Basics Flashcards

1
Q

Elie Metchnikoff

A

First coined the name “macrophage” to describe large mononuclear phagocytic cells he observed in tissues in 1882.

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2
Q

Mononuclear phagocyte system

A

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.

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3
Q

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.

A

Van Furth’s mononuclear phagocyte system

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4
Q

Argument against mononuclear phagocyte system

A

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)

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5
Q

microRNA

A

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.

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6
Q

Classical Dendritic Cells

A

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

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7
Q

Macrophages and DC precursor

A

A bone marrow resident LIN-CD117+CD135+ clonotypic precursor with plasmacytoid dendritic (pDC), classical (cDC) and monocyte potential.

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8
Q

Common monocyte progenitor (CMoP)

A

A bone marrow resident LIN-CD117+ precursor with monocyte potential that is the direct progeny of macrophage and dendritic cell precursors (MDPs)

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9
Q

Necrosis

A

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

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10
Q

Anticipatory Inflammation

A

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.

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11
Q

C3a

A

Induces:
Mast cell degranulation
Chemotaxis

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12
Q

C5a

A

Induces:
Chemotaxis
Smooth muscle contractions (broncospasms)
Vascular permeability
Mast cell degranulation (histamine & tnf)

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13
Q

Time monocytes are in blood

A

10-20 hrs

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14
Q

Origin of monocytes

A

Bone marrow–> myeloid blast–>monocyte–>blood–>tissue

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15
Q

Steps to diapedesis

A

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

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16
Q

Types of macrophages

A

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

17
Q

Three most important macrophage functions

A

Phagocytosis
APC
Cytokine secretion

18
Q

Cd31/cd47

A

Binds macrophages to neutrophils for “don’t eat me” signal

“Eat me” signal: sp-a, sp-d, igm

19
Q

Enzymes of macrophage lysosome

A

Lipase
NADPH Oxidase
SOD

No mop

20
Q

IFN gamma

A

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
21
Q

IL1

A

Pyrogen

22
Q

IL6

A

Pro-inflammatory

Increases liver secretion of acute phase proteins (complement, c-reactive)

Stimulates B lymphocytes to produce antibodies

Reduces macrophage inflammation by alt activation

23
Q

IL8

A

Neutrophil chemotactic

24
Q

IL10

A

Induces Th2 (& secreted by Th2)

Induces B cell proliferation and antibody production

Suppresses Th1, CTL, IL2, INFg, proinflammatory cytokines and respiratory burst

25
Q

IL12

A

Increases:

  • NK cells
  • Th1
  • CTL
26
Q

TNF

A

Release cytokines for inflammation

Proinflammatory

27
Q

TGFbeta

A

Increase in apoptosis of many cells (t cells)

Decrease in neutrophil and monocyte activation

Decrease inflammation

28
Q

MIP

A

MIPalpha/CCL3
-recruits & activates polymorphonuclear cells

MIPbeta/CCL4
-recruits monocytes

29
Q

Monocyte –> M1 macrophage

A

IFNgamma stimulates

30
Q

Monocyte—>M2

A

IL4
IL13
IL10

31
Q

M1 Secretes

A

TNF
IL12
NO
ROS

32
Q

M2 Secretes

A

ILbeta
IL6
IL8
VEGF

33
Q

Opsonin

A

C3

IgG