Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets Victor Nizet, MD Journal of Allergy and Clinical.

Slides:

Advertisements

Similar presentations

Immunity to bacteria Barrier defenses of human body.

Advertisements

Complement. Innate Immunity Defensive mechanisms include : 1) Innate immunity (Natural or Non specific) 2) Acquired immunity (Adaptive or Specific ) Cell-mediated.

THE COMPLEMENT SYSTEM. The complement system The complement system is a set of plasma proteins that act in a cascade to attack and kill extracellular.

The Complement System A group of > 30 plasma proteins which comprise the primary soluble component of innate immunity. Rapidly activated in response to.

Innate Immunity Review on your own: Self-Test Questions:

Components of the Immune System.

Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy Yitzhak Katz, MD, Nelly Rajuan, MSc, Michael R. Goldberg,

Innate Immunity: The Immediate Response to Infection

D-dimer: A biomarker for antihistamine-resistant chronic urticaria

Hal M. Hoffman, MD, Lori Broderick, MD, PhD

Monoclonal antibodies and fusion proteins in medicine

Jason E. Hawkes, MD, Tom C. Chan, MD, PhD, James G. Krueger, MD, PhD

Doina M. Racila, MD, Joel N. Kline, MD, MSc

Fatty acids, inflammation, and asthma

Figure 1 Mechanisms of differential complement activation and

Laurent L'homme, PhD, David Dombrowicz, PhD

Advances in food allergy in 2015

Homozygous C1 inhibitor deficiency: The conclusion of a long search

Santa Jeremy Ono, BA, PhD, Mark B. Abelson, MD

Jason E. Hawkes, MD, Tom C. Chan, MD, PhD, James G. Krueger, MD, PhD

Hal M. Hoffman, MD, Lori Broderick, MD, PhD

Biologic Therapy and Novel Molecular Targets of Severe Asthma

Is 9 more than 2 also in allergic airway inflammation?

Fatty acids, inflammation, and asthma

David J. Cousins, PhD, Joanne McDonald, BSc, Tak H. Lee, MD, ScD

Antimicrobial peptides and the skin immune defense system

The 3 major types of innate and adaptive cell-mediated effector immunity Francesco Annunziato, PhD, Chiara Romagnani, MD, PhD, Sergio Romagnani, MD Journal.

IL-33 in clinical practice: Size matters?

TH17 and TH22 cells: A confusion of antimicrobial response with tissue inflammation versus protection Mübeccel Akdis, MD, PhD, Oscar Palomares, PhD,

Epithelium: At the interface of innate and adaptive immune responses

Peter M. Elias, MD, Yutaka Hatano, MD, PhD, Mary L. Williams, MD

Biologics and biomarkers for asthma, urticaria, and nasal polyposis

Role of IgE in autoimmunity

Ricardo U. Sorensen, MD, Luke A. Wall, MD

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation Leif Bjermer, MD Journal of Allergy.

Phillip Lieberman, MD, David Golden, MD

Food allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention, and management Scott H. Sicherer, MD, Hugh A. Sampson, MD Journal.

What is an “eosinophilic phenotype” of asthma?

Weiguo Chen, PhD, Gurjit K. Khurana Hershey, MD, PhD

Liam O’Mahony, PhD, Mübeccel Akdis, MD, PhD, Cezmi A. Akdis, MD

H. William Kelly, PharmD Journal of Allergy and Clinical Immunology

Autophagy: Nobel Prize 2016 and allergy and asthma research

IL-2– and CD25-dependent immunoregulatory mechanisms in the homeostasis of T-cell subsets Sven Létourneau, DPhil, Carsten Krieg, PhD, Giuseppe Pantaleo,

Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment

Chemokines and their receptors in allergic disease

Cagri Yildirim-Toruner, MD, Betty Diamond, MD

Primary immunodeficiencies may reveal potential infectious diseases associated with immune-targeting mAb treatments László Maródi, MD, PhD, Jean-Laurent.

