except the upper right quadrant:

Lymphatic System - See text p. 710-720 and figure 22.1 and 22.2 - System of vessels throughout the body that carry lymph (purified blood plasma) - clear, watery fluid - in many ways is similar to blood plasma - only 1/2 the concentration of plasma proteins than in blood plasma - few to no cells are present - Considered to be outside of the cardiovascular system - Serves as a drainage system - lymph fluid lymph vessels lymph nodes - nodes serve as filters for interstitial fluid that has come from cardiovascular system - vessels similar to capillaries - drain extracellular space in body - Edematous condition - buildup of extracellular fluid (ECF), or interstitial fluid (ISF) - diuretics flush the body of excess water - e.g. Lasix, Diamox - Dynamic equilibrium exists between cardiovascular system and lymphatic system - blood plasma contained in vessels - certain amount leaks out into periphery - picked up by lymphatic system and cleansed - returned to vascular system lymph from the entire body except the upper right quadrant: thoracic duct left subclavian vein brachiocephalic vein superior vena cava right atrium lymph from the upper rt. quadrant: right lymphatic duct right atrium Filtration Across Capillaries - Four opposing forces at work in controlling the filtration of fluid - Amount leaving vessels = amount entering (under normal conditions) 1. Pushing forces: a. capillary hydrostatic pressure (CHP) - also known as capillary pressure - water pressure exerted by fluid inside capillaries - if unopposed, fluid will be pushed out of capillaries b. tissue hydrostatic pressure (THP) - also known as interstitial fluid pressure - water pressure exerted by fluid outside the capillaries - if unopposed, fluid will be pushed into capillaries * note: CHP and THP are opposing forces 39 Dr. Hutz

2. Pulling forces: a. tissue osmotic pressure (TOP) - also known as interstitial osmotic pressure - attempts to pull fluids out of the capillaries - due to proteins in the interstitial spaces - fluid will be picked up by lymphatic system and returned to the heart b. plasma osmotic pressure (POP) - also known as oncotic pressure - attempts to pull fluid into capillaries - due to proteins circulating in the blood stream -- albumin, mainly * note: TOP and POP are opposing forces - Analogy: beaker of water divided by a semipermeable membrane - contains glucose on one side -- can t cross membrane - only water can pass through membrane - concentration of water on glucose side - water will move down its concentration gradient as... - glucose exerts an osmotic pressure that draws water toward it * note: many substances provide an osmotic pressure - Scenarios: 1. High blood pressure - CHP - fluid moves out of capillaries 2. Dehydration - vascular fluid - CHP - THP > CHP - fluid moves into vessels - POP > TOP - blood has less fluid, but greater concentration of proteins - fluid moves down its concentration gradient - fluid moves into vessels under osmotic draw from proteins in blood Immunology 1. Terms a. antigen - also called immunogens - substance that has never been seen before by body - e.g. virus, protein, DNA, polysaccharide b. antibody - also called agglutinogens - attacks foreign antigens - found in plasma 2. Macromolecules - large molecules that elicit an immune response a. carbohydrates b. proteins c. DNA CourseNotes 40

3. Haptens - small molecules that won t elicit an immune response until after conjugation to a larger, immunogenic molecule Defense Against Infection 1. Nonspecific host defense mechanisms - see text p. 725-730 - considered to be innate -- born with it a. mechanical factors 1. skin - largest organ of the body 2. mucous membranes - secrete mucus - line nose, mouth and throat - sticky, humidified, trap dirt 3. cilia - serve as brush to trap dirt, bacteria, etc. 4. saliva - contains lysozyme - an enzyme that can break up microorganisms - allows you to spit the toxins, bacteria, etc. out of your body * note: functions as both a mechanical factor and a chemical factor 5. defecation 6. urination b. chemical factors 1. ph - scale of 0 to 14 (7 is neutral) - body is 7.4 -- range is from 7.0-8.0 - stomach ph 2.5 -- comparable to ph of lemon juice - vagina ph 6 or less -- kills bacteria in vagina 2. lysozyme - in tears and saliva 3. complement factors - present in blood and tissue - can increase an immune response 4. lymphokines - produced by lymphocytes a. interferon (IFN) - can inhibit cell replication - used as therapy with some cancers b. interleukins (IL) - identified IL-1 to IL-16 so far - can activate certain T-cells - involved in mounting an immune response against microorganisms - some activate B-cells 41 Dr. Hutz

5. histamine - released in an inflammatory response - produced by and basophils, eosinophils and mast cells - a major component of immune response - released at site of tissue injury - causes localized dilation of blood vessels 6. phagocytosis = cell eating - certain types of cells convert to macrophages and engulf bacteria 2. Specific host defense mechanisms - see text p. 730-742 - this is acquired immunity - specific recognition - also called exact recognition - one specific type of antibody for each antigen - major components are T and B lymphocytes a. concepts involved: 1. memory (recollection phenomenon) - example: erythroblastosis fetalis - first pregnancy takes a long time to build antibodies against the Rh factor - this is why the baby is not affected - next time Rh factor is present -- antibody production is rapid 2. amplification - rapid cloning response - after exposure to a foreign antigen, an amplification cascade is created - on subsequent exposures, immune response is mounted quite rapidly antigen enters body antibodies produced recognize foreign antigen bind antigen negate effects of antigen b. antibody production theories: 1. clonal selection theory - certain cells (plasma cells) have antibodies on their surface that recognize the antigenic determinants of antigens a. antigenic determinant (of antigen) fits into receptor on surface of plasma cell b. lock and key fit c. builds clones of plasma cells - build antibodies to break apart antigen * note: theory says clones exist even for antigens that the body has never seen - plasma cells in body have the lock that will fit with any key - even synthetic compounds CourseNotes 42

