Acute Phase Reactants HO-IS WEEK-07 PDF

7 ACUTE PHASE REACTANTS acute phase reactants protein in nature produced by the liver produced in response to inflammation, infection or injury produced within 12-24 hours in response to increase cytokines. Cytokines like Interleukin 1 beta, Interleukin 6 and Tumor Necrosis Fa...

7 ACUTE PHASE REACTANTS acute phase reactants protein in nature produced by the liver produced in response to inflammation, infection or injury produced within 12-24 hours in response to increase cytokines. Cytokines like Interleukin 1 beta, Interleukin 6 and Tumor Necrosis Factor (TNF alpha) are mainly produced by monocytes and macrophages at the site of inflammation. C-REACTIVE PROTEIN positive acute phase reactant ring-shaped protein composed of five identical subunits. Functions: opsonization complement activation inflammation Marker for pneumococcal infection The protein precipitates with C-substance derived from polysaccharide of a bacteria.  Early marker for persons at risk for Coronary Heart Disease (CRP binds to Atherosclerotic plaques) A significant risk factor for men and women are conditions like myocardial infarction (heart attack) and ischemic stroke (brain attack) >2mg/dl is significant threshold for high cardiovascular risk. Fat or lipid accumulation in the vascular intima or blood vessels Deposition of WBCs, platelets and calcium and other cells Buildup of WBCs will result to release of soluble mediators trapped along fat depositions in the blood vessels Elevation of CRP is the result of damage. serum amyloid a An apolipoprotein synthesized in the liver. Associated with HDL (high density lipoprotein) cholesterol, removes cholesterol from cholesterol-filled macrophages at the sight of injury. ALPHA 1 ANTITRYPSIN Major component of alpha 1 band of serum electrophoresis AAT acts a protease inhibitor specifically for elastase, an enzyme released from leukocytes during its bacterial activity. PREMATURE EMPHYSEMA IN THE RESPIRATORY TRACT the body shall send WBC onto the respiratory tract to eliminate the injurious agent or pathogen like Streptococcus pneumonia. After they have performed their functions, WBCs are normally neutralized inhibited by alpha 1 antitrypsin to release digestive enzymes. In other words, the AAT stops the WBC from digesting other organisms or performing its immunological functions because the pathogen is already eliminated. This is done by the AAT among normal individuals in order to maintain an intact alveolar sac. Problem with AAT deficiency is when WBCs have already neutralized or eliminated the pathogen; there will be no one to neutralize the enzymes released by WBC. THE EFFECT: the WBCs will continuously release elastase which digests the alveolar sac or respiratory tract thereby leading to emphysema. EMPHYSEMA - the lung of the patient is infiltrated with fluids or obstructed by other substances. AAT becomes a risk if it is deficient and may cause premature emphysema, thereby, normal concentrations of alpha 1 antitrypsin in the body would be INCREASED AMOUNTS. FIBRINOGEN The most abundant coagulation factor in plasma. Produced in the liver. substrate that prevents the body from suffering any bleeding disorders when it is converted to fibrin. HAPTOGLOBIN Prevents the loss of hemoglobin and its constituent iron into the urine Evaluates the degree of hemolytic transfusion reaction and hemolytic disease of the newborn Hemoglobin has a nephrotoxic risk Low levels of haptoglobin in a blood sample may indicate the severity of hemolytic transfusion reactions and HDN. The relationship is inversely proportional. Haptoglobin will only be decreased once it binds itself to the free hemoglobin. CERULOPLASMIN Copper Binding protein that has enzymatic activities. It imparts blue color to protein and it is a marker for Wilson’s disease Wilson’s Disease is an autosomal recessive inherited disorder in Copper Metabolism. Results to copper deposition in the cornea, skin, liver and brain KAYSER-FLEISCHER RINGS Copper due to the deficiency in ceruloplasmin, precipitates or deposits itself on the cornea of the patient MENKES KIKY HAIR SYNDROME Hair becomes “kinky” -- the curls are different than a normal individual due to copper metabolism disorder WILSON’S DISEASE Another example of copper