Dr. Grace's Role of Phagocytes in Acute Inflammation PDF

# The Role of Phagocytes in Acute Inflammation ## Introduction The entrance of bacteria or chemical agents brings about a reaction called acute inflammation. The inflammatory response is a complex sequence of events involving the chemical mediators and cells of immunity. ## Tissue Injury Tissu...

# The Role of Phagocytes in Acute Inflammation ## Introduction The entrance of bacteria or chemical agents brings about a reaction called acute inflammation. The inflammatory response is a complex sequence of events involving the chemical mediators and cells of immunity. ## Tissue Injury Tissue injury, regardless of the type, can cause inflammation. Trauma, burns, chemicals, or infections can damage tissue resulting in inflammation. A bacterial infection is used in this note to illustrate acute inflammation. There are two types of inflammation: - Local inflammation - Systemic inflammation ### Local Inflammation Local inflammation is an inflammatory response confined to a specific area of the body. Symptoms of local inflammation include: - Heat - Redness - Swelling - Pain - Loss of function Redness, heat and swelling result from increased blood flow and increased vascular permeability. Pain is caused by swelling and by chemical mediators acting on pain receptors. Loss of function results from tissue destruction, swelling, and pain. ### Systemic Inflammation Systemic inflammation is an inflammatory response that occurs in many parts of the body. In addition to the local symptoms at the sites of inflammation, three additional features can be present: 1. **Red Bone Marrow:** The red bone marrow produces and releases large numbers of neutrophils, which promote phagocytosis. 2. **Pyrogens:** Pyrogens are chemicals released by microorganisms, macrophage neutrophils and other cells stimulating fever production. Pyrogens affect the body's temperature-regulating mechanism in the hypothalamus. Heat is conserved, and body temperature increases - **Fever**. Fever promotes the activities of the immune system such as phagocytosis and inhibits the growth of some microorganisms. 3. **Increased Vascular Permeability:** In severe cases of systemic inflammation, increased vascular permeability is so widespread that large amounts of fluid are lost from the blood into the tissues. The decreased blood volume can cause shock and death. ## Acute Inflammatory Response ### Local Vasodilation and Increase Blood Flow When bacteria enter the tissue, it causes the release of vasoactive agents such as histamine and bradykinin by basophils and mast cells The dilation of blood vessels increases or causes fluid and protein to leak into the tissue. Increased vascular permeability allows fibrinogen to enter the tissue from the blood. Fibrinogen is converted to fibrin, which prevents the spread of infection by walling off the infected area (coagulation). The combined effects of increased blood flow and leakage of fluid and protein cause the area to be red, swollen, warm and painful. ### Adherance of Phagocytes Increase in blood flow and vasodilation changes the streamline flow of blood to non-zonal flow. The change in inflow causes the heavier leucocytes to marginate and impinge on the vessel wall. The inflamed vessels stimulate the phagocytes to become sticky and adhere to the endothelium of vessels at the site. ### Migration and Chemotaxis of Phagocyte The adhered phagocytes pass through the walls of blood vessels into the tissue by squeezing through intercellular junctions in the vascular epithelium, a process known as diapedesis. The junctions reform unaltered behind the emerging cell. The escaped phagocytes are attracted to the site of injury by chemical substances released by bacteria and white blood cells involved in the attack. These substances are known as chemotactic factors, while the movement of the phagocytes towards the direction of increasing concentration of the chemotactic factor is known as chemotaxis. The chemotactic factors bind to membrane receptors of the phagocyte, and the binding cause an increase in oxygen consumption, depolarization of the phagocyte membrane and influx of calcium. ## Phagocytosis of Bacterial or Foreign Body When the phagocyte gets close to the foreign particle, it extends its free foot known as pseudopodia and encloses the particle in a vesicle. The membranes attaching the vesicle to the cell membrane break up so that the vesicle is now within the cytoplasm and is called **phagosome**. The phagocyte uses its two weapons to destroy the organism: - **It discharges its digestive enzymes in its granule** into the vesicle. The emptying of the digestive enzymes in the granules is known as **degranulation**. - **The membranes of the phagocytic vesicles generate toxic reactive oxygen species namely, toxic radicals, superoxide, and hydrogen peroxide.** These toxic substances are highly bactericidal. But *M. tuberculosis* has a thick waxy mycolic acid capsule that protects it from these toxic substances. *M. tuberculosis* is able to reproduce inside the phagocyte and eventually kill the immune cell. ### Activation of NADPH by Oxygen **Superoxide (reactive O₂ specie)** **Hydrogen peroxide dismutase** **Myeloperoxidase** **Hypochlorite (ClO^-)** **Formation of toxic reactive oxygen species that kills bacterial.** ### Release of Cytokines during Phagocytosis Cytokines are also known as interleukins when their amino acid composition is known. They are also known as glycoprotein hormones released by a number of phagocytes, e.g., when neutrophils are activated by phagocytosis of bacteria, they secrete endogenous pyrogen (which causes fever) and lysozymes. If activated because they consume viruses, they secrete alpha interferon. Note, if the phagocyte is a macrophage, they secrete alpha interferon, pyrogens, lysozymes colony-stimulating factors, GM-CSF, granulocyte colony-stimulating factor and components of complement system. ## Diagram of a Phagocyte This diagram depicts bacteria entering the skin through a cut and being engulfed by a phagocyte. - **Bacteria entering through the skin:** Bacteria enter through a skin cut. - **Epidermis:** The epidermis is the outer layer of skin. - **Antibody coated bacteria (opsonization):** Bacteria are coated with antibodies which help the phagocytes recognize and engulf them. - **Antibody:** Antibodies are proteins that bind to bacteria. - **Activation of Complement:** Complements are a group of proteins that help the immune system fight infection. - **Phagocyte (Neutrophil):** Phagocytes are white blood cells that engulf and destroy bacteria. - **Dilation increased permeability of vessel:** The blood vessels dilate and become more permeable so that white blood cells can reach the site of infection. - **Mast cells:** Mast cells are specialized cells that release histamine and other chemicals that cause inflammation. - **Lysosomal enzyme:** Lysosomal enzymes are enzymes that destroy bacteria. - **Capillary:** Capillaries are tiny blood vessels that allow white blood cells to reach the site of infection. - **Dermis:** The dermis is the inner layer of skin. ## The entering of bacteria through a cut in the skin produces a local inflammatory reaction and phagocytosis by phagocytes. The diagram shows that, following a cut in the skin, bacteria enter the body and are opsonized by antibodies. Phagocytes recognize the bacteria and are activated by complement. They then engulf the bacteria in a vacuole and digest them using lysosomal enzymes.