What is the group of proteins that, when activated, can cause cell lysis and inflammation: T cells, B cells, new complexes, complement system, or autoantibodies?

The Complement System is the Group of Proteins That Causes Cell Lysis and Inflammation

The complement system is the group of proteins that, when activated, can cause cell lysis and inflammation, not T cells, B cells, new complexes, or autoantibodies. 1

Mechanism of Complement-Mediated Cell Lysis and Inflammation

The complement system consists of over 50 proteins that function as a tightly regulated proteolytic cascade in the innate immune system. When activated, this system leads to:

• Cell lysis: Through the formation of the membrane attack complex (C5b-9), which creates pores in cell membranes 1, 2
• Inflammation: Via the production of anaphylatoxins (C3a and C5a) that trigger inflammatory responses 1
• Opsonization: Coating of pathogens with complement proteins (primarily C3b) to facilitate phagocytosis 1, 3

Activation Pathways of the Complement System

The complement system can be activated through three distinct pathways:

1. Classical pathway: Activated by antigen-antibody complexes (immune complexes)
2. Alternative pathway: Activated spontaneously on pathogen surfaces
3. Lectin pathway: Activated by mannose-binding lectin recognition of carbohydrates on microbial surfaces 4

All three pathways converge at the formation of C3 convertase, which cleaves C3 into C3a and C3b, leading to downstream activation of C5 and formation of the membrane attack complex.

Regulation of Complement Activity

Tight regulation of complement activation is crucial to prevent damage to host tissues. Several membrane-bound regulatory proteins protect host cells:

• Decay-accelerating factor (CD55): Accelerates the decay of C3/C5 convertases
• Membrane cofactor protein (CD46): Serves as a cofactor for factor I-mediated cleavage of C3b
• CD59: Inhibits the formation of the membrane attack complex 5

Dysregulation of these protective mechanisms can lead to inappropriate complement activation and tissue damage.

Complement in Disease Pathology

Complement dysregulation contributes to numerous pathological conditions:

• Autoimmune diseases: In systemic lupus erythematosus and C3 glomerulopathies, inappropriate complement activation causes tissue damage 4, 1
• Sepsis and inflammation: Excessive complement activation contributes to the inflammatory cascade in sepsis 4, 2
• Membrane-mediated cytotoxicity: Sublytic complement activation can trigger regulated cell death pathways involving receptor-interacting protein kinases (RIPK1 and RIPK3) and mixed lineage kinase domain-like protein (MLKL) 6

Diagnostic Implications

Complement-mediated disorders often show characteristic patterns:

• Immune complex-mediated MPGN: Shows immunoglobulin and C3 deposits, indicating classical pathway activation 4
• C3 glomerulopathy: Characterized by C3 deposits without immunoglobulins, suggesting alternative pathway dysregulation 4

Clinical Relevance

Understanding the complement system is essential for diagnosing and treating numerous conditions:

• Atypical hemolytic uremic syndrome: Caused by dysregulation of the alternative complement pathway 2
• Antibody-mediated rejection in transplantation: C4d and C3d deposition in capillaries indicates complement activation 4
• Therapeutic targeting: Complement inhibitors like eculizumab and ravulizumab are effective in treating complement-mediated disorders 2

In summary, while T cells, B cells, and autoantibodies play important roles in immunity, it is specifically the complement system that functions as a group of proteins capable of directly causing cell lysis and inflammation through its coordinated proteolytic cascade.