Research and Reports in Immunology

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Review Article - Research and Reports in Immunology (2023) Volume 6, Issue 5

Impact of complement on cell-mediated graft rejection

Karnail Singh*

Department of Surgery, Emory University School of Medicine, Atlanta, Georgia

Corresponding Author:
Karnail Singh
Department of Surgery
Emory University School of Medicine Atlanta
Georgia
E-mail: Karnailsingh@gmail.com

Received: 25-Sep-2023, Manuscript No. AARRI-23-114297; Editor assigned: 27-Sep-2023, Pre QC No. AARRI-23-114297(PQ); Reviewed: 12-Oct-2023, QC No. AARRI-23-114297; Revised: 17-Oct-2023, Manuscript No. AARRI-23-114297(R), Published: 24-Oct-2023,DOI:10.35841/aarri-6.5.171s

Citation: Singh K. Impact of complement on cell-mediated graft rejection. Res Rep Immunol.2023; 6(5):171

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Introduction

The complement system comprises a group of plasma and cell surface proteins that play a critical role in immune defense against pathogens and in the clearance of immune complexes. It is composed of more than 30 proteins that interact through a cascade of enzymatic reactions, ultimately leading to the formation of the membrane attack complex (MAC) and opsonization of pathogens for phagocytosis. Additionally, complement components can also contribute to inflammatory responses and immune regulation. The involvement of the complement system in graft rejection is multifaceted. While complement activation can be protective against infections, it can also inadvertently harm transplanted organs. Here's how the complement system can impact cell-mediated graft rejection [1].

Complement Activation and Inflammation: During the initial phases of transplantation, ischemia-reperfusion injury (IRI) can activate the complement system. This leads to the generation of pro-inflammatory molecules, causing tissue damage and creating an inflammatory microenvironment that promotes T cell activation and infiltration into the graft. This early inflammation sets the stage for subsequent cell-mediated graft rejection.

Complement and Alloreactive T Cells: Complement activation products, such as C3a and C5a, can attract and activate immune cells, including T cells. Alloreactive T cells recognize and attack graft antigens, initiating the cell-mediated immune response. Complement components can act as costimulatory signals for T cell activation and may contribute to the development of effector T cells that target the graft [2].

Complement-Mediated Antibody-Dependent Cytotoxicity (CDC): In addition to cell-mediated immunity, the complement system can facilitate graft rejection via antibody-dependent mechanisms. Alloantibodies binding to graft antigens can trigger complement activation, leading to CDC. This process can result in direct cell lysis and tissue damage, further exacerbating graft rejection.

Complement and Graft Vasculature: The complement system can also affect the graft's vascular system. Complement activation can lead to endothelial cell injury and dysfunction, which, in turn, promotes T cell infiltration into the graft. This endothelial damage can disrupt blood flow and exacerbate graft ischemia, contributing to rejection [3].

Understanding the impact of complement on cell-mediated graft rejection has significant therapeutic implications. Researchers and clinicians are exploring various strategies to modulate the complement system to improve transplant outcomes:

Complement Inhibition: Targeting specific complement components or pathways has shown promise in preventing graft rejection. Eculizumab, a monoclonal antibody that inhibits C5 activation, has been used to treat complementmediated diseases and has shown potential in reducing graft injury. However, long-term safety and efficacy data are still needed [4].

Complement Receptor Blockade: Blocking complement receptors on immune cells may hinder their recruitment and activation within the graft. Small molecule inhibitors or antibodies targeting complement receptors, such as C3aR and C5aR, are under investigation. Complement-Targeted Therapies: Developing therapies that specifically target complement activation at the graft site could minimize offtarget effects. Nanoparticle-based delivery systems and local complement inhibition strategies are being explored. Combined Approaches: Combining complement inhibition with conventional immunosuppressive regimens may provide synergistic benefits in preventing graft rejection while minimizing the risk of infection [5].

Conclusion

The impact of the complement system on cell-mediated graft rejection is a complex and evolving field of research. While complement activation is essential for immune defense, it can also contribute to the destruction of transplanted organs. Understanding the precise mechanisms by which complement influences graft rejection is crucial for developing targeted therapies that can improve transplant outcomes. Future research will likely uncover new insights into the role of complement in graft rejection and provide innovative strategies to modulate its activity. Ultimately, the goal is to strike a delicate balance between suppressing the immune response to prevent graft rejection while preserving the body's ability to defend against infections and maintain overall immune homeostasis. As our understanding of complementmediated graft rejection deepens, the prospects for successful organ transplantation will continue to improve, offering hope to countless individuals in need of life-saving transplants.

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