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113 Cards in this Set
- Front
- Back
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Immunity |
Condition of being resistant to infection |
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Immune Response |
Coordinated response of cells and molecules of the immune system |
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Categories of immunity |
*Natural or innate (born with) *Acquired (antibodies to specific antigens) |
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Natural / Innate Immunity |
*prevents deeper tissue penetration of microorganisms
*major components: - skin - mucous membranes - phagocytic leukocytes - natural killer cells (non-B, non-T lymphs) - complement |
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External Defense System |
*Unbroken skin (pH of skin 5.6)
organ specific mechanisms: *respiratory tract: mucous, cilia *urinary tract: flushing action, slight acidity *digestive tract: HCl gastric juice, pH 2 *tears and saliva: lysozyme |
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Acquired (adaptive) Immunity |
*second major defense *less rapid than innate *consists of lymphocytes & their products (antibodies) *recognize infectious and non-infectious substances and develop a specific immune response *memory of antigen is developed = quicker, stronger immune response with next exposure |
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Humoral Immunity
(1/2 types of acquired / adaptive immunity) |
*antibodies produced by B-lymphocytes |
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Cell-mediated immunity
(2/2 types of adaptive / acquired immunity) |
*T-lymphocytes *Intracellular microbes |
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Natural and Acquired Immunity
*Acquired *Specific *Response *Memory |
Natural: Acquired: No Specific: No Response: Identical for all challenges Memory: No
Acquired: Acquired: Yes Specific: Yes Response: Specific for a particular agent Memory: Yes |
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Neutrophils |
Reference: 60-80% WBC differential Main WBC in acute inflammation Characterized by: - segmented nucleus - cytoplasmic granules |
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Neutrophil's Primary Granules |
*enzymes with antibacterial activity *released into phagocytic vesicles within the cell |
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Neutrophil's Secondary Granules |
*enzymes associated with plasma membrane *released outside of the cell |
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Neutrophil's Tertiary Granules |
plasminogen activator |
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Neutrophil's Lysosomes |
acid hydrolases |
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Neutrophil's role in inflammation |
*phagocytosis
(chemotactic factors attract neutrophils to areas of injury) |
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Monocytes |
Reference: 3-8% WBC differential *Mononuclear cell *Digestive vacuoles *Hydrolytic enzymes |
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Macrophages |
*found in almost all tissues *phagocytic cells *important in first line of defense in innate immune response
*respond to chemotactic stimuli *antigen-presenting cells (to diff. WBC) *help induce inflammation
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Basophils |
Reference: 0-1% WBC differential
*release pro-inflammatory chemicals from granules when activated: - histamine - PAF (platelet activating factor) - Heparin (works with antithrombin) |
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Mast Cells |
*connective tissue throughout the body
*derived from same precursor cells as basophils, but mature in tissue site
*inflammatory response in allergic reactions, chronic inflammation |
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Stimuli for mast cell degranulation |
*injury *immune response *complement (C3a, C5a) *cytokines (interleukin-1, IL-8) |
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Eosinophils |
Reference: 2-3% WBC differential
Role: *allergic reactions, parasitic infections *control inflammatory reaction - release enzymes that breakdown histamine, leukotrienes |
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Definition of inflammation |
*tissue and vascular reactions resulting from non-lethal injury
*delivery of fluid, dissolved substances, cells from the circulating blood and tissues to an area of injury
(tissue must be alive to undergo inflammatory reaction) |
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Benefits of inflammation |
*localizes area of injury *neutralizes offending agent *removes dead cells, debris *sets stage for repair processes |
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itis |
inflammation, without specifying cause |
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Is infection always the cause of inflammation? |
*inflammation and infection are NOT SYNONYMOUS - infection is just ONE cause of inflammation |
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acute inflammation |
*almost immediate reaction of local tissues and blood vessels to injury *less than 2 weeks resolution |
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chronic inflammation |
*longer time frame (6 weeks or >)
*persistence of injurious agent
*characterized by infiltration with mononuclear cells (lymphocytes, macrophages) |
