Study Guide Weeks 1-11 PDF

Study Guide Hypersensitivity A. Define hypersensitivity 1. Increased immune response to the presence of an antigen which produces undesirable clinical effects 2. Note that the four types of hypersensitivity reactions do not necessarily occur i...

Study Guide Hypersensitivity A. Define hypersensitivity 1. Increased immune response to the presence of an antigen which produces undesirable clinical effects 2. Note that the four types of hypersensitivity reactions do not necessarily occur in isolation B. Describe the four types of hypersensitivity, including the time course of each 1. Type I – Immediate Hypersensitivity, Atopy i. IgE is produced instead of IgG (a) Mast cell degranulation (b) Histamine released ii. Response to allergens (a) Normally harmless substances which cause an allergic response (a) Examples include: (i) Shellfish (ii) Pet dander (iii) Dust mites (iv) Peanuts (v) Latex (vi) Insect venom iii. Anaphylaxis = systemic Type I response 2. Type II – Cytotoxic reactions to self-antigens i. Immune response to one’s own tissues (a) Complement activation, agglutination, phagocytosis (a) Examples: (i) Hemolytic diseases of newborn (ii) Myasthenia gravis ii. Cross-reaction between exogenous and endogenous body tissues (a) Examples: (a) Hemolytic streptococci / mitral valve disease (b) Guillian-Barre syndrome 3. Type III – Immune Complex Diseases i. Antigen-antibody complexes depositing around small blood vessels (a) Complement cascade, acute inflammation, tissue injury ii. Examples: (a) Rheumatoid arthritis (b) Nephritis (c) Pericarditis (d) Vasculitis (a) Systemic lupus erythematosus (cell nucleus is antigen) 4. Type IV – Cell-mediated immunity i. Delayed reaction to allergen, usually 48-72 hours (a) Based on macrophage to T-cell interactions which take time to occur ii. Examples: (a) Transplant rejections (b) Delayed contact dermatitis (e.g., poison ivy)  Study Guide Connective Tissue - Bone A. Describe the general structure of bone 1. Cortical bone (also known as Compact Bone) i. Tough outer layer ii. Majority of bone in the body iii. Covered by periosteum on superficial surface (a) This contains blood vessels 2. Cancellous Bone (also known as Trabecular Bone or Spongy Bone) i. Spongy, mesh plates ii. In contact with bone marrow B. Describe the cellular and non-cellular components of bone 1. Cellular Component i. Osteoblasts (a) Immature bone cells (b) Secrete extra-cellular matrix to give bone its material properties (c) Eventually can: (a) Become osteocytes (see below) (b) Become bone lining cells (c) Die via apoptosis ii. Osteocytes (a) Mature bone cells (b) Maintain extracellular matrix (a) Response to mechanical loading (b) Response to hormones iii. Osteoclasts (a) Break down extracellular matrix (a) Releases minerals into the blood stream (b) Provides space for osteoblasts to secrete new extracellular matrix iv. Bone Lining Cells 2. Non-cellular Component (extracellular matrix, secreted by osteoblasts) i. Non-mineralized (a) Osteoid is the main non-mineralized component (a) Collagen is main protein in osteoid ii. Mineralized (a) Hydroxyapatite is main mineralized component C. Differentiate between the two classifications of bone based on the tissue’s maturity level 1. Immature bone = woven bone i. Also known as “primary bone” ii. Found during fracture repair process (and also in fetal growth) iii. Weaker than mature bone (a) Irregular collagen structure  (b) Less mineral content in osteoid 2. Mature bone = lamellar bone i. Also known as “secondary bone” ii. Forms in remodeling process (i.e. woven bone has stressors placed upon it, and remodels) iii. Stronger than woven bone (a) Osteon structure of concentric rings (a) Adapted based on stressors placed upon it (b) Osteocytes houses in lacunae (c) Haversian canals contain blood vessels and lymphatic vessels (d) Volkmann’s canals connect osteons together (b) More mineral content in osteoid 3. Both, cortical bone and cancellous bone can exist in immature forms D. Describe the process of fracture repair 1. Occurs by regeneration and remodeling i. No scar ii. Return to optimal functioning possible 2. Duration is dependent upon