Immunology 101: Implications for Medical Device Failure. Joshua B. Slee, PhD Assistant Professor of Biology

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1 Immunology 101: Implications for Medical Device Failure Joshua B. Slee, PhD Assistant Professor of Biology

2 Learning Goals Understand innate and adaptive immunity Explain how innate and adaptive immunity work together to fight infections Discuss how the inflammatory response can be regulated

3 Basic Immunity Outside Inside Physical & Chemical Barriers (skin & mucus membranes)

4 Barriers to infection Epithelial layers produce protective substances Acidic ph Antimicrobial peptides Psoriasin Why does our skin secrete psoriasin?

5 Immunity Outside Inside X Physical & Chemical Barriers (skin & mucus membranes) Innate Immunity First line of defense Non-specific No memory Same response to repeat infection -content/uploads/how-to-keep-your- Home-Germ-Free.jpg Adaptive Immunity Max response in days Specific Memory More rapid response to repeat infection

6 Innate Pathogen Recognition Lymphocyte (white blood cell) Innate Immune System PAMPs Pathogen-Associated Molecular Patterns PRRs Pattern Recognition Receptors Germ-line encoded recognition molecules Host-Pathogen Arms Race

7 Inflammatory Response

8 Hallmarks of Inflammation

9 Phagocytosis

10 Neutrophil - Phagocytosis

11 Adaptive Pathogen Recognition Antibodies (products of B cells) Adaptive Immune System Randomly generated (B and T cell receptors) These bind to very specific antigens, rather than generic molecules found on many pathogens

12 Adaptive Immunity

13 Adaptive Memory Memory is the hallmark of adaptive immunity Why vaccines work!

14 Teamwork is Key! Innate and adaptive immunity work cooperatively Activation of innate immune responses produces cytokines

15 Questions?

16 Medical Issues Related to Innate Immunity Restenosis Cracked pacemaker lead insulation Post-surgical complications of cardiopulmonary bypass

17 Slee JB et al. Polymers 2014

18 Biocompatibility The condition of being compatible with living tissue or a living system by not being toxic or injurious and not causing immunological rejection Merriam-Webster Dictionary

19 CD47 Don t Eat Me! Expressed in virtually all cells CD47-SIRPα interaction inhibits immune response Over-expressed in most cancer cells Slee JB et al. Polymers 2014

20 Using CD47 to prevent implantable device rejection Pacemaker leads Cardiopulmonary bypass tubing Hemodialysis tubing Vascular stents Artificial heart valves Glucose sensors

21 Does CD47 prevent in vitro blood cell attachment?

22 In vitro THP-1 Attachment Assay THP-1 = human monocyte-derived macrophage cell line 3 day incubation Count adhered Cells CD47-modified vs Control Surfaces

23 Adhered Cells/200X field THP-1 Attachment Assay A. Unmodified Recombinant CD47 CD47 Peptide Nuclei B Slee JB et al. J. Vis. Exp * * Unmodified Recombinant Peptide CD47 CD47 Peptide

24 Does CD47 prevent ex vivo blood cell attachment?

25 Slee JB et al. J. Vis. Exp Chandler Loop Apparatus

26 Adhered Cells/200X field A. Chandler Loop Assay Unmodified Recombinant CD47 CD47 Peptide Nuclei B * * Slee JB et al. J. Vis. Exp Unmodified Recombinant Peptide CD47 CD47 Peptide

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28 Does CD47 prevent in vivo cell attachment?

29 Vascular Stents Restenosis

30 CD47 Prevents Cell Attachment In Vivo Bare Metal Stent CD47 Peptide Stent 2,000X 10,000X Slee JB et al. Biomaterials. 2016

31 CD47 Prevents Restenosis In Vivo Bare Metal Stent CD47 Peptide stent * * CD47 decreases restenosis measures by almost 30% Slee JB et al. Biomaterials. 2016

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33 Summary Pathogens and foreign objects trigger an inflammatory response in the body. Innate Immunity is the non-specific way the body deals with eliminating pathogens and foreign objects from the body. Adaptive Immunity is the specific way the body deals with eliminating pathogens from the body. CD47 is a marker of self to immune cells. CD47 can be used on medical devices/implantable materials to prevent the inflammatory response.

34 Thank You! Questions? Joshua B. Slee, PhD Assistant Professor of Biology DeSales University