Innate Immunıty

4. Ways in which Microorganisms can Resist Body Defenses by Circumventing the Complement Pathways

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 alternative complement pathway.

Ways in Which Microorganisms Can Resist Body Defenses by Circumventing the Complement Pathways

Bacterial capsules can interfere with the complement pathways in a number of ways.

  • Some capsules prevent the formation of C3 convertase, an early enzyme in the complement pathways. Without this enzyme, the opsonins C3b and C4b, as well as the other beneficial proteins are not produced.

  • Other capsules, rich in sialic acid, a common component of host cell glycoprotein, have an affinity for serum protein H, a complement regulatory protein that leads to the degradation of the opsonin C3b by factor I and the formation of C3 convertase. (Serum protein H is what normally leads to the degradation of any C3b that binds to host glycoproteins so that we don’t stick our own phagocytes to our own cells with C3b.)

  • Some capsules simply cover the C3b that does bind to the bacterial surface and prevent the C3b receptor on phagocytes from making contact with the C3bThis is seen with the capsule of Streptococcus pneumoniae  .

  • Capsules can resist unenhanced attachment by preventing the endocytic pattern recognition receptors on phagocytes from recognizing the bacterial cell wall components and mannose-containing carbohydrates

An outer membrane molecule of Neisseria gonorrhoeae   called Protein II and the M-protein of Streptococcus pyogenes   allow these bacteria to be more resistant to phagocytic engulfment. The M-protein of S. pyogenes  , for example, binds factor H of the complement pathway and this leads to the degradation of the opsonin C3b by factor I and the formation of C3 convertase. S. pyogenes also produces a protease that cleaves the complement protein C5a. A Yersinia protein degrades C3b and C5a.

Some gram-negative bacteria attach sialic acid to the LPS O antigen and this prevents the formation of the complement enzyme C3 convertase that is needed for the eventual formation of all the beneficial complement proteins such as C3b, C5a, nd MAC. Blood-invasive strains of Neisseria gonorrhoeae  , as well as Bordetella pertussis   and Hemophilus influenzae   are examples of Gram-negative bacteria that are able to alter their LPS in this maner. Other gram-negative bacteria, such as Salmonella  , lengthen the LPS O antigen side chain and this prevents the formation of MAC. Neisseria meningitidis   and Group B Streptococcus  , on the other hand, produces capsular polysaccharides composed of sialic acid and as mentioned above, sialic acid prevents MAC lysis.

In addition, some viruses adsorb to complement receptors on body cells to begin their life cycle. The Epstein-Barr virus (EBV), for example, adsorbs to CR2 complement receptors found on B-lymphocytes and epithelial cells.

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