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BME 103 Exam 3
Exam 3 Flashcards
118
Engineering
Undergraduate 2
04/11/2011

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Term
Macrophage inflammatory protein (MIP)
Definition
recruit monocytes
Term
Interleukin (IL)-8
Definition
attract more neutrophils
Term
IL-1 and Tissue Necrosis Factor (TNF) alpha
Definition
promote cell migration by increasing the expression of CAMS on the vascular endothelium
Term
TNF alpha
Definition
activate neutrophils and macrophages
Term
Activate and/or promote migration of lymphocytes
(Antigen Presenting Function)
Definition
point of communication or crossover between innate and acquired immune response
Term
Silicosis
Definition
silica particles remain in the lung tissue -- fibrosis
macrophages lyse after being unable to digest silica
particles return to tissue and cytokines release
stimulate fibroblasts to form fibrous tissue
impaired oxygen intake by the patient
Term
Frustrated phagocytosis
Definition
non-degradable material is much larger than the cells -- release of lysosomal enzymes and other products into the environment
Term
Eosinophils
Definition
one type of granulocyte -- small phagocytic capacities
attach to and destroy parasites
detox inflammation -- induce agents and prevent the spread of inflammation outside of a localized area
Term
Basophils
Definition
type of granulocyte
found in blood, similar to mast cells
release heparin, histamines, bradykinins, serotonin
involves allergic reaction
Term
Termination
Definition
Agonist: similar chemical makeup structure to cytokinds, binds the same receptors, does not stimulate inflammatory signals
Term
Transforming growth factor beta (TGF) beta
Definition
produced by macrophages and lymphocytes -- inhibiting activation of inflammatory cells
Term
Four cardinal signs of inflammation
Definition
rubor (redness)
tumor (swelling)
calore (tissue heating)
dolore (pain)
Term
Acute Inflammation
Definition
alteration of vascular caliber, changes in macrovasculature, emigration of leukocytes form microcirculation
Term
Alteration of vascular caliber
Definition
following brief vasoconstriction
vasodilation leads to increased blood flow and blood pooling -- creating redness and warmth (rubor and calor)
Term
Changes in microvasculature
Definition
increased permeability for plasma proteins and cells creating swelling (tumor)
fluid loss results in concentration of red blood cells and slowed blood flow (stasis)
Term
Emigration of leukocytes from microcirculation
Definition
due to stasis and activation leads migration towards offending agent
Term
Edema
Definition
swelling of local tissue and leakage of plasma proteins
Term
Extravasation
Definition
movement of neutrophils out of the blood vessels and into the tissue
Term
neutrophils
Definition
make up 65% of granulocytes
first inflammatory cells recruited to a site of inflammation
Term
Steps of Leukocyte extravasation
Definition
rolling, activation, arrest/adhesion, transendothelial migration
Term
Necessary for leukocytes to leave the vessel lumen
Definition
endothelial cells need to be activated and upregulate CAMS that can interavt with complementary adhesion molecules on leukocytes
Term
Causes up-regulation of CAMS on endothelial cells
Definition
inflammatory mediators such as TNF, IL-1, histamine, and others produced by tissue resident inflammatory cells
Term
Granulocytes
Definition
leukocyte

neutrophils, eosinphils, basophils

granular appearance, phagocytic, aid inflammation
Term
monocytes
Definition
leukocyte

mature to macrophages

large phagocytic capability -- 5x that of neutrophils
Term
lymphocytes
Definition
leukocytes
t cells and b cells

acquired immunity, produced antibodies
Term
Megakaryocytes
Definition
leukocyte

make platelets

non-nucleated, only in bone marrow, aids in clotting
Term
Monocyte response in injuries
Definition
arrive later than neutrophils, become the dominant cell type over days to weeks

greater and more sustainable killing capacities, compared to neutrophils

differentiated to tissue macrophages when they arrive at a tissue

have killing mechanisms and antigen presenting functions
Term
chemotaxis
Definition
leukocytes follow chemical gradients to the site of injury

soluble bacterial products, complement components -- C5a

cytokines -- chemokine family (IL8)