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events in inflammation |
*increased vascular permeability *emigration of leukocytes *phagocytosis |
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rubor |
modern term: erythema meaning: redness |
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calor |
modern term: heat meaning: heat |
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dolor |
modern term: pain meaning: pain |
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tumor |
modern term: edema meaning: swelling |
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functio laesa |
modern term: altered function meaning: altered function (twisted ankle > can't walk properly) |
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two stages of acute inflammation |
*vascular stage - vasodilation - increased vascular permeability
*cellular stage - emigration of leukocytes from microcirculation and accumulation at site of injury |
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vasodilation
(vascular stage of acute inflammation) |
*follows a transient constriction of the arterioles *arterioles (1st), venules (2nd) = increased capillary blood flow *site of injury becomes congested - erythema, warmth *induced by several mediators such as histamine and nitric oxide |
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increased vascular permeability
(vascular stage of acute inflammation) |
*immediately follows vasodilation
*outpouring of protein-rich fluid (exudate) into extravascular spaces
- causes fluid to move from vascular compartment to albumin (proteins)
- dilutes the offending agent
*fluid loss results in increased concentration of RBCs, WBCs, platelets, clotting factors
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formation of endothelial gaps during increased vascular permeability
(vascular stage of acute inflammation) |
*chemical mediator binding to endothelial receptors causes contraction of endothelial cells and separation of intercellular junctions
- elicited by histamine, bradykinin, leukotrienes, etc. |
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inflammation: lymphatics and flow of lymph |
*increase in drainage of fluid from the area of injury *lining cells in lymphatics separate, allowing materials from the tissues into the lymphatics |
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3 responses of vascular permeability changes |
*immediate transient response *immediate sustained response *delayed hemodynamic response |
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immediate transient response |
*minor injury *develops rapidly, short duration (15-30 mins) *mediated by histamine acting on endothelium *affects venules (only) |
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immediate sustained response |
*occurs with more serious types of injury (burns, bacterial infections, etc.) *continues for several days *affects all levels of microcirculation |
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delayed hemodynamic response |
*increased permeability begins after 2-12 hrs and lasts several hours or days *mediated by bradykinin, factors derived from complement, and factors from dead neutrophils in exudate *involves venules and capillaries *occurs with injuries resulting from radiation |
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inflammatory mediators |
- vasoactive amines - plasma enzyme systems - arachidonic acid metabolites - miscellaneous cellular products |
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vasoactive amine: histamine |
Causes: vasodilation, increased vascular permeability
Located: in granules of mast cells, basophils, platelets
From: degranulation during physical injuries, immunologic reactions, complement proteins |
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plasma factors |
*mediators formed thru the action of proteolytic enzymes - factor XII - bradykinin - complement system |
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arachidonic acid metabolites |
*derived from phospholipids of cell membranes thru activation of phospholipase A2 *cyclooxygenase pathway *lipoxygenase pathway *have a broad range of vascular and chemotactic effects in inflammation
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platelet activating factor |
*platelets, basophils, mast cells, neutrophils, monocytes / macrophages, endothelial cells Effects: *platelet aggregation *increased degranulation *bronchoconstriction (constriction of airwaves) *vasodilation *increased vascular permeability *increased WBC adhesion to endothelium *promotion of chemotaxis *increased oxidative burst |
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miscellaneous cell products
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*O2 metabolites and lysosomal contents of neutrophils and macrophages *cytokines *nitric oxide *cell adhesion molecules (CAMs) |
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nitric oxide
(miscellaneous cell products) |
- produced by macrophages, endothelial cells - vasodilation, cytotoxic free-radical |
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cytokines (miscellaneous cell products) |
*Interleukins 1 & 8 (IL-1, IL-8) *Tumor necrosis factor (TNF) |
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cell adhesion molecules (CAMs)
(miscellaneous cell products) |
*selectins, endothelial adhesion molecules, integrins
