Ch 14 - Host Defenses PDF

Chapter 14 -- Host Defenses Involve a multilevel network in innate nonspecific protections and specific immunities that are referred to as *the first, second,* and *third* line of defense 1^st^ and 2^nd^ Innate, natural defenses: present at birth, provide nonspecific resistance to infection 3^rd^...

Chapter 14 -- Host Defenses Involve a multilevel network in innate nonspecific protections and specific immunities that are referred to as *the first, second,* and *third* line of defense 1^st^ and 2^nd^ Innate, natural defenses: present at birth, provide nonspecific resistance to infection 3^rd^ Adaptive immunities: specific, must be acquired. These systems do not operate in a separate fashion; most of these defenses overlap and are even redundant in some of their effects **Lines of defense** **First line of defense**: - innate, [nonspecific] barriers against microorganisms - includes any barrier that blocks invasion at the portal of entry. - Access to the internal environment is prevented. **Second line of defense**: - innate, [nonspecific], - more internalized system of protective cells and fluids including responses such as inflammation and phagocytosis. - Acts rapidly at local and systemic levels once the first line of defense has been broached.   **Third line of defense "Adaptive Immunity"**: - acquired, **specific** immunity - highly specialized response wherein the full capabilities of the immune system are brought to bear on individual invading microbes. - Utilizes specific lymphocytes and antibodies to chemically attack specific microorganisms. [First line of defense -- Physical or Anatomical Barriers ] - Skin and mucous membranes of respiratory, urogenital, eyes, and digestive tracts - Outermost layer of skin is composed of epithelial cells compacted, cemented together, and impregnated with keratin; few pathogens can penetrate if intact - Flushing effect of sweat glands - Blinking and tear production - Stomach acid - Mucous coat impedes attachment and entry of bacteria - Nasal hair traps larger particles *Nonspecific chemical defense* - Sebaceous secretions - **Lysozyme**, an enzyme that hydrolyzes the cell wall of bacteria, in tears - High lactic acid and electrolyte concentration in sweat - Skin's acidic pH - Hydrochloric acid in stomach - Digestive juices and bile of intestines - Semen contains an antimicrobial chemical - Vagina has acidic pH [Immunology] - Is the study of all biological, chemical, and physical events surrounding the function of the immune system - [Immune System] does not exist in a single, well defined space; it includes a large, complex and diffuse network of cells and fluids that permeate the whole body - Large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue. - Includes: - Fluids - Tissues/organs - Cells - [Surveillance] - to constantly scout the body for the presence of foreign material - Organs - Tissues - Other compartments - [Recognition] - be able to distinguish between self (self markers) and foreign (foreign markers or *antigens*) - Attack against and destruction of foreign invaders Definitions: - White blood cells (leukocytes) -- innate capacity to recognize and differentiate any foreign material - Nonself -- foreign material - Self -- normal cells of the body - Pathogen recognition receptors (PRRs) -- receptors on WBCs for PAMPs - Feelers for sensing pathogens - Best understood -- toll like receptors (TLRs) - In the membrane of phagocytes - Pathogen-associated patterns (PAMPs) -- molecules shared by microorganisms Immune System Subdivisions - Extracellular fluid (ECF) - just outside cells - reticuloendothelial system (RES) - connective tissue fluids and fibers - blood stream - lymphatic system ***Reticuloendothelial System* (RES)** - Network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs - Inhabited by phagocytic cells -- **mononuclear phagocyte system** -- macrophages ready to attack and ingest microbes that passed the first line of defense ***Blood -- origin, composition, and function*** - Whole blood consists of plasma and formed elements (blood cells) - **Serum** is the liquid portion of the blood after a clot has formed -- minus clotting factors - **Plasma** -- 92% water, metabolic proteins, globulins, clotting factors, hormones, and all other chemicals and gases to support normal physiological functions *Survey of blood cells* - Formed by [hemopoiesis] occurs in red bone marrow - include: - erythroctyes = RBC - Most numerous - Carry oxygen and carbon dioxide - thrombocytes = platelets - leukocytes = WBC - Granulocytes - Agranulocytes - Stem cells -- undifferentiated cells, serve as precursors to new blood cells - Erythrocytes: develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobin - Platelets: formed elements in circulating blood that are *not* whole cells *[Leukocytes : Granulocytes ]* - Neutrophils -- 55-90% - lobed nuclei with lavender granules; phagocytes - Eosinophils -- 1-3% - orange granules and bilobed nucleus; destroy eukaryotic pathogens - weak phagocytes, high during worm infections - Basophils -- 0.5% - constricted nuclei, dark blue granules; release potent chemical mediators - immediate allergy and inflammation by releasing histamine - Mast cells: nonmotile elements bound to connective tissue *[Leukocytes : Agranulocytes ]* - Lymphocytes -- 20-35%, specific immune response - B (humoral immunity): activated B cells produce antibodies - T cells (cell-mediated immunity): activated T cells modulate immune functions