Benjamin Chaigne, MD, Hervé Watier, MD, PhD

Anaphylaxis Journal of Allergy and Clinical Immunology

Erika von Mutius, MD, MSc Journal of Allergy and Clinical Immunology

The arsenal of virulence factors expressed by GAS to thwart the host innate immune response. The arsenal of virulence factors expressed by GAS to thwart.

Innate immune responses to infection

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment Eli O. Meltzer, MD, Robert B. Berkowitz,

Complement disorders and hereditary angioedema

Endotoxin and the lung: Insight into the host-environment interaction

Measles and immunomodulation

Stefan Schülke, PhD, Stefan Vieths, PhD

Cure of HIV infection: Is the long wait over?

TH2 adjuvants: Implications for food allergy

Immune pathomechanism of drug hypersensitivity reactions

Asthma: The past, future, environment, and costs

Environmental factors and eosinophilic esophagitis

Kinase inhibitors in clinical practice: An expanding world

The complement system in the airway epithelium: An overlooked host defense mechanism and therapeutic target? Hrishikesh S. Kulkarni, MD, MSCI, M. Kathryn.

The use of serum-specific IgE measurements for the diagnosis of peanut, tree nut, and seed allergy Jennifer M. Maloney, MD, Magnus Rudengren, BSc, Staffan.

The future of biologics: Applications for food allergy

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment Eli O. Meltzer, MD, Robert B. Berkowitz,

Natural history of cow’s milk allergy

Primary prevention of asthma and allergy

Itching as a systemic disease

Presentation transcript:

Understanding how leading bacterial pathogens subvert innate immunity to reveal novel therapeutic targets Victor Nizet, MD Journal of Allergy and Clinical Immunology Volume 120, Issue 1, Pages 13-22 (July 2007) DOI: 10.1016/j.jaci.2007.06.005 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Mechanisms by which the bacterial pathogen SA subverts host innate immune defense. Phagocyte recruitment is limited by binding of CHIPS to chemokine receptors. Complement activation is blocked by protein Efb binding of soluble C3 and inhibition of the both the classic/lectin and alternative C3 convertases by SCIN. Golden carotenoid pigment provides an antioxidant shield whereas catalase detoxifies hydrogen peroxide. Resistance to cationic antimicrobial peptides is afforded by positive charge modifications of the cell wall, aureolysin-mediated proteolysis, and binding/inactivation by staphylokinase. Protein A binds Fc domains of Igs in a nonopsonic manner, whereas fibrinogen binding clumping factor and the surface polysaccharide capsule and poly-N-acetylglucosamine (PNAG) act to cloak surface bound opsonins from phagocyte recognition. The heptameric pore-forming toxins γ-hemolysin and PVL preferentially target leukocyte membranes. The plasminogen (PG) binding protein staphylokinase (SAK) activates the zymogen to the active protease plasmin, which can degrade complement opsonin C3b and the immunoglobulin Fc domain. Journal of Allergy and Clinical Immunology 2007 120, 13-22DOI: (10.1016/j.jaci.2007.06.005) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Mechanisms by which the bacterial pathogen GAS subverts host innate immune defense. Phagocyte recruitment is reduced by peptidases ScpA and SpyCEP/ScpC that degrade the chemokines C5a and IL-8, respectively. Complement deposition is limited by M protein binding of host counterregulatory factors C4BP and FH. Phagocytic uptake is reduced by Mac-1/2 binding of phagocyte Fc receptors. Resistance to cationic antimicrobial peptides is afforded by D-alanyl modification of cell wall teichoic acids, cysteine protease SpeB-mediated degradation, and binding/inactivation by protein streptococcal inhibitor of complement (SIC). M protein and protein H bind Fc domains of Igs in a nonopsonic manner, and proteolytic inactivation of Ig is a property of SpeB, Mac-1/2, and endopeptidase S. DNase production facilitates escape from NETs, and the pore-forming cytolysins streptolysin S (SLS) and streptolysin O (SLO) exhibit lytic activity against host neutrophils and macrophages. Journal of Allergy and Clinical Immunology 2007 120, 13-22DOI: (10.1016/j.jaci.2007.06.005) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions