Basics Flashcards
Elie Metchnikoff
First coined the name “macrophage” to describe large mononuclear phagocytic cells he observed in tissues in 1882.
Mononuclear phagocyte system
A term introduced by van furth that encompasses myeloid immune cells other than polymorphonuclear granulocytes and initially included monocytes and macrophages, and then, following their discovery, dendritic cells.
Dogma created in 1968 that the homeostasis of tissue-resident macrophages relies on the constant recruitment of blood monocytes i.e. The two related cell types arise from a continuum of differentiation.
Van Furth’s mononuclear phagocyte system
Argument against mononuclear phagocyte system
1) monocytes do not substantially contribute to most tissue macrophage compartments in the steady state or during times of inflammation
2) adult tissue macrophages are derived from embryonic precursors that seed the tissues before birth
3) tissue macrophages an maintain themselves in adults by self renewal
(Based mostly on murine studies)
microRNA
A class of short endogenous non-coding RNA’s that modulate the proteome through binding to complementary mRNAs and repressing translational initiation or inducing mRNA degradation. This post-transcriptional regulation of gene expression depends on an imperfect match of short seed sequences with their target mRNA and hence each miRNA has potential to suppress multiple targets.
Classical Dendritic Cells
A term introduced by Ralph Steinman that should be reserved for short lived, FLT3 (fms-like tyrosine kinase 3 or CD135) ligand dependent cells with migratory capability and a potential to efficiently stimulate naive T cells
Macrophages and DC precursor
A bone marrow resident LIN-CD117+CD135+ clonotypic precursor with plasmacytoid dendritic (pDC), classical (cDC) and monocyte potential.
Common monocyte progenitor (CMoP)
A bone marrow resident LIN-CD117+ precursor with monocyte potential that is the direct progeny of macrophage and dendritic cell precursors (MDPs)
Necrosis
A form of uncontrolled cell death caused by factors that are external to the cell or tissue-such as infection, toxins or trauma, that result in the unregulated destruction of cellular components
Anticipatory Inflammation
The finding in mice that the abundance of circulating LY6C^hi monocytes is under circadian control, which might have evolved to prepare the organism for insults.
C3a
Induces:
Mast cell degranulation
Chemotaxis
C5a
Induces:
Chemotaxis
Smooth muscle contractions (broncospasms)
Vascular permeability
Mast cell degranulation (histamine & tnf)
Time monocytes are in blood
10-20 hrs
Origin of monocytes
Bone marrow–> myeloid blast–>monocyte–>blood–>tissue
Steps to diapedesis
Injury:
- bacteria enter
- Tissue Macrophages phagocytose bacteria and secrete cytokines
- —tnf, il beta, inf gamma,il8
- mast cells degranulate and produce histamine and thrombin
- endothelial integrin expression
Rolling (selectins)
Adhesion (Integrins)
Binding
Diapedesis
Types of macrophages
Skin: langerhan cells
Liver: Kupffer cells
Spleen: red pulp, marginal zone, sinusoidal macrophages and tingible body macrophages in the white pulp germinal center
Lung: alveolar macrophage
— giant cells are formed when they wall off an indigestible particle
Brain: microglia
Bone: osteoclast
Three most important macrophage functions
Phagocytosis
APC
Cytokine secretion
Cd31/cd47
Binds macrophages to neutrophils for “don’t eat me” signal
“Eat me” signal: sp-a, sp-d, igm
Enzymes of macrophage lysosome
Lipase
NADPH Oxidase
SOD
No mop
IFN gamma
Produced by Th1 cells after IL-12 stimulation
Binds to IFNGR on macrophage and activates cell
Leads to increase in:
- phagocytosis
- Digestion (lysosomal enzyme)
- APC
- Jak-STAT pathway
IL1
Pyrogen
IL6
Pro-inflammatory
Increases liver secretion of acute phase proteins (complement, c-reactive)
Stimulates B lymphocytes to produce antibodies
Reduces macrophage inflammation by alt activation
IL8
Neutrophil chemotactic
IL10
Induces Th2 (& secreted by Th2)
Induces B cell proliferation and antibody production
Suppresses Th1, CTL, IL2, INFg, proinflammatory cytokines and respiratory burst
IL12
Increases:
- NK cells
- Th1
- CTL
TNF
Release cytokines for inflammation
Proinflammatory
TGFbeta
Increase in apoptosis of many cells (t cells)
Decrease in neutrophil and monocyte activation
Decrease inflammation
MIP
MIPalpha/CCL3
-recruits & activates polymorphonuclear cells
MIPbeta/CCL4
-recruits monocytes
Monocyte –> M1 macrophage
IFNgamma stimulates
Monocyte—>M2
IL4
IL13
IL10
M1 Secretes
TNF
IL12
NO
ROS
M2 Secretes
ILbeta
IL6
IL8
VEGF
Opsonin
C3
IgG
