Barrier, Acute Phase Proteins

(1). Barrier (barrier) Acute phase proteins (Acute-Phase Reactants) The entry of germs requires an immediate response involving various soluble (dissolved, humoral) components in the form of various types of proteins.Acute-phase reactants(acute phase reagent) is a normal component of serum whose levels can increase quickly to at least 25% if there is infection or injury/trauma to the tissue.Acute phase reagents include Creactive protein, serum amyloid A, complement components, mannose-binding protein, alpha1antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin. Acute phase reagents are mainly produced by liver hepatocytes (parensim cells) within 12-24 hours in response to increased cytokine levels. The cytokines IL-1, IL-6 and TNF-a are mainly produced by monocytes and tissue macrophages in tissue that is damaged and an inflammatory reaction occurs. (a). C-Reactive Protein C-reactive protein (CRP) is a low molecular weight protein present in serum,originally thought to be an antibody against pneumococcal C polysaccharide. CRP levels increase rapidly within 4 to 6 hours after infection, surgery, or other trauma. CRP levels can increase dramatically in a short time, reaching a hundred - thousand times, the peak value is reached within 48 hours. This CRP protein also decreases rapidly with the cessation or disappearance of the stimulus. CRP has a plasma t1/2 of approximately 19 hours. Elevated CRP levels are commonly found in conditions such as bacterial infections, rheumatic fever, viral infections, malignant diseases, tuberculosis, and after heart attacks. A person's median CRP value increases with age, reflecting the presence of subclinical inflammation.C-reactive protein is a homogeneous molecule with a molecular weight of 118,000 daltons, composed of five identical subunits held together by noncovalent bonds. The CRP protein is a member of a family called pentraxins, a group of proteins that are all proteins with five subunits. CRP is like an antibody, because it is capable of opsonization (foreign particle coating), agglutination, precipitation, and complement activation via the classical pathway. However, CRP differs from antibodies in that its binding is calciumdependent (Ca-dependent binding) and its binding is nonspecific, with the main substrate being phosphocholine, a common constituent of microbial membranes. CRP also binds small ribonuclear proteins, phospholipids, peptidoglycan, and other constituents of bacteria, fungi, and parasites. In addition, CRP binds to specific receptors on monocytes, macrophages, and neutrophils, which promotes phagocytosis. Thus, CRP can be considered a nonspecific molecule that is a primitive form of antibody, capable of acting as a defense against microorganisms or foreign cells until specific antibodies can be produced. (b). Serum Amyloid A Serum amyloid A is another major protein whose concentration can increase up to a thousand-fold, as occurs with CRP. Serum amyloid is an apolipoprotein synthesized in the liver and has a molecular weight of 11,685 daltons. Normal levels in the blood are around 30ug/ml. In plasma, serum amyloid is associated with HDL cholesterol, and is thought to play a role in cholesterol metabolism. By removing cholesterol from cholesterol-filled macrophages at the site of tissue injury, serum amyloid A contributes to cleansing the wound area. Serum amyloid A also facilitates the recycling of cell membrane cholesterol and phospholipids for reuse in building new cell membranes that are needed during acute inflammation. It has been demonstrated that the increase in serum amyloid A in bacterial infections is much greater than in viral infections. (c). Complement Complement in the immune system refers to a series of serum proteins that are normally present and whose overall function is to mediate inflammation. There are nine such proteins activated by antibodies that bind to part of what is known as the classical cascade (classical pathway); several other proteins are involved in alternative pathways triggered by microorganisms. The main functions of complement are opsonization, chemotaxis, and cell lysis. (d). Mannose-Binding Proteins Mannose-bound proteins (PTMs), also called mannosebinding lectins, are trimers that act as calcium-dependent opsonins. Mannose-bound proteins are able to recognize foreign carbohydrates such as mannose and several other sugars found mainly in bacteria, fungi, viruses, and some parasites. NCDs are widely distributed on mucosal surfaces throughout the body. PTM It has many similarities to the C1q component, when bound to complement it activates the complement cascade and helps to promote phagocytosis. The normal concentration of PTM in the blood is up to 10 ug / ml. Lack of PTM has been associated with recurrent fungal infections. (e). Alpha1-Antitrypsin