathogen peptide and a self-peptide share a similar shape. When the expanded clone later meets the self-peptide on host tissue, the same receptor binds. The cell is already an effector, so it attacks. The response was triggered by infection, but the damage lands on self.
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Molecular mimicry is a mechanism by which an immune response raised against a pathogen cross-reacts with a self-antigen. The trigger is structural similarity: a peptide from the pathogen binds the same MHC molecule and presents a shape similar enough to a self-peptide that the same T cell receptor recognizes both. The lymphocyte is not self-reactive by origin; it was selected against the pathogen, and its cross-reactivity with self is an accident of resemblance.

The sequence matters. First, the pathogen peptide is presented and activates a T cell clone. That clone expands and becomes an effector population. Later, when the same T cell encounters the self-peptide displayed on host tissue, the receptor binds, the cell is already activated, and it attacks the tissue. The same logic applies to antibodies: an antibody generated against a pathogen protein can bind a self-protein with similar surface structure. The response is misdirected, but the effector machinery itself is functioning normally.

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