Term
| Macrophage inflammatory protein (MIP) |
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Definition
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Term
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Definition
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Term
| IL-1 and Tissue Necrosis Factor (TNF) alpha |
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Definition
| promote cell migration by increasing the expression of CAMS on the vascular endothelium |
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Term
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Definition
| activate neutrophils and macrophages |
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Term
Activate and/or promote migration of lymphocytes
(Antigen Presenting Function) |
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Definition
| point of communication or crossover between innate and acquired immune response |
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Term
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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 |
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Term
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Definition
| non-degradable material is much larger than the cells -- release of lysosomal enzymes and other products into the environment |
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Term
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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 |
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Term
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Definition
type of granulocyte
found in blood, similar to mast cells
release heparin, histamines, bradykinins, serotonin
involves allergic reaction |
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Term
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Definition
| Agonist: similar chemical makeup structure to cytokinds, binds the same receptors, does not stimulate inflammatory signals |
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Term
| Transforming growth factor beta (TGF) beta |
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Definition
| produced by macrophages and lymphocytes -- inhibiting activation of inflammatory cells |
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Term
| Four cardinal signs of inflammation |
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Definition
rubor (redness)
tumor (swelling)
calore (tissue heating)
dolore (pain) |
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Term
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Definition
| alteration of vascular caliber, changes in macrovasculature, emigration of leukocytes form microcirculation |
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Term
| Alteration of vascular caliber |
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Definition
following brief vasoconstriction
vasodilation leads to increased blood flow and blood pooling -- creating redness and warmth (rubor and calor) |
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Term
| Changes in microvasculature |
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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) |
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Term
| Emigration of leukocytes from microcirculation |
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Definition
| due to stasis and activation leads migration towards offending agent |
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Term
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Definition
| swelling of local tissue and leakage of plasma proteins |
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Term
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Definition
| movement of neutrophils out of the blood vessels and into the tissue |
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Term
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Definition
make up 65% of granulocytes
first inflammatory cells recruited to a site of inflammation |
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Term
| Steps of Leukocyte extravasation |
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Definition
| rolling, activation, arrest/adhesion, transendothelial migration |
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Term
| Necessary for leukocytes to leave the vessel lumen |
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Definition
| endothelial cells need to be activated and upregulate CAMS that can interavt with complementary adhesion molecules on leukocytes |
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Term
| Causes up-regulation of CAMS on endothelial cells |
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Definition
| inflammatory mediators such as TNF, IL-1, histamine, and others produced by tissue resident inflammatory cells |
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Term
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Definition
leukocyte
neutrophils, eosinphils, basophils
granular appearance, phagocytic, aid inflammation |
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Term
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Definition
leukocyte
mature to macrophages
large phagocytic capability -- 5x that of neutrophils |
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Term
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Definition
leukocytes
t cells and b cells
acquired immunity, produced antibodies |
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Term
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Definition
leukocyte
make platelets
non-nucleated, only in bone marrow, aids in clotting |
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Term
| Monocyte response in injuries |
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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 |
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Term
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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 |
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Term
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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 |
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Term
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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 |
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Term
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Definition
| one of the fundamental ways that the body produces ATP and produces reactive species |
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Term
| Reactive Oxidative species |
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Definition
kills foreign invaders -- unstable
degrade biomaterial implants and damage the implant, damage inflammatory cells |
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Term
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Definition
| chemical mediator secreted by leukocytes |
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Term
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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 |
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Term
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Definition
| technological process that allows for the individual measurements of cell fluorescence and light scattering. |
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Term
| Fluorescence Activation Process |
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Definition
| antibodies recognize specific molecules in the surface of some cells, antibodies are conjugated to fluorochromes, |
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Term
| Advantages of flow cytometry |
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Definition
| ideal for flowing cells, same as physical conditions, not stationary cells, can find cell information without harming the cell |
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Term
| Light Scattering, 2 Parameter Histogram |
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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 |
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Term
| ____, _____, _____ increases as cells are activated |
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Definition
| size, granularity, adhesiveness, vacuole storage space |
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Term
| Platelet activation and coagulation |
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Definition
| increased granularity increases intracellular area, increases cell storage (cytokines and growth factors) , ready to recruit cells and kill other cells |
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Term
| Fibroblasts when activated |
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Definition
| increase in size, not granularity -- size increases and adhesiveness increases |
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Term
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Definition
| different fluorescence colors on each axis, can determine the amount of cell activation based on the fluorescence. |
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Term
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Definition
Know the 4 or 5 steps in which the fibrous capsule forms
clotting, angiogenesis, fibroblasts |
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Term
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Definition
blood clotting
acute inflammation
migration and proliferation of fibroblasts and endothelial cells
angiogenesis
ecm formation
formation of granulation tissue
remodeling/fibrous encapsulation |
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Term
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Definition
fresh blood clot
factor xiii crosslinks fibrin
vessels and fibroblasts invade fibrin meshwork
immature scar tissue forms beneath |
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Term
| Granulation tissue deposition |
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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) |
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Term
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Definition
| development/sprouting of new blood vessels -- helps with regeneration / cancer formation |
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Term
| Angiogenesis in cancer tumors |
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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 |
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Term
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Definition
| stabilize blood vessels -- make the walls thicker and makes the wall more mature |
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Term
| Foreign body reaction sequence |
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Definition
| monocyte -- macrophage phagocytoses the invader -- forms FOREIGN body giant cells |
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Term
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Definition
| stabilize blood vessels -- make the walls thicker and makes the wall more mature |
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Term
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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 |
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Term
| Spindle shaped fibroblasts |
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Definition
| recruited in fibrous encapsulation -- aggressive -- produce lots of ECM Molecules |
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Term
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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. |
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Term
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Definition
| extrusion, resorption, integration, encapsulation |
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Term
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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, |
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Term
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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 |
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Term
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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 |
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Term
