Human Disease 1

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Human Disease 1
2012-02-05 19:39:32

Human disease exam 1
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  1. Disease
    • Impairment of health, abnormal function/condition, discomfort or dysfunction, no longer healthy
    • loss or limitation of function
  2. Symptoms
    what patient complains of; rash, pain, swelling, upset stomach; descriptive/qualitative
  3. Signs
    • quantitative changes; raised body temp, inc wbc count; measured
    • defined in context of clinical tests (sometimes can see signs before symptoms- proactive)
  4. Congenital and hereditary disease
    developmental disturbance; genetic or environmental
  5. inflammatory disease
    reaction by body to an agent by means of inflammatory process
  6. degenerative disease
    abnormal degeneration
  7. metabolic disease
    distrubance in one or more metabolic pathways
  8. neoplastic disease
    abnormal cell growth leading to benign or malignant tumors
  9. Cellular response progression
    adaptation-->reversible injury-->irreversible injury-->cell death
  10. hypertrophy
    • enlargemnt of cell size
    • physiological and pathological conditions (chronic heart disease)
  11. hyperplalsia
    • increase in cell #
    • lymphnodes, spleen
  12. atrophy
    wasting of cell; decreased size
  13. metaplasia
    change in cell architecture and often fucntion
  14. autophagy
    • digestion and exocytosis of self
    • cellular self digestion
  15. Characteristics of cellular responses to injury
    • 1. response depends on type of injury, duration, and severity
    • 2. depends on type, status, adaptability and genetic makeup of injured cell
    • 3. localized effect on a cell can have rapid secondary effects with result in cell injury or death
    • 4. function is lost before cell death with occurs before morphological changes are observed
  16. Targets for cellular injury
    • Necrosis: ATP, membrane damage (mitochondria, plasma membrane, lysosome), cytoskeletal damage
    • Apoptosis: mitochondria, DNA damage
  17. Ischemia
    • Blockage of blood flow
    • Decreased oxidative phosphorylation and ATP; decrease in Na pump activity...leads to cellular swelling, blebs, ER swelling, decr glycogen; clumping of nuclear chromatin; lipid deposition
  18. Changes in cells upon injury
    • Reversible: swelling of ER and mito, membrane blebs, clumping of chromatin
    • Irreversible (necrosis): swelling of ER and loss of ribosomes, lysosome rupture, myelin figures, nuclear condensation, swollen mito with amorphous densities -- LOSS OF MEMBRANE INTEGRITY, BREAKDOWN OF GENETIC MATERIAL, LOSS OF MT FXN
  19. Necrosis
    • sequence of morphological changes that follow cell death in living tissues; cell swelling, denaturation of cytoplasmic proteins and breakdown of cell organelles and membranes; Loss of membrane integrity
    • Release of cytoplasmic components
    • Inflammation!
  20. Apoptosis
    • programmed cell death characterized by DNA fragmentation and apoptotic bodies
    • Occurs during: embriogenesis, hormone-dep physio involution, cell deletion in proliferating populations, deletion of autoreactive T cells, mild injurious stimulus that causes DNA damage
    • No inflammation! Phagocytosis of apoptotic bodies
  21. Cellular aging
    • Environmental insults-->free radicals-->damage to proteins and organelles
    • Calorie restriction-->activation of DNA-stabilizing proteins--|DNA damage
  22. Immunity
    • reaction by organism involving cells of immune system in response to a foreign substance
    • recognition and removal of foreign substance
  23. Major classes of immune response
    • Innate (natural immunity): present before exposer, does not change its response upn repeated exposure; conserved across all species; fast; macrophages, granulocytes (mast, neutrophils, basophils, eosinophils); complement; skin/mucus membranes
    • Acquired (specific) immunity: stimulated by exposure; response is enhanced with each exposure; found in bony fish through mammals; slow; memory; antibodies; t and b cells
  24. Humoral immune response
    mediated by moleculres known as antibodies, released by B cells, bind foreign substances and lead to elimination
  25. Cell Mediated immune response
    mediated by cells known as T cells which fxn to activate other immune cells and/or kill infected cells
  26. Central features of acquired immune response: Specificity
    Immune responses are specific for distinct antigens
  27. Central features of acquired immune response:Diversity
