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An Sc 411 > Lec 3: Phagocytosis > Flashcards

Lec 3: Phagocytosis Flashcards

1
Q

What are some clinical signs of SLE?

A
  • synovitis, dermal reactions, oral erosions and ulcers, myositis, neuritis, meningitis, arteritis, myelopathy, pleuritis
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2
Q

What are 2 examples of prion diseases?

A

BSE and CWD

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3
Q

What are 3 different ways to group immune system responses?

A

innate vs adaptive
humoral vs cell mediated
local vs systemic

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4
Q

How is phagocytosis a prototypical innate defence system?

A
  • essential feature of immune system
  • after physical barriers, come in direct contact with immune cells
  • phagocytosis broadly used across evolution
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5
Q

What are some phagocytes in tissue?

A

dendritic cells, microglia, macrophages, Kupffer cells

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6
Q

What are some phagocytes in blood?

A
  • neutrophils

- monocytes

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7
Q

Who created the phagocytic theory?

A

Elie Metchnikoff

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8
Q

How can phagocytosis be pro or anti inflammatory?

A
  • phagocyte + pathogen = pro inflammatory

- phagocyte + apoptotic body = anti inflammatory

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9
Q

What was phagocytosis originally developed for?

A
  • control of normal cellular turnover

- dates back to biofilms

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10
Q

Is phagocytosis highly conserved?

A
  • yes, conserved over millions of years of evolution

- also highly integrated into innate and adaptive arms of immunity

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11
Q

Why do mammals have the most phagocyte differentiation?

A
  • the most evolutionarily advanced
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12
Q

What does phagocytosis serve as a platform mechanism for?

A
  • antimicrobial killing and degradation
  • host cell turnover during inflammation
  • immunomodulation
  • antigen presentation
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13
Q

How do different phagocytes use this mechanism differently?

A
  • macrophages good at phagolysosome degradation
  • dendritic cells good at antigen presentation
  • neutrophils release cytotoxic molecules
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14
Q

What are considered professional phagocytes?

A
  • monocytes, macrophages, immature dendritic cells, neutrophils
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15
Q

What are some examples of paraprofessional phagocytes?

A
  • retinal epithelial cells (eat dying rod cells)
  • thyroid and bladder epithelial cells (eat erythrocytes)
  • fibroblasts, platelets
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16
Q

What was one experiment that showed that most cells have the machinery to phagocytose?

A
  • fibroblast cells were able to stably express a phagocytosis receptor
17
Q

What are the 7 steps in phagocytosis?

A
  1. chemotaxis
  2. adherence: receptor binding and recognition
  3. receptor activation: cross linking and overcoming threshold of activation
  4. induction of phagocytic signalling cascades
  5. pseudopod formation and internalization
  6. initiation of intracellular degradative mechanisms, killing responses (NO; RB) and release of pro inflammatory mediators
  7. digestion and release of degradation products
18
Q

Give an example of an amoeba using phagocytosis for not immune purposes?

A
  • particles (bacteria) from extracellular milieu serve as essential nutrient source
19
Q

What are 4 survival strategies used by intracellular pathogens?

A
  1. prevent fusion of lysosomes to the phagosome
  2. escape from phagosome before fusion of lysosomes (i.e. intracytoplasmic)
  3. “tough it out” within phagolysosome
  4. hijack other receptors and hang out in other place within cell without phagosome formation
20
Q

Define phagocytosis.

A

Internalization of particles that are bigger than 1 micron in diameter. Receptor mediated; clathrin-independent. e.g. bacteria apoptotic cells. Involved in immunity, tissue turnover and repair

21
Q

Define endocytosis.

A

Internalization of particles that are smaller than 1 micron in diameter. Receptor mediated; clathrin-dependent. e.g. viruses, small immune complexes. Involved in down regulation of surface receptors, nutrient uptake and synaptic vesicle recycling

22
Q

Define pinocytosis.

A

“Cell drinking” - non receptor mediated (non specific); clathrin dependent. Involved in uptake of fluid and soluble molecules from extracellular environment

23
Q

How does the innate immune system detect foreign invaders?

