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168 Cards in this Set
- Front
- Back
Parenchyma |
made of functional cells (cells that actually do the organ's work) |
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Stroma |
supporting structures (mostly connective tissue) |
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Regeneration |
process of restoring full function to damaged tissue |
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In order to regenerate, tissues require the presence of ___________ and an intact ____________ |
stem cells; ECM |
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What is the ECM use for? |
- cell migration - maintain cell polarity - contains essential cells and chemicals for repair |
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Why must regeneration be tightly controlled? |
uncontrolled cell division leads to cancer |
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Repair |
proliferative response that "patches" rather than restores a tissue |
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Repair is a tissue response to what? |
- wound - inflammatory processes in internal organs - cell necrosis in tissues incapable of regeneration |
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Repair involves what? |
tissue regeneration and formation of fibrous tissue (scar formation) |
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Static |
populations of cells in any given tissue tend to be relatively stable, showing little or no change |
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Cells remain relatively stable due to a balance of: |
- proliferation - differentiation - cell death |
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What are the 4 phases of the cell cycle? |
G1, S, G2, M |
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Non-dividing cells stay in which phase of the cell cycle? |
5th phase, G0 |
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Labile |
continuously dividing throughout life ex: GI epithelium |
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Stable |
quiescent low levels of replication usually in response to stimuli ex: liver cells |
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Permanent |
non-dividing, have left the cell cycle - neurons |
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Regeneration requires __________ |
stem cells |
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Stem cells |
undifferentiatied biological cells that can differentiate into specialized cells and can divide to produce more stem cells |
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What happens when a stem cell divides? |
One daughter cell remains a stem cell while the other differentiates |
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Pluripotent cells |
can give rise to all tissues of the body e.g. embryonic stem cells |
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Multipotent cells |
more restricted but still have capacity to make multiple differentiated cell types e.g. hematopoetic cells |
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adult stem cells are very restricted and are usually: what type? |
multipotent or unipotent |
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What tissues have adult stem cells been identified in? |
skin lining of the gut cornea hematopeoietic tissue CNS |
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Adult stem cells can give rise to which kind of cells? |
progenitor cells |
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Chronic inflammation often leads to __________ |
fibrosis |
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Which type of tissue would you expect to find stem cells? |
Labile |
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Would you expect to find stem cells in skin? Bone marrow? Adipose? GI tract? |
Yes, you would find stem cells in all of those tissues |
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What triggers cell division? |
growth factors |
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growth factors |
chemicals that control many cellular function including: - proliferation - survival - locomotion - contractility - differentiation - angiogenesis |
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What kinds of cells secrete growth factors? |
- macrophages - fibroblasts - endothelial cells - platelets |
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Growth factors act as what? |
ligands |
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What do ligands do? |
float in environment and Bind to receptors on the membrane of target cells |
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some receptors need to __________ after binding to their respective ligand |
dimerize/trimerize |
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Briefly explain the process of growth factors and cell signaling |
- GF binds to receptor - triggers dimerize/trimerize (changes shape) - activation follows - cascade of events occurs - triggers transcription and translation - certain genes are turned on |
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Activation of cell division is often through ? |
phosphorylation |
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G protein |
7 pass membrane receptor, causes phosphorylation |
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When are G proteins activated? |
by binding of a growth factor to its receptor |
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What does not occur when a growth factor binds to its receptor? |
transcription of genes involved in triggering apoptosis |
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Functions of the ECM |
- provides support for anchorage and migration of cells - defines cell polarity - contributes to proliferation and differentiation - scaffolding for renewal of tissues - storage of regulatory molecules |
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What are the 3 types of ECM? |
- basement membrane
- interstitial matrix - granulation tissue |
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What 3 molecules make up the ECM? |
- fibrous molecules - adhesive molecules - proteoglycans and hyaluronic acid |
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Fibrous molecules serve what purpose for the ECM? |
provide structure |
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Adhesive molecules serve what purpose for the ECM? |
establish cell to ECM and cell to cell interactions |
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What purpose to proteoglycans and hyaluronic acid serve to the ECM? |
bind water create turgor/firmness in tissues produce gel, soft tissue |