and kill foreign cells - Monocytes, macrophages -- 3-7% - largest of WBCs, kidney-shaped nucleus; phagocytic - Macrophages: final differentiation of monocytes - Dendritic cells: trap pathogens and participate in immune reactions **Lymphatic Fluid** - Lymph is a plasma-like liquid carried by lymphatic circulation - Formed when blood components move out of blood vessels into extracellular spaces - Made up of water, dissolved salts, 2-5% proteins - Transports white blood cells, fats, cellular debris, and infectious agents **Lymphatic Vessels** - Lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus - Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles - Functions to return lymph to circulation; flow is one-direction -- toward the heart -- eventually returning to blood stream Lymph organs/tissues - [Primary organs] -- sites of origin and maturation of lymphocytes - Bone marrow - Thymus gland - high rate of growth and activity until puberty, then begins to shrink; site of T-cell maturation - [Secondary organs and tissues] -- circulatory-based locations where encounters with microbes and immune responses take place - Lymph nodes - small, encapsulated, bean-shaped organs stationed along lymphatic channels and large blood vessels of the thoracic and abdominal cavities - Spleen - structurally similar to lymph node; filters circulating blood to remove worn out RBCs and pathogens - Misc: - GALT - gut-associated lymphoidal tissue (clusters of lymphoid tissue) - Peyer's patch - MALT - SALT -- Skin associated *Two unique properties of leukocytes* - [Diapedesis] - the ability to squeeze out of blood vessels and go into tissue spaces - [Chemotaxis] - the ability to migrate to chemical stimulus usually at a site of inflammation or infection Actions of the second line of defense - Recognition - Inflammation - Phagocytosis - Interferon - Complement Role of inflammation 1. Mobilize and attract immune cells and chemicals to the site of the injury 2. set in motion mechanism to repair tissue damage and localize and clear away harmful substances 3. To destroy and block microbes from further invasion **Inflammation** - Body response to injury; aids in destruction and spread of microbes - classics signs: - rubor -- redness - increased circulation and vasodilation in injured tissues in response to chemical mediators - calor -- heat - Increased blood flow - tumor -- swelling - increased fluid escaping into the tissue as blood vessels dilate -- edema; WBC's, microbes, debris, and fluid collect to form pus; prevents spread of infection - dolor -- pain - Nerve endings stimulated Fever - Abnormally elevated body temperature - [hypothalamus] is responsible for setting core body temperature (98.6^o^) - circulating [pyrogen] will cause a resetting of body temperature to higher setting - Exogenous pyrogens -- products of infectious agents - Endogenous pyrogens -- liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF) - pyrogen = microbe products, blood products, vaccines, cytokines Benefits to fever \-\-- yes, there are! - Inhibits multiplication of heat sensitive microbes - prevents the nutrition of bacteria by reducing the availability of iron - increases metabolism helps stimulate immune reactions **Phagocytosis** General activities of phagocytes: - To survey tissue compartments and discover microbes, particulate matter, and dead or injured cells - To ingest and eliminate these materials - To extract immunogenic information from foreign matter - Includes: - Neutrophil - Eosinophils - monocyte = macrophages - Neutrophils -- - general-purpose; react early to bacteria and other foreign materials, and to damaged tissue - Eosinophils - - attracted to sites of parasitic infections and antigen-antibody reactions - monocyte = macrophages - fixed macrophages - permanent residents in certain tissues - wandering macrophages - do not reside permanently in any tissue Cytokines **-** chemical mediators that regulate, stimulate, and limit immune reactions - produced by white blood cells and damaged tissue cells - examples: histamine, interleukin 1, interleukin 2, interferon **Interferon** - Cytokine produced & released by host cells to nonspecifically inhibit the spread of viral particles - Interferon alpha -- lymphocytes and macrophages - Interferon beta -- fibroblasts and epithelial cells - Interferon gamma -- T cells - produced in response to viruses, intracellular parasites, cytokines - Causes inhibition of virus replication inside cells and suppress tumors **Complement System** - Complex system involved at several levels of immunity - consists of 26 blood proteins that work in concert to destroy bacteria and some viruses - Complement proteins are activated by cleavage (cascade reaction) - blood proteins = **complement factors** are produced by liver, lymphocytes, monocytes *2 pathways -- classic and alternate* - work in a cascade reaction like blood clotting - activated by microbes, parts of microbes, cytokines - end product = **membrane attack complex** or **MAC** - **MAC** is a large ring shaped protein Functions of complement - **MAC** = Kill the microbe by digesting holes in surface - act as chemotactic agent - stimulate inflammation - Opsonization = coats the microbe to augment phagocytosis Natural Killer cell Type of T cell with natural nonspecific cytotoxic powers - destroys virus infected cells, tumor cells - found in spleen blood, lungs, lymph nodes, bone marrow - stimulated by cytokines..... to be continued with 3^rd^ line of defense