Key Concepts:

Figure 1. Structure of the human mannose-binding lectin, the best-characterised collectin molecule. Note the bouquet-like structure of the molecule, a structure that has been validated by electron microscopy studies.

Figure 2. Structure of the mammalian macrophage mannose receptor. The molecule contains eight CRDs arranged in tandem. Only CRD4 and CRD5 possess the appropriate structural features required for calcium-dependent carbohydrate binding.

Figure 3. ‘Nonself’ discrimination in the cytosol by NLR and RLR proteins. There are two main families of PRMs that detect PAMPS in the cytosol, the nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) and the RIG-I-like receptors (RLRs). NLRs form two distinct types of signalling complexes when triggered by PAMPs, the signalosome and the inflammasomes. (a) The NLR signalosome or NOD signalosome forms in response to muropeptides from bacterial cell walls. NOD proteins signal via RIP2 to activate the transcription factors NFB and MAPK, resulting in production of cytokines and chemokines. (b) There appear to be multiple NLR inflammasomes of distinct composition that involve distinct NLRs. The IPAF inflammasome forms in response to bacterial flagellin, the NALP1 inflammasome forms in response to lethal toxins from Anthrax, and the NLRP3 inflammasome forms in response to bacterial toxins such as -toxin and aerolysin. Upon recognition of these PAMPS the inflammasome signals through an array of molecules including the bipartite adaptor protein apoptosis-associated speck-like protein containing a C-terminal CARD (ASC) and eventually leads to activation of caspase-1 which in turn liberates active forms of IL-1 and IL-18. (c) Viral nucleotides trigger the RLRs, RIG-1 and MDA5, to signal activation of transcription factors responsible for production of IFN.

Figure 4. ‘Self–nonself’ discrimination by the alternative pathway of complement. Fluid-phase C3 is normally hydrolysed at a slow rate by the ‘C3 tickover’ process to generate C3b. The C3b possesses a highly reactive thioester group, which can covalently attach some C3b molecules to the surface of both pathogens and self (host) cells. Following recruitment of factor B and the action of factor D, a C3 convertase (C3bBb) is formed consisting of a fragment of factor B (Bb) and C3b. On host cell surfaces, this C3 convertase is rapidly inactivated by a number of host factors. In contrast, on the surface of microorganisms, the C3 convertase is stabilised by properdin (factor P), is not inactivated by host factors and generates massive number of C3b fragments. The C3b coats the surface of the microorganism and acts as an opsonin as well as initiating the formation of the membrane attack complex and eventual cell lysis.