Lecture C2 Flashcards

1
Q

monocytes are precursor cells of _______ (4)

A

macrophages, osteoclasts, microglia, other tissue-resident macrophages

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2
Q

monocytes size? description?

A

-12-20 um in diameter in circulation
-large nuclei that is indented or C-shaped

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3
Q

Phagocytes were discovered by ____ who drank _____

A

-Metchinkoff
-cholera and sour milk

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4
Q

Phagocytosis (def.)

A

cellular uptake of particulates (>0.5 um) within a PM envelope

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5
Q

Professional or dedicated phagocytes primary function is ______

A

phagocytosis

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6
Q

Professional phagocytes cells - dedicated to phagocytosis (4)

A

-polymorphonuclear neutrophils
-monocytes
-monocyte-derived macrophages
-tissue-resident macrophages

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7
Q

Non-professional phagocytes are cells that can ____

A

perform phagocytosis but are not dedicated to phagocytosis

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8
Q

Non-professional phagocytes cells (3)

A

-epithelial cells
-fibroblasts
-dendritic cells (DC)

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9
Q

Phagocytosis is important for: ______ (3)

A

-innate immune response
-clearing dead cells during homeostasis/remodelling
-response to damage

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10
Q

Phagocytosis phases (4)

A

1) detection of the particle to be ingested
2) activation of the internalization process
3) formation of a specialized vacuole called phagosome
4) phagosome maturation

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11
Q

phagocytic cup is responsible for ____

A

membrane bending during phagocytosis

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12
Q

phagosome is formed from _____. phagosome + lysosome = _____

A

-endosome + endocytotic vesicle
-phagolysosome

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13
Q

Two classes of PM receptors that mediate phagocytic recognition

A

-non-opsonic receptors
-opsonic receptors

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14
Q

non-opsonic receptors do what?

A

directly bind distinct molecular patterns on the particle to be ingested

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15
Q

opsonic receptors do what?

A

detect host-derived proteins bound to target particles/binds on other proteins that bind to target particles (ex. antibody)

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16
Q

Receptors directly recognizing ___________ (PAMPs) are the ______ (PRRs). Some of these PRRs are ______ for phagocytosis.

A

-pathogen associated molecular patterns
-pattern-recognition receptors
-nonopsonic receptors

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17
Q

Normal cells express the “don’t eat me” signaling molecule ____ on their cell surface. It interacts with the ______ on phagocytes.

A
  • CD47
  • antiphagocytic receptor SIRPα
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18
Q

During apoptosis, dying cells express greater amounts of ______. ______ on phagocytes bind to directly to PS. CRT connected to ____ on phagocytes

A

-phosphatidylserine (PS)
-C1q and calreticulin (CRT)
-CD91

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19
Q

The complement cascade does what?

A

recognizes, engages, and destroys a pathogen

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20
Q

Opsonins (def.)

A

extracellular proteins that bind to substances or cells and induce phagocytes to phagocytose targets with the opsonins bound

21
Q

center of complement cascade

A

C3 is cleaved by C3 convertase to produce C3a and C3b

22
Q

C3a is a ______ for neutrophils and monocytes, whereas C3b is an _____

A

-vasodilator and chemoattractant
-opsonin for pathogens and debris

23
Q

The complement cascade is activated by three different pathways: _______

A

-classical (antibody binding to antigen) pathway
-lectin pathway
-alternative pathway

24
Q

classical (antibody binding to antigen) pathway to complement cascade

A

-antigen-antibody complex interacts with C1 complex
-This activates C1 complex
-Activated C1 complex cleaves C4 and C2
-Cleaved C4 & C2 fragments form C3 convertase

25
Q

lectin pathway to complement cascade

A

-Lectins bind to carbohydrates (oligosaccharides) on pathogen surface
-This activates mannose-associated serine proteases (MASPs)
-MASPs cleave C4 and C2
-Cleaved C4 & C2 fragments form C3 convertase

