Nutrition And Immune Health: Complement System Part 2 PDF

Complement The complement system is a group of heat- labile proteins normally found in blood and tissue fluids (except urine and CSF). They are mainly produced by the liver.  The basic complement proteins are termed C1 to C9, in addition to factor B, D and properdin and some complement reg...

Complement The complement system is a group of heat- labile proteins normally found in blood and tissue fluids (except urine and CSF). They are mainly produced by the liver.  The basic complement proteins are termed C1 to C9, in addition to factor B, D and properdin and some complement regulatory proteins. Most of them are normally found in an inactive form. Activation of complement occurs through interaction of complement factors in a sequential manner one step after the other. The product of one reaction forms the enzyme for the next, and so on. This mode of activation is called complement activation cascade.  When they become activated, some complement factors are split into a small fragment (a) which is considered a by- product, and a large fragment (b) which continues the activation process.  There are 3 pathways for complement activation: The classical pathway The lectin Alternative pathways  The early steps in all pathways involve a series of cleavage reactions which end with the production of an enzyme, C3 Convertase, that splits the third complement C3 into C3a and C3b. C3b becomes attached to microbial surface and initiates the late steps of the complement cascade  1- The classical pathway The reaction starts by binding of the first complement (C1) to the Fc portion of the antibody molecule attached to the antigen (e.g. a bacterial cell). This causes activation of C1 which acts as an enzyme that cleaves 2 other complement proteins, C4 and C2,  The resultant C4bC2b is the C3 convertase of the classical pathway, that splits C3 into C3a and C3b. C3b adheres to the microbial surface to start the late steps of complement activation. by cleavage of C5 into C5a and C5b. C5b binds to the terminal complement components C6, C7, C8 and C9 sequentially to form a complex, called membrane attack complex (MAC).  This complex (C5b,6,7,8,9) forms a hollow cylinder that becomes inserted into the target cell membrane, allowing free passage of water and solutes across the membrane which leads to cell death (osmotic lysis).  2- The lectin pathway: This pathway is activated when a plasma protein, mannose binding lectin (MBL), binds to mannose residues on microbial surface. MBL is structurally similar to C1 and activates C4, C2.  3- The alternative pathway The alternative pathway is triggered when C3b becomes deposited on the surface of microbe. Here, C3b forms stable bonds with microbial products, such as endotoxins and Zymosan of yeast cell wall, and is thus protected from degradation.  The microbe-bound C3b forms a complex with factor B: this complex is the C3 convertase of the alternative pathway. Factor D and properdin also help in the generation and stabilization of the C3 convertase. This convertase breaks down more C3 resulting in the attachment of more C3b to the microbial surface.  Functions of complement : 1- Direct cytolysis: Insertion of the MAC into the cell surface leads to killing of many cells, e.g: Bacterial and tumor cells, through osmotic lysis.  2- Opsonization: During complement activation, C3b becomes deposited on the surface of the pathogen (antigen). Phagocytic cells recognize C3b bound to the pathogen via their C3b receptors. This facilitates the attachment , subsequent uptake and killing of the C3b-coated pathogen by the phagocytic cell..  3- Immune complex clearance: C3b receptors are also found on RBCs. These recognize C3b bound to soluble immune complexes. Erythrocytes bind the immune complexes via these receptors and transport them to organs rich in fixed phagocytes ( e.g. liver and spleen).  4- Inflammatory response: During complement activation, the byproduct C3a and C5a are produced. These molecules, known as anaphylatoxins Complement activation Thank You For Your Attention! NUTRITION AND IMMUNE HEALTH: Considerations for Athletes Lecture content provided by GSSI, a division of PepsiCo, Inc. Any opinions or scientific interpretations expressed in this presentation are those of the author and do not necessarily reflect the position or policy of PepsiCo, Inc.  Digestion and Absorption of Carbohydrates, Proteins and Fats Carbohydrates, fats, and proteins are the major nutrients the body needs for growth, repair, movement, and maintaining tissue and organ function. These macromolecules are broken down and absorbed into the body at different rates and into specific forms as they travel through the organs in the digestive system. Severe Calorie Restriction Protein Calorie Malnutrition Increases risk of infection Severe Energy Restriction Increased stress hormones (cortisol) Impacts immunity Most athletes don’t have a severe restriction but may have low energy Woodward B. Nutr. Rev. 1998;56:S84-S92 CARBOHYDRATE INTAKE IS RELATED TO THE IMMUNE FUNCTION OF AN ATHLETE Suboptimal CHO may alter the Immune Response to Exercise & Inflammation Exercising on a low CHO diet (