*WBCs activated, integrins on surface interact with endothelial adhesion molecules, leading to extravasation |
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vascular phase summary |
*vasoconstriction followed by vasodilation *vasodilation of arterioles and venules, increase in capillary blood flow, heat and redness *increased vascular permeability, outpouring of protein-rich fluid into extravascular spaces *loss of proteins reduces capillary osmotic pressure and increases interstitial osmotic pressure *fluid accumulation in tissue spaces (tumor, dolor, functio laesa) *stagnation of flow, clotting of blood in area (keeping it localized) |
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Leukocyte Extravasation |
*as fluid leaks out of microcirculation, the viscosity of blood increases *circulation slows
*extravasation: movement out of the vascular compartment into the tissue |
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Leukocyte Extravasation Events |
*Margination *Rolling *Adhesion *Pavementing *Transmigration |
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Margination (leukocyte extravasation) |
accumulation of leukocytes along the endothelial surface (due to slowing of blood)
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Rolling
(leukocyte extravasation)
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tumbling of leukocytes along the endothelial surface (break and reform bonds) |
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Adhesion (leukocyte extravasation) |
firm adherence of leukocytes to endothelial surface (firmly adhere to endothelial cells)
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pavementing (leukocyte extravasation) |
lining of adhered leukocytes along the endothelial surface
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transmigration (leukocyte extravasation) |
leukocytes move across endothelium (diapedesis) |
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Selectins |
*trans-membrane glycoproteins, expressed on the surface of leukocytes and activated endothelial cells *slow movement of leukocytes along the endothelium via weak adhesive interactions - rolling |
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E- and P- selectins |
expressed on endothelial cells and bind to oligosaccharides on surface of leukocytes |
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L-selectins |
expressed on neutrophils and bind to endothelial mucin-like molecules (GlyCAM-1) |
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integrins |
*tight adhesion *when on surface of leukocytes, must be activated for tight adhesion to occur - induced by PAF *activated integrin binds to ICAM-1 - immunoglobulin superfamily of CAMs expressed on the surface of endothelial cells |
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Mechanism of CAM Modulation (adhesion molecules) |
*redistribution of preformed adhesion molecules to the cell surface @ P-selectin: -- following injury, distributed to cell surface, binds to leukocytes -- induced by: histamine, thrombin & PAF @ E-selection, ICAM-1, VCAM-1 -- induced by: IL-1 and TNF |
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Mechanism of CAM Modulation
(binding activity) |
*increased binding activity
-- induced by chemotactic agents
-- conformational change of CD11a/CD18 integrins causing increased affinity for ICAM-1 |
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Chemotaxis |
*process by which leukocytes emigrate in tissues toward site of injury - movement occurs along chemical gradient |
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Types of chemotactic agents |
*exogenous (released by something thats not 'you') - bacterial products *endogenous - damaged tissues - C5a - Leukotriene B4 - IL-8 |
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Phagocytosis (& process) |
*RecognitionIs and attachment of particle to be ingested by the leukocyte
*Process: - adhere / binding - engulfment / ingestion - fusion - degradation or killing of ingested material |
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Neutrophilic Kill Mechanism |
*requires O2, NADPH, and NADPH oxidase *Respiratory (oxidative) burst - NADPH + 2O2 + 2e- >>> 2O2- + NADP+ + H+ *Within lysosome 2O2- + 2H+ >>> H2O2 + O2 *Myeloperoxidase (neutrophilic granules) H2O2 + Cl- >>> HClO (HClO is bacterial agent |
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Complement System |
*Important in both innate and humoral immunity, and the inflammatory response *Consists of a group of proteins (C1-C9), found in serum, and tissue fluids *Present in inactive precursors (for reaction to occur, components must be activated in proper sequence) |
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Complement Functions
(prob on test) |
*Lysis of immunogens such as bacteria, allografts (transplant tissue), tumor cells
*anaphylatoxin-- production of mediators that modulate immune and inflammatory responses
*opsonization (making something more suspectible to phagocytosis)
*chemotaxis |
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Classical Pathway (2nd or 3rd time fighting antigen -- acquired or innate) |
* C1q binds to the Fc region of antibodies (IgG and IgM) that have interacted with the antigen *results in activation of: C1r, which activates C1s *C1qrs complex activates C4 - C4a and C4b; and C2 - C2a and C2b *C4bC2b complex = C3 convertase *C3b combines with C4bC2b to form C4bC2bC3b = C5 convertase |
