Question

A patient has a genetic disorder that makes it impossible for her to synthesize complement protein 8 (C8). Is her complement system nonfunctional? What major effects of complement could still be produced?

Short answer

The patient's complement system is not completely nonfunctional without Complement Protein 8 (C8). While it's true that the absence of C8 prevents the formation of the membrane attack complex (MAC), a mechanism to directly kill bacteria, other functions of the complement system like promoting inflammation and opsonization can still take place.

Step-by-step solution

Understanding the Complement System

Firstly, it's important to comprehend what the complement system is. The complement system comprises many distinct proteins, including C8, that enhance the ability of antibodies and phagocytes to clear microbes from an organism.

Role of Complement Protein 8

Complement Protein 8 (C8) is part of the membrane attack complex (MAC) of the complement system. MAC is responsible for punching holes in the cell membranes of pathogens, leading to their destruction. If C8 is absent, this part of the complement cascade cannot occur, however, it does not make the whole system nonfunctional.

Effects of Lack of Complement Protein 8

While the absence of C8 might make the patient more susceptible to specific infections, other functions of the complement system, such as promoting inflammation and opsonization, would still occur, as they are not reliant on the formation of the MAC.

Key concepts

Complement Protein C8

Complement Protein C8 is a crucial component of the immune system, playing a vital role in protecting the body against pathogens. It is especially important in the formation of the membrane attack complex (MAC), a structure that helps destroy harmful microbes. C8 collaborates with other complement proteins to form this complex and creates pores in the cell membranes of invading organisms, leading to their death.
C8’s role in MAC makes it indispensable for direct destruction of pathogens. However, even without C8, other aspects of the complement system still function. This protein is part of a wider network designed to enhance the immune system's capacity to eliminate microbes. While C8 specializes in direct lysis of pathogens, its absence does not completely deactivate the complement system.
The genetic inability to produce C8 means that the membrane attack complex cannot form fully, potentially making a person more prone to certain infections. Nevertheless, other immune pathways, like inflammation and opsonization, remain active, continuing to provide immune defense in other ways.

Membrane Attack Complex

The membrane attack complex (MAC) is a group of proteins, initiated by the complement system, that collectively form a structure capable of breaching the membranes of pathogens. This breach occurs through the formation of pores, leading to the contents leaking out of the pathogen cells, ultimately killing them.
MAC is composed of complement proteins C5b, C6, C7, C8, and C9 working together in a complex sequence. The process begins with C5b binding to the pathogen's surface, subsequently allowing the attachment of C6 and C7. The complex becomes anchored to the membrane as C8 and multiple C9 molecules join, culminating in the formation of a ring-like structure that punctures the cell membrane.
Creating these pores within the pathogen's membrane is a direct and effective method of cell lysis, especially crucial when dealing with bacteria and other microbes that can evade other immune responses. The integrity of the pathogen's cell is compromised, causing osmolysis. Without an intact MAC, due to the absence of C8, this specific immune mechanism is impaired, although other immune functions still persist in defending the body.

Immune Response

The immune response is an intricate system of defenses the body employs to identify and neutralize foreign invaders such as bacteria, viruses, and other pathogens. It consists of both innate and adaptive immunity components, working harmoniously to protect the body.
The complement system is a part of this immune response, acting immediately to target pathogens as part of the innate immune response. It supports other immune activities by enhancing the ability of antibodies and phagocytes, such as macrophages and neutrophils, to attack and destroy invading organisms.
Despite the lack of C8 and the MAC's inability to form, the immune system remains robust, thanks to other pathways. For example:

• Activation of phagocytosis – where immune cells engulf and digest pathogens.
• Mediation of inflammation – increasing blood flow and delivering more immune cells to the infection site.
• Triggering adaptive immune responses – developing more targeted responses to specific pathogens over time.

These remaining functions ensure continued immune protection and maintain the body's capability to respond to various attacks.

Opsonization

Opsonization is a critical immune process whereby pathogens are marked for destruction by immune cells. It involves the coating of the pathogen's surface with molecules that make it easier for immune cells to identify and engulf them.
In the complement system, specific proteins bind to the surface of pathogens, acting as tags. These tags are recognized by phagocytic cells, such as macrophages and neutrophils, which are then attracted to and engulf the opsonized pathogens. This process enhances the speed and efficiency of pathogen clearance from the body.
Even if complement protein C8 is not synthesized, opsonization remains functional. This is because opsonization does not depend on the membrane attack complex. The complement system can still label invaders effectively, ensuring that other immune mechanisms can operate without impediment. The process amplifies immune response efficiency, providing a vital backup when direct cell lysis by MAC is unavailable.