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collagen accounts for how much of body weight? |
20-30% |
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What is the basic structure of collagen? |
3 polypeptides twisted around each other in a triple helix |
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Which type of collagen are the most common in the body? |
I, III, and V |
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Collagens I, III, and V are known as what? |
fibrillar collagens |
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Fibrillar collagens are ideal for what? |
structures that provide support like bone and tendon - very stable and very high tensile strength |
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Which vitamin is required as a cofactor in the production of collagen? |
Vitamin C |
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Elastin |
fibrous protein allows tissues to be stretched or otherwise deformed, and still return to their original shape |
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What are the adhesive proteins |
sticky proteins - Laminin and fibronectin both are glycoproteins that bind to integrins on cells and promote cell to ECM interactions |
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Where are laminins abundant? |
in the basement membrane |
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Fibronectin |
V-shaped molecules important in forming new epithelial coverings for wound healing (guide cell migratioN) |
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What do cellular adhesion molecules do |
mediate cellular interactions |
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What are the 4 molecules that are part of the cellular adhesion molecules |
1) immunoglobulin family 2) cadherins 3) integrins 4) selectins |
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Immunoglobulin family |
mediate binding between similar cells or different cells |
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Cadherins |
join cells of similar type |
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Desmosomes |
strong cell junctions |
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Integrins |
bind to collagen, laminins, fibronectins, fibrinogen link cell-to-cell or cell-to-ECM mediate inside-out or outside-in signaling stopping of WBC |
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selectins |
play a role in maringation and rolling of leukocytes |
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The bristles of proteoglycans are made up of what? |
disaccharides called glycosaminoglycans (GAGs) |
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Basic structure of proteoglycans |
central core protein + extensive sugars |
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Proteoglycans are excessively negatively charged, meaning what? |
Good ability to attract water |
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Most GAGS create hydrated gels that can what? |
resist compression |
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Proteoglycans and hyaluronic acid help to do what? |
help tissues resist compression |
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Stages of tissue healing |
- inflammation - proliferation and migration of new cells - angiogenesis and formation of granulation tissue - creation of new ECM - wound contraction - tissue remodelling; strengthening of new tissue |
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What are the 3 phases of cutaneous wound healing? |
- inflammation - proliferation - maturation |
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What does healing begin with? |
thrombosis |
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How is a scab formed? |
Clot structured by fibrin forms mesh that traps RBC, debris held together by fibronectin |
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Fibroblasts do what? |
lay down collagen |
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pericytes |
contractile cells |
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What shows up at the site of injury to start rebuilding? |
fibroblasts, pericytes, and smooth muscle cells |
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Angiogenesis results in the creation of? |
granulation tissue |
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What are the 2 methods to get new blood vessels? |
1) Mobilzation of endothelial precursor cells from bone marrow 2) Mobilization of pre-existing endothelial cells |
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What occurs during the mobilization of pre-existing endothelial cells? |
New blood vessels branch off pre-existing vessels - make new BV from existing - endothelial cells divide repeatedly, extending outward from existing BVs |
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What is granulation tissue characterized by? |
formation of numerous small blood vessels and the proliferation of fibroblasts |
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New vessels are leaky, causing __________ |
edema |
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Leaky vessels leads to what? |
exudation and deposition of plasma proteins |
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deposited proteins provide what - for fibroblasts and endothelial cells? |
provisional stroma - supply scaffolding for cells to move |
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Migration of fibroblasts to the site of injury is triggered by what? |
multiple growth factors e.g. TGF (transforming growth factor) |
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TGF is produced by: |
all cells at the injury site |
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Functions of TGF |
- fibroblast migration and proliferation - increased synthesis of collagen and fibronectin -decreased degradation of ECM - chemotaxis - angiogenesis |
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When does the repair phase begin? |
when macrophages arrive |
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Collagen synthesis begins within how many days after injury? |
3-5 days |
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vascular regression |
transformation of the richly vascularized granulation tissue into a pale, avascaular scar |
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fibroblasts differentiate into what? |
myogibroblasts |
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what do myofibroblasts do? |
contract, making the wound tissue tighter |
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matrix metalloproteases |
enzymes responsible for ECM degradation |
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MMPs are produced by what cells? |
