Transcript Innate immunity

Innate Immunology
Clarence Lam, Sanket Patel, Tairan Yang, Narthaanan Srimurugathasan
PHM142 Fall 2016
Instructor: Dr. Jeffrey Henderson
Outline
1. Introduction and components of innate immunity
2. Differentiation from blood cells and mechanisms of
phagocytosis
3. Mechanisms of neutrophils, HOCl, and of eosinophils HOBr
4. Arthritis as an autoimmune disease
What is innate immunity?
Components of innate immunity
• Epithelial barriers
• Mucous membranes
• Phagocytes (neutrophils, macrophages)
• Mast cells
(Lee and Cohen, 2014)
(Alberts, 2002)
(Alberts, 2002)
(Urb, Sheppard, 2012)
Cells of Innate Immunity
• Monocytes & macrophages
• Mast cells
• Natural Killer cells
• Dendritic cells
• Granulocytes:
• Basophils
• Eosinophils
• Neutrophils
Immunobiology: The Immune System in Health and Disease, 5th ed., 2001 (Page 55)
Phagocytosis
Principles of Human Physiology, 5th ed., 2012 (Page 116)
Inside the Neutrophil Phagosome
Hampton, M. B., A. J. Kettle, and C. C. Winterbourn. Blood: Inside the Neutrophil Phagosome: Oxidants, Myeloperoxidase, and Bacterial Killing.
92 Vol. American Society of Hematology, 11/01/1998. Web. 24 Sep. 2016.
Eosinophils: Function and Mechanism
• Involved in immune responses to allergic inflammation and parasitic
infection
• Play an important role in allergic rhinitis, chronic rhinosinusitis, and
asthma
• Activated by many different molecules including IL-3, IL-4, IL-5, IL-13,
and GM-CSF
• Activated eosinophils release MBP, ECP, EPO and EDN, which exert a
range of biological effects on host cells and microbial targets.
• Eosinophil peroxidase (EPO): Br– + H2O2 + H+ → HOBr + H2O
Autoimmune disease
• Leukocytes consider the body’s own cells as foreign, and
consequently attack and destroy healthy body tissue
• May result in:
• Destruction of body tissue
• Abnormal growth of an organ
• Changes in organ function
• Common examples:
• Rheumatoid Arthritis (RA)
• Systemic Lupus Erythematosus
• Celiac Sprue Disease
Rheumatoid Arthritis
• Primarily attacks joints
• Activated leukocytes purposely generate hydrogen peroxide and
other toxins to target
antigens
• Autoimmune response
is inflammation and
pain
Cornish, A. L., Campbelll I. K., McKenzie, B. K., Chatfield, S. & Wicks, I. P. (2009). G-CSF and GMCSF as therapeutic targets in rheumatoid arthritis. Nature Reviews Rheumatology, 5. Retrieved
from http://www.nature.com/nrrheum/journal/v5/n10/full/nrrheum.2009.178.html
Mechanism of Action
Fe2+
H2O2
Cl-
HO-
O2
HOCl
Fe3+
HO●
O2●-
NO●
HO●
Cl-
ClONOO-
Stages of Rheumatoid Arthritis
Stages of rheumatoid arthritis. (2010). Retrieved from http://physioclinic.sg/conditions-treated/arthritis/rheumatoid-arthritis/
Summary
• Innate immunity consists of epithelia, phagocytes (neutrophils, macrophages), and mast cells
• Epithelium acts as a physical and chemical barrier against infection
• Macrophages and neutrophils have cell surface receptors and pattern recognition receptors to
recognize and ingest microbes via phagocytosis; mast cells modulate innate immunity by
increasing blood flow and mucus secretion
• Hydrogen peroxide is generated by neutrophils at site of action
• Phagosomal NADPH oxidase converts molecular oxygen to toxic superoxide
• Myeloperoxidase converts hydrogen peroxide to hypochlorous acid, a bactericidal oxidant
• Eosinophil peroxidase (EPO) converts hydrogen peroxide into reactive species: Br– + H2O2 + H+ →
HOBr + H2O
• Autoimmune diseases occur when leukocytes consider the body’s own cells as foreign, and
consequently attack and destroy healthy body tissue
• Rheumatoid arthritis is an autoimmune disease that results in the inflammation of joint
References
•
Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Innate Immunity. Available from:
http://www.ncbi.nlm.nih.gov/books/NBK26846/
•
Cornish, A. L., Campbelll I. K., McKenzie, B. K., Chatfield, S. & Wicks, I. P. (2009). G-CSF and GM-CSF as therapeutic targets in rheumatoid arthritis.
Nature Reviews Rheumatology, 5. Retrieved from http://www.nature.com/nrrheum/journal/v5/n10/full/nrrheum.2009.178.html
•
Lee, R. J., & Cohen, N. A. (2014). Bitter and sweet taste receptors in the respiratory epithelium in health and disease. Journal of Molecular Medicine
(Berlin, Germany), 92(12), 1235–1244. http://doi.org/10.1007/s00109-014-1222-6
•
Janeway, C., Travers, P., Walport, M., & Shlomchik, M. (2001). Immunobiology: The immune system in health and disease. New York: Garland Science.
•
Kariya, Shin, Mitsuhiro Okano, and Kazunori Nishizaki. "Biological Basis and Clinical Implications of Immunological Molecules Involved in Eosinophilic
Inflammation in Allergic Rhinitis, Chronic Rhinosinusitis, and Asthma." Advances in Cellular and Molecular Otolaryngology, vol. 3,
2015.doi:10.3402/acmo.v3.26601.
•
Hampton, M. B., A. J. Kettle, and C. C. Winterbourn. Blood: Inside the Neutrophil Phagosome: Oxidants, Myeloperoxidase, and Bacterial Killing. 92 Vol.
American Society of Hematology, 11/01/1998. Web. 24 Sep. 2016.
•
Heinecke, J. W. "Eosinophil-Dependent Bromination in the Pathogenesis of Asthma." The Journal of clinical investigation, vol. 105, no. 10, 2000., pp.
1331-1332doi:10.1172/JCI10072.
•
Henderson, J. (2016). Unit 2 – Iron. [PDF Document]. Retrieved from http://phm.utoronto.ca/~jeffh/phmunit2cb.pdf
•
Martin, L. J. (2015). Autoimmune disorders. Retrieved from https://medlineplus.gov/ency/article/000816.htm
•
Stanfield, C. L. (2012). Principles of human physiology. Glenview, Illinois: Peason Education.
•
Stages of rheumatoid arthritis. (2010). Retrieved from http://physioclinic.sg/conditions-treated/arthritis/rheumatoid-arthritis/
•
Urb, M., & Sheppard, D. C. (2012). The Role of Mast Cells in the Defence against Pathogens. PLoS Pathogens, 8(4), e1002619.
http://doi.org/10.1371/journal.ppat.1002619