**2. Structure and function of CRP**

CRP was first described in 1930 by Tillet and Francis at Rockefeller University. [9] They observed a precipitation reaction between serum from patients suffering acute pneumococcal pneumonia and the extracted polysaccharide fraction C from the pneumococcal cell wall. This reaction could not be observed when using serum of neither healthy controls nor the same pneumonia patients after they had recovered. In view of the fact that the polysaccharide fraction was a protein the C-reactive component in the serum was named C-reactive protein. [9] By the 1950s CRP had been detected in more than 70 disorders including acute bacterial, viral, and other infections, as well as non-infectious diseases such as acute myocardial infarction, rheumatic disorders, and malignancies. [10] All of these disorders of disparate etiology had in common the theme of inflammation and/or tissue injury. [11]

CRP is composed by five identical subunits arranged in a cyclic pentameter shape. The whole protein has a diameter of 102 Å (1 Ångström = 10-10 m) and a molecular weight of 118 000 Daltons. [12] All subunits have the same orientation; therefore the whole protein has two faces, a 'recognition' face exhibiting five phosphocholin-binding sites and an 'effector' face containing complement and Fc-receptor-binding sites. [12] The principal ligand to CRP with the highest binding affinity is phosphocholin, which is found in lipopolysaccharid and cell walls of many bacteria and micro-organisms as well as in the outer leaflet of most biological membranes. [12]

After binding to a macromolecular ligand CRP is recognized by the component C1q of the complement system and activates it on the classical pathway. CRP-ligand complexes bind to the Fc-receptor on neutrophil granulocytes, macrophages, etc as well and thus promote phagocytosis of the pathogen. CRP further activates monocytes and macrophages and stimulates the production of pro-inflammatory cytokines such as Interleukin-1 and Tumor necrosis factor α. [12, 13]
