2310 ch 15.pptx

Chapter 15 innate immunity Host defenses against microbes are organized in three levels. • does not involve recognition of foreign substances • general in action. • internalized system of protective cells • nonspecific • acquired as each foreign substance is encountered by lymphocytes • memory...

Chapter 15 innate immunity Host defenses against microbes are organized in three levels. • does not involve recognition of foreign substances • general in action. • internalized system of protective cells • nonspecific • acquired as each foreign substance is encountered by lymphocytes • memory provides longterm immunity The second and third lines of defense involve cells of the immune system. • A healthy, functioning immune system is responsible for: • surveillance of the body (blood, lymph, extracellular fluid) • recognition of foreign material • destruction of entities deemed to be foreign • The cells of the immune system recognize foreign markers and should ignore self markers. • Autoimmune disorders result from the immune system attacking self cells. Blood is a fluid connective tissue in which living blood cells (formed elements) are suspended in a fluid matrix (plasma). Formed elements include: • erythrocytes (red blood cells) • leukocytes (white blood cells) • platelets Blood cell formation is referred to as hematopoiesis. The formed elements have different functions, but a similar life history. All arise from a stem cell called a hematopoietic stem cell (HSC) found in the red bone marrow. 2nd and 3rd line leukocytes are circled Leukocytes are used in the body’s immune system. • Leukocyte: leuko (white) & cyte (cell) = white blood cell (WBC). • Less than 1% of total blood volume. • The only formed elements that are complete cells (contain nuclei, organelles). • Circulatory system is means of transport but can leave bloodstream and move into surrounding fluid and tissues. Once out of the bloodstream, WBC’s move using amoeboid motion and positive chemotaxis. • Most WBC are found in connective tissues. • WBC counts in blood can increase 2X in a few hours in response to infection. Called diapedesis. Leukocytes are grouped into two categories on the basis of structural and chemical characteristics. Granulocytes (large cytoplasmic granules, lobed nucleus) • neutrophils, basophils, eosinophils Agranulocytes (very small granules, rounded nucleus) • lymphocytes & monocytes Neutrophils are aggressive antibacterial cells. • neutrophils are attracted to sites of inflammation and are active phagocytes • granules contain lysozyme and other antimicrobial agents • can degranulate and create a killing zone that kills many bacteria at once Eosinophils congregate at sites of allergy, inflammation, or parasitic infection.  commonly in mucous membranes  release toxic compounds by exocytosis at sites of parasitic infection  secret enzymes that limit the action of inflammatory chemicals  promote basophil action Basophils secrete chemicals that aid in the mobility and actions of other WBCs. • at site of injury enhances local inflammation by secreting heparin to prevent blood clotting and histamine to dilate blood vessels • activate and attract neutrophils and eosinophils Lymphocytes play a major role in the immune system. • besides connective tissues, they are also active in lymphoid tissues • involved in: o killing diseased self cells (viral infections, cancerous cells) o making antibodies (immunoglobulins) to disable foreign cells or viruses and mark them for destruction When circulating monocytes leave the bloodstream they differentiate into macrophages. • they are actively phagocytic for pathogens and cellular debris • present antigens to activate cells of the immune system • also form dendritic cells that reside in tissues and MPS • differentiated monocytes often take up residence near portals of entry or filtration organs, waiting to attack foreign intruders The mononuclear phagocyte system is a continuous connective tissue framework used by phagocytic cells. • Support network of connective tissue fibers connecting cells, tissues, and organs of the body. • Provides a passage way for phagocytes. The immune system is not an organ system, but a cell population that inhabits all organs and defends the body from agents of disease. • It is especially concentrated in the lymphatic system. • network of organs and vein-like vessels that recover fluid • inspect it for disease agents • activate immune responses • return fluid to the bloodstream Lymphatic Organization • Lymph moves in one direction only: from the extremities to the heart. • Lymphatic tissues are composed of aggregates of lymphocytes and macrophages that populate many organs in the body. • Defense cells are especially concentrated in lymphatic organs. • Immune cells originate and mature in primary lymphatic organs. • They reside and carry out their functions in secondary lymphatic organs. Lymphatic capillaries penetrate nearly every tissue of the body. • Closed at one end. • Gaps between cells are large enough to allow bacteria and cells to enter lymphatic