Exam 2

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1
Material intended to interface with biological systems to evaluate, treat, augment, or replace any body part
Biomaterial
2
Fixation, framework, reinforcement, regulation, delivery vehicle, barrier
Roles of biomaterials
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(role of biomaterials) Restores and hold tissues in their normal anatomical position and alignment
Fixation
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(role of biomaterials) serves as a framework to support cell migration into defect from surrounding tissues
Framework
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(role of biomaterials) maintains shape of defect and prevents distortion of surrounding tissue
Reinforcement
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(role of biomaterials) moves exogenous cells, growth factors, and genes
delivery vehicle
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(role of biomaterials) to prevent infiltration of surrounding tissue that may impede the process of regeneration
barrier
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What are the 2 main parts of blood
formed elements and blood plasma
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aqueous part of blood
blood plasma
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how much of blood plasma is water
91.5% water, 8.5% protein
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cellular and cell fragment part of blood
formed elements
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What are the 3 components of formed elements
red blood cells, white blood cells, platelets
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Are red blood cells part of immune system
no
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Are white blood cells part of immune system
yes
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Do white blood cells contain hemoglobin
no
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What is the most common white blood cell
neutrophils (60-70%)
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ability of a biomaterial to perform with an appropriate host response in a specific application
Biocompatability
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3 phases of reaction to implants
onset, progression, resolution
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(phases of reaction to implants) hemostasis (blood clotting), inflammation, cell migration
onset
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(phases of reaction to implants) tissue rebuilding, matrix deposition, angiogenesis
progression
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(phases of reaction to implants) tissue remodeling, matrix contraction , cell maturation/death
resolution
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if something is too larger for phagocytes to eat, the body will try to encapsulate the invader in whate
Fibrous Capsule
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What cell is progenitor of granulocytes (neutrophils) and monocytes
myloid progenitor cell
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What cell is progenitor of T cell, B cell, and NK cells
lymphoid progenitor cell
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Nonspecific, defensive response of body to tissue damage
Innate (Nonspecific) Immunity
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Do innate immune cells do not recognize specific invaders
no
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binding sites only found on bacteria, free DNA implying dead cells, etc.
danger signals
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Do innate immune cells detect danger signals
yes
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What are the 4 main components of innate immunity
anatomical barriers (skin), physiologic barriers (temperature of body), phagocytic cells, inflamation
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The ability of the body to defend itself against specific invading agents
adaptive (nonspecific) immunty
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Do acquired immune cells do not recognize specific invaders
yes
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Part of innate immunity, plasma proteins that attack invaders and induce lysis
complement
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rupture of cell membrane (kills cell)
lysis
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How do acquired immune cells recognize specific invaders
antibodies
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process where more blood and immune cells are sent to site of tissue damge
Inflamation
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vasodilation and increased blood vessel permeabilty, emigration of immune cells to damaged tissue, tissue repair or replacement
The 3 steps of inflamation
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innate immunity response to tissue injury that occurs after weeks to months
Chronic Inflamation
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Immediate innate immunity response to tissue injury
acute inflamation
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The 4 types of leukoytes
granulocytes, monocytes, lymphocytes, and the one that turns into platelets
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molecules released during blood clotting cascade that causes pain associated with inflamation
kinins
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The 3 main types of granulocytes
neutrophils, eoinophils, basophils
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Do granulocytes phagocytose foreign invaders
yes
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What is the precursor to macrophages
monocytes
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When do moncytes turn into macrophages
when leave blood
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Can produce molecules that recruit more circulating monocytes, induce division, and cause immobilization. Also causes fibrous scarring and radicals that kills cells
macrophage activation
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Cationic proteins in neutrophil granules do what 3 things
increase vascularpermeability, immobilize neutrophils, act as chemotactic for mononuclear phagocytes (monocytes and macrophages)
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What are 2 significant components of neutrophil granules
cationic proteins, neutral proteases
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enzyme that breaks down proteins
pretease
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neutral proteases in neutrophil granules do what
degrade tissues and generate mediators
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What is produced by neutrophils during phagocytosis that damages invaders as well as tissues (but hopefully kills more invaders)
oxygen derived free radicals
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What happens when the foreign material is too large for a neutrophil to engulf and the neutrophils decide to increase inflammation and release more enzymes (neutral protesases) and radicals to break stuff down
frustrated phagocytosis
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Receptor proteins in phagocytes that detect pathogens
toll-like receptors TLRs
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(T/F) During neutrophil recruitment, the rolling step occurs as the cells briefly bind to the vascular endothelium through low-affinity interactions facilitated by the upregulation of integrins
false, its selectins not integrins
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Of the different components of innate immunity, which is the least likely to affect the response to an implanted biomaterial?