chemotactic agents bind to surface receptors and change the cell functions to induce calcium mobilization and assembly of cytoskeletal contractile elements
Term
Steps of Phagocytosis
Definition
1. pseudopodia engulf the foreign invader
2. ingestion forms a phagosome, which travels towards a lysosome
3. fusion of the lysosome and phagosome forms a phagolysosome -- releasing lysosomal enzymes
4. lysosomes digest the ingested material
5. release of digestion products from the cell
Term
Oxidative Burst
Definition
reactive oxygen species formed in intracellular granules through oxidative burst includes:
increased oxygen consumption
glycogenesis
increased glucose oxidation
formation of superoxide ion

kills foreign organisms
oxidative tissue damages
promotes corrosion and oxidative degradation of biomaterials in the body
Term
glycogenesis
Definition
one of the fundamental ways that the body produces ATP and produces reactive species
Term
Reactive Oxidative species
Definition
kills foreign invaders -- unstable
degrade biomaterial implants and damage the implant, damage inflammatory cells
Term
Cytokines
Definition
chemical mediator secreted by leukocytes
Term
Macrophages
Definition
form once monocytes attach to tissues
job is to phagocytose, produce reactive oxidative species, connect to each other to form large cells

antigen presenting function of macrophages: present foreign antigens -- allows acquired b cells and t cells to the body's material from invading material
Term
Flow Cytometry
Definition
technological process that allows for the individual measurements of cell fluorescence and light scattering.
Term
Fluorescence Activation Process
Definition
antibodies recognize specific molecules in the surface of some cells, antibodies are conjugated to fluorochromes,
Term
Advantages of flow cytometry
Definition
ideal for flowing cells, same as physical conditions, not stationary cells, can find cell information without harming the cell
Term
Light Scattering, 2 Parameter Histogram
Definition
larger and more granular cells scatter light more

y axis measures 90 degree light scatter -- measures changes in granularity

x axis uses forward light scatter -- changes in size
Term
____, _____, _____ increases as cells are activated
Definition
size, granularity, adhesiveness, vacuole storage space
Term
Platelet activation and coagulation
Definition
increased granularity increases intracellular area, increases cell storage (cytokines and growth factors) , ready to recruit cells and kill other cells
Term
Fibroblasts when activated
Definition
increase in size, not granularity -- size increases and adhesiveness increases
Term
2 Parameter Histogram
Definition
different fluorescence colors on each axis, can determine the amount of cell activation based on the fluorescence.
Term
Wound healing procedure
Definition
Know the 4 or 5 steps in which the fibrous capsule forms
clotting, angiogenesis, fibroblasts
Term
Steps of WOund healing
Definition
blood clotting
acute inflammation
migration and proliferation of fibroblasts and endothelial cells
angiogenesis
ecm formation
formation of granulation tissue
remodeling/fibrous encapsulation
Term
Scab formation
Definition
fresh blood clot
factor xiii crosslinks fibrin
vessels and fibroblasts invade fibrin meshwork
immature scar tissue forms beneath
Term
Granulation tissue deposition
Definition
remodeling -- due to death of cells following injury and their removal -- local decreased tissue mass
fibroblasts and vascular endothelial cells are recruited to site
begin to form granulation tissue (ECM and new blood vessels)
Term
Angiogenesis
Definition
development/sprouting of new blood vessels -- helps with regeneration / cancer formation
Term
Angiogenesis in cancer tumors
Definition
blood vessel network is extensive but leaky -- generate vessels at high speeds -- no time to stabilize the network -- good for cells in metastasis state -- leaks nutrients and oxygen
Term
Pericytes
Definition
stabilize blood vessels -- make the walls thicker and makes the wall more mature
Term
Foreign body reaction sequence
Definition
monocyte -- macrophage phagocytoses the invader -- forms FOREIGN body giant cells
Term
Pericytes
Definition
stabilize blood vessels -- make the walls thicker and makes the wall more mature
Term
fibrous encapsulation
Definition
end stage of healing response
usually four or more weeks after implantation
relatively acellular fibrous capsule