fibroblasts, macrophages, neutrophils, synovial cells, epithelial cells |
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What do MMPs do? |
allow cells to move through the ECM digest clotting factors, various adhesion molecules, ECM proteins |
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Basal cells are attached by what? |
cadherins |
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True/False: Fibrosis is associated with granulation tissue
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False: fibrosis has nothing to do with granulation, occurs during later events |
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What is the correct oder of steps in wound healing? |
- Macrophage recruitment, angiogenesis, collagen deposition, ECM remodelling |
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What are the 2 forms of healing of wounds? |
- primary intention - secondary intention |
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Healing by primary intention refers to wounds with what? |
very minimal tissue loss - e.g. surgically-created wounds |
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Healing by secondary intention occurs when? |
When there is tissue damage, usually resulting from accidents - bigger wounds, ragged edges, no sutures |
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What pulls the edges of a wound together? |
myofibroblasts |
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What are some factors that may affect healing? |
- nutritional status - circulatory status - hormones - infection - pre-existing conditions (DM) - location/size of wound - contaminants in wound |
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How can hormones affect healing? |
anti-inflammatory hormones such as glucocorticoids can inhibit collagen synthesis and act as anti-inflammatory agents |
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True/False: Collagen fibers eventually replace granulation tissue in primary intention |
True |
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True/False: Healing by primary intention does not involve granulation tissue |
False |
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True/False: In Healing by primary intention, granulation tissue forms after collagen fibers are deposited |
False: Granulation tissue begins forming within 24 hours of injury |
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What are some complications in cutaneous wound healing? |
- deficient scar formation - excessive formation of repair components - contractures - wound dehiscence - keloid scars - adhesions |
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Contracture occurs: |
when an excess of wound contraction leads to physical deformity |
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What is contractures characterized by? |
skin constriction and functional limitations |
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What are contractures due to? |
"over-enthusiastic" myo-fibroblasts |
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If a contracture occurs in the digestive tract, what can result? |
Can lead to a stricture that will block passage of GI contents |
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What is a wound dehiscence? |
when the wound ruptures along the surgical suture |
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What could cause a wound dehiscence? |
If ECM synthesis is impaired, scar tissue may be weak and may fail |
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When does a wound dehiscence most often occur? |
in abdominal surgery |
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Wound dehiscence occurring from an abdominal surgery can lead to an incisional _________ |
hernia |
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What is an incisional hernia |
part of internal organ pushes through opened wound blood supply may be cut off, leading to ischemia and necrosis |
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Keloid scars are due to what? |
deposition of excess collagen |
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When do adhesions occur? |
Can result when scar tissue begins replacing damaged tissue in wounds involving serous membranes |
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Where are adhesions especially common? |
in thoracic and abdominal surgeries |
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parenchymal scarring is called: |
cirrhosis |
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Kidney damage is ________ |
permanent |
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If damage is confined to the tubules in the cortex, is it able to be repaired? |
Yes, repair can occur as long as basement membrane is intact |
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Tubulorrhexis |
scarring of the tubules of the kidney due to damaged basement membrane |
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Damage to the medulla results in: |
scarring, creates blockages to urine flow |
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Can lung tissue regenerate? |
Yes, if basement membrane undamaged |
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What happens if inflammatory mediators can't clean up debris in alveoli? |
Intraalveolar fibrosis can result |
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When the basement membrane in the lungs is damaged, what results? |
fibrosis |
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What happens when the basement membrane in the lungs is damaged? |
fibroblasts and myofibroblasts secrete ECM into alveoli |
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Are neurons capable of regeneration? |
No |
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What must neurons do to re-establish function? |
Surviving neurons have to take over job of dead ones |
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The scar tissue that replaces dead neurons is made up of what? |
astroycytes and microglia |
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In which nervous system can neurons regenerate axons? |
Peripheral nervous system |
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If severed ends of nerves get out of line, or too much inflammation or scar tissue intervenes, it can develop a ______________ |
traumatic neuroma |
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What is a traumatic neuroma |
Mess of Schwann cells, axons, fibroblasts |
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True/False: Hyperactive fibroblasts could cause wound dehiscence |
True: Hyperactive myofibroblasts cause wound dehiscence |
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What does innate immunity involve?
