Robbins Chapter 3 Flashcards
Extracellular fibrillar networks that concentrate antimicrobial substances at sites of infection and trap microbes, helping to prevent their spread
Neutrophil Extracellular Traps (NETs)
How are NETs formed?
Start with ROS-dependent activation
Arginine deaminase converts arginines to citrulline -> chromatin decondensation
Other enzymes enter nucleus and cause further chromatin decondensation
The nuclear chromatin in the NETS (including histones and associated DNA) have been postulated to be involved in which disease?
SLE (and other systemic autoimmune disease)
Nuclear chromatin as a source of nuclear antigens
What are the major opsonins?
- Immunoglobulin (IgG) antibodies
- Mannose binding lectin
- Collectins
The most potent bactericidal system of neutrophils
H2O2-MPO-halide system
(important in formation of reactive oxygen species and killing of microbes)
Inherited deficiencies of components of phagocyte oxidase cause this immunodeficiency disease
Chronic granulomatous disease
3 different types of nitric oxide synthase (NOS)
- endothelial (eNOS)
- neuronal (nNOS)
- inducible (iNOS)
In cell proliferation in regeneration/repair, what is the most important source of growth factors?
Macrophages activated by the tissue injury
How are hepatocytes primed for cell proliferation in the process of regeneration?
Cytokines such as IL-6 secreted by Kupffer cells prime the hepatocytes and makes them competent to receive signals from growth factors
Main type of macrophages involved in repair
Alternatively activated M2 type
Signaling pathway that regulates the sprouting and branching of new vessels
Notch
Most important cytokine for the synthesis and deposition of connective tissue proteins
TGF-beta
Fibroblasts that acquire features of smooth muscle cells including the presence of actin filaments
Myofibroblasts
(these contribute to the contracture of the scar over time)
During scar formation, MMPs are activated to remodel the deposited ECM and their activity is shut down by…
TIMPs (tissue inhibitors of metalloproteinases)
Which cytokine activates macrophages as part of the classical pathway?
IFN gamma
What is the main role of macrophages activated by the alternative pathway?
Termination of inflammation and promote tissue repair
Which pathway of macrophage activation results in production of ROS, NO and lysosomal enzymes which enhance their ability to destroy microbes
Classically activated pathway
Which subset of CD4+ T cells produces the cytokine IFN-gamma and activates macrophages by the classical pathway?
Th1
Which subset of CD4+ T cells secretes IL-4, IL-5 and IL-13 which recruit and activates eosinophils and are responsible for the alternative pathway of macrophage activation?
Th2 cells
Which subset of CD4+ T cells secretes IL-17 and other cytokines which are responsible for recruiting neutrophils and monocytes into the reaction?
Th17
What is contained in the granules of eosinophils?
Major basic protein - a highly cationic protein that is toxic to helminths
What is the role of CRP and SAA (serum amyloid A) in acute inflammation?
Bind to microbial cell walls, may act as opsonins and fix complement
Cytokines that stimulate the production of prostaglandins in the hypothalamus resulting in fever
TNF and IL-1
Cytokines that are the most notable in sepsis
TNF
IL-1
Inherited defect in phagolysosome function
Chediak-Higashi syndrome
What are the major opsonins?
IgG antibodies
C3b
Mannose-binding lectin
Collectins
What are 3 examples of macrophage receptors that enable binding to microbes?
- Mannose receptors
- scavenger receptors (binds LDL)
- Integrins (e.g. MAC-1)
Enzyme contained in the azurophilic granules of neutrophils
In the presence of Cl- converts H2O2 to hypochlorite
Myeloperoxidase (MPO)
The most potent bactericidal system of neutrophils
H2O2-MPO-halide system
Result of an inherited deficiency of MPO
Minimal increase in susceptibility to infection
Antioxidants that protect healthy cells from damage by reactive oxygen species (name 5)
- the enzyme superoxide dismutase
- catalase
- glutathione peroxidase
- ceruloplasmin
- iron-free fraction of plasma transferrin
Inherited deficiency of components of phagocyte oxidase (NADPH oxidase)
Chronic granulomatous disease
Major inhibitor of neutrophil elastase
Alpha-1- antitrypsin
Part of NETs which have been postulated as source of nuclear antigens in systemic autoimmune diseases (e.g. SLE)
Nuclear chromatin, including histones and associated DNA
3 main microbicidal substances produced by macrophages and neutrophils
- reactive oxygen species
- NO
- lysosomal enzymes
Major responses of Macrophages to activating stimuli
- Cytokine production
- Induction of NO by transcriptional activity of iNOS
Major response of Neutrophils to activating stimuli
- reactive oxygen species (respiratory burst)
- degranulation (induced by cytoskeletal rearrangement)
- secretion of lysosomal enzymes
- NET formation
