Pharmaceutical Microbiology II PDF

Pharmaceutical Microbiology II Pharmacy department Dr/ Fahad Alzowahi Assistant professor in Microbiology  Brief History of immunology The Latin term immunis, meaning “exempt” is the source of the English word immunity, meaning the state of protection and defense f...

Pharmaceutical Microbiology II Pharmacy department Dr/ Fahad Alzowahi Assistant professor in Microbiology  Brief History of immunology The Latin term immunis, meaning “exempt” is the source of the English word immunity, meaning the state of protection and defense from infecti- ous disease. Perhaps the earliest written reference to the phenomenon of immunity can be traced back to Thucydides, describing a plague (black death) in Athens, he wrote in 430 BC that only those who had recovered from the plague, they would not acquire the disease second time. The first recorded attempts to induce immunity, were performed by the Chinese and Turks in the fifteenth century.  Various reports suggest that the dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted into small cuts in the skin give protection and mild symptoms during the infection with smallpox virus in the future (a technique called variolation). In 1798 (Edward Jenner) First demonstration of smallpox vaccination. Louise Pasteur 1884: Discovered the method which lead to reduce intensity of disease by using attenuated vaccine. Metchnikoff in 1884: He injected some types of fish by bacteria, it was noted that bacteria are engulfed by cells and eaten them (phagocytosis).  Gorge Nuttal in 1888: he was the first person who had explain the serum contain antibody. In 1890- (Emil von Behring) and (Shibasaburo Kitasato) this was the demonstration period of antibody activity against diphtheria and tetanus toxins, it was the beginning time of humoral theory of immunity (Table-1). Table (1): Nobel prizes in immunological researches  Immunology Immunology is the branch of biomedical science concerned with the body's defense reactions. Immunity (from Latin word immunis, meaning exempt) means the host defense or protection against foreign bodies or invading pathogens (e.g. bacteria, viruses, fungi, and parasites). immune response is the response of the immune system against a foreign body or invading patho- gen. There are two types of immune responses (innate and acquired). Immune response may be humoral or cell mediated. Immune system: - Immune system is a biological system consisting of structures and processes within the human body to protect it from pathogens (from viruses to parasitic worms). - It consists of a network of cells, tissues, and organs that work together to defend the body against pathogens. Organs of the immune system: There are two groups of immune organs; 1- Central immune organs (primary lymphoid organs): - They are responsible for production and maturation of lymphocytes. - They comprised the followings: Bone marrow. Thymus gland. 2- Peripheral immune organs (secondary lymphoid organs): - They serve two basic functions, they are a site of further lymphocyte maturation, and they efficiently trap antigens for exposure to T and B cells. - They include the followings: Lymph nodes.  Spleen.  Tonsils.  Vermiform appendix.  Peyer's patches. (Figure-1).  Tonsils Vermiform appendix Fig. (1): Lymphoid organs of human body.  Types of immunity There are two types of immunity provided by the immune system: innate (natural) immunity and acquired (adaptive) immunity (figure-2). Innate From the fetus stage Passive Active by Passive Active by Antibody infection Maternal Vaccination transfer Fig. (2): Types of immunity  Innate immunity It is also known as natural or non-specific immunity. It is present from the fetus stage and is not related to previous exposure to any stimuli. It protects the body from all invaders, because it is not specific. It does not become more efficient on subsequent exposure to the same pathogens. It comprises four types of defensive barriers:  Anatomical and physical barriers.  Physiologic and chemicals mediated barriers. Phagocytic and (cellular) barriers.  Inflammatory barriers as the following table-2: Table (2): Summary of innate (nonspecific) host defenses. 1) Anatomical and physical barriers: Corneal layer of the skin: it is composed mainly of keratin that prevents invasion of bacteria and other harmful microorganisms. Tracheal cilia: they drive away the bacteria and dust trapped in mucous and prevent them from entering into the lungs in the respiratory system. Digestive tract peristalsis: it helps to keep the gastrointestinal tract free from microorganisms. Hairs within the nose: they filter air containing microbes, dust, and pollutants. Flushing action: the flushing action of tears, saliva, and urine prevents infection of the eyes, mouth, and urinary tract, respectively.  