anatomical barrier as biomaterial is implanted
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What immune cells induce other cells to undergo apoptosis?
NK cells or T cells
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Which has greater killing capacity, neutrophil or macrophage
macrophage
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Which arrives to site of tissue damage first, neutrophil or macrophage
neutrophil
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white blood cells that include T cell and B cells
Lymphocytes
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Cells that recognise specific antigens on surface of infected cells
T cells
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Cells that produce and secrete antibodies
B cells
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Memory cells (lymphocytes)
remeber past infections
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lymophocytes that produce antibodies and seek out and kill invaders
Effector cells (lymphocytes)
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main phagocytic cell
macrophage
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Where are leukocytes made
in bone marrow
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Where do lymphocytes mature
lymphoid tissue
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Where are granulocytes stored
bone marrow
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seek out and causes apoptosis in cancer cells and virus-infected cells
Natural Killer (NK) Cells
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4 steps of stage of neutrophil extravasation
rolling, activation, arrest and adhesion, migration
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(stage of neutrophil extravasation) While neutrophils are carried along by blood, they roll along endothelial cells of blood vessels by briefly binding to them
Rolling
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What is neutrophil rolling mediated by
selectins
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transmembrane glycoproteins that bind to sugars and neutrophils
Selectins
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Movement of neutrophils out of blood vessels into tisuse
Extravasation
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(stage of neutrophil extravasation) When chemoattractants induce a conformation change in integrins in neutrophils to make them have a higher affinity for CAMs in endothelial cells of blood vessels
activation
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(stage of neutrophil extravasation) When the neutrophil stops due to strong interaction between integrins of neutrophil and CAMs of endothelium
arrest and adhesion
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(stage of neutrophil extravasation) when neutrophil squeezes between endothelim cells
neutrophil migration
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transmembrane proteins involved in both cell–cell and cell–matrix contacts
Integrins
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cellular eating and breakdown of foreign material
Phagocytosis
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What immune cells are phagocytes
neutrophils and macrophages
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1.Chemotaxis: danger signal like free DNA trigger secretion of chemokines which attracts phagocytes
2.Adherence: the phagocyte binds to the foreign material
3.Ingestion: the phagocyte takes the foreign material inside its cell wall
4.Digestion: lysosomes (granules) bind to the foreign material and attacks it
5.Killing: If the foreign material was a microbe, it gets kills by digestion
5 stages of phagocytosis
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(step of phagocytosis)) chemoattractant danger signals like free DNA trigger secretion of chemokines attracts phagocytes
chemotaxis
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The phagocyte binds to the foreign material (stage of phagocytosis)
Adherence
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the phagocyte takes the foreign material inside its cell wall (stage of phagocytosis)
ingestion
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lysosomes (granules) bind to the foreign material and attacks it (stage of phagocytosis)
digestion
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Do activated macrophages present antigens
yes
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Granulocyte involved in allergies and parasite defense
eosinophils
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Is acute inflamation supposed to be localized
yes
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How do IL-1 and IL-1Ra relate to acute inflamation
checks in balances mechanism
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How is the severity of inflamatory response determined
relative amounts of IL-1 and IL-1Ra
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Another term for granulocyte
polymorphonucleocytes (PMNs)
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A forein substance that is used to idenfity a pathogen
antigen
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2 main types of acquired immunity
humoral immunity, cell-mediated immunuty
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Humoral immunity
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cell-mediated immunity
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Small cell fragments produced by magarkaryocytes
platelets
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What is function of platlet
stimulates blood clotting
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throbosis
blod clotting
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Do monocytes have multi-part nuclei
no
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Assay that measures cellular metabolic activity as an indicator of cell viability, proliferation, and cytotoxicity
MTT assay
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Assay used to measure the number of viable cells in a cell culture
MTT assay
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Tissue that has a pebby granular appearance
Granulation tissue
