Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group Gut bacteria and AS

Hi Kevin,

Below I've pasted in a some more detailed comments drawing distinctions between the innate and adaptive immune systems.

The innate immune system represents a critical host response operational as the first line of defence against pathogens and a system that precedes the adaptive immune response. Whilst the adaptive immune system has elegant specificity and recall potency the system is sluggish in the face of an urgent invasion by a pathogen. The innate immune system on the other hand offers a predefined or prefabricated immediate response to the challenge, and it is critically dependent upon non-variant, genetically encoded receptors for highly conserved microbial structures known as pathogen associated molecular patterns (PAMP). These innate immune system receptors are called pattern-recognition receptors (PRR). The innate immune system also affects the outcome of infection by promoting in a complementary sense the generation of an adaptive immune response by the up-regulation of co-stimulatory molecules.

Among the PRR, toll-like receptors (TLR’s) play a central role. Once microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLR’s and an immune response initiated. TLR’s are membrane surface receptors that recognize molecules that are broadly shared by pathogens but distinguishable from host molecules. They are present in vertebrates and invertebrates, as well as plants, and thus appear to be one of the most ancient conserved components of the immune system.

Because the specificity of Toll-like receptors (and other innate immune receptors) cannot easily be changed in the course of evolution, these receptors recognize molecules that are constantly associated with threats and are highly specific to these threats, that is, cannot be mistaken for self molecules. Pathogen-associated molecules that meet this requirement are usually critical to the pathogen’s function and cannot be eliminated or changed through mutation; they are said to be evolutionarily conserved.

In 2010 it was shown by peripheral whole blood cell gene expression profiling of AS patients that there was an up regulation of TLR4 and TLR5, supporting the importance of these TLR subtypes in AS pathogenesis, in particular the TLR sub-types responsible for the innate immune response against Gram-negative bacteria.

Lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria is the main ligand of TLR4 and the main ligand for TLR5 is flagellin, a primary component of bacterial flagella that extends from the outer membrane of Gram-negative bacteria.