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Alternative Pathway (no antibodies against it -- first time, acquired) |
*C3 binds microbial (antigen) causing direct activation - C3a and C3b *C3b binds and factor B combines with it = C3 convertase *factor D splits B - Ba and Bb; Bb binds with C3b *C3 is split by C3bBb - C3a and C3b *C3bBbC3b = C5 convertase |
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Mannose - binding lectin pathway |
*mannose molecules (only found on microorganisms) on surface of antigen *mannose-binding lectin (MBL) binds to mannose *MASPs (Mannose-Binding Lectin Associated Serine Proteases) binds to MBL *MASP activates C4 - C4a and C4b; and C2 - C2a and C2b *C4bC2b = C3 convertase *C4C2bC3b = C5 convertase
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Terminal Pathway |
*C5 is split into C5a and C5b *C5b binds to antigen surface *C5bC6C7C8C9 = MAC *C8 makes tons of C9 to generate a pore - resulting in lysis |
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Systemic Responses |
(under optimal conditions, the inflammatory response will remain confined to localized area but.... that's not always the case) *Fever *Leukocytosis *Increase in circulating proteins (produced by liver) |
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Fever |
*pyrexia *caused by cytokine-induced increase in hypothalamic set-point *does not usually rise above 105 degrees F (97-99.5 is normal temp) |
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Pyrogens |
*fever producing mediators *exogenous (from microorganisms): act indirectly on hypothalamus *endogenous (from WBC): act directly on hypothalamus *Examples: - lipopolysaccharide from Gram negative bacteria - injured cells - malignant cells |
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Cytokine action on hypothalamus (mechanism of fever) |
*cross the blood brain barrier via specific transport mechanisms *IL-1 excites neurons in the anterior hypothalamus *hypothalamus produces and releases prostaglandins (PGE2), causing elevation of the thermoregulatory set point *body initiates heat-promoting mechanisms; vasoconstriction- decrease heat loss; shivering - energy / heat production |
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Intermittent (fever patterns) |
temperature returns to normal at least once every 24 hours (different bacterial infections, ex. sepsis) |
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Remittent (fever patterns) |
temperature does not return to normal, varies a few degrees up or down (viral upper respiratory infections - flu) |
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Sustained (fever patterns) |
temperature remains above normal, not much variation
(drug-induced; penicillin, cocaine, amphetamines) |
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Recurrent / Relapsing
(Fever patterns) |
one or more episodes of fever lasting several days with one or more days of normal temperature in between episodes
(malaria; lyme disease) |
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Pros vs. Cons of Fever |
Pros: - improve efficiency of leukocyte killing - impair replication of microorganisms Cons: - may enhance host's susceptibility to the effects of endotoxins |
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Leukocytosis |
15.0 - 20.0 x 10^9 / L in acute inflammation (norm: 4.0 - 11.0 x 10^9 / L) Cause: IL-1 and TNF signal bone marrow to increase rate of WBC release |
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When do these occur: *Neutrophilia *Lymphocytosis *Eosinophilia |
Neutrophilia: bacterial infections
Lymphocytosis: infections, mono, rubella Eosinophilia: bronchial asthma, allergies, parasitic infection |
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Leukopenia |
*decrease in WBC Associated conditions: - typhoid fever - viral infections - rickettsial infections - some protozoa |
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Circulating Plasma Proteins |
*increase in acute phase reactants (APR) - IL-1, 6, TNF, target liver - reach max. levels in 10-40 hrs - non-specific proteins * examples: - complement - clotting factor - c-reactive protein (CRP) |
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c-reactive protein
(acute phase reactants) |
*better test than ESR
*assists complementary binding to foreign and damaged cells
*enhances phagocytosis
*reference range: <800 ug/dL |
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Erythrocyte Sedimentation Rate (ESR) |
*nonspecific measure of inflammation *fibrinogen coat surface of RBC *rouleaux formation (coin stack) - heavier (if not coated with fibrinogen, slower time to sediment) *measures rate that RBC sediment in 1 hr *reported as: mm of plasma present at the top of the tube (mm/hr) |
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Leukocyte induced tissue injury |
*activated WBC mechanisms do not distinguish between offending agent and host *circumstances: - bystander tissues are injured as part of normal defense against infectious agents - normal attempt to clear damaged and dead tissues - inflammatory response is directed against host tissues (autoimmune) or host reacts excessively against nontoxic environmental substances (allergies) |
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Acute Leukocyte induced tissue injury |