capillary. • Gaps open when extracellular fluid pressure is high, and close when it is low. • The clear, colorless fluid inside the capillary is called lymph. • Lymph originates as extracellular fluid drawn into lymphatic capillaries. • Transports numerous white blood cells, fats, cellular debris, and infectious agents that have gained access to tissue spaces. Lymphatic capillaries recover extracellular fluid before it can return to the bloodstream. • Fluid continually filters from the blood capillaries into the tissue spaces. • Blood capillaries reabsorb 85% of fluid but 15% (2 to 4 L/day) of the fluid enters the lymphatic system. As lymph returns to the bloodstream it will pass through a lymph node. • Small bean-shaped secondary organs. • Stationed along lymphatic channels. • Major aggregations in armpit, groin, and neck. • Ideal for filtering out materials that have entered the lymph and to provide appropriate cells for immune reactions. The thymus is the site of T-cell maturation. • Triangular primary lymphatic organ in the pharyngeal region. • Largest proportionally at birth. • Exhibits high rates of growth and activity until puberty. • Shrinks gradually through adulthood. The spleen serves as a filter for blood instead of lymph. • Secondary lymphoid organ in the upper left portion of the abdominal cavity. • Its immunologic function is to filter pathogens from the blood for phagocytosis by macrophages. • It also removes worn-out red blood cells from circulation but this isn’t an immunologic function. Associated lymphoid tissues are discrete bundles of lymphocytes beneath the skin and mucosal surfaces all over the body • Positioned to act quickly on pathogens. • Often named for location: G(ut)ALT, M(ucosa)ALT, S(kin)ALT, and B(ronchus)ALT. • Can be temporary like breasts of pregnant and lactating women. The first line of defense includes physical and chemical barriers that shield the sterile tissues. Few pathogens can penetrate unbroken skin. • Epithelial cells of the uppermost layer of the epidermis are compacted, cemented together, and impregnated with keratin. • Thick , tough layer that is highly impervious and waterproof. • Skin cells are constantly being shed. Accessory structures associated with skin act as barriers. Sweat glands: • Flushing effect of sweat glands helps remove microbes. • Sweat is acidic creating an acid mantle. • Sweat contains antimicrobial peptides. Sebaceous glands: • Fatty acids contribute to the acid mantle and have antimicrobial properties. Mucous membranes provide barrier protection but without a keratinized layer like skin. • Mucous membranes line the eye and the digestive, urinary, and respiratory tracts. • Mucous coat impedes the entry and attachment of bacteria. • Blinking and tear production rid the eye of irritants. • Lysozyme that hydrolyzes peptidoglycan in the cell walls of bacteria is found in tears and saliva. Respiratory Tract Defenses • Nasal hair traps larger particles. • Copious flow of mucus and fluids during allergies and colds exerts a flushing action. • Ciliated epithelium moves foreign particles entrapped in mucus in the lungs toward the pharynx for removal. Genitourinary Tract Defenses • Protection through the continuous trickle of urine through ureters and bladder emptying that flushes the urethra. • Vaginal secretions provide cleansing of the lower reproductive tract in females. • Semen has antimicrobial chemicals. • Vagina has a protective acidic pH maintained by normal biota. Digestive Tract Defenses • Flow of saliva carries microbes to harsh conditions of stomach. • Defecation and vomiting mechanically rid the tracts of pathogens. • Stomach contains hydrochloric acid. • Intestines contain digestive juices and bile. The resident microbiota provides microbial antagonism. • Blocks access of pathogens to epithelial surfaces. • Creates unfavorable environments for pathogens by competing for nutrients or by altering local pH. • Trains the immune system to keep commensals in check but to eliminate pathogens. General Activities of Phagocytes • To survey the tissue compartments and discover microbes, particulate matter, and injured or dead cells. • To ingest and eliminate these materials. • To recognize immunogenic information (antigens) in foreign matter. Neutrophils and macrophages are professional phagocytes. Neutrophils: • React early in the inflammatory response to bacteria, foreign materials, and damaged tissue. • Common sign of bacterial infection is a high neutrophil count in the blood. Monocytes are transformed into macrophages after emigrating out of the bloodstream into the tissues due to chemical stimuli. • Increase in size. • Enhanced development of lysosomes and other organelles. • Not only are macrophages dynamic scavengers, but they also process foreign substances and prepare them for reactions with B and T lymphocytes. Pathogen-associated molecular patterns (PAMPs) are recognized by phagocytes and other defensive cells. • PAMPs serve as signal molecules on the surfaces of microbes. • Not present in mammals. • Examples of PAMPs: • Peptidoglycan • Lipopolysaccharide • Double-stranded RNA found in viruses Pattern recognition receptors (PRRs) recognize and bind PAMPs and trigger the immune system. • Found on the surfaces of phagocytes, dendritic cells, endothelial cells, and lymphocytes. • Toll-like receptor one example of a PRR. Phases of Phagocytosis Phagolysosome Formation and Killing 1. Lysosomes migrate to the scene of the phagosome and fuse with it to form the phagolysosome. 