- explanation for theory: cross reactivity - synthesized antigen has cross reactivity with normal antigen that is already present in the body -- similar antigenic determinants - example: paraquat - weed killer that was sprayed on marijuana plants as a defoliant - plants that survived were imported into the U.S. - people that smoked these plants developed lung diseases - theory holds: humans have receptors for paraquat on their lungs 2. clonal deletion theory - explains tolerance to self antigens - i.e. plasma cells that would normally destroy own antigens are deleted - when this is no longer functioning properly, autoimmune diseases arise 3. molecular mimicry - plays a role in autoimmune responses - no longer recognize own antigens as self - foreign antigen can mimic a normal antigen - may be only slightly different than normal antigen - alerts immune system - body has difficulty distinguishing between them - attacks own antigens c. lymphocytes 1. T-cells - produced in bone marrow - mature in thymus gland - this lies over the heart - gets smaller with age - types: a. helper T-cells - secrete lymphokines -- help B-cells to produce antibodies - e.g. interferon, interleukins b. suppresser T-cells - involved in controlling overproduction of antibodies - need to shut down B-cells after antibodies are no longer needed c. cytotoxic T-cell - this is a T-cell - also called a killer T-cell - destroy specific cells that have specific antigens on them - involved in: 1. viral infection 2. fungal infection 3. graft rejection * note: not to be confused with natural killer (NK) cell - neither T-cell nor B-cell - destroys all invading organisms -- not specific 43 Dr. Hutz

2. B-cells - produced in bone marrow, or elsewhere - unknown site of maturation -- possibly aorta - function in antibody production after antigen/antibody binding aggregation of Ag/Ab complexes antigens are neutralized complexes are opsonized macrophages engulf the complexes d. scenario: antigen enters the body 1. foreign microbe - antigen on surface - enters body for first time 2. macrophages - engulfs and displays surface Ag of microbe 3. inflammatory reaction - this is local - involves histamine (basophils, mast cells) 4. macrophages attempt to engulf microbe engulfs antigen-and-microbe presents initiating antigen on its surface more macrophages 5. IL-1 is produced - raises body temperature -- fever - this reduces microbial growth to an extent 6. natural killer cells - attack infected body cells 7. monocytes - mature to become macrophages 8. helper T-cells (CD4 cells) - are activated - produce lymphokines - replication of T-cells - T-cells bind antigen - stimulate B-cells to produce antibodies 9. T-cytotoxic cells - recognize and destroy infected cells - in number as well CourseNotes 44

10. suppresser T-cells - in number - attempt to shut down immune response (if it s required) - may take several days 11. memory cells persist - if body ever sees microbe again -- antibody production within hours * note: antibodies - don t technically destroy the invader themselves - activate complement - makes holes in foreign cell's membrane - cell swells and ultimately bursts - plasma cell can produce 2,000 antibodies/sec. when it s maximally engaged Autoimmune Disorders - Body produces antibodies against self - see molecular mimicry earlier in the notes - Sometimes age related 1. Juvenile diabetes - also known as Type-1 diabetes and insulin-dependent diabetes mellitus - possibly virus involved -- has antigen - puts antigen on pancreas cells - pancreas cells producing insulin - body sees cells of pancreas as foreign - antibodies produced against β-islet cells of pancreas - these cells produce insulin - individual can no longer regulate glucose levels 2. Grave s Disease - George and Barbara Bush had this - hyperthyroid condition - body sees thyroid tissue as foreign - builds antibodies against thyroid gland - specifically against certain receptors - thyroid enlarges - thyroid must be surgically removed or destroyed via radioactive iodine 3. Myasthenia gravis - type of muscular dystrophy - antibodies are built against neurotransmitter receptors at the neuromuscular junction - alters the way nerves innervate muscle -- interferes with muscle coordination 4. Rheumatic fever - body sees some heart tissue as foreign and builds up antibodies against it - particularly valvular tissue - sometimes need valve replacements - use pig valves - use artificial valves 45 Dr. Hutz

5. Systemic lupus erythematosus (SLE) - develop anti-nuclear antibodies (ANAs) - body sees own DNA as foreign - extremely debilitating - causes problems with most organs to some degree - connective tissue disorders - febrile - muscle weakness - joints - skin conditions - lymph - anemia - pleurisy - pericarditis 6. Arthritis - certain forms - components of joints seen as foreign - increases with age 7. Endometriosis - still in question as to whether it is autoimmune - endometrial (uterine) tissue is disseminated throughout body - tissues on ovary, lungs, colon - bleeds monthly - extremely painful - treatment - danazol - GnRH- A - surgery 8. Savage syndromep - premature ovarian failure - menopause occurs at age 25 - ovaries are devoid of follicles and egg cells 9. Addison s disease - dysfunction of adrenal cortex - body unable to deal with stress by secreting glucocorticoids - body sees parts of adrenal gland as foreign Immunotherapy - Takes advantage of many components of the immune system - Example: interleukin-2 (IL-2) - controls certain types of colon cancer a. inject IL-2 b. take blood sample c. remove WBCs d. incubate them in IL-2 e. re-inject WBCs into individual CourseNotes 46