Exam I (2.2) Flashcards
Host Reaction to Biomaterials and Their Evaluation
1
Q
Hematopoiesis
A
-White blood cells and leukocytes of the immune system
- They support homeostasis by removing foreign cells/pathogens
2
Q
Hematopoietic stem cells
A
- When in their niche, they stay undifferentiated
- Upon removal, form into either red or white blood cells
- Occur via the myeloid or lymphoid pathway
3
Q
Myeloid pathway results
A
- Platelets, mast cells, blood cells
- Eventually (after more differentiation), neutrophils and macrophages
- Polymorphonuclear leukocytes (PMNs), important for defense
- Created in the bone marrow
4
Q
Lymphoid pathway results
A
- Natural killer cells, small lymphocytes (T/B cells), then eventually plasma cells
5
Q
T/B Cells’ purpose
A
- Body continually updates the immune system via these cells
- Created in bone marrow, then mature in the spleen (B cells) or the thymus gland (T cells)
- Transported in the lymph nodes
6
Q
Lymphatic system
A
- Responsible for constant pathogen surveillance
- Allows for the rapid development of immune response
- Receives excess water from veins (lymph)
- Lymph nodes store B and T lymphocytes
- Organs involved: thymus, spleen, tonsils, appendix
7
Q
Regular repair steps
A
1) Blood clots
2) Neutrophils (PMNs) are first on the scene, alerting others
3) Macrophages/lymphocytes recruited
4) New blood vessels form
5) Fibroblasts deposit ECM
8
Q
Biomaterials and Inflammation
A
- Body is unable to get rid of the foreign material
- A large fibrous capsule is formed at the site of implantation
- If the material degrades, granulation tissue forms
- Fibrosis always occurs
- Frustrated phagocytosis can happen (persists for lifetime of implant)
9
Q
Innate immune response
A
- Primitive, evolutionary, non-specific response
- Rapid, needed to mobilize adaptive response
10
Q
Innate components
A
- Physical barriers, opsonizing blood proteins (label unwanted bodies for clearance)
- Lectins: mannose-binding lectin (MBL) binds to carbs on bacteria cell wall, setting off cleavage pathway so that WBC’s are recruited
- leftover cleaved C proteins act as binding for defense cell receptors
- Dendritic cells are resident defense cells
- membrane attack complex
11
Q
Membrane attack complex
A
- When C5 is cleaved, a part of it forms a complex that begins poking holes in the bacteria
- C9 further binds, and can enlarge these holes (lysis)
12
Q
Crossover between immune and adaptive responses
A
- When cytokines are released, adaptive response is initiated
- Antigen-presenting cells take pieces of pathogen and present it to T cells
- MHC is a label that marks a cell as one of yours
13
Q
T-cells
A
- Every T cell recognizes one antigen (via one receptor)
- T-cells with new types of receptors are constantly generated, covering as much diversity as possible
- Helper T (CD4+): orchestraters, can activate B cells, express cytokines, and activate macrophages/neutrophils
- Cytotoxic T (CD8+): non-specific natural killer cells, can generate “memory” in the body for long term
14
Q
Adaptive Immunity
A
- Antibodies/immunoglobins, which are produced by B-Cells
- Immunoglobins: IgG, IgA, IgM, IgE, IgD
- both immediate and delayed mediators (to return things to normal after)
15
Q
T-Cells vs. B-Cells
A
- T-cells recognize antigen molecules only presented by antigen-presenting cells
- B-cells recognize directly!
- T-cells (cytotoxic) induce cell death for antigen-presenting, or have infected cells undergo apoptosis
16
Q
Complement system
A
- Part of the innate immune system
- Complement activation initiates innate response, regulates the adaptive response
- Proteins are constantly expressed in the blood, bind in high density to foreign bodies (opsonizing)
- Stimulates phagocytosis, inflammation, membrane attack complex, etc
17
Q
What are the pathways of activation?
A
- Classical, lectin, and alternative
- Converge on C5 activation
18
Q
Classical pathway
A
- Immune complexes (ICs), composed of antigen-antibody binding, are activators
- Long enzyme cascade, hinging on cascade of various proteins
- Upon cleavage of C5, defense cells are attracted, and membrane attack complex (MAC) can form
19
Q
Lectin pathway
A
- MBL plasma concentration increases with infection
- Binds to complex carbs on the bacteria cell wall
- Binds MBL-associated serine proteases, leads to cleaving of necessary proteins
20
Q
Alternative pathway
A
- Most biomaterials activate complement via AP!
- C3 is constantly hydrolyzing its thioester group to form C3(H2O), binds to factor B
- With factor D, C3 is cleaved multiple times
- Eventually, following cascade, C5 convertase is formed, and MAC can occur
21
Q
How is complement controlled?
