- Author
-
J.W. Hoepel
- Title
- Unraveling the mechanisms of antibody-dependent inflammation
- Supervisors
- Award date
- 10 February 2021
- Number of pages
- 240
- ISBN
- 9789464163520
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Antibodies cannot only bind to and neutralize pathogens, but have several additional effector functions. The most frequently mentioned “textbook” effector functions include antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC). In this thesis, we further establish an important additional effector function of human antibodies: antibody-dependent inflammation (ADI). ADI is important to provide proper immune responses upon infection with various types of pathogens, but can also have adverse effects when activated excessively or undesirably. Because of its inflammatory potential, ADI is tightly controlled and critically depends on the fulfillment of four criteria: (1) the formation of immune complexes, (2) the availability of a co-stimulus (provided by other receptors such as TLRs), (3) the intrinsic properties of the antibody (isotype, subclass, and glycosylation), and (4) the location of the antibody-immune complexes. Understanding these ADI “safety switches”, which combined determine when and where ADI is activated in the human body gives insight in how our immune system is regulated but also how over activation of ADI causes disease. This thesis also described how ADI could be activated or inhibited therapeutically, to promote host defense or to counteract chronic or excessive inflammation.
- Persistent Identifier
- https://hdl.handle.net/11245.1/99ee561e-7fa6-44e3-ba08-e5e07bad64da
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: Introduction
Chapter 2: FcγR-TLR cross-talk enhances TNF production by human monocyte-derived DCs via IRF5-depedent gene transcription and glycolytic reprogramming
Chapter 3: Fc gamma receptor IIa suppresses type I and III interferon production by human myeloid immune cells
Chapter 4: IgG subclasses shape cytokine responses by human myeloid immune cells through differential metabolic reprogramming
Chapter 5: Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses
Chapter 6: IgG immune complexes break immune tolerance of human microglia
Chapter 7: FcγRIII stimulation breaks the tolerance of human nasal epithelial cells to bacteria through cross-talk with TLR4
Chapter 8: Serum IgA immune complexes promote proinflammatory cytokine production by human macrophages, monocytes, and Kupffer cells trough FcαRI-TLR cross-talk
Chapter 9: General discussion
Summary; Samenvatting; PhD portfolio; List of publications; Curriculum Vitae; Dankwoord
- Supplementary materials
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