A
  • germline encoded (not adaptive)
  • limited number of receptors
  • target motifs that are not found in eukaryotes and that have essential role for biology of pathogen
  • these are “PRRs” that detect “PAMPs)
24
Q

What kind of receptors do phagocytes contain?

A
  • a number are involved in innate immunity (TLRs)

- only a fraction of them are phagocytic receptors

25
Q

What are the 2 types of phagocytic receptors? Give examples.

A
  • direct recognition (e.g. scavenger or mannose receptors)

- indirect recognition (e.g. antibodies, complement, focolins and collectins)

26
Q

Define affinity.

A

Strength of a non covalent binding interactions; the higher the affinity the higher the likelihood two partners will exist in a complex

27
Q

Define avidity.

A

Increased ‘apparent’ affinity of a molecule for its ligand due to the presence of multiple binding sites on both partners

28
Q

IgG is always present in serum. How is this relevant?

A
  • only want it activated when there is lots of pathogen (threshold activation)
  • affinity and avidity allows you to define the threshold
29
Q

Describe how the phagolysosome is formed.

A
  • once target is bound and activation signals have been provided, the phagosome must be taken into cell
  • requires actin rearrangements, myosin interaction with actin (stimulates entry) and dynamin (helps contract and pinch off the membrane)
  • phagosome fuses with primary, secondary granules and lysosomes forming destructive phagolysosome
30
Q

What does the phagolysosome of neutrophils contain?

A
  • antimicrobial peptides
  • lysosomal enzymes (e.g. cathepsin G, elastase)
  • reactive oxygen and nitrogen compounds
31
Q

What is different during phagolysosome formation of macrophages and neutrophils?

A
  • primary and secondary granules do not appear to be present
32
Q

Describe reactive oxygen intermediates.

A
  • produced in the phagolysosome by NADPG oxidase
  • quite rapid
  • NADPH oxidase complex consists of membrane and cytosolic components which assemble in response to phagocytic signal
33
Q

Describe reactive nitrogen intermediates and give an example.

A
  • e.g. nitric oxide
  • produced in the cytoplasm by the inducible nitric oxide synthase (iNOS) and then diffuses into the phagosome to react with internalized microbes
  • requires transcriptional induction of iNOS gene expression (e.g. in response to IFN-y and LPS in macrophages)
  • slower and long lasting
34
Q

How is apoptosis anti inflammatory?

A
  • activation of specific proteases and nucleases leads to death characterized by chromatin condensation, protein and DNA degradation, loss of plasma membrane lipid asymmetry and disintegration of the cell into membrane bound fragments
  • cell death through apoptosis will contain its contents to prevent inflammation
  • phagocytosis results in release of anti inflammatory mediators including TGD-b, IL10 and prostaglandin E2
35
Q

Describe how Kupffer cells and splenic macrophages remove senescent erythrocytes from the liver and spleen.

A
  • CD47 is receptor expressed on healthy erythrocytes
  • CD47 binds to SIRP-1a on macrophage surface
  • CD-47 binding increases the threshold of activation needed to induce phagocytosis
  • live erythrocytes are not removed prematurely
36
Q

How does autoimmune hemolytic anemia (AIHA) occur?

A
  • reduction of CD47-SIRPa inhibitory signalling to splenic macrophages
37
Q

How does phagocytosis relate to SLE?

A
  • SLE characterized by formation of autoantibodies to self antigens primarily against nucleic acids (may also target RBCs, platelets, lymphocytes, clotting factors, immunoglobulin)
  • immune complexes activates complement and attracts neutrophils
  • enzymes released from neutrophils cause damage to endothelial cells of basement membrane
38
Q

How does phagocytosis relate to prion diseases?

A
  • high beta sheet formation of prion protein harder to digest as a phagocyte
  • translocation of infectious prion proteins across intestinal epithelium
  • protein will enter secondary lymphoid organs from gut and then go to brain

An Sc 411 (21 decks)

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