Humoral Immunity, APP, and Cytokines PDF

Immune effector mechanisms Lecture 5  Outline The main objectives: Describe the effector mechanisms of humoral and cell mediated immunity Illustrate the importance cytokines, complement and acute phase proteins. Topics: ▪ Definition of cell mediated and humoral immunity ▪ C...

Immune effector mechanisms Lecture 5  Outline The main objectives: Describe the effector mechanisms of humoral and cell mediated immunity Illustrate the importance cytokines, complement and acute phase proteins. Topics: ▪ Definition of cell mediated and humoral immunity ▪ Components involved: ✔ Acute phase proteins ✔ Cytokines ✔ Complements ✔ Antibodies ▪ Effector mechanisms of innate immunity (inflammation): ✔ Causes ✔ Types and molecules ✔ Pathogenesis ✔ Outcome ✔ Granuloma Effector mechanisms Defined as how the immune system cells and components recognize and eliminate antigens. Different effector mechanisms involved in innate and adaptive immunity. The difference between humoral and cell mediated immunity. Humoral immunity Cell mediated immunity Mechanism By producing By producing cells antibodies Cells involved B-cell T-cells Mode of action Antibody neutralize Cell to cell contact and kill the toxins, opsonize target antigen, By producing molecules mainly cytokines or enzymes Purpose Mainly to eliminate Mainly to eliminate intracellular extracellular antigens antigens, tumors and graft rejections Acute phase proteins (APP) Acute phase proteins are plasma proteins that their concentration changed in response to infection, inflammation or tissue damage (trauma, surgery, MI or tumors). APPs at which their concentration increase known as positive APP, the ones at which their concentration reduce known as negative APP APPs are also known as Acute Phase Reactants. Sources of acute phase proteins include liver, macrophages and neutrophils. APP are normally produced in the body but at a low concentration. The concentration of these proteins changed in acute phase of diseases. They act early in case of inflammation or damage. APPs In case of injury or inflammation, immune cells such as neutrophils and macrophages secrete proteins known as cytokines (IL-1, IL-6 and TNFα) which will stimulate the liver to produce APPs. On the other hand, negative effect will occur for negative acute phase proteins. Example of negative acute phase proteins ▪ Albumin ▪ Transferrin ▪ Why these proteins decreased in case of inflammation? In order to save amino acids for synthesis of positive acute phase proteins. ▪ Low level of albumin and transferrin can be an indication of inflammation, however, low level can be found in other conditions. Examples of positive APP APP and their physiological role in the Function body C-reactive protein Opsonization, complement activation. High level can been seen in MI, during pregnancy, elderly and obesity. Serum Amyloid Transport cholesterol from dying cells to the liver Recruitment of immune cells at site of injury Fibrinogen Clot formation Trap microbes at site of injury and can act as chemotaxis. Haptoglobin Binds hemoglobin Inhibit microbe iron intake Cerloplasmin Binds copper and oxidizes iron  Importance of Acute phase proteins Act as soluble pattern recognition molecules. Act as opsonins Ability to activate complement Ability to agglutinate microorganism preventing their spread it is. Clinical significance of acute phase proteins Measurement of acute-phase proteins, especially C-reactive protein, is a useful marker of inflammation. To monitor treatment and disease progression To predict the risk for certain diseases such as heart disease. ::CRP is one of the major APP. It binds to C-polysaccharide cell wall of many bacteria and fungi. The binding result in the activation of complement and the pathogen will be cleared either by complement mediated lysis or complement mediated phagocytosis. Innate immunity cytokines Lecture 6 Cytokines They are low molecular weight secreted proteins. Most of the cytokines produced by immune cells, however, other body cells can produce cytokines such as endothelial, epithelial, fibroblast and bone marrow stroma. There are more than 200 cytokines Presence of PAMPs and DAMPs stimulate the production of different types of cytokines. Cytokines are very potent proteins, thus, they are produced at a very low concentration and once the stimulus is removed their level will decline rapidly. Features of cytokines: Pleiotropic effect They are like hormones in their action They are redundant in their activity They are often produced in a cascade They can act synergistically or antagonistically Cytokines Importance: they can mediate ▪ cell division, ▪ inflammation, ▪ cytotoxicity , ▪ differentiation, ▪ proliferation, ▪ migration ▪ repair. Cytokine is a general name; other names include: Lymphokine: cytokines made by lymphocytes Monokine: cytokines made by monocytes Chemokine: cytokines with chemotactic activities Interleukin: cytokines made by one leukocyte and acting on other leukocytes. The important group of cytokines in immunology are interleukins  :: M-CSF macrophage colony stimulating factor G-CSF granulocytes CSF Cytokines MCP monocyte chemotactic protein Cytokines are divided into Cytokine group Function Examples Hematopoietins Ability to support proliferation of Colony stimulating factors hematopoietic precursors (M-CSF, G-CSF) Interferons Ability to interfere with viral replication IFNγ Chemokines Attract white cells to the site of MCP-1 and IL-8 infection/inflammation Interleukins Act as communicator between IL-1 to IL-18 leucocytes Tumor necrosis Have cytotoxic activity towards TNFα factor transformed cells (cancer cells) Cytokine effect on target cell is through binding to receptor on the target cells Cytokines related disease Overexpression or underexperssion of cytokines or cytokine receptors associated with number of disease such as: ❖ Toxic shock syndrome caused enterotoxins produced by Staph-aureus or Strept-pyogenes, lead to overexpression of cytokines. ❖ Bacterial Septic Shock caused by endotoxins produced by enterobacterecia lead to overproduction of cytokines. ❖ Cancers ❖ Autoimmunity and allergy, asthma and inflammatory disease. Cytokine-related therapies Cytokines can be used in treatment of certain diseases such as immunodeficiency, preventing graft rejection and treating cancers. ::The organism produce toxins (enterotoxins) which activate large number of T-cell. These T-cells produce excessive amount of cytokines which lead to disruption of cytokines network and cause symptoms like fever, blood clotting, diarrhea, low blood pressure, and shock. The condition can be fatal. Superantiges Endotoxins produced by E.coli, klebsiella pneumonia, enterbacter aerogenes, pseudomonas aeruginosa and neisseria meningitidis. These endotoxins lead to activation of macrophages and overproduction of cytokines mainly IL-1 and TNF alpha. Cancers such as adult T-cell leukemia caused by human T-cell leukemia virus which lead to activation of T-cell and production of cytokines that lead to uncontrolled growth of T-cell. Other malignancy include myeloma and lymphoma, overproduction of cytokines play role in these malignancy. Autoimmune diseases such as SLE and others are caused either by overproduction of cytokines or abnormal cytokine receptors.