Innate Immunıty

2. The Lectin Pathway

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 pages.

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 pages 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 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:

We will now take a closer look at the lectin pathway.

The Lectin Pathway

The lectin pathway is mediated by mannan-binding lectin (also known as mannan-binding protein or MBP). MBP is a protein that binds to the mannose groups found in many microbial carbohydrates but not usually found in the carbohydrates of humans. The MBP is equivalent to C1q in the classical complement pathway.

Activation of The lectin pathway begins when mannan-binding protein (MBP) binds to the mannose groups of microbial carbohydrates. Two more lectin pathway proteins called MASP1 and MASP2 (equivalent to C1r and C1s of the classical pathway) now bind to the MBP This forms an enzyme similar to C1 of the classical complement pathway that is able to cleave C4 and C2 to form C4bC2a, the C3 convertase capable of enzymatically splitting hundreds of molecules of C3 into C3a and C3b.

The beneficial results are the same as in the classical complement pathway above:

  • trigger inflammation (C5a>C3a>c4a);

  • chemotactically attract phagocytes to the infection site (C5a);

  • promote the attachment of antigens to phagocytes via enhanced attachment or opsonization (C3b>C4b);

  • serves as a second signal for the activation of naive B-lymphocytes (C3d);

  • cause lysis of gram-negative bacteria and human cells displaying foreign epitopes (MAC); and

  • remove harmful immune complexes from the body (C3b>C4b).

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