multiple factors i. Fracture site ii. Type iii. Treatment iv. Soft tissue involvement v. Individual factors, including (a) Age (b) Immunocompetency (c) Nutritional status 3. Phases of healing i. Internal bleeding delivers cells to the site of injury, which secrete a number of growth factors, and eventually results in clotting (a) Fibroblasts (b) Platelets (c) Osteoprogenitor cells (a) Bone precursor cells (b) Can become osteoblasts, osteoclasts, etc. (d) Mesenchymal cells (a) Can become (i) Fibroblasts (ii) Chondroblasts (produce cartilage) (iii) Osteoprogenitor cells (e) Inflammatory cells ii. Hematoma forms (a) Lasts about a week iii. Inflammation occurs (a) Granulation tissue forms (a) Fibrosis  (b) Neovascularization (new blood vessel formation) iv. Soft callus forms after about 2 weeks (a) Osteoclasts clear necrotic bone (b) Periosteum and endosteum regenerate (a) Different into (i) Hyaline cartilage (soft callus) (ii) Bony spicules (hard callus) (c) Soft callus formation immobilizes fracture site v. Hard callus begins to develop (1+ week after soft callus) (a) Fibrocartilage (b) Endochondral ossification occurs (a) Transformation of cartilage to bone vi. Remodeling occurs (a) Months to years (b) Woven bone replaced with lamellar bone (c) Excessive callus is resorbed (d) Bone remodels in relation to mechanical stresses placed upon it (Wolff’s law!)  Study Guide Skeletal Muscle Injury Repair A. Describe the process of repair following a muscle strain or contusion 1. Hemostasis and hematoma formation 2. Degeneration i. Necrosis (a) Neutrophils are the first on the scene ii. Chemotactic agents released to attract inflammatory mediators 3. Inflammation i. Begins within 24-48 hours following injury ii. Phagocytosis of cellular debris iii. Macrophages cause stimulation of satellite cells (a) Migrate to the region (b) Differentiate (c) Various cytokines released (see Point C) iv. T-lymphocytes dominate after macrophages wane (a) Various cytokines released (see Point C) 4. Regeneration i. 6-8 weeks after injury ii. Remodeling occurs after regeneration 5. Fibrosis may occur (but not necessarily) i. Less functional B. Describe the role of the basement membrane in muscle healing 1. Basement membrane must remain intact for regeneration to occur i. Division of satellite cells maintain this (a) Combine with other myogenic cells (b) Fuse with remaining muscle fibers ii. If basement membrane is not intact, fibrosis results (a) Maintains structural integrity of muscle (b) Lacks functional capacity (c) Increased risk of re-injury C. State the five effects that cytokines can have on satellite cells / muscle cells during repair 1. Enhanced resistance to oxidative stress i. Cell survival 2. Block myofibrogenesis i. Improved muscle healing 3. Proliferation i. Cell division 4. Differentiation i. Fusion to myofibers 5. Angiogenesis i. Vascular supply to new muscle cells  Study Guide Immune System A. Compare the functions of innate immunity vs. adaptive immunity 1. Innate immunity i. Innate immunity is non-specific to a given pathogen (a) Eliminate pathogen rapidly (b) Mediate initiation and development of adaptive immunity (c) Work with adaptive immune response to eliminate pathogen 2. Adaptive immunity i. Specific to different pathogens, and develops a “memory” to fight them in the future (a) Specific response to a given pathogen (a) Pre-activation required (i) Days to weeks (b) Re-activated if a high enough threat is sustained (activation threshold) (b) Continually develops throughout life B. Name the key components of innate immunity (Table 7-2) 1. Exterior defenses i. Epithelial barriers ii. Mucosa iii. Secretions 2. Cellular components / Phagocytes (leukocytes) i. Natural killer cells ii. Neutrophils iii. Monocytes/Macrophages iv. Neutrophils, Eosinophils, Basophils v. Mast Cells and platelets 3. Soluble mediators i. Complement (a) A system of proteins which induces the acute inflammatory response (b) Damage microbial membranes to kill cells and aid in phagocytosis ii. Cytokines (a) Proteins/glycoproteins which modify cellular behavior C. Describe the key types of cytokines 1. Chemokines i. Small cytokines that cause