2. Granules containing antimicrobial chemicals are released into the phagolysosome. • Reactive oxygen chemicals such as peroxidases, superoxides, singlet oxygen, and hydroxyls (-OH) • Enzymes and acid chemicals such as lactic acid, lysozyme, proteolytic and hydrolytic enzymes. 3. Causes death of the bacteria within 30 minutes. Five Signs and Symptoms of the Inflammatory Response 1. Rubor: redness caused by increased circulation and vasodilation in injured tissues. 2. Calor: warmth from the increased flow of blood. 3. Tumor: swelling from increased fluid in tissues. 4. Dolor: pain caused by the stimulation of nerve endings. 5. Loss of function. All signs of inflammation serve as a warning that injury has taken place. Chief functions of inflammation: • To mobilize and attract immune components to the site of the injury. • To set in motion mechanisms to repair tissue damage and localize and clear away harmful substances. • Destroy microbes and block their further invasion. Major Events in Inflammation Immediate reactions to injury are controlled by nervous stimulation, chemical mediators, and cytokines. • Earliest changes occur in arterioles, capillaries, and venules. • Injured blood vessels immediately constrict. • Chemical mediators and cytokines are released by blood cells, tissue cells, and platelets. • The interaction of these chemical messengers is complex. • Some of them encourage immune reactivity; some of them discourage or dampen that response; some act on the blood vessels in the area; and some regulate the growth or activation of white blood cells. Vascular reactions cause edema and enable leukocyte migration. • Blood vessels dilate which increases blood flow. • Vasoactive substances cause endothelial cells in postcapillary venules to contract and form gaps. Blood-borne components escape into extracellular space (exudate). Local swelling and firmness (edema) follows due to accumulation of exudate into the tissues. • Influx of fluid dilutes toxic substances. • Neutrophils are recruited to stop bacterial infection. Leukocytes and their phagocytic debris form pus. Long-lived inflammatory reactions attract monocytes, lymphocytes, and macrophages. • Macrophages clear pus, cellular debris, dead neutrophils, and damaged tissue. • B lymphocytes react with foreign molecules and produce antibodies. • T lymphocytes kill intruders directly. Fever is a systemic response often complementing inflammation. Fever: • An abnormally elevated body temperature. • Nearly universal symptom of infection. • Also associated with certain allergies, cancer, and other organic illnesses. Benefits: • Inhibits multiplication of temperature-sensitive microorganisms. • Impedes the nutrition of bacteria by reducing the availability of iron as macrophages stop releasing their stored iron. • Increases metabolism and stimulates immune reactions and naturally protective physiological processes. Pyrogens reset the hypothalamic thermostat to a higher setting. • The hypothalamus regulates body temperature. • Exogenous pyrogens originate from outside the body. • Products of infectious agents such as viruses, bacteria, protozoans, and fungi. • Endotoxin • Endogenous pyrogens originate from inside the body. • Released by monocytes, neutrophils, and macrophages during the process of phagocytosis. • Examples are cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). It can be a difficult decision to suppress fever or not. Some advocates: • Slight to moderate fever in an otherwise healthy person should be allowed to run its course. • Potential benefits and minimal side effects. All medical experts agree: • High and prolonged fevers are risky and should be treated. • Fevers in those with cardiovascular disease, head trauma, seizures, and respiratory ailments should also be treated. Antimicrobial Proteins: Interferon • Class of small proteins produced naturally by certain WBCs and tissue cells. • Involved in defenses against viruses and other microbes and in immune regulation and intercommunication. • Interferon is not virus specific. Synthesis in response to one cell type will also protect against other cell types. • In all cases they bind to the cell surface receptors and induce changes in gene expression. Complement consists of 30+ blood proteins that work together to destroy bacteria and some viruses. • Three pathways trigger complement. • Outcomes: enhanced inflammation and phagocytosis, membrane attack complex. • The complex can digest holes in membranes. Antimicrobial Proteins: Antimicrobial Peptides • Short proteins capable of inserting themselves into bacterial membranes. • Between 12 and 50 amino acids.