26
Q

alternative pathway to complement cascade (minor pathway)

A

-C3 autoactivates in a process known as tick-over
-C3 undergo spontaneous hydrolysis of a reactive thiol-ester to create C3(H2O)
-C3(H2O) binds to factor B and properdin to form C3bBbP (amplifies production of C3 convertase)

27
Q

C3 convertase is a ____

A

serine protease

28
Q

complement cascade past C3 convertase

A

-The C3 convertases cleave C3 to C3a and C3b
-Add C3b to the other C3 convertases to make C5 convertases
-C5 convertases cleave intact C5 to C5a and C5b.
-Binding of C5b with C6, C7, C8, and finally C9 results in the assembly of C5b-9 or membrane attack complex

29
Q

C3a and C5a are what?

A

powerful anaphylatoxins; immunomodulators

30
Q

Opsonization occurs as C3b label target cells as ____

A

foreign (bacteria) or nonviable (apoptotic cells)

31
Q

Macrophages are _____

A

phagocytic cells and antigen-presenting cells

32
Q

Macrophages general function

A

-takes up antigen by phagocytosis
-breaks down antigen in lysosome
-class II MHC protein binds antigen fragment
-MHC protein presents the antigen to T cell receptor on T cell (activates T cell)

33
Q

Tissue-resident macrophage in adult tissues have ______: derived from ______ or ______ (two pop’n)

A
  • multiple origins
    -circulating monocytes
    -yolk sac progenitors
34
Q

Tissue-resident macrophage populations arise from _____ and maintain themselves locally

A

embryonic precursors

35
Q

macrophages of the brain (____) come from which pop’n?

A

-microglia
-yolk sac

36
Q

macrophages of the epidermis, lung and liver come from which pop’n?

A

yolk sac -> fetal liver

37
Q

macrophages of the heart, pancreas, gut, dermis come from which pop’n?

A

yolk sac -> fetal liver -> bone marrow

38
Q

microglia (def.) + general function

A

-tissue-resident macrophages in the brain
-Major component of immune defense in the CNS (eats up debris) + Tile across the brain with discrete territories under normal conditions

39
Q

microglia key functions (6)

A

-neurogenesis & neuronal function
-surveillance
-phagocytosis
-inflammation
-blood-brain barrier permeability
-synapse monitoring and pruning

40
Q

Microglia in different brain regions have _____

A

distinct morphology

41
Q

In general, microglia change from the ______ to the ______ morphology when activated (usually with disease, injury and illness)

A

-“ramified” : small cell body, thin long processes
-“ameboid” : large cell body, thick small processes

42
Q

A change in microglia morphology and number often indicates ______

A

-activation

43
Q

Microglia in Alzheimer’s disease

A

-Microglia cluster around AB plaques and engulf them (GOOD)
-Some microglia migrate to other regions, release undigested AB aggregates to new regions (BAD - spread injury)

44
Q

Synapses elimination by microglia

A

-microglia expresses receptors for complement proteins on low activity synapses and engulfs them
-diseases like schizophrenia due to high level of complement proteins and excessive synaptic elimination

45
Q

Complement proteins for synapse elimination (4)

A

-iC3b
-CR3
-C1q
-C4

46
Q

Kupffer cells are found with ____

A

sinusoid lining of the liver

47
Q

Kupffer cells make up _____ of all the macrophages in the entire human body

A

80-90%

48
Q

Kupffer cells function

A

-recognize and phagocytose aged erythrocytes
-remove any bacteria or debris present in the portal blood

49
Q

Clearing of RBC: ______ interactions inhibit phagocytosis of RBCs by the macrophage. _____ exposed on the RBC membrane can directly bind its receptors on the macrophages to give a pro-phagocytic signal. _______ facilitates phagocytosis.

A

-CD47–SIRPα
-Phosphatidylserine (PS)
-Band 3 clustering and opsonization with natural occurring antibodies (Nabs) and complement on the RBC