Inflammation: Soluble and Cellular Effector Mechanisms in Innate Immunity Flashcards
Inflammation:
A physiologic process by which vascularized tissues respond to injury.
Chronic inflammation:
Longer duration than acute.
Accumulation of fluid, plasma proteins and neutrophils –> influx of lymphocytes, macrophages and possibly ending in fibroblast growth. May result in granuloma.
Prostaglandins:
Oxidative derivative of fatty acid that mediates signs of inflammation (fever, pain, vascular permeability)
Leukotrienes:
Inflammatory mediators derived from oxidation of arachidonic acid. Mediate vasoconstriction, increased vascular permeability, endothelial adhesiveness and neutrophil chemotaxis.
IL-1/IL-6/TNF-alpha have effects on (4):
- Liver.
- Acute-phase proteins. - Bone marrow endothelium.
- Neutrophil mobilization. - Hypothalamus.
- Increased body temperature. - Fat, muscle.
- Protein and energy mobilization.
Initiates the alternative pathway:
Pathogen surface + C3b
Initiates the lectin pathway:
Mannose-binding lectin
Initiates the classical pathway:
Antibodies IgG, IgM, IgA
Different compliment pathways converge at:
Cleavage of C3 —> C3a and C3b
C1-INH:
Soluble regulatory protein that acts on C1 in the classical pathway.
Factor I/Factor H:
Soluble regulatory protein that acts on C3-convertase.
CD55:
Membrane bound regulatory protein that acts on C3- and C5-convertase.
- Decay Accelerating Factor (DAF)
CD59:
Membrane bound regulatory protein that acts on the MAC.
- MAC-inhibitory protein.
PAMPS:
- Pathogen Associated Molecular Patterns
- Found on pathogens
- Link to PRRs
TLRs:
- Toll Like Receptors
- Type of PRR
- Can be on membrane or in endosome.
- Turn on cytokines or interferon pathway.
Consequences of TLR to innate immunity (3):
- Secretion by macrophages and dendritic cells of cytokines.
- Improve phagocytosis by macrophages.
- Enhanced ability of dendritic cells to induce adaptive immunity.
DAMPS:
- Damage Associated Molecular Patterns
- Not associated with pathogens.
- From necrosis (not apoptosis).
- Bind to PRRs
- Promote and exacerbate acute inflammatory response.
Three sources of neutrophils:
- Circulating in the blood.
- Neutrophils stimulated to differentiate and mobilize from precursors in the bone marrow.
- Stores in venules (margination).
Neutrophil response to chemokines:
- Margination, or rolling slowly along the blood vessel wall.
- Definitive sticking/adherence mediated by selectins and intergrins.
- Pass through gaps in endothelial cells (diapedisis).
- Migrate to inflammatory site.
Extravasation:
Passage of cells from interior of blood vessels to the extravascular space.
Actions of interferon alpha and beta (3):
- Inhibiting viral replication.
- Inhibit viral binding to neighboring cells.
- Eliciting and activating NK cells to deliver a “lethal hit”.
To induce eosinophil degranulation helper T cells release (3):
- IL-5
- IL-3
- GMCSF
Growth factors for mast cells (3):
- IL-3
- IL-5
- GMCSF
Mast cells have high affinity Fc receptor for:
IgE
Glucocorticoids:
- Produced by adrenal cortex.
- Immunosuppression.
- Down-regulate inflammation.