neutrophils suggest persisting inflammatory challenge

presence of foreign body giant cells suggests production of small particles by corrosion, degradation, dissolution or wear
Term
Spindle shaped fibroblasts
Definition
recruited in fibrous encapsulation -- aggressive -- produce lots of ECM Molecules
Term
Chronic Inflammation
Definition
triggers autoimmune response
common to see between the end of acute inflammation and full development of granulation tissue

includes the presence of a granuloma: layer of FBGC surrounding a nonphagocytosable particle -- FBGCs contained within a ring of large modified macrophages called EPITHELOID cells.
Term
4 modes of resolution
Definition
extrusion, resorption, integration, encapsulation
Term
Extrusion
Definition
pouch contiguous with this tissue forms if the implant is in contact with the epithelial tissue, material can be forced out of the body,
Term
Resorption
Definition
works for biodegradable materials, fibrous capsule may or may not form.

if fibrous capsule forms, the capsule can either collapse or be replaced by an appropriate tissue
Term
Integration
Definition
occurs in limited cases, ex. implantation of pure titanium in bone

resolution type is characterized by a close approximation of host tissue to the implant -- no intervening fibrous capsule
Term
encapsulation
Definition
traditional response to nonresorbable materials -- chronic inflammation/granuloma generation is not included -- no resolution.
Term
Epithelium
Definition
stratified -- epidermis on top
connective tissue -- dermis -- underneath

separated by basement membrane
Term
Steps of Wound Healing
Definition
inflammatory response (reaction--hemostasis and phagocytosis

proliferative phase--regeneration

maturation phase -- remodeling
Term
Skin Repair
Definition
dermal wound
requires granulation tissue formation
1. blood clotting and formation of fibrin network forms to prevent fluid loss.
2. acute inflammation -- localized response and cellular migration -- removal of debris and deposition of hyaluronic acid in the ECM
3. inflammatory response triggers fibroblast influx -- deposite ECM, marks begining of granulation tissue formation
4. collagen III is randomly oriented and dsposited in the ECM
5. neovascularization and angiogenesis occur
6. collagen III is replaced with collagen I -- larger and oriented along the principal stress lines of the tissue
7. collagen accumulates for 2-3 months
8. blood vessels resorb and the scar becomes pale and avascular --
Term
Skin regeneration
Definition
occurs for epidermal wounds -- full regeneration of the defect is possible via reepithelialization

cannot take plase in the presence of a nondegradable implant in the epidermis

begins as the cells at the edge of the defect flatten to cover more of the wound by dissolution of attachments to the ECM at the edge of the wound to allow migration of these cells behind the advancing front to gradually form a thin covering over the wound site

when the defect has been covered and epithelial cells make contact with each other, the reattach to the ECM and regain cuboid morphology

the skin now has the same structure and properties as the tissue before the injury did
Term
Fibrosis
Definition
myofibroblasts disappear by apoptosis, but if there is continuous collagen secretion and remoledling and contraction can lead to connective tissue contracture
Term
Factors affecting the in vivo response to a biomedical implant
Definition
materials of manufacture

intended additives, process contamination, and residues

leachable substances

degradation products

properties and characteristics of the final products

alternation in load or strain in the area around the implant
Term
Materials of manufacture
Definition
problems may be patient specific (genetic disorder, autoimmune response), material can generate inflammatory response
Term
intended additives, contamination, residues
Definition
processing the materials in a clean room, prevents dust contamination from the air, need to keep everything in tight control to create antiseptic material
Term
Leachable substances
Definition
may be biocompatible when they're in the scaffolding material, but may release toxic substances upon degradation
Term
degradation products
Definition
particulates may cause failure of implant if they are too large to phagocytose
Term
Factors in developing animal models
Definition
choice of animal
choice of implantation site
length of study
biomaterial consideration (dose and administration)
inclusion of proper control
Term
Choice of animal
Definition
smiliarity in physiology and healing response to that which would occur in humans for a given application

newer materials usually are first tested in small animal models (rat, rabbit), and the move to larger models (goat, dog, sheep, cow)
Term
Choice of implantation site
Definition
should be as close to possible to that which will be used in the final application.