    # of lymphocytes which recognized distinct regions (or epitopes) is very large
  28. Central features of acquired immune response: Memory
    exposure of immune system to a foreign antigen enhances its ability to respond again to taht antigen
  29. Central features of acquired immune response: Self-limitation
    immune response is down regulated after a period of tiem
  30. Central features of acquired immune response: Discrimination of self
    no immune response to your own proteins or other molecules
  31. Antigen vs epitope
    • Antigen is molecule recognized by immune system
    • epitope is section of antigen that is physically interacting with antibody or t cell receptor
  32. Primary vs memory response
    • acquired immune system remembers exposure to particular antigen before- mounts stronger faster response after first exposure
    • clonal expansion
  33. 3 phases of acquired immune response
    • 1. Cognitive: recognition of antigen
    • 2. Activation: proliferation and differentiation of lymphocytes which recognize antigens
    • 3. Effector: fxnal consequenceof an active lymphocyte
  34. How innate and acquired stimulate and enhace each other
    • antibodies promote phagocytosis
    • complement activation
    • cytokines
    • innate immune response results in production of protein and lipid mediators which fxn to enhance acquired immunity and vice versa
  35. Clonal selection hypothesis
    one lymphocyte = one antigen recognition (epitope)
  36. organization and fxn of lymph nodes
    • why we need immune cells circulating- infection or foreign body can be anywhere, so b and t cells and lymphocytes need to be everywhere to fight and control infection
    • macrophage comes into contact with b and t cells in lymph node- b and t cells becomes activated and leave lymph node- find infection while circulating
    • lymph node is focal point for b and t cell activation
  37. T-helper cell vs cytolytic T cell
    • Helper- cytokines; MHC class II
    • cytolytic- kill cell; MHC class I
  38. Leukocytes
    • White blood cells!!
    • Monocytes
    • Granulocytes
    • T-Helper cells
    • cytolytic T cells
  39. Macrophage fxn
    • 1. inflammation and wound healing
    • 2. produces cytokines and chemokines which activate and recruit lymphocytes respectively, to the site of injury
    • 3. antigen presenting cells
    • 4. binds to and ingest particles coated with antibodies and/or complement to clear the material from circulation or from tissue
  40. Granulocytes fxn
    • 1. neutrophils: phagocytic, first at site of infection, short lived, activated by cytokines and by proteins of the extracellular matrix
    • 2. eosinophils: receptors to a class of antibodies known as IgE. secrete granules. involved in sites of allergic reactions and contribute to tissue injury and inflammation
    • 3. basophils: also have receptors for IgE and produce chemical mediators of immediate hypersensitivity
  41. MHC class I and MHC class II
    • Most polymorphic of any proteins in human population!
    • Reason: different sets of MHC class I and II bind different sets of peptides; broad
    • If we all expressed the same MHC class I and II molecules, then diseases would evolve so that it could avoid being bound by these molecules
    • We express multiple alleles of MHC molecules. A, B, and C code for class I and differ at antigen binding site.
  42. Cytokine properties
    • 1. produced during effector phase of both innate and acquired immune response and regulate immune and inflammatory responses
    • 2. secretion is brief and regulated
    • 3. produced by multiple cell types
    • 4. act on different cell types
    • 5. stimulation may have multiple effects on target cells
    • 6. different cytokines can have similar effects
    • 7. can influence synthesis of other cytokines
    • 8. can influence synthesis of other cytokines
    • 9. initiate their action of other cytokines
    • 10. receptor expression is also regulated
    • 11. production usually requires new mRNA and protein synthesis
    • 12. act as growth factor
  43. Specificity of T and B cells
    How does it work?
    • random somatic recombination
    • V-D-J rearrangement during development
  44. TNFalpha, IL-1, and IFNgamma
    • TNFalpha and IL-1: Inflammation
    • Increase leukocyte adhesion by upregulation of selectins and ICAM-1
    • INFgamma- produced by t cells and is an important cytokine for activating macrophages
  45. Chemokine
    • Chemo-attractant
    • IL-8: produced by macrophages, important mediator of the immune reaction in the innate immune system response.
