Immunology Lecture Notes PDF

Immunology Dr. Alaa Abouelfetouh Youssef Associate Prof. of Microbiology Microbiology and Immunology Dept. Faculty of Pharmacy, Alexandria University and AlAlamein International University  Immunology is the branch of biology concerne...

Immunology Dr. Alaa Abouelfetouh Youssef Associate Prof. of Microbiology Microbiology and Immunology Dept. Faculty of Pharmacy, Alexandria University and AlAlamein International University  Immunology is the branch of biology concerned with the body’s defense reactions. The word immunity is derived from the Latin word immunis, meaning free of burden. Immunology 4  In our environment, we are surrounded by large variety of pathogenic microorganisms (bacteria, viruses, fungi, and parasites), which are able to cause disease if given the right opportunity. If microorganisms never encountered resistance from the host, we would constantly be ill and eventually die of various diseases. Immunology 5 Bruce Alan Beutler, an American immunologist and geneticist who discovered the Toll-like receptors (TLR), together with Jules A. Hoffmann, French biologist received one-half of the 2011 Nobel Prize in Physiology or Medicine, for "their discoveries concerning the activation of innate immunity" (the other half went to the Canadian Ralph M. Steinman for "his discovery of the dendritic cell and its role in adaptive immunity Immunology 7 In general we have two kinds of defenses: a-Innate (nonspecific) resistance b-Specific (acquired) resistance or immunity Immunology 8 a-Innate (nonspecific) resistance It acts as the first line of defense against infectious agents (immunity's early warning system). It is nonspecific (it provides protection against any pathogen, regardless of species). Immunology 9  It includes a first line of defense (skin and mucous membranes), and a second line of defense (phagocytes, inflammation, fever and antimicrobial substances). It has no memory component (it can’t recall a previous contact with a foreign antigen). Immunology 10 b-Specific (acquired) resistance or immunity It is the third line of defense. It is acquired during life. It is based on a specific response to a specific microbe once it has breached the innate immunity defenses. It has long-term memory for a specific antigen. It is based on specialized immune lymphocytes (B and T cells), and specific proteins (antibodies). Immunology 11  Innate immunity Adaptive immunity First line of defense Second line of defense Third line of defense Intact skin Phagocytes, such as Specialized neutrophils, lymphocytes: T cells Mucous eosinophils, dendritic and B cells membranes and cells and their secretions macrophages Antibodies Normal Inflammation microbiota Fever Antimicrobial substancesImmunology 12  Nonspecific (innate) Resistance First line of defense I- Physical factors ØSkin, mucous membranes, mucus, lacrymal apparatus, salivary glands, hairs, cilia, urine, vomiting and defecation. II-Chemical factors ØSebum, perspiration, lysozyme, gastric juice. Immunology 13  I- Physical factors: qSkin (physical barrier): Consists of: - the dermis, the inner, thicker portion composed of connective tissue. - the epidermis, the outer thinner portion, consists of epithelial cells. The top layer of epidermal cells is dead and contains a protective protein called keratin. The intact, healthy epidermis provides a very strong physical barrier to the entrance of microorganisms (those most likely to cause infection are the staphylococci that normally inhabit the epidermis, hair follicle, sweat and oil glands of the skin). These infections frequently occur as a result of burns, cuts, and stab wounds. Immunology 14 A section through human skin Immunology 15 qMucous membranes (physical barrier): Also consist of an epithelial layer and an underlying connective tissue layer. Mucous membranes line the entire gastrointestinal, respiratory and genitourinary tracts. Although mucous membranes inhibit the entrance of many microorganisms, they offer less protection than the skin. qMucus: A slightly viscous glycoprotein produced by the goblet cells of the mucous membranes. Immunology 16 The arrow points to a goblet cell in a mucous membrane epithelial layer Immunology 17  Physical factors: - Lachrymal apparatus of the eye produces the tears which protect the eye surface through diluting and washing away any microorganism or irritating substance. - Salivary glands produce saliva which dilute the numbers of microorganisms and wash them from both the surface of the teeth and the mucous membranes of the mouth. Immunology 18 Immunology 19 - Mucus-coated hairs in the nose filter inhaled air and trap microorganisms, dust and pollutants. - Mucus-coated cilia of the lower respiratory tract propel inhaled dust and microorganisms upward toward the throat. - Flow of urine prevents microbial colonization of the urinary tract. Vaginal secretions likewise move microorganisms from the female body. - Defecation and vomiting also expel microbes and microbial toxins out of the body. Immunology 