accessible site (subcutaneous pouch) is used for a first screening of the inflammatory response to the new material.

should be assessed for:
reduction in macrophage number and other inflammatory cells at a site that is not well vascularized, -- represents a lack of access to these cells, rather than anti-inflammatory properties of the material

see if the surrounding cells have the ability to proliferate and migrate

see effect of alterations in mechanical factors on the behavior of the surrounding cells
Term
Length of Study
Definition
Toxicity testing
Acute toxicity: single exposure -- within 24 hour observation
Sub-Acute toxicity -- repeat or continuous exposure -- 12-28 hours
Sub-Chronic exposue -- repeat or continuous exposure -- 30 days
chronic toxicity -- repeat or continuous exposure -- over 30 days

can provide info on the localized inflammatory response to the biomaterial -- combination of response to surgery, inflammation, and tissue remodeling/resolution around the implant
Term
Biomaterial consideration (dose and administration)
Definition
direct implant or injection of soluble products
shape of implant affects its "dose"

carried out to screen novel materials to gain insight into the degree and type of inflammatory response, or to assess inflammatory response to the material in a form very similar to that which will be implanted (shape is important)

For direct implantation, consider:
implant weight/size
surface area
topography
number of implants per animal

Stainless steel cages enables investigators to examine the inflammatory response without providing contact between the material and surrounding tissue
-- good for assessing the rxn to a soluble fraction of the biomaterial
Term
inclusion of proper control
Definition
includes contralateral tissue, or an unfilled surgical implant site
material and device controls may be needed to compare the new implant with a standard material or previous version of the device
Term
Acquired immunity
Definition
memory immunity, differentiaties self from foreign invaders, mediated by lymphocyte constantly circulating the blood and tissues, consists of:

antibody response -- humoral response
lymphocyte mediated response -- cell mediated response
Term
immunotoxicity
Definition
refers to the adverse effects on the function of the immune system or other body systems as a result of alterations in immune system function

allergies and autoimmune diseases have developed after biomaterial implantation
Term
four characteristics of acquired immune response
Definition
specificity, diversity, self/nonself recognition, immunologic memory
Term
humoral immunity
Definition
based on the actions of antibodies against foreign substances -- plays a large role in response to foreign agents such as bacteria
Term
cellular immunity
Definition
specialized lymphocytes and its primary function is in the detection of altered self cells (viral infections or cancer)
Term
innate immunity
Definition
within 12 hours
epithelial barriers, phagocytes, NK cells -- generated very fast, nonspecific immune response
Term
adaptive, acquired immunity
Definition
b lymphocytes -- produce antibodies
T lymphocytes -- produce effector cells
takes more than one day, to several weeks to develop
Term
how innate and acquired responses work together
Definition
neutrophils produce cytokinds that activate antigen dependent cells
macrophages use antigen presentation to present antigens to t cells and b cells
Term
Humoral immunity
Definition
b cell/antibody mediated immune response
Term
cellular immunity
Definition
t cell/antibody mediated immune response
Term
antigen
Definition
foreign substance recognized by immune response
Term
antibody
Definition
immune system related protein called an immunoglobin -- binds to a specific antigen
Term
epitope
Definition
specific site on an antigen recognized by the antibody
Term
hapten
Definition
low molecular weight substance that combines with a larger molecule to produce a much greater immune response than to either the hapten or carrier alone
Term
adjuvant
Definition
substance that non-specifically enhances immune response to antigens, possibly by increasing their uptake by phagocytic cells, or promoting the time the antigen remains in the body
Term
Major Histocompatibility complex
Definition
presented with antigen to help recognition of self vs. non-self -- controlling humoral and cell mediated immune responses
Term
MHC Class I Molecules
Definition
found on all nucleated cells (not red blood cells

cytotoxic t cells recognize peptides bound to class 1 MHC molecules
Term
Class II MHC molecules
Definition
found on antigen presenting cells -- dendritic cells, macrophages, b cells, and other cells,