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What gives the pebby granular appearance of granulation tissue
vascular buds
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appearance of many vascular buds sprouting from existing blood vessels
neovascularization
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Process that leads to the formation of granulation tissue
neovascularization
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when a biomaterial is implanted into an organ, where does the granulation tissue develop
as a barrier between the biomaterial and organ tissue
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cell type that maintains the extracellular matrix to support connective tissues
fibroblast
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What materials do fibroblast synthesize
collagen and protoeoglycans
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A specialized type fof fibroblast that has features of smooth muscle
myofibroblast
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Where does myofibroblasts arise
in granulation tissue
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What are the purpose of myofibroblasts
to act akin smooth muscle to contract to close wounds
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Unavoidable process that takes place when a material becomes implanted into the body
Foreign body reaction
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Type of cells that are much larger than normal cells that attempt to phagocytose a foreign body that is too big to get eaten by normal phagocytic cells
foreign body giant cells (FBGCs)
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How are FBGCs made
fusion of monocytes/macrophages
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Do FBGCs have 1 nucelus
no
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Will foreign body response be stronger in a rougher or smoother biomaterial
rougher
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Will foreign body response be stronger or weaker with a high surface area to volume ratio
stronger
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Will foreign body response be stronger or weaker with a low surface are to volume ratio
weaker
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Will foreign body response be stronger if an implant is a cube or a sphere of the same volume
cube (since more surface area)
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What process involves granulation tissue maturation
fibrous encapsulation
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What marks granulation tissue maturation
presence of larger blood vessels and lignment of collagen fiber
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Does fibrous encapsulation lead to scar formation
no because scars form from the collapse of the capsule
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Is fibrous encasupation an acceptable result of implantation
yes
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Is a thicker or thinner fibrous capsule preferable
thinner
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What causes a thicker fibrous capsule
the more the implant irritates/damages cells, the thicker the capsule
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What are 4 factors that affect the thickness of a fibrous capsule
1. amount/composition of small small particulates
2. rubbing (mechanical factors)
3. shape of implant (surface area to volume ratio)
4. electrical currents
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Why does rate of shedding of small particulates from an implate correlate with increased fibrous capsule size
small particulates can by cytotoxic
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Why do electrical currents lead to an increase in fibrous capsule thickness
can cause corrosion of implant
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Acute inflammation is characterized by what cell
neutrophils and macrophages
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Chronic inflammation is characterized by what cell
lymphocytes and plasma cells
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Layer of epithelioid cells (modified macrophages), then layer of FBGCs, then a particle that is too big to phagocyse in the middle
granuloma
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What surrounds granulomas
layer of lymphocytes
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New equilibrium state after wound heals
resolution
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What are the 4 main types of resolution
extrusion, resorption, integration, encapsulation
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top layer of skin
epithelial tissue
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occurs in epithelial tissue (top layer of skin), foreign body is forced out by a pouch that forms around it contiguous with the surrounding tissue
extrusion
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What type of resultion is a splinter working its way out
extrusion
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When a biomaterial biodegrades and its parts get consumed by the body
resorption
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Traditional response to nonresorbable materials
fibrous encapsulation
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When a fibrous capsule does not form around an implant
integration
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What is one biomaterial that the resolution type can be integration when implanted in bone
titanium
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Wound healing type where the lost tissue is replaced with scar tissue
Tissue repair
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Does scar tissue have the same or different structure, biochemical composition, and mechanical properties as the native tissue
different
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Wound healing type where the lost tissue is replaced with tissue of the same type as the original
Tissue regeneration
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In what layer of skin tissue can regeneration occur
epidermal layer (epidermis)
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Top layer of skin