A
- Negatively regulated pathways, ensure inflammation is localized to the site of injury
- Decay or dissociation of convertase complexes
- Proteolytic degradation of active components
- Control proteins for various components
- Cell membrane-bound regulators protect bystander cells
22
Q
Complement receptors
A
- Blood and immune cells express receptors for complement proteins
- Neutrophils, monocytes, B/T cells, RBC’s, antigen-presenting cells, platelets, etc
23
Q
Additional pathways
A
- C3a, C4a, C5a leads to histamine release and smooth muscle contraction (allergic reaction)
24
Q
Heparin
A
- Powerful anticoagulant
25
Q
System toxicity
A
- Failures of implants due to this are rare
- Standards involve how quickly the substance becomes toxic
- Limited (less than 24 hours), prolonged (24 hours - 30 days), permanent (more than 30 days)
- Toxic substances released can be adsorbed into tissue or distributed by the blood/lymph system (or, upon phagocytosis, tiny matter distributes easily)
- Possible effects can occur in unrelated organs, and can take years to develop
26
Q
Hypersensitivity
A
- Immune system overreacts to a small amount of foreign bodies
- Condition resulting in overreaction upon contact with foreign substances
- Requires previous exposure
27
Q
Intolerance
A
- Inherited reaction that does NOT depend on previous sensitization
28
Q
Haptens
A
- Lead to allergic reactions after combining with proteins in the body (like metal ions)
29
Q
Metal/metal alloy toxicity
A
- Implants can be made with essential or nonessential metals
- Essential: normally in body, critical for function (cobalt, iron, copper), become toxic in excess or when oxidized
- Nonessential: might mimic or displace essential metals, can lead to delayed hypersensitivity (gold, nickel, etc)
- Chronic inflammation can cause release of metal ions
30
Q
Delayed hypersensitivity
A
- Types I-IV, reaction mechanisms differentiate
- I-III are associated with humoral antibodies, B-lymphocytes
- IV are T-cell mediated, delayed, brought on by “memory”
31
Q
Hemostasis
A
- Blood coagulation and formation of clots
- Interconnected/plays a role in inflammation, wound healing, and the innate/adaptive immune responses too
32
Q
Coagulation
A
- Formation of a thrombus
- Activated through intrinsic or extrinsic pathways
- Involves platelets
- Anticoagulants and fibrinolysis (which degrades thrombus) are involved in negative regulation
33
Q
Platelet structure
A
- Lack a nucleus, disc shaped
- Made up of fragments of mature blood cells
- Have a phospholipid bilayer membrane with essential membrane-bound receptors
- Membrane also contains a connected network of internal tubes to better release granules
34
Q
Glycoproteins in platelets
A
- GP Ib can bind connective tissue such as collagen
- GP IIb / GP IIIa binds to adhesive plasma proteins like fibrinogen
35
Q
What are the kinds of granules secreted by platelets?
A
- Dense: Contain ADP, calcium ions, and serotonin (stimulates other platelets to activate, serotonin can widen veins and activate inflammation)
- Alpha: Platelet factor 4 and beta thromboglobin, as well as plasma proteins (neutralizes heparin and attracts fibroblasts for wound healing)
- Lysosomal: contain enzymes for acid hydrolysis (released last)
36
Q
Heparin
A
Capable of deactivating coagulation
37
Q
Platelet activation process
A
- Platelets become sticky, adopt an irregular shape with spiny pseudopods
- Adhere to injury or biomaterial via binding GP proteins, and secrete granules
- Many processes are undergone to continue activation of other platelets
- Thrombin is secreted to turn fibrinogen into fibrin, stabilizing thrombosis
38
Q
How are platelets activated by adsorbed proteins?
A
Unclear part of the mechanism
39
Q
Coagulation cascade: intrinsic pathway
A
- Triggered by biomaterials/external factors
- Factor XII absorbs to changed surfaces
(DO MORE WORK…) - Factor VIII acts to localize reaction
40
Q
Coagulation cascade: extrinsic pathway
A
- Triggered by tissue-derived factors
- Dependent on calcium
- Results in thrombin, converting to fibrin and helping to stabilize the clot
41
Q
Anti-coagulation measures
A
- Anti coagulation includes dilution by blood flow, localization of critical reactions to platelet surface, and inhibitors like antithrombin III
- Coagulation cofactors can also be degraded
42
Q
Fibrinolysis
A
- Also aides in preventing over-coagulation
- Removes unnecessary fibrin, improves blood flow and facilitates
- Plasminogen (also) circulates and adheres to fibrin clots to degrade
43
Q
Crosstalk
A
- Reb Blood Cells, White Blood Cells, and neutrophils assist in the process too
44
Q
Sepsis
A
- Possible consequence where pathogenic organisms with toxins are overly present in blood/tissue
45
Q
Biofilm
A
- A community of bacteria that attaches to, and further grows upon, surfaces of both abiotic materials and host tissue
- Sugar molecules are released that act as support
- Can produce enzymes that degrade the material surface
- Develops diversity, with dormant bacteria within that resist antibiotics
- Additionally, new strains of tolerant bacteria can form when antibiotic treatment is attempted
46
Q
Attachment of the biofilm
A
- Planktonic (free floating) bacteria attach via protein adsorption, glycocalyx involvement, or physical trapping due to topography
- Can colonize a variety of surfaces with different conditions
- Protein gene expression can change up to 70% after attachment
47
Q
EPS (slime)
A
- Similar to the ECM, acts as support and can provide tensile strain
- 10% cells, 90% EPS matrix in biofilm, can hold onto water and make a hydrophilic barrier
- NOT structurally stable, so constantly fragmenting and leaking into blood stream
48
Q
“Race to the Surface”
A
- Bacteria, host cells, and proteins all interact and compete for adhesion
49
Q
Strategies for avoiding biofilm
A
1) Killing (ex: covering surface with anti-microbial peptides)
2) Antifouling (superhydrophobic or hydrophilic surfaces, steric hindrance repulsion)
3) Affecting biofilm formation (enzyme modified surfaces)
