USMLE (United States Medical Licensing Examination) Step 1 Practice Exam

What is the primary pathophysiological mechanism of acute rheumatic fever?

1. Molecular mimicry

2. Direct bacterial invasion

3. Primary viral infection

4. Autoimmune destruction

The correct answer is: Molecular mimicry

The primary pathophysiological mechanism of acute rheumatic fever is molecular mimicry. This phenomenon occurs when the immune response generated against streptococcal antigens (specifically those from group A Streptococcus, such as the M protein) inadvertently targets similar antigens present in human tissues. In this case, the body’s immune system recognizes these bacterial antigens as foreign and mounts an attack against them. However, because these antigens share structural similarities with proteins found in human tissues—such as cardiac, neural, and connective tissue—the immune response can cross-react with and damage these tissues. This molecular mimicry is central to the development of rheumatic fever, leading to complications such as carditis, arthritis, and chorea. While direct bacterial invasion does not play a significant role in acute rheumatic fever, as the disease is primarily a post-infectious immunological condition rather than an infectious one, and viral infections do not cause rheumatic fever, focusing on molecular mimicry provides essential insight into the underlying mechanisms of this illness and its autoimmune-like manifestations.