Complement fixation

Complement Fixation

Complement fixation is a crucial immunological reaction that involves the binding of complement proteins to antibodies that are attached to antigens. This process is a part of the immune system's response to pathogens and is used in various diagnostic tests to detect the presence of specific antibodies or antigens in a sample.

Overview

Complement fixation is a part of the complement system, which is a component of the innate immune system. The complement system consists of a series of small proteins found in the blood, generally synthesized by the liver, and is activated through a cascade of enzymatic reactions. The primary function of the complement system is to enhance ("complement") the ability of antibodies and phagocytic cells to clear pathogens from an organism.

Mechanism

The complement fixation process involves several key steps:

1. Antigen-Antibody Complex Formation: When an antibody binds to its specific antigen, it forms an antigen-antibody complex. This complex can activate the complement system.

2. Activation of the Complement Cascade: The binding of the first component of the complement system, C1, to the Fc region of the antibody initiates the classical pathway of complement activation. This leads to a cascade of reactions involving other complement proteins such as C2, C3, C4, and so on.

3. Formation of the Membrane Attack Complex (MAC): The terminal components of the complement cascade (C5b, C6, C7, C8, and C9) form the membrane attack complex, which can insert into the cell membrane of the pathogen, leading to cell lysis and death.

4. Opsonization and Phagocytosis: Complement proteins can also opsonize pathogens, marking them for destruction by phagocytes such as macrophages and neutrophils.

Diagnostic Use

Complement fixation tests (CFTs) are used in the laboratory to detect the presence of specific antibodies or antigens in a patient's serum. These tests are based on the principle that if the complement is fixed by an antigen-antibody complex, it will not be available to lyse indicator cells (such as sheep red blood cells). The absence of hemolysis indicates a positive test result, meaning the specific antibody or antigen is present.

Applications

Complement fixation tests have been historically used to diagnose infections such as syphilis, tuberculosis, and certain viral infections. Although newer methods such as ELISA and PCR have largely replaced CFTs due to their higher sensitivity and specificity, CFTs are still used in some settings.

Limitations

While complement fixation tests are useful, they have limitations, including:

- Sensitivity: CFTs are less sensitive compared to modern techniques like ELISA. - Complexity: The tests require careful handling and precise conditions to avoid false results. - Time-Consuming: CFTs are more time-consuming than newer diagnostic methods.

Also see

- Complement system - Antigen-antibody complex - Immunology - Diagnostic tests