Coughing and sneezing: both processes eject pathogens and other irritants from the respiratory tract. Blood clot: if the skin is broken the blood clot serves as primary glue on the edges of wound and stops entry of pathogens, preventing infection of the wound. Trapping effect: the trapping effect of mucus that lines the respiratory and gastrointestinal tract protects the lungs and digestive systems from infection. Defecation and vomiting: these processes expel microorganisms. Fever: it is a systemic response to infection. After exposure to foreign invaders, leukocytes may release chemicals called pyrogens, which cause the body  temperature to rise. Fever appears to cause the spleen to sequester zinc and iron, which are required by bacteria to multiply. 2) Physiologic and chemicals mediated barriers: Sweat: it has high lactic acid and electrolyte concentrations, which are inhibitory to many microbes including bacteria and fungi. Sebum: it is produced by sebaceous gland in the skin. It contains fatty acids which inhibits bacterial growth. Earwax (cerumen): it is a yellowish waxy substance secreted in the ear canal of humans and other mammals. It protects the skin of the ear canal, assists in cleaning and lubrication, and also provides some protection from bacteria, fungi, insects, and water. Enzymes: Lysozyme: it is found in tears, saliva, breast milk, and nasal secretions. It can breakdown the cell wall of bacteria causing cell lysis. Phospholipase: it is found in tears, saliva, breast milk, and nasal secretions. It can destabilize bacterial membranes. Gastric acid (HCl): it is produced in the stomach and destroys bacteria and almost all important bacterial toxins found in food.  Gastric proteases: they destroy microorganisms found in the food. Defensins (defensive peptides): they are small, cationic, cysteine-rich proteins found in all vertebrate and invertebrate organisms, in human they are found in the lung and gastrointestinal tract and have antimicrobial activity. They are active against bacteria, fungi, and many viruses. Most defensins act by binding to the microbial cell membrane, forming pore-like membrane defects that allow efflux of essential ions and nutrients. In addition, neutrophils contain these peptides to assist in killing phagocytosed bacteria.  Interferons (IFNs): they are a type proteins produced by the body's cells as a defensive respo- nse to viruses. They are able to hinder reproduction of viruses. IFNs also activate macrophages and natural killer (NK) cells. Complement system: a system of heat-labile plasma proteins (over 20 different proteins) that acts as an effector mechanism in immune defense against infection by microorganisms. Activation of the complement system can occur in two ways: classical and alternative pathways. In either pathway, it involves a sequence of steps involving various complement proteins leading to the formation of membrane attack complex (MAC) taht opens holes in the target cell's membrane and causes lysis. Generally, complement system helps or complements the ability of antibodies and phagocytic cells to clear pathogens. 3) Phagocytic and (cellular) barriers: various cells endocytosis and break down foreign macromolecules. Neutrophils (polymorphonuclear cells (PMNs): they are granular leukocytes and the most abundant type of leukocytes (comprise about 50- 70% of total leukocytes) in the human body and form an essential part of the innate immune system. The natural role of neutrophils is to defend the body against bacteria, (figure-3).  Fig. (3): (A) Schematic diagram and (B) photomicrograph of a neutrophil. Eosinophils: they are granular leukocytes whose natural role is to defend the body against parasites. They comprise about 1-3% of total leukocytes, (figure-4). Fig. (4): (A) Schematic diagram and (B) photomicrograph of blood smear showing an eosinophil.  Basophils: they are granular leukocytes and the least common type of leukocytes (comprise about 0.5-1% of total leukocytes) of the granulocytes. Basophils release histamine important in defense against parasites, and play a role in allergic reacti- ons, particularly type I hypersensitivity reactions, (figure-5). Fig. (5): (A) Schematic diagram and (B) photomicrograph of blood smear showing a basophil.  Natural killer (NK) cells: they are a type of lymph- ocytes that specialize in detecting and killing virally-infected cells and tumor cells. They produce chemicals called perforins, which create channels in the target cell membrane and lead to destruct- tion of the target cell, (figure-6). Fig. (6): (A) Schematic diagram and (B) photomicrograph of natural killer cells.  Macrophages: they are leukocytes within tissues, produced by the differentiation of monocytes in tissues, (figure-7). Fig. (7): (A) Schematic diagram of macrophage and (B) photomicrograph of blood smear showing a monocyte that macrophage originated from it. Specialized cells, such as blood monocytes, neutrophils, and tissue macrophages serve a process known as phagocytosis.  