epidermis
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In what layer of skin tissue must tissue repair occur because regeneration cannot occur
demal layer (dermis)
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Layer of skin below the epidermis
dermis
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what are the 1st 2 immune cells to appear at the site of an injury
neutrophils then macrophages
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the ability of a medical device to perform with an appropriate host response in a specific application
biocompatability
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Negative effects of a biomaterial appearing within 24 hours after administration
acute toxicity
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Negative effects of a biomaterial appearing after 90 days after administration
chronic toxicity
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Cells that can continuously multiply throughout life
labile cells
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What type of cells do skin and bone fall under
labile cells
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Cells that can regenerate after injury but do not normally replicate
stable cells
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What type of cells do the cells of the kidney, pancreas and parechymal cells of the liver fall under
stable cells
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Cells that cannot reproduce themselves if damaged after birth
permanent cells
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What are some permanent cells
nerve cells, skeletal and cardiac muscle cells
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What type of cells mediate the aquired immune response
lymphocytes
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Where are lymphocytes stored in the body
constatnly circulate in blood and tissue
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Broad term refering to the adverse effects on fuction of immune system
Immunotoxicisity
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Term for immune system dysfunction
allergies
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Term for when the immune system attacks the cells of the body
autoimmune disease
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Developing allergies or an autoiummune diseases as a result of a biomaterial is called what
immunotoxic response
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The 4 characteristics of the acquired immune response
1. specficity, 2. diversity, 3. self/nonself recognition, 4. immunologic memory
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What type of cell makes antibodies
B cells
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Type of aquired immunity based on the actions of antibodies (made by B cells)
Humoral immunity
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Why is humoral immunity called that
humoral = stuff in blood = antibodies
167
cells of the body
self cells
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Type of aquired immunity based on the actions of T cells that detect altered self cells
Cellular immunity
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special protein that binds to specific antigens
antibody
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substance that can be used by the acquired immune system to detect a foreign invader
antigen
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As an antibody is a protein, what is its ligand?
antigen
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Binding site on antibody protein for antigens
epitope
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low molecular weight substance that combins with a larger molecule to produce a greater immune response
hapten
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substance that nonspecifically inhances the immune response to antigen
adjuvant
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What are the 3 types of lymphocytes
T cells, B cells, and NK cells
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genetic complex that is presented with an antigen to effect an immune response
Major histocompatibility complex (MHC)
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Antigens that are made by cells of the body, self cells
endogenous antigens
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What is the purpose of endogenous antigens
They can tell the immune system if a self cell is healthy or altered by virus or cancer
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What class of MHC displays endogenous antigens
class 1
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Antigens produced outside of the body
Exogeneous antigens
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How do exogeneous antigens enter cells
phagocytosis
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What class of MHC display exogeneous antigens
class 2
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What type of cells display class 1 MHC molecules
most cells of the body
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What type of immune cells recognize class 1 MHC molecules
Tc cells (T cytotoxic cells)
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What type of cells display endogenous antigens
most cells of the body
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What type of immune cells recognize endogenous antigens
Tc cells (T cytotoxic cells)
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What type of cells display class 2 MHCs
antigen presenting cells (APCs)
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What type of immune cells recognize class 2 MHCs
Th cells (T helper cells)
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What type of cells display exogenous antigens
antigen presenting cells (APCs)
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What type of immune cells recognize exogenous antigens
Th cells (T helper cells)
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What are some antigen presenting cells APCs
macrophages (innate immunity cell type), B lymphocytes (acquired immunity cell type),
192
T cells, B cells, and NK cells
