Lec 4 phagocytosis Flashcards

1
Q

What is phagocytosis

A

the process of ingestion or engulfment and destruction of foreign particles such as bacteria and dead cells by the phagocytic cells.

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2
Q

What are phagocytes

A

white blood cells that protect the body by ingesting(phagocytosing) harmful foreign particles , bacteria and dead or dying cells.

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3
Q

Which cells are professional phagocytes

A
Neutrophils
Monocytes
Macrophages
Dendritic cells
Mast cells
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4
Q

What cells are non professional phagocytes?

A

Fibroblasts

Osteocytes

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5
Q

What is the function of fibroblasts?

A

Phagocytose collagen in the process of remolding scares`

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6
Q

Which professional phagocytes are found in the blood?

A

Neutrophils

Monocytes

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7
Q

Which professional phagocytes are found in the Bone marrow?

A

Macrophages

Monocytes

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8
Q

Which professional phagocytes are found in the gut and intestinal peyer’s patches?

A

Macrophages

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9
Q

Which professional phagocytes are found in the skin?

A

Dendritic cells
Conventional macrophages
Mast cells

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10
Q

What are the steps/stages of phagocytosis?

A
  1. Migration / Margination / Diapedesis
  2. Chemotaxis
  3. Adherence / attachment
  4. Ingestion / engulfment
  5. Destruction of the microbe (killing process)
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11
Q

What is meant by migration?

A

migration of leucocytes and phagocytes from the venules to the tissues(site of infection)

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12
Q

What do the macrophages produce during migration?

A

cytokines ,TNF-alpha and IL1

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13
Q

What is the function of cytokines ,TNF-alpha and IL1

A

activate the endothelial cells of the nearby venules to produce adhesion molecules(selectins) and chemokines.

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14
Q

What does activation of selectins and chemokines result in?

A

Margination - adherence of leucocytes to the endothelium

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15
Q

What else to cytokines ,TNF-alpha and IL1 mediate ?

A

Diapedesis - migration of leucocytes and monocytes from the blood through the endothelial wall of blood vessels to the tissues

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16
Q

What occurs In margination?

A

Selectins cause leukocytes to adhere to blood vessel walls

17
Q

What occurs In diapedesis/ emigration?

A

Leukocytes squeeze between endothelial cells into tissue space

18
Q

What is chemotaxis

A

Attraction of neutrophils and macrophages to the site of infection.

19
Q

What is chemotaxis mediated by

A

chemotactic substances liberated from microbes and damaged tissues

20
Q

What are some examples of the chemotactic substances liberated from microbes and damaged tissues

A
  • Serum complement C5a,C3a
  • Interleukin 8 (IL8)
  • Leukotrienes(cytokines)
21
Q

What is attachment of phagocytes to the microbe mediated by?

A
  • Common phagocytic receptors( PRRs such as Toll-like receptors, scavenger receptors etc.…)
  • Specific Opsonin receptors (Fc receptor for IgG and the complement receptors for C3b,iC3b and C4b)
22
Q

Where are the attachment receptors expressed?

A

on surface of phagocytic cells

23
Q

What do the attachment receptors attach?

A

They attach PAMPs expressed on microbes (and not on host cells)

24
Q

What is the function of the scavenger receptors in phagocytosis?

A

Bind to many microbial ligands (LPS, LTA, etc)

25
Q

What is the function of the macrophage mannose receptors in phagocytosis?

A

Bind to mannose-containing microbial carbohydrates

26
Q

What is the function of the B-glucan receptors in phagocytosis?

A

Bind to glycan in microbial cell walls

27
Q

What are the opsonin receptors?

A
  1. Complement receptors

2. Immunoglobulin Fc receptors

28
Q

What is the opsonin on complement receptors?

A

C3b or its cleavage products

29
Q

What is the opsonin on immunoglobulin Fc receptors?

A

antibody

30
Q

What occurs in the ingestion / engulfment ?

A

1/ phagocyte extends pseudopods around the microbe

  1. These fuse and the organism is included into a vacuole called phagosome.
  2. Lysosomal granules then fuse with the phagosome forming the phagolysosome.
31
Q

What are the mechanisms of intracellular killing?

A

Oxygen dependent mechanism

Oxygen independant mechanism

32
Q

What occurs in the oxygen dependant mechanism?

A
  1. Formation of the phagosome
  2. Increase in the activity of NADPH phagosome oxidase
  3. Increased oxygen consumption with an increased formation of ROS - RESPIRATORY BURST
  4. NADPH utilized to reduce molecular oxygen bound to cytochrome causes a burst of O2 consumption
  5. As a result, O2 is converted to superoxide anion, hydrogen peroxide singlet oxygen, and hydroxyl radicals (all of which are powerful microbial agents)
33
Q

What are the most important toxins in the oxygen dependant mechanism?

A
  1. superoxide anion
  2. nitric oxide
  3. hydrogen peroxide
34
Q

What occurs in the O2 independent process of intracellular killing?

A
  1. Phagosome fuses with lysosome and creates a phagolysosome
  2. Lysosomal enzymes kill most bacteria within 30 mins
  3. Digestion occurs
35
Q

What are some examples of the lysosomal enzymes which kill bacteria during O2 independent intracellular killing?

A
  • Lysosome : destroys cell wall peptidoglycan
  • Lipases and proteases
  • RNAses and DNAses
  • Lactoferrins present in neutrophil granules remove essential iron from bacteria
36
Q

What occurs after digestion during O2 independent intracellular killing?

A

residual boy with undigestable material is discharged

37
Q

What are additional killing factors during O2 independent intracellular killing?

A
  • increased glycolysis renders the medium acidic (ph 4) by its end product (pyretic acid)
  • this is bactericidal to most bacteria
38
Q

What do lysozyme and lactoferrins act as in the O2 independent mechanisms?

A

they act as bacteriostatic substances, which are O2 independent and function under anaerobic conditions

39
Q

What is the final step in O2 independent intracellular killing?

A

Hydrolytic enzymes digest the killed organisms and the degraded products are released to the exterior