Process of phagocytosis: 1- Microorganism becomes attached to membrane evaginations called pseudopodia. 2- Microorganism is ingested, forming phagosome. 3- Phagosome fuses with lysosome. 4- Lysosomal enzymes digest captured material. 5- Digestion products are released from cell, (figure- 8). Fig. (8): Phagocytosis process by phagocytic cell. 4) Inflammatory barriers: Inflammation is an innate immune defense against injury, infection, or allergy, so, it is a mechanism used to protect the body from invasion by foreign organisms and to repair tissue trauma. Tissue damage and infection induce leakage of vascular fluid, containing serum proteins with antibacterial activity, and influx of phagocytic cells into the affected area. Tissue damage caused by a wound or by an inva- ding pathogenic microorganism induces a complex sequence of events collectively known as the inflammatory response.  There are three major events of an inflammatory response;  Vasodilation: an increase in the diameter of blood vessels, resulting in tissue redness (erythema) and an increase in tissue temperature. Increased capillary permeability: influx of fluid and cells from the congested blood capillaries into the surrounding tissues. The fluid is accumulated (now called exudate) and contributes to tissue swelling (edema). Leukocytes migration: it is facilitated by the incr- eased permeability of the capillaries.The migration of leukocytes is a multistep process that includes; 1- Margination: the adherence of the leukocytes to the tunica intima (inner endothelial wall) of the blood vessels. 2- Diapedesis or extravasation: the movement of leukocytes through intacted capillary walls into the tissue. 3- Chemotaxis: the migration of phagocytes through the tissue to the site of the invasion. As phagocytic cells accumulate at the site and begin to phagocytose bacteria, they release lytic enzymes, which can damage nearby healthy cells. The accumulation of dead cells, digested injury material and fluid, forms a substance called pus, (figure-9).  Tissue damage (1) Tissue damage causes release of vasoactive and chemotactic factors that trigger a local (4) Phagocytes and increase in blood flow and antibacterial exudate destroy capillary permeability bacteria) (2) Permeable capillaries allow an influx of fluid (exudate) and (3) Phagocytes migrate to site of cells inflammation (chemotaxis) Fig. (9): Inflammation process steps.  Cardinal signs of inflammation: Inflammation is normally characterized by about five distinct signs:  Pain (dolor): due to chemicals released by damaged cells.  Swelling (tumor): due to an influx of fluid into the damaged region.  Redness (rubor): due to vasodilatation.  Heat (calor): due to an increase in blood flow into the damaged region.  Loss of function (functio laesa): due to increased swelling and pain.  The major events in the inflammatory response is that, a bacterial infection causes tissue damage with release of various vasoactive and chemotactic factors. These factors induce increased blood flow to the infected area, increased capillary permea-bility, and an influx of white blood cells, including phagocytes and lymphocytes, from the blood into the tissues. The serum proteins contained in the exudate have antibacterial properties, and the phagocytes begin to engulf the bacteria. Advantages of inflammation: Destroy or killing and remove the injurious agent to prevent additional injury to the tissue. Healing or repair of the damaged tissue. Disadvantages of inflammation: It is usually associated with pain process. May lead to rupture of the inflamed organs as in perfor- ating appendicitis. May lead to excessive tissue adhesion as in pleuritis. May lead to development of chronic inflammatory disease such as arthritis, glomerulonephritis, and allergic bronchitis.  Factors affecting innate immunity Age: adults have active defense and perfect innate immunity, while children have low immunity, because the immune system is incomplete and have inactive leukocytes. Race: some races have active innate immunity against some diseases, while others have not. Environmental conditions: the persons in low or neutral temperature have more active innate immunity than persons in hot or very hot areas. Healthy environment leads to active innate immunity, while contamination or pollution leads to decreased innate immunity  Nutrition: the nutrient can be used for structural buildings and functions of the immune cells. In general, good nutrition leads to good immunity. Vitamins (e.g. C and A) are used as cofactors in immune activity. Genetic control: innate immunity can be genetically transformed from parents to offspring according to Mendel's laws. So, the activity of immune system depends on the genetic active immune cells.