The complement system immunology bridges innate and adaptive immunity. This network of proteins orchestrates critical complement immune responses, ensuring protection against pathogens and maintaining host homeostasis.
The complement network is a complex collection of more than 30 soluble and membrane-bound proteins. They work in concert to seek out, opsonise and destroy pathogens. As an underlying mechanism, immune system complement can be used to support the performance of antibodies and phagocytic cells.
The complement immune system in immunology is a fast-response system that kills pathogens directly by forming a hole in their membranes. Complement proteins are precisely programmed to prevent injury to host tissue, highlighting the precision of this immune protection.
The complement system was identified only in the late 19th century by Jules Bordet, and its function involved antibody-based bacterial lysis. In the subsequent decades, decades of research revealed the importance of complement immunity and revolutionised how we thought about host-pathogen interactions.
The immune complement system is the anti-microbe first line of defence. Profound functions: opsonisation, chemotaxis, direct lysis. The complement system in immunity connects the two arms of the immune response:
A new generation of studies has identified the complement system as being responsible for tissue homeostasis, apoptotic cell clearance and inflammation control.
Fig. 1 Complement activation pathways and assembly of the terminal pathway.1, 2
There are three primary pathways through which the complement system is activated:
Table. 1 Three primary ways in which the complement system is activated.
Pathway | Trigger | Key Component | Mechanism |
---|---|---|---|
Classical Pathway | Activation occurs when antibodies (IgG or IgM) bind to antigens, forming immune complexes. | C1 complex (C1q, C1r, C1s) |
|
Lectin Pathway | Activation is initiated by pattern recognition molecules such as mannose-binding lectin (MBL) or ficolins binding to pathogen-associated molecular patterns (PAMPs). | MBL-associated serine proteases (MASPs) |
|
Alternative Pathway | Spontaneous hydrolysis of C3 or direct interaction with pathogen surfaces. |
Factor B Factor D Properdin |
|
All three pathways converge at the cleavage of C3, leading to:
The activated complement system does this by means of a series of proteolytic steps that initiate effector molecules. There are three main kinds of functions.
The complement system enhances pathogen clearance through:
The immune complexes are cleared by the complement system. C3b attaches to these complexes, which they then dissolve and clear from the spleen and liver.
Table. 2 Key roles in immune complex handling.
Step | Molecule Involved | Outcome |
---|---|---|
Immune complex binding | C3b | Solubilization of immune complexes |
Transport to phagocytes | CR1 | Clearance via liver and spleen |
Complement fragments (e.g., C3a, C5a) act as anaphylatoxins, inducing:
The complement system's regulation involves several key players and mechanisms, which ensure precise control of activation and termination.
Table. 3 Soluble regulators of complement system.
Regulator | Function | Pathway Targeted |
---|---|---|
C1 Inhibitor | Inhibits C1r and C1s, preventing activation of the classical pathway | Classical Pathway |
Factor H | Promotes C3b inactivation by factor I; prevents alternative pathway amplification | Alternative Pathway |
Factor I | Cleaves C3b and C4b to inactive fragments in the presence of cofactors | All Pathways |
C4-binding Protein (C4BP) | Accelerates decay of C3 convertase in the classical and lectin pathways | Classical and Lectin Pathways |
Vitronectin | Prevents MAC formation by inhibiting C5b-7 complex integration | Terminal Pathway |
Table. 4 Membrane-bound regulators of complement system.
Regulator | Function |
---|---|
CD55 (Decay-Accelerating Factor, DAF) | Disrupts C3/C5 convertase complexes, halting complement system activation |
CD46 (Membrane Cofactor Protein, MCP) | Serves as a cofactor for factor I-mediated cleavage of C3b and C4b |
CD59 (Protectin) | Inhibits assembly of the MAC |
Complement receptors on immune cells also play a regulatory role. For example:
The complement deficiency can lead to pathological conditions.
Complement activation, regardless of the pathway, converges on the generation of three broad effector pathways that serve to enable the complement to fulfill its physiological imperatives in host defense.
A primary opsonin called C3b adheres to microbe surfaces and labels organisms for phagocytosis by immune cells, including macrophages and neutrophils. This is an activity that bridges innate and adaptive immunity through improved antigen presentation.
Anaphylatoxins (C3a, C5a) are chemoattractants that attract immune cells to the point of infection. Degranulation of mast cells and basophils by such fragments also encourages inflammation.
The terminal pathway culminates in the assembly of MAC (C5b-C9), which forms transmembrane pores, leading to osmotic lysis of targeted cells. This is particularly effective against Gram-negative bacteria.
Table. 5 Effector functions of complement fragments.
Fragment | Effector Function |
---|---|
C3b | Opsonization, immune complex clearance |
C3a | Anaphylatoxin, induces inflammation |
C5a | Strong anaphylatoxin, chemotaxis |
MAC (C5b-C9) | Membrane attack and cytolysis |
Even though we know that complement protects, the breakdown of the complement system leads to everything from autoimmune disease and infectious disease to cancer.
Table. 6 Complement roles in disease categories.
Disease Category | Complement Mechanism | Example |
---|---|---|
Autoimmune Diseases | Aberrant activation and immune complex buildup | SLE, RA |
Infectious Diseases | Pathogen evasion of complement attack | Neisseria meningitidis |
Cancer | Immunosuppression via complement regulators | Breast, lung cancer |
The close relationship between the complement system and disease highlights its dual nature as a guardian and potential adversary of human health. Advances in therapeutic targeting (especially monoclonal antibodies and small molecule inhibitors) have opened up new opportunities for precision medicine. In addition, the development of robust assays for complement activity can help to better study complement-related diseases.
Complement components and split products are invaluable for disease researches. We offer complement testing services, including:
If additional help is needed, please directly contact us and consult our technical supports for more detail.
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