*acute respiratory distress syndrome- neutrophils *acute transplant rejection- lymphocytes, antibodies, complement *asthma- eosinophils, IgE *glomerulonephritis- antibodies, complement, neutrophils, monocytes *septic shock- cytokines |
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Chronic Leukocyte induced tissue injury |
*rheumatoid arthritis- lymphocytes, macrophages, antibodies *atherosclerosis- macrophages *chronic lung disease- macrophages *chronic transplant rejection- lymphocytes, macrophages, cytokines |
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Chronic inflammation |
*self-perpetuating, weeks, months, years - characterized by infiltration of mononuclear cells (lymphs, macrophages, etc.) - attempted connective tissue repair *develops from recurrent acute inflammatory response or low-grade response that does not evoke acute response *persistent, recurrent inflammation may promote DNA change > cancer |
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resolution |
restoration of original structure and function |
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repair |
replacement of damaged tissue with scar tissue |
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ability of tissues to regenerate
(easily, well, or poorly) |
*limited to cells that are able to undergo mitosis Easily: - epithelial tissue (skin, mucous membranes) Well: - cells of liver, renal tubules, secretory elements of certain glands Poorly: - glomeruli - skeletal muscle - heart - CNS > doesn't regenerate at all peripheral nerves > can regenerate but very long time |
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first step of preparation of injured site for either regeneration or repair |
*debridement - phagocytosis of debris *drainage of exudate *vascular dilation and permeability are reversed |
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phases of healing |
*inflammatory phase *proliferative phase - new tissue to fill space *remodeling phase - remodel scar tissue |
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proliferative phase |
*begins 3-4 days after initial injury; continues for as long as two weeks
*fibrin clot must be dissolved *granulation tissue forms in wound area *new connective tissue and capillaries that replace fibrin plug *provides framework for scar tissue formation
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remodeling phase |
remodel scar tissue
begins about 3 weeks after injury; normally complete within two years |
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angiogenesis |
*production of new blood vessels from preexisting vessels
*requires O2 and nutrients
*capillary buds are produced
*loop formation occurs when young capillaries join (anastomose)
*differentiation of new capillaries into arterioles and venules |
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angiogenesis plays a role in; |
- tissue repair
- tumor cell growth (release growth factors to produce blood supply)
- formation of collateral circulation (formation of new blood vessels to compensate for aim that are blocked) |
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vascular endothelial growth factor (VEGF)
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*stimulated by cytokines, growth factors, tissue hypoxia *receptors on vascular endothelial cells |
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proliferation of fibroblasts |
*proliferate at site of injury *synthesize collagen for tissue repair |
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collagen |
*most abundant protein in the body
*the material of tissue repair
*hydroxylation of proline and lysine is necessary for collagen polymerization and function
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collagen synthesis |
*precursor procollagen is produced; hydroxylation of proline and lysine *glycosylation of hydroxylysine *triple helix (3 chains of procollagen) secreted out of fibroblast *terminal peptides are cleaved from the ends of procollagen > tropocollagen *collagen fibrils form by cross-linkage of hydroxylysines *aggregation of fibrils to form fibers |
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epithelialization |
*epithelial cells migrate under the clot/scab
*a proteolytic enzyme severs the connection between the clot and the wound surface
*epithelial cells connect and form a seal |
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remodeling (maturation) phase |
*wound contraction - myofibroblast
*scar tissue is remodeled
*capillaries disappear
*scar gain strength as more collagen is deposited |
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roles of the macrophage |
*primary phagocyte in debridement
*secretes: - fibroblast-activating factor - angiogenesis factors - epithelial stimulating factor |
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hypovolemia
(dysfunctional wound healing) |
*vasoconstriction prevents delivery of inflammatory cells to site of injury
*reduced O2 delivery |
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nutritional state
(dysfunctional wound healing) |
*insufficient levels of glucose, protein, vit. c
(scurvy - lack of vit c)
*procollagen not hydroxylated sufficiently - blood vessels, skin, tendons, etc. become fragile; poor wound healing |
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keloid
(dysfunctional wound healing) |
*raised scar, extends beyond original wound boundaries
*imbalance between collagen synthesis (more) and collagen lysis (less) |