Alpha1-antitrypsin (AAT) is the main component of the alpha band when plasma is electrophoresed. Although its name suggests that alpha1-anitrypsin only acts against trypsin, it turns out that this compound is a general inhibitor of plasma proteases released from leukocytes, especially elastase. Elastase is an endogenous enzyme that can degrade elastin and collagen. In chronic lung inflammation, lung tissue is damaged due to the activity of alpha 1 antitrypsin. In the immune system, alpha1-antitrypsin acts to "mop up" or counter the effects of neutrophil invasion during the inflammatory response. Besides that, alpha 1-antitrypsin also regulates the expression of proinflammatory cytokines such as tumor necrosis factoralpha, interleukin-1a, and interleukin-6. Alpha1-antitrypsin deficiency can cause early emphysema, especially in individuals who smoke or who are exposed to hazardous materials from the occupational environment. In conditions of alpha1-antitrypsin deficiency, the body lacks or does not inhibit proteases in the lower respiratory tract, which results in damage to parenchymal cells resulting in emphysema or idiopathic pulmonary fibrosis. It is estimated that as many as 60,000 Americans suffer from alpha 1-antitrypsin deficiency. There are at least 17 alleles of the AAT coding gene that are associated with decreased enzyme production. One particular gene variant is associated with decreased secretion of alpha1-antitrypsin from the liver, and such people are at risk of developing liver disease and emphysema. Inheritance of the most severe homozygous gene variants can lead to the development of cirrhosis, hepatitis, or hepatoma in early childhood. Alpha1antitrypsin can also react with serine proteases, especially those produced by agents that trigger the complement cascade or fibrinolysis. After binding to alpha1-antitrypsin, the protease becomes completely inactive and is then cleared from the area of tissue damage and then catabolized. (f). Haptoglobin Haptoglobin is an alpha2-globulin withbind a molecular weight of 100,000 daltons. Its main function is to irreversibly to free hemoglobin released by intravascular hemolysis. Once bound, this complex is rapidly cleared by Kupffer cells and parenchyma inhaptoglobin the liver, thereby preventing loss ofsynthesis free hemoglobin. The increase in plasma is the result of de novo by theA liver and not the result of the release of haptoglobin produced elsewhere. twofold -10x increase in haptoglobin can be seen in cases of inflammation, stress, or tissue necrosis. Early in the inflammatory response, haptoglobin levels may drop due to intravascular hemolysis. however, Normal plasma concentrations range from from 40 to 290 mg/dL.Haptoglobin plays an important role in protecting the kidneys damage and preventing the loss of iron which is excreted in the urine. However, its most important function isbytofree provide protectionFree against damageisdue to oxidative stress mediated hemoglobin. hemoglobin a strong oxidizing agentparts that can produce peroxides and hydroxyl radicals. Haptoglobin can also bind ofproteins single-stranded proteins and pieces with of damaged proteins to prevent these from aggregating/combining blood vessels. (g). Fibrinogen Fibrinogen isThe thefibrinogen largest component ofiscoagulation factors in plasma, and forms fibrin clots. molecule a dimer with a molecular weight offibrinogen 340,000 daltons. Normal levels range from 100-400 mg/dL. A small portion of is broken down by thrombin to form fibrils that form fibrin clots. This accelerates wound closure and stage stimulates endothelial cell adhesion and proliferation,which is an important for the healing process. Clot formation also createsFibrinogen a barrier that helps prevent the further spreadcell of microorganisms in the body. also functions to promote red blood aggregation, and increased fibrinogenin levels disease, especially women.contribute to an increased risk of coronary artery (h) Ceruloplasmin Ceruloplasmin is composed of Ita single polypeptide chaintransport with a protein molecular weight of 132,000 daltons. is the primary copper insixhuman plasma, binding 90-95% of the copper found in acts plasma by attaching copper ions per molecule. In addition, ceruloplasmin as ferroxidase, which oxidizes ironferritin from Fe2+ to Fe3+. This reaction can function as a waylevels to release iron from to switch to binding with transferrin. Decreased ofdisorder ceruloplasmin are found in Wilson'levels s disease, an autosomal recessive genetic characterized by increased of copper in tissues. Normally, copper circulating in theand bloodreturned is thentocompletely absorbed by the liver and bound to ceruloplasmin the plasma or excreted into the bile ducts. In Wilson' s disease, copper accumulates in the liver and then in other tissues such as the brain, cornea, kidneys, and bones.