Lecture C2 Flashcards by Tami Ojewole

monocytes are precursor cells of _______ (4)

macrophages, osteoclasts, microglia, other tissue-resident macrophages

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monocytes size? description?

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

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Phagocytes were discovered by ____ who drank _____

-Metchinkoff
-cholera and sour milk

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Phagocytosis (def.)

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

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Professional or dedicated phagocytes primary function is ______

phagocytosis

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Professional phagocytes cells - dedicated to phagocytosis (4)

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

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Non-professional phagocytes are cells that can ____

perform phagocytosis but are not dedicated to phagocytosis

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Non-professional phagocytes cells (3)

-epithelial cells
-fibroblasts
-dendritic cells (DC)

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Phagocytosis is important for: ______ (3)

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

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Phagocytosis phases (4)

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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phagocytic cup is responsible for ____

membrane bending during phagocytosis

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phagosome is formed from _____. phagosome + lysosome = _____

-endosome + endocytotic vesicle
-phagolysosome

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Two classes of PM receptors that mediate phagocytic recognition

-non-opsonic receptors
-opsonic receptors

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non-opsonic receptors do what?

directly bind distinct molecular patterns on the particle to be ingested

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opsonic receptors do what?

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

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

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

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

CD47
antiphagocytic receptor SIRPα

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

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

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The complement cascade does what?

recognizes, engages, and destroys a pathogen

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Opsonins (def.)

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

center of complement cascade

C3 is cleaved by C3 convertase to produce C3a and C3b

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

-vasodilator and chemoattractant
-opsonin for pathogens and debris

The complement cascade is activated by three different pathways: _______

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

classical (antibody binding to antigen) pathway to complement cascade

-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

lectin pathway to complement cascade

-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

alternative pathway to complement cascade (minor pathway)

-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)

C3 convertase is a ____

serine protease

complement cascade past C3 convertase

-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

C3a and C5a are what?

powerful anaphylatoxins; immunomodulators

Opsonization occurs as C3b label target cells as ____

foreign (bacteria) or nonviable (apoptotic cells)

Macrophages are _____

phagocytic cells and antigen-presenting cells

Macrophages general function

-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)

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

- multiple origins -circulating monocytes -yolk sac progenitors

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

embryonic precursors

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

-microglia -yolk sac

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

yolk sac -> fetal liver

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

yolk sac -> fetal liver -> bone marrow

microglia (def.) + general function

-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

microglia key functions (6)

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

Microglia in different brain regions have _____

distinct morphology

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

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

A change in microglia morphology and number often indicates ______

-activation

Microglia in Alzheimer’s disease

-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)

Synapses elimination by microglia

-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

Complement proteins for synapse elimination (4)

-iC3b -CR3 -C1q -C4

Kupffer cells are found with ____

sinusoid lining of the liver

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

80-90%

Kupffer cells function

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

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.

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