metabolism disorder COMPLEMENT C3 The most abundant complement in the serum Pathways: Classical pathway: Activated by antigen- antibody complexes. Alternative pathway: Activated by microbial surfaces and other foreign substances. Mannose-binding lectin pathway: Activated by mannose-binding lectin, a protein that binds to carbohydrates on the surface of microorganisms. MUST REMEMBER! The fall of AAT The fall of complement The fall of fibrinogen The fall of haptoglobin 7 CYTOKINES CYTOKINES “cyto” = “cell”; “kines” = “kinetics” (movement) Cytokines are substances that induce the movement of the cell or their immunological function. Major cytokines - small soluble proteins that regulate the immune system. These substances are induced in response to specific stimuli (bacterial lipopolysaccharides, flagella of some motile microorganisms and other products of these microorganisms) through the ligation of cell adhesion molecules or through the recognition of foreign antigens by host lymphocytes. cytokine storm The resulting network of cytokine expression regulates the leukocyte activity and leads to the elimination of the infection. Massive overproduction and dysregulation of the cytokines. Leads to shock, multiorgan failure and even death. INTERLEUKINS Are currently numbered from IL1 to IL32 soluble substances that allows communication within WBCs in the human body INTERLEUKIN 1 a family that consists of IL-1 alpha, IL-1 beta and IL1 RA (receptor antagonist) IL-1 alpha IL-1RA Remains intracellular within the monocytes and macrophages competitively binds to the IL-1 receptor, can only be released after cellular death. preventing IL-1 from exerting its Helps with the attraction of inflammatory cells where the inflammatory effects. infection has occurred IL-1 BETA Induces fever, activation of phagocytes and production of acute phase reactants Cleaved intracellularly and then secreted by monocytes. INTERLEUKIN-2 T INTERLEUKIN-6 cell growth factor stimulates the production of acute-phase proteins stimulates the growth and division of T cells, allowing promotes the differentiation of B cells into plasma cells for a rapid expansion of the immune response. promotes the production of neutrophils  HOT T-BONE STEAK INTERLEUKIN 1 interleukin 2 interleukin 6 tumor necrosis factor This is against tumor cells, cytotoxic activity against tumor and virally infected cells Tumor Necrosis Factor Alpha The most prominent member of the TNF family. Consists of at least 19 peptides that has diverse biological function. Two Forms: Membrane Bound Soluble Forms cause vasodilation (widens) and increase vascular permeability (movement of the blood in the blood vessels increase).  Membrane Bound TNF Mediates all cytotoxic and inflammatory effects of TNF through cell to cell contact Soluble Form TNF Arises from the cleavage of the membrane bound form by TNFa– converting enzyme. This is secreted by activated monocytes and macrophages Can activate T cells through its ability to induce expression of MHC Class II molecules, vascular adhesion molecules and chemokines Enhances antigen presentation and activate T cells to respond to the pathogen that triggered the initial inflammatory response Tumor Necrosis Factor Receptor 1 (TNF R1) Tumor Necrosis Factor Receptor 2 (TNF R2) Expressed in most tissues and binds to the soluble TNF alpha Usually expressed in epithelial cells and immune cells. It is the primary mediator of TNF alpha signal Activated by membrane bound TNF alpha transduction in most cell types. 7 interferons interferons Viral replication interfering substances Proteins produced by virally infected cells and protect neighboring cells Exert a virus non-specific but host specific antiviral activity IFN alpha Secreted by leukocytes, major producers are NK cells IFN beta Secreted by double stranded RNA fibroblasts, major producers are fibroblasts IMMUNE, Component of the specific immune IFN gamma response to viral and other pathogens, major producers are Th1 cells chemokines Motility & migration of WBCs on the site of inflammation or infection Alpha Group - CXC Single amino acid between first and second cysteine Beta Group - CC Has adjacent Cysteine residues Third Group - C Lacks one of the cysteines CX3C Last major group, has 3 amino acid between the cysteine