lymphocyte
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Cells that are not part of the body as detected by the immune system
nonself cells
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Why are organ rejected
The immune system detects the cells of the organ as nonself
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What are TCRs
T cell receptors
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What is the main difference between antibodies (made from B cells) and TCRs (on T cells)
antibodies are released into the blood while TCR remain bound on the cell membrane
197
Why does the immune system detects the cells of a trasplanted organ as nonself
different people have different endogenous MHC molecules
198
What type of T cells kill target cells by inducing apoptosis
Cytotoxic T lymphocytes (CTLs)
199
What type of T cells supprese the activity of other immune cells
T reg cells (regulatory T lymphocytes)
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What does Th cell do when they are activated by an exogenous antibody on an APC
produce cytokines that communicate with B and Tc cells
201
How is a Tc cell activated
detects alter self cells by recognizing damaged endogenous antigen when it reads class I MHC
202
What does a Tc cell do when activated by an altered self cells
forms a clonal population memory Tc cells to remeber the altered self cell and CTLs to kill the altered self cell
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What is the result of Tc and B cell activation
rapid mitosis to form a clonal population effector and memory cells
204
What are effector cells
short-lived cells that perform some action, like killing altered self cells or producing lots of antigens
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What are memory cells
long-lived cells that maintain their specificity for a detected antigen
206
What is the effector cell of Tc cells
TCL cells
207
What is the memory cell of Tc cells
memory Tc cells
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What is the effector cell of B cells
plasma cells
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What is the memory cell of B cells
memory B cells
210
What make plama cells special
have more machinery to produce more antibodies than regular B cells
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What does stimulation by cytokines released by Th cells do to Tc cells
aids in activation of Tc cells (cytokines not nessary or Tc activation)
212
How is a Th cell activated
Recieves info about an exogenous antigen from the MHC on the APC in addition to the co stimulatory signal given by the APC
213
Why is a co stimulatory signal required for Th activation
To ensure that the Th cell is actually recieving a signal from an APC
214
How are B cells activated
must recieve detection of exogenous antigen from antibody AND cytokines from Th cells
215
What do B cells do when activated
produce memory B cells and plasma cells
216
What is similar between Tc and NK cells
They both detect altered self cell
217
What is similar between TCLs and NK cells
They both induce apoptosis in altered self cells
218
Why are NK cells often classified under innate immunity as opposed to acquired immunity despite being lymphocytes
Have fixed set of receptors for foreign epitopes and do not require antigen presenentation for activation
219
What happens when an NK cell activates
induced apoptosis in altered self cell (same way as TCLs) AND secrete cytokines to communicate with innate and aquired immune system
220
What are the 4 ways that antibodies can act to remove pathogens
agglutination, precipitation, neutralization, lysis
221
When multiple large particles with antigens on surface are bound into a clump by antibodies
agglutination
222
When a complex of antibodies and antigen becomes so large that it is no longer soluble
precipitation
223
When an antibody blocks the active/toxic site of a foreign substance
neutralization
224
Whn an antibodies directly attacks an invading organism
lysis
225
What cell produces antibodies
B cell
226
What shape is an antibody
Y shaped
227
What is the top of the Y shape of an antibody called
variable portion
228
What is the variable portion of an antigen for
antigen binding
229
What is the bottom of the Y shape of an antibody called
constant portion
230
What is the constant portion of an antigen for
binding to receptors on immune cells
231
How many peptide chains are antibodies composed of
4
232
How are the peptides chains of antibodies arranged
2 pairs of connected heavy and light chains (4 total peptide chains)
233
How can the migration patterns of different types of lymphocytes and phagocytes be controlled separately?
different types of lymphocytes and phagocytes possess receptors for different chemokines
234
extracellular maxtrix proteins are detected by what class of receptor
Integrins
235
An antibody made against substances formed by a person's own body
Autoantibodies
236
The inactivation and/or destruction of B cells that can make autoantibodies, so that they cannot respond to an antigenic stimulus can induce in the body a state of ___________ to itself
immunologic tolerance
237
Prevention of an immune response against a particular antigen
immunologic tolerance
238
absence of the normal immune response of a T cell to a particular antigen or allergen
anergy
239
What causes phagocytic white cells like neutrophils and macrophages to migrate toward the site of infection?
chemoattractants
240
What are some innate (nonspecific) immunity cells
neutrophils, macrophages, NK cells
241
What are some aquired (specific) immunity cells
T and B cells
242
What happens when platelets get activated
They increases in size, bind together, and extend lammelopodia to facilitate blood clotting
243
Do platelets have nuclei
no
244
Are platelets cells
cell fragments
245
Property of not causeing blood clotting or complement activation when in contact with blood
hemocompatability
246
an insoluble protein that is produced in response to bleeding and is the major component of the blood clot
fibrin
247
What cells have CD4 proteins but not CD8 proteins on their surface
Th cells
248
What cells have CD8 proteins but not CD4 proteins on their surface
Tc cells
249
What
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