20 The ciliary escalator Immunology 21 II- Chemical factors: Sebum: produced by sebaceous (oil) glands of the skin. One of its components is unsaturated fatty acids, which inhibit the growth of certain pathogenic bacteria and fungi. Perspiration produced by sweat glands of the skin, helps maintain body temperature, eliminate certain wastes, and flush microorganisms from the surface of the skin. Immunology 22  Lysozyme, an enzyme capable of breaking down the peptidoglycan of the cell wall of gram positive bacteria and to a lesser extent the gram negative. Lysozyme is found in perspiration, tears, saliva, nasal secretions, urine and tissue fluids, where it exerts its antimicrobial activity. Immunology 24  Gastric juice: -Produced by the stomach glands. -Mixture of HCl, mucus and enzymes. -Its very high acidity (pH 1.2-3) destroys bacteria and most bacterial toxins, except those of Staphylococcus aureus and Clostridium botulinum. However, many enteric pathogens are protected by food particles and can enter the intestine. -Helicobacter pylori uses the ammonia (produced in the catabolism of protein) in neutralizing HCl, so it can live in the stomach. Its growth initiates an immune response that results in gastritis and ulcers. Immunology 25 Normal microbiota and innate immunity Normal microbiota assist in preventing the overgrowth of pathogens (microbial antagonism). They prevent pathogens from colonizing the host by: - competing with them for nutrients - producing harmful substances to the pathogens, e.g., in the large intestine, E. coli produces bacteriocins that inhibit the growth of Salmonella and Shigella. -altering conditions that affect the survival of the pathogens (pH and oxygen availability), e.g., the normal microbiota in the vagina, alter pH preventing overpopulation by Candida albicans, a pathogenic yeast that causes vaginitis. Immunology 27 Immunology 29 Immunology 30  Nonspecific (innate) Resistance Second line of Defense When microbes penetrate the first line of defense, they encounter a second line of defense. ØIt includes phagocytosis, inflammation, fever and antimicrobial substances. Immunology 31  Formed elements of blood Blood consists of a fluid (plasma) and formed elements; erythrocytes, leucocytes, and platelets. leucocytes play the key role of the immune system. Leucocytes are divided into two main categories: -Granulocytes -Agranulocytes Immunology 32  Granulocytes B -Neutrophils Highly phagocytic and motile. Active in the initial phases of infection. -Basophils Release substances as histamine, important in inflammation and allergic responses. -Eosinophils Produce toxic proteins against certain parasites. Immunology 33  Agranulocytes -Dendritic cells Have long extensions that resemble the dendrites of nerve cells. Are especially abundant in the epidermis of the skin, mucous membranes, and lymph nodes. Kill microbes by phagocytosis and act as antigen presenting cell to initiate adaptive immune responses. Immunology 35  Agranulocytes L - Monocytes Are not actively phagocytic until they leave blood circulation, enter body tissue and develop into highly phagocytic macrophages. -Lymphocytes Play the key role in specific immunity. B cells responsible for antibody production and T cells for cell-mediated immunity. B & T cells occur in lymphoid tissues of the lymphatic system. Immunology 36 Immunology 37 -Natural killer (NK) cells Found in blood, spleen, lymph nodes and red bone marrow. Kill wide variety of infected body cells and tumor cells. Attack any body cells that display abnormal or unusual plasma membrane protein molecules. Immunology 38  Phagocytosis From Ancient Greek (phagein) , meaning "to devour", (kytos) , meaning " cell", and -osis, meaning "process“. It is the cellular process of engulfing solid particles by the cell membrane. in the immune system, it is a major mechanism used to remove pathogens and cell debris. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed. Immunology 40  Phagocytosis can be divided into four phases: chemotaxis, adherence, ingestion, and digestion. Immunology 41 Immunology 42  Chemotaxis -Is the chemical attraction of phagocytes to microorganisms. -Example of chemotactic chemicals are: microbial products, components of white blood cells and damaged tissue cells, and complement fragments (C5a). Immunology 43  Adherence -Adherence is the attachment of phagocyte’s plasma membrane to surface of the microorganism or other foreign material. -Microorganisms can be more readily phagocytized by coating with molecules like complement (C3b), and antibodies (opsonization). Immunology 44  Ingestion -The microbe is engulfed by means of pseudopodes. -Inside the phagocyte cell, the microbe is contained in a phagosome or phagocyte vesicle. -pH inside phagosome is about 4, which activates enzymes. Immunology 45  Digestion Within the cytoplasm, the lysosomes that contain digestive enzymes and bactericidal substances fuse with the phagosomes forming phagolysosomes (kill most types of bacteria in 10-30m). Immunology 