Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • ASCI Milestone Awards
    • Video Abstracts
    • Conversations with Giants in Medicine
  • Reviews
    • View all reviews ...
    • Neurodegeneration (Mar 2026)
    • Clinical innovation and scientific progress in GLP-1 medicine (Nov 2025)
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • ASCI Milestone Awards
  • Video Abstracts
  • Conversations with Giants in Medicine
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Mechanisms of human autoimmunity
Michael D. Rosenblum, Kelly A. Remedios, Abul K. Abbas
Michael D. Rosenblum, Kelly A. Remedios, Abul K. Abbas
View: Text | PDF
Review Series

Mechanisms of human autoimmunity

  • Text
  • PDF
Abstract

Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Studies in humans and experimental animal models are revealing the genetic and environmental factors that contribute to autoimmunity. A major goal of research in this area is to exploit this knowledge to better understand the pathogenesis of autoimmune diseases and to develop strategies for reestablishing the normal balance between effector and regulatory immune responses.

Authors

Michael D. Rosenblum, Kelly A. Remedios, Abul K. Abbas

×

Figure 1

Three major phases of autoimmune disease.

Options: View larger image (or click on image) Download as PowerPoint
Three major phases of autoimmune disease.
Autoimmunity is initiated by a...
Autoimmunity is initiated by a combination of genetic predisposition and environmental triggers. Patients in the initiation phase of disease are typically unaware of clinical symptoms (subclinical). Patients present with clinical disease during the propagation phase, which is characterized by self-perpetuating inflammation and tissue damage due to cytokine production, epitope spreading, and a disrupted effector T cell/Treg (Teff/Treg) balance. Autoimmune reactions resolve with the activation of cell-intrinsic (inhibitory pathways) and cell-extrinsic (Tregs) mechanisms to limit effector responses and restore the Teff/Treg balance. Patients in this phase often suffer from relapsing and remitting disease as a result of a persistent struggle between pathogenic effector responses and regulation.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts