USMLE Guide: Immunology of Complement System

Introduction

The complement system is an integral part of the immune system and plays a crucial role in host defense against infections, immune complex-mediated diseases, and tissue damage. Understanding the immunology of the complement system is essential for medical professionals, especially those preparing for the USMLE exam. This guide aims to provide a comprehensive overview of the immunology of the complement system, covering its components, activation pathways, functions, and clinical relevance.

Components of the Complement System

The complement system consists of numerous proteins, categorized into three main components:

1. Complement Proteins

   • C1-C9, factor B, factor D, and properdin
   • Synthesized mainly in the liver and released into the bloodstream

2. Complement Regulatory Proteins

   • Factors H, I, and DAF (decay-accelerating factor)
   • Prevent inappropriate complement activation on host cells

3. Complement Receptors

   • Found on various immune cells, including phagocytes, B cells, and T cells
   • Facilitate complement-mediated immune responses

Activation Pathways

The complement system can be activated through three distinct pathways:

1. Classical Pathway

   • Initiated by antigen-antibody complexes or by binding of C-reactive protein (CRP) to microbial surfaces
   • Involves sequential activation of C1, C4, C2, C3, C5, C6, C7, C8, and C9

2. Lectin Pathway

   • Activated by mannose-binding lectin (MBL) or ficolins binding to microbial surfaces
   • Leads to the activation of C4, C2, C3, C5, C6, C7, C8, and C9

3. Alternative Pathway

   • Spontaneously activated at a low level on host cells
   • Amplified by microbial surfaces lacking complement regulatory proteins
   • Involves the activation of C3, C5, C6, C7, C8, and C9

Functions of the Complement System

The complement system serves several important functions within the immune system:

1. Opsonization

   • Coating of pathogens or immune complexes with complement proteins to facilitate phagocytosis by phagocytes

2. Inflammation

   • Activation of complement proteins leads to the release of anaphylatoxins (C3a, C4a, and C5a), promoting inflammation

3. Membrane Attack Complex (MAC) Formation

   • Assembly of C5b, C6, C7, C8, and C9 proteins to form a pore-like structure on bacterial membranes, causing lysis

4. Clearance of Immune Complexes

   • Complement receptors on erythrocytes and phagocytes aid in the clearance of immune complexes from circulation

Clinical Relevance

Understanding the immunology of the complement system is crucial for diagnosing and managing various diseases. Some clinically relevant aspects include:

1. Complement Deficiencies

   • Genetic deficiencies in complement proteins can lead to increased susceptibility to infections and autoimmune diseases.

2. Autoimmune Diseases

   • Dysregulation of the complement system can contribute to the pathogenesis of autoimmune diseases, such as lupus and rheumatoid arthritis.

3. Hereditary Angioedema

   • Deficiency or dysfunction of C1 inhibitor leads to uncontrolled activation of the complement system, resulting in recurrent angioedema attacks.

4. Complement-Mediated Glomerulonephritis

   • Inappropriate complement activation on glomerular basement membranes can cause kidney damage and glomerulonephritis.

Conclusion

Understanding the immunology of the complement system is essential for medical professionals preparing for the USMLE exam. This guide has provided a comprehensive overview of the complement system's components, activation pathways, functions, and clinical relevance. Mastery of this topic will aid in diagnosing and managing various diseases and contribute to a strong foundation in immunology.