chemically-induced migration of leukocytes to enhance inflammation (a) Increase vascular permeability (b) Activate vascular epithelial tissue (c) Change blood flow 2. Interferons i. Produced by cells infected with viruses ii. Increase resistance to viral replication 3. Acute phase proteins  i. Pro-inflammatory cytokines which promote a variety of effects (a) Altered metabolism (b) Altered blood flow (c) Production of other proteins D. Describe the two key components of adaptive immunity 1. Humoral immunity 2. Cell-mediated immunity E. Differentiate between antigen and immunogen 1. Antigen - Any molecule which binds to an antibody or T-cell receptor 2. Immunogen – An antigen which provokes an immune system response i. Example – Adjuvant – immunostimulatory substance meant to increase response to a vaccine F. Differentiate between active and passive immunity 1. Active immunity = protection following exposure to a given antigen, providing a long-lasting protection i. Natural immunity (a) Example – exposure to influenza virus from somebody coughing ii. Artificial immunity (a) Example – exposure to influenza virus antigens from a vaccine (b) Prepares immune system to quickly produce a specific-immune response at a later time 2. Passive Immunity = antibodies or sensitized lymphocytes from an immune individual are transferred to a non-immune individual i. Produces a temporary response ii. Examples (a) Natural – Transplacental transfer of antibodies (b) Artificial – Inoculation of antibody G. Briefly describe the structure and function of an antibody 1. Produced by B lymphocytes 2. Has two sites key regions i. Fragment antigen binding site (a) binds to antigens (b) Has variable regions which allow for antigen specificity ii. Constant regions H. Briefly describe the roles of each of the five major immunoglobulin (Ig) classes 1. IgM i. first antibody in immune response ii. activates complement 2. IgG i. major antibacterial and antiviral antibody in blood ii. activated by second immune response (a) long-lasting immunity iii. passed through placenta 3. IgA i. Predominant on mucus membranes  ii. Found in various bodily secretions (a) Prevents adherence of pathogens to mucosal surfaces 4. IgE i. Found on mast cells and basophils ii. Responsive to parasites iii. Associated with allergic reactions 5. IgD i. Antigen receptor on mature naïve B cells I. Describe the clinical relevance of cell-mediated immunity 1. Protection from intracellular pathogens 2. Part of: i. Tissue transplant rejections ii. Some autoimmune diseases J. Describe the process of cell mediated immunity 1. Macrophages and dendritic cells phagocytose antigens 2. Then travel to lymph nodes 3. Present antigens to T-cells 4. If antigen matches T-cell receptor (TCR) it can become activated 5. If activated the T-cell replicates - “Clonal expansion” i. Destruction of pathogen in lymph node ii. Travel throughout body to attack pathogen iii. Activation of B cells and other cells important to immune response (e.g. macrophages) iv. Memory T-cells formed (a) Effective for rapid response to second exposure K. Describe the formation of T-lymphocytes 1. Cells from bone marrow enter the thymus to mature i. T-cell receptors formed ii. Cells that recognize “self” are destroyed (a) If this fails, autoimmune disease results 2. After maturation, they exit thymus to go to secondary lymphoid tissue (lymph nodes, spleen) L. Describe the formation/maturation of B-lymphocytes 1. Exit bone marrow i. Express IgM and IgD 2. Upon antigen activation, B-cells divide 3. Produce antibodies i. Secreted 4. Eventually mature to: i. plasma cells ii. Memory B Cells (a) Upon reactivation, generate a secondary antibody response M. Order the five phases of the immune response 1. Recognition 2. Amplification 3. Effector  4. Termination 5. Memory N. Differentiate between primary and secondary immunodeficiency 1. Primary – Deficit of T-cells, B-cells or lymphoid tissue i. Congenital 2. Secondary – Underlying diseases which depresses or blocks immune response O. Name five sources of iatrogenic immunodeficiency 1. Cytotoxic drugs 2. Corticosteroids 3. Immunosuppressive drugs 4. Radiation therapy 5. Splenectomy  Study