46  Lysosomal bactericidal factors include: a-Hydrolyzing enzymes such as lysozyme. lipase, protease, deoxyribonuclease, ribonuelease. b- Toxic oxygen products such as, hydrogen peroxide, singlet oxygen, hydroxyl radicals, and superoxides. After the digestion of the phagolysosomal contents, the indigestible materials are discharged outside the cell. Immunology 47 Immunology 48  Microbial evasion of phagcytosis Inhibition of adherence by M protein (Streptococcus pyogenes) and by capsule (Streptococcus pneumonia and Hemophilus influenzae). Killing of the phagocyte by leukocidin (Staph. aureus), or by Streptolysin (Streptococcus pyogenes). Lysis of phagocyte membrane by membrane attack complex by Trypanosoma cruzi. Inhibition of fusion of phagosome and lysosome by Mycobacterium tuberculosis, Leishmania, Chlamydia and HIV. Remaining dormant within the phagocyte for months and even years, like Brucella. Biofilms: the phagocytes cannot detach bacteria from the biofilm. Immunology 49  Bacterial capsule Staphylococcal biofilm on a glass cover slip Immunology 50 Inflammation Damage to the body’s tissues (caused by microbial infection, physical or chemical agents) triggers a defensive response called inflammation. Inflammation is usually characterized by four symptoms: redness, pain, heat and swelling. Immunology 52  Inflammation has beneficial functions: - To destroy and remove the injurious agents and their toxins. - To limit the microbial effects on the body by confining or walling off the injurious agent and its by-products. - To repair or replace the damaged tissue. Immunology 53 The process of inflammation can be divided into three stages: 1-Vasodilatation and increased permeability of blood vessels 2-Phagocyte migration and phagocytosis, 3-Tissue repair Immunology 54  Vasodilation and increased permeability of blood vessels -Caused by chemical mediators, released by damaged cells (especially mast cells in the connective tissues) in response to injury, such as histamine, leukotrienes and prostaglandins. Release of such mediators can be also stimulated by complement components, C3a and C5a. -Vasodilation increases blood flow to the damaged area causing redness (erythema) and heat. -Increased permeability permits fluid to move from the blood into tissue spaces (edema), also defensive substances retained in blood pass through the walls of blood vessels and enter the injured area, in addition to delivering clotting elements of the blood to the injured area. Immunology 55  The blood clots that form around the site of activity prevent the microbe (or its toxins) from spreading to other parts of the body. As a result, pus (mixture of dead cells and body fluids) might be collected in a cavity formed by the breakdown of body tissues, forming an abscess. Immunology 57  Phagocytic migration -One hour after inflammation is initiated, phagocytes appear on the scene. -Neutrophils appear in the site of infection at the initial stage of inflammation. Monocytes follow the granulocytes. -Once monocytes are contained in the tissue they develop into macrophages (wandering macrophages). -The phagocytes engulf and kill large numbers of microorganisms and damaged tissues, they eventually die and are converted to pus. The pus is pushed to the surface of the body or into an internal cavity for discharge. Immunology 58 Immunology 60  Tissue repair The process by which tissues replace dead or damaged cells. Skin has a high capacity for regeneration, whereas cardiac muscle tissue does not. Repair begins during the active phase of inflammation, but can’t be completed until all harmful substances have been removed or neutralized at the site of injury. Immunology 61  Fever (abnormally high body temperature) -Body temperature is controlled by the hypothalamus (body's thermostat). It is normally set at 37°C. -Infection causes a rise in the body temperature that is attributed to IL-1, a cytokine released from macrophages. This causes the hypothalamus to release prostaglandins that reset of the hypothalamic thermostat at higher temperature. Immunology 63 -This leads to constriction of blood vessels, increase in metabolic rate and shivering (chill, definite sign that body temperature is rising). -Temperature remains elevated till cytokines are eliminated. Thermostat is then reset at 37°C. As infection subsides, heat losing mechanisms as vasodilation and sweating go into operation (indication that body temperature is falling). Immunology 64  Fever may be considered as a defense against disease: -IL-1 helps step up the production of T lymphocytes. -High body temperature intensifies the action of interferon (antiviral proteins). -A variety of bacteria and viruses grow more slowly at elevated temperatures. -Also elevated temperatures speed up body reactions that aid tissue repair. However, as a rule, death results if body temperature rises above 44 to 46°C. Immunology 65  Antimicrobial substances Among the most important of these are the proteins of the complement system and interferons. Immunology 67