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- mechanical defenses - chemical defenses - inflammation - commensal bacteria (normal flora) - cells |
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Mechanical defenses of innate immunity include: |
- skin - mucuous membranes |
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epidermis |
thin outer layer of epithelial tissue |
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What does the epidermis contain? |
Langerhans cells, dead cells, and keratin |
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dermis |
thick inner layer of connective tissue |
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Sebum |
oily substance produced by sebaceous glands that forms a protective layer over skin |
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What does sebum contain? |
unsaturated fatty acids which inhibit growth of certain pathogenic bacteria and fungi |
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Chemical defenses of the innate immune system include: |
- sebum - pH - perspiration - lysozyme |
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granulocytes |
cytoplasmic granules |
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Where are neutrophils formed? |
from stem cells in bone marrow |
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what are the 3 ways neutrophils directly attack microorganisms? |
- phagocytosis of microbes - release of anti-microbial granules (degranulation) - form neutrophil extracellular traps |
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what are NETs composed of? |
composed of granule proteins and DNA |
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Where are monocytes/macrophages derived from? |
the myeloid cell line |
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Macrophages |
large, long-lived phagocytes that reside in tissues |
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Macrophages are a major player in ______________ |
inflammatory response |
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Along with dendritic cells, macrophages are major _________________ |
antigen-presenting cells |
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Antigen presenting cells (APC) |
initiate immune responses by displaying antigens from pathogens to lymphocytes |
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What do macrophages get activated by? |
cellular mediators released by damaged cells or by cells of the immune system molecules located on or released from the microorganism itself |
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Once activated, what do macrophages upregulate? |
major histocompatibility complex II (MHC-II) |
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What are the different cytokines that activated macrophages release? |
tumor necrosis factor and interleukin-1 |
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What do TNF and interleukin-1 stimulate? |
expression of adhesion molecules on endothelial cells to promote leukocyte margination, rolling, and extravasation |
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TNF stimulates |
dendritic cells and causes them to migrate to the nearest lymph nodes |
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Chemokines stimulate ___________ and ___________ of leukocytes into the infected tissue |
motility and migration |
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MHC-II is responsible for ? |
antigen presenting |
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What happens if a macrophage cannot digest what it engulfs? |
may form a granuloma may become an epithelioid cell or may fuse with other macrophages to form a multinucleated giant cell |
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What happens when a macrophage becomes an epithelioid or giant cell? |
macrophages stop phagocytosing and simply become storage cell |
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Dendritic cells are |
phagocytic APCs |
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where do dendritic cells reside? |
in epithelial tissues and migrate to lymphoid tissues when they are exposed to an antigen |
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What do dendritic cells express? |
MHC-II molecules - cell adhesion molecules - receptors for chemotaxis |
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Where do natural killer cells descend from? |
lymphoid lineage |
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Natural killer cells are the first line of defence against ___________ and some __________ |
viral infections; tumour cells |
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Natural killer cells are full of what? |
granules containing perforin and granzymes - also have receptors for antibodies |
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perform and granzymes trigger what? |
apoptosis in target cells |
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Where is MHC-I found? |
found on all nucleated cells (identifies self) |
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How do NK cells know what cells to kill? |
NK cells express inhibitory receptors that prevent them from killing all cells that express MHC-I - cells that don't have MHC-I, NK cell will kill it |
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When does the activation of T cells by macrophages occur? |
After phagocytosis |