Guide Inflammation A. Name the four signs of inflammation and relate them to the precipitating events (Table 6-3) 1. Erythema (redness) – Vasodilation and increased blood flow 2. Heat - Vasodilation and increased blood flow 3. Edema – Increased vascular permeability and hydrostatic pressure, causing filtration into interstitial spaces 4. Pain – Multiple causes i. Direct trauma ii. Edema causing pressure iii. Nerve endings swelling iv. Chemical mediation B. Differentiate acute vs. chronic inflammation 1. Acute i. Chiefly edema (including fluid and plasma proteins) and neutrophilic migration 2. Chronic i. Includes lymphocytes, plasma cells, and macrophage infiltration (a) Attracted by chemotaxis from other cells (b) Promote growth of endothelial cells and fibroblasts (a) Granulation tissue forms ii. Angiogenesis / Neovascularization iii. Fibrosis iv. Tissue destruction C. Provide examples of conditions that would cause acute and chronic inflammation 1. Acute i. Infections ii. Tissue necrosis iii. Foreign bodies iv. Immune Reactions 2. Chronic i. Extensive necrosis ii. Sites where regeneration of tissue parenchyma is not possible (a) Heart (b) CNS (c) PNS iii. Underlying cause is not addressed (a) Persistent injurious agent iv. Repeated episodes of acute inflammation D. Briefly describe granulomatous inflammation 1. Aggregate of macrophages and lymphocytes E. Differentiate exudate, transudate, and effusion 1. Exudate is high protein fluid with high cellular content i. Dependent upon increased vascular permeability  2. Transudate is low protein fluid with minimal cellular content i. Dependent upon Starling’s forces causing filtration ii. No increase in vascular permeability 3. Effusion is the leakage of either of these into anatomic space (or potential space) i. Can be exudate or transudate F. Describe the role of vascular alterations in inflammation 1. Goal: increase movement of plasma proteins and circulating cells out of intravascular space to get to the site of injury i. Process of “exudation” (a) Increased capillary permeability (a) Increased inter-endothelial spaces (b) Fluid and protein leakage ii. Vasodilation (a) Increased blood flow to the area [initially] iii. Decreased blood flow to the area (a) After leakage of fluid out of the area (b) Increased viscosity of the blood iv. Clotting of fluid due to increased fibrinogen v. Migration and accumulation of leukocytes (a) Destroy pathogen G. Describe the role of leukocytes in inflammation and the process by which this occurs 1. Role i. Remove / eliminate injurious stimulus ii. Release toxic substances to kill, inactivate, and degrade pathogens iii. Clean up the area by phagocytosis iv. Release growth factors for healing/regeneration 2. Process i. Stasis = Engorgement of blood vessels causing a slowing of blood flow in the region ii. Margination = Accumulation of leukocytes to endothelial cells of blood vessel walls (a) Possible because of adhesion molecules (a) Bind leukocytes to other leukocytes (b) Bind leukocytes to capillaries / venules iii. Diapedesis = Leukocytes actively migrate out of blood vessel, by squeezing between endothelial cells, to reach the interstitial space iv. Chemotaxis = The use of chemotactic agents (chemokines) which attract other cells to move into the area H. Briefly describe the role of the lymphatic system in the inflammatory response 1. Lymphatic vessels drain exudate from the interstitium i. Reduce edema ii. Removal of inflammatory stimuli iii. Removal of leukocytes 2. Phagocytes present antigens to immunocompetent B and T cells in the lymph nodes i. Proliferation of lymphocytes ensues ii. Lymphadenopathy = enlargement of lymph nodes  iii. Further adaptive immune response as necessary I. Define lymphangitis 1. Inflammation of the lymphatic vessels i. Red streaks under the skin ii. Painful to palpation J. Describe the key inflammatory mediators 1. Histamine i. Synthesized and stored in granules within mast cells, basophils, and platelets ii. Effects (a) Endothelial contraction (a) Increased vascular permeability (b) Exudation (b) Vasodilation (c) Bronchoconstriction iii. Inactivated in 100mg/dL), but below diabetes threshold (e.g.,