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Definition
| traditional response to nonresorbable materials -- chronic inflammation/granuloma generation is not included -- no resolution. |
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Term
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Definition
stratified -- epidermis on top
connective tissue -- dermis -- underneath
separated by basement membrane |
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Term
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Definition
inflammatory response (reaction--hemostasis and phagocytosis
proliferative phase--regeneration
maturation phase -- remodeling |
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Term
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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 -- |
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Term
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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 |
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Term
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Definition
| myofibroblasts disappear by apoptosis, but if there is continuous collagen secretion and remoledling and contraction can lead to connective tissue contracture |
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Term
| Factors affecting the in vivo response to a biomedical implant |
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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 |
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Term
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Definition
| problems may be patient specific (genetic disorder, autoimmune response), material can generate inflammatory response |
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Term
| intended additives, contamination, residues |
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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 |
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Term
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Definition
| may be biocompatible when they're in the scaffolding material, but may release toxic substances upon degradation |
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Term
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Definition
| particulates may cause failure of implant if they are too large to phagocytose |
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Term
| Factors in developing animal models |
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Definition
choice of animal
choice of implantation site
length of study
biomaterial consideration (dose and administration)
inclusion of proper control |
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Term
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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) |
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Term
| Choice of implantation site |
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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 |
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Term
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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 |
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Term
| Biomaterial consideration (dose and administration) |
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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 |
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Term
| inclusion of proper control |
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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 |
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Term
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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 |
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Term
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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 |
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Term
| four characteristics of acquired immune response |
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Definition
| specificity, diversity, self/nonself recognition, immunologic memory |
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Term
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Definition
| based on the actions of antibodies against foreign substances -- plays a large role in response to foreign agents such as bacteria |
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Term
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Definition
| specialized lymphocytes and its primary function is in the detection of altered self cells (viral infections or cancer) |
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Term
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Definition
within 12 hours
epithelial barriers, phagocytes, NK cells -- generated very fast, nonspecific immune response |
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Term
| adaptive, acquired immunity |
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Definition
b lymphocytes -- produce antibodies
T lymphocytes -- produce effector cells
takes more than one day, to several weeks to develop |
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Term
| how innate and acquired responses work together |
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Definition
neutrophils produce cytokinds that activate antigen dependent cells
macrophages use antigen presentation to present antigens to t cells and b cells |
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Term
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Definition
| b cell/antibody mediated immune response |
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Term
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Definition
| t cell/antibody mediated immune response |
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Term
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Definition
| foreign substance recognized by immune response |
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Term
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Definition
| immune system related protein called an immunoglobin -- binds to a specific antigen |
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Term
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Definition
| specific site on an antigen recognized by the antibody |
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Term
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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 |
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Term
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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 |
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Term
| Major Histocompatibility complex |
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Definition
| presented with antigen to help recognition of self vs. non-self -- controlling humoral and cell mediated immune responses |
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Term
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Definition
found on all nucleated cells (not red blood cells
cytotoxic t cells recognize peptides bound to class 1 MHC molecules |
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Term
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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 |
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Term
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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 |
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Term
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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 |
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Term
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Definition
found in the bone marrow and mature in the thymus
antigen presentation: activation of T cells (binding between TCR and antigens |
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Term
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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) |
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Term
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Definition
| two light chains, two heavy chains -- can bind two antigens -- one on each arm |
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Term
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Definition
| antigen binding site -- alpha chain and beta chain |
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Term
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Definition
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Term
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Definition
| agglutination, precipitation, neutralization, lysis |
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Term
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Definition
75% of antibodies
generic antibody structure
can bind two antigen molecules
most prevalent antibody class
activates complement system |
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Term
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Definition
generic antibody structure
bind two antigen molecules
allergic reactions |
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Term
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Definition
includes a J (joining) chain - allows for dimerization
can bind four antigen molecules at once -- important in agglutination reactions |
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Term
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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 |
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Term
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Definition
| occurs when multiple large particles with antigens on their surfaces are bound into a clump by antibodies -- so they cant function properly |
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Term
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Definition
| complex of antibody and antigen become so large that it is no longer soluble -- interferes with function of foreign substance |
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Term
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Definition
| antibodies bind and cover the active or toxic sites on a foreign substance |
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Term
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Definition
| splitting of cells, cells split up and burst |
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Term
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Definition
express MHC II molecules on their membranes
macrophages (major point of interaction between innate and acquired immune response)
B lymphocytes
dendritic cells |
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Term
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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 |
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Term
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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) |
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Term
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Definition
secrete cytokines that attract fresh macrophages, neutrophils, and other lymphocytes and other cytokines to direct recruits
help activate B cells |
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Term
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Definition
| track down infected cells and kill them |
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Term
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Definition
IgE mediated
Ag induces cross linking of IgE bound to mast cells and basophils with release of vasoactive mediators |
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Term
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Definition
antibody mediated
IgG or igM mediated cytotoxic hypersensitivity --
Blood mismatch |
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Term
| Type III Hypersensitivity |
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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 |
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Term
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Definition
| T cells -- helper t cells release cytokinds that activate macrophages that direct cellular damage |
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