  46. Allograft
    transplant btwn 2 genetically different individuals of same species
  47. Alloreactivity
    • immune response to allograft
    • MHC class I and II are major antigens that stimulate this
  48. Effector mechanisms for tissue rejection
    Alloreactive CD4+ or CD8+ T cells or specific alloantibodies are capable of mediating allograft rejection
  49. Prevention and treatment of Allograft rejection
    • 1. Suppresion of recipients immune system: inactivation of T cells using immunosuppressive drugs; total lymphoid irradation; use antibodies to block T cell activation; graft recipient may be made tolerant to allograft
    • 2. graft may be made less immunogenic
  50. Graft vs Host Disease
    • initiated mature T cells in donor's bone marrow which recognizes host alloantigens
    • tissue destruction is thought to be mediated primarily be NK cells
  51. Inflammatory response
    • protective response induced by the body due to some insult with the idea of removing whatever caused the insult and heal the resulting damage associated with it
    • both immune mediated and nonimmune mediated
    • Trauma: not antigen driven
  52. Acute inflammation
    • quick to respond- with in minutes
    • neutrophils
    • edema- build up of fluid and proteins in tissue; breakdown of epithelium
  53. Chronic inflammation
    • longer duration
    • macrophages and lymphocytes
    • increased damage to tissue and fibrosis
  54. Signs of acute inflammation
    heat, redness, swelling, pain, and loss of fxn
  55. Endothelial contraction
    • main mechanism of vascular permeability associated with acute inflammation
    • break down of cell-cell jxns
  56. localize inflammatory response
    • 1. cell brought in can eliminate problem
    • 2. inflammatory process can cause damage, so want it kept in small area
  57. E-, p-, and l-selectin
    • selectins bind carbohydrates- low affinity binding allows for rolling
    • upregulated by granules and exposure to inflammatory mediators
  58. Integrins (LFA1 and MAC1)
    • found on leukocyte in inactive form.
    • when exposed to TNF, will change conformation and bind to ICAM-1 and PECAM
    • diffusion mediated process- adhesion happens in close proximity to where damage is
  59. Signals and processes required for migration of leukocytes
    • Chemotactic gradient- move toward higher concentration. fMLP, C5a, LTB4, IL-8
    • proteases degrade matrix so leukocytes can make their own road- causes some tissue damage
  60. Fxn of reactive oxygen intermediates
    • 1. very important anti-microbial. produced with phagosomes (macrophages and neutrophils)
    • 2. cause tissue damage- produced locally to constrain this
  61. Released from granules
    • histamine: inc vascular permeability-edema (mast cells)
    • lysosomal enzymes: (macrophages and neutrophils)
  62. Leukotrienes and prostaglandins
    • Cell membrane phospholipids-->arachidonic acid
    • 1. 5-lipoxygenase-->5-HPETE-->Leukotriene (vasocontriction, increased permeability)
    • 2. Cyclooxygenase-->Prostaglandin (potentiate edema)

    increase vascular permeability
  63. IL-1 and TNFalpha
    • wound healing and drive fibrosis
    • increase leukocyte adherence
  64. Complement
    • 1. lectin: mannose binding lectin
    • 2. classic: most active and efficient pathway; antibody mediated (effector molecule made in liver)
    • 3. alternative: inefficient

    • C3a chemotaxis, stimulates mast cell degranulation
    • C3b coats microbe to enhance ability to be phagocytosed
    • C5a stimulates vasodilation by causing histamine relase; promotes leukocyte adhesion by upregulating expression of selectins and activating integrins
  65. Membrane attack complex
    lysis of microbes
  66. Chronic inflammation
    • 1. mononuclear phagocytes, t lymphocyes, plasma cells, and mast cells
    • 2. tissue destruction
    • 3. new vessel formation and fibrosis
    • - persistent infection, continual exposure to toxic material, autoimmune diseases, interference with normal repair process
  67. Granuloma
    • Giant cell, epitheliod cell, macrophage, lymphocyte, fibroblast.
    • wall off substances that it perceives as foreign but is unable to eliminate
    • special type of inflammation
  68. resolution of inflammatory response
    • removal of edema fluid and proteins by drainage into lymphatics or by macrophage pinocytosis
    • phagocytosis and apoptotic neutrophils and necrotic debris by macrophages
    • removal of macrophages
  69. Repair process
    • Regeneration of cells lost during the inflammatory process
    • replacement of cells with connective tissues- results in scarring
  70. Repair process growth factors
    • 1. Epidermal GF
    • 2. Platelet derived GF
    • 3. Fibroblast GF
    • 4. Transformting FGbeta
  71. ECM components
    • Basement membrane: fibrous structural proteins- collagens, laminin and proteoglycans
    • Interstitial matrix: fibronectin, laminin, elastin, vitronectin and collagen; proteoglycan and hyaluronan
  72. ECM functions
    • 1. support for cells
    • 2. control of cell growth
    • 3. cell orientation
    • 4. cell differentiation
    • 5. scaffolding for tissue renewal
    • 6. cell migration
    • 7. storage and presentation of regulatory molecules
  73. granulation and fibrosis
    wound healing. fibrosis occurs when wound is too deep