helper t cells recognize peptides bound to class II MHC molecules
Term
endogenous antigens
Definition
1. degraded into peptides in the cytoplasm
2. bind to MHC I molecules in the rough ER
3. transported to the cell membrane
5. may be produced after alternation of a native cell due to toxic and carcinogenic properties of the biomaterialhig
Term
exogenous antigens
Definition
1. produced outside the host cell and enter through phagocytosis
2. degraded into peptide fragments during endocytosis
3. fragments bind to MHC II molecules in the endocytic vesicles
4. transported to cell membrane
5. more commonly found as a direct result of biomaterial implants
degraded into peptide
Term
T cells
Definition
found in the bone marrow and mature in the thymus
antigen presentation: activation of T cells (binding between TCR and antigens
Term
B cells
Definition
formed in bone marrow and mature in lymphoid tissues (lymph node and spleen)
antigen presentation is not required
co-stimulation by binding with antigens/secreted products from Th cells is neede for full cell activation
once activated -- proliferate to form memory cells (antibodies) and effector cells (soluble antibodies)
Term
antibodies
Definition
two light chains, two heavy chains -- can bind two antigens -- one on each arm
Term
t-cell receptor
Definition
antigen binding site -- alpha chain and beta chain
Term
Classes of antibodies
Definition
igG, igE, igA, igM
Term
antibody action
Definition
agglutination, precipitation, neutralization, lysis
Term
igG
Definition
75% of antibodies
generic antibody structure
can bind two antigen molecules
most prevalent antibody class

activates complement system
Term
igE
Definition
generic antibody structure
bind two antigen molecules
allergic reactions
Term
IgA
Definition
includes a J (joining) chain - allows for dimerization
can bind four antigen molecules at once -- important in agglutination reactions
Term
igM
Definition
J chain allows for pentamerization -- can bind up to 10 antigens at once -- most effective class for cell or bacterial agglutination

activates complement system
Term
Agglutination
Definition
occurs when multiple large particles with antigens on their surfaces are bound into a clump by antibodies -- so they cant function properly
Term
precipitation
Definition
complex of antibody and antigen become so large that it is no longer soluble -- interferes with function of foreign substance
Term
Neutralization
Definition
antibodies bind and cover the active or toxic sites on a foreign substance
Term
Lysis
Definition
splitting of cells, cells split up and burst
Term
Antigen Presenting Cells
Definition
express MHC II molecules on their membranes

macrophages (major point of interaction between innate and acquired immune response)
B lymphocytes
dendritic cells
Term
Antigen Binding sites
Definition
chains are covalently linked by disulfide bonds
one antibody can bind two antigens -- each site can bind different antigens depending on the antibody type

three domains: cytosolic, transmembrane, extracellular
Term
Activation of T Cells
Definition
t cell mobilized
encounter a cell (APC) in the blood that has digested an antigen and is displaying the fragments bound to its MHC molecules -- cytokinds help the t cell mature
MHC antigen complex activates the t cell receptor and the t cell secretes cytokinds -- spurs the growth of t cells (helper and cytotoxic)
Term
Helper T Cells
Definition
secrete cytokines that attract fresh macrophages, neutrophils, and other lymphocytes and other cytokines to direct recruits

help activate B cells
Term
cytotoxic t cells
Definition
track down infected cells and kill them
Term
Type 1 Hypersensitivity
Definition
IgE mediated
Ag induces cross linking of IgE bound to mast cells and basophils with release of vasoactive mediators
Term
Type II Hypersensitivity
Definition
antibody mediated
IgG or igM mediated cytotoxic hypersensitivity --

Blood mismatch
Term
Type III Hypersensitivity
Definition
immune complex mediated: large number of immune complexes are precipitated within a localized area or if the antigen is present in the blood.

complex -- calls inflammatory responses mediated by massive infiltration of neutrophils
Term
Type IV Hypersensitivity
Definition
T cells -- helper t cells release cytokinds that activate macrophages that direct cellular damage
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