THE COMPLEMENT SYSTEM: AN OVERVIEW
Innate immunity refers to antigen-nonspecific defense mechanisms that a host uses immediately or within several hours after exposure to an antigen  . This is the immunity one is born with and is the initial response by the body to eliminate microbes and prevent infection.

Unlike adaptive immunity, innate immunity does not recognize every possible antigen. Instead, it is designed to recognize a few highly conserved structures present in many different microorganisms. The structures recognized are called pathogen-associated molecular patterns and include LPS from the gram-negative cell wall, peptidoglycan, lipotechoic acids from the gram-positive cell wall, the sugar mannose (common in microbial glycolipids and glycoproteins but rare in those of humans), bacterial DNA, N-formylmethionine found in bacterial proteins, double-stranded RNA from viruses, and glucans from fungal cell walls. Most body defense cells have pattern-recognition receptors for these common pathogen-associated molecular patterns  and so there is an immediate response against the invading microorganism. Pathogen-associated molecular patterns can also be recognized by a series of soluble pattern-recognition receptors in the blood that function as opsonins and initiate the complement pathways. In all, the innate immune system is thought to recognize approximately 103 molecular patterns. All of this will be discussed in greater detail in upcoming sections.

The innate immune responses involve:

  • phagocytic cells (neutrophils, monocytes, and macrophages);
     

  • cells that release inflammatory mediators (basophils, mast cells, and eosinophils);
     

  • natural killer cells (NK cells); and
     

  • molecules such as complement proteins, acute phase proteins, and cytokines.

Examples of innate immunity include anatomical barriers, mechanical removal, bacterial antagonism, pattern-recognition receptors, antigen-nonspecific defense chemicals, the complement pathways, phagocytosis, inflammation, and fever. In the next several sections we will look at each of these in greater detail.

We will now take a closer look at the 3 pathways of the complement system.

The Complement System  

The complement system refers to a series of proteins circulating in the blood and bathing the fluids surrounding tissues. The proteins circulate in an inactive form, but in response to the recognition of molecular components of microorganism, they become sequentially actived, working in a cascade where in the binding of one protein promotes the binding of the next protein in the cascade.

There are 3 complement pathways that make up the complement system: the classical complement pathway, the lectin pathway, and the alternative complement pathway. The pathways differ in the manner in which they are activated and ultimately produce a key enzyme called C3 convertase:

1. The classical complement pathway is activated by antigen-antibody complexes.
 

2. The lectin pathway is activated by the interaction of microbial carbohydrates with mannose-binding proteins in the plasma and tissue fluids.
 

3. The alternative complement pathway is activated by C3b binding to microbial surfaces and to antibody molecules .

The end results and defense benefits of each pathway, however, are the same. All complement pathways carry out 6 beneficial innate defense functions. They:

    1. trigger inflammation  ;

    2. chemotactically attract phagocytes to the infection site;

    3. promote the attachment of antigens   to phagocytes (enhanced attachment or opsonization  );

    4. cause lysis of gram-negative bacteria and human cells displaying foreign epitopes  ;

    5. plays a role in the activation of naive B-lymphocytes  ; and

    6. remove harmful immune complexes from the body.

We will now look at each of these complement pathways and see how they function to protect the body.

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