PHAGOCYTOSIS

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PHAGOCYTOSIS

• Chapter 15

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• What is a Phagocyte?
• A cell that engulfs and digests material such as
  cell debris and microbes, including invading
  organisms.
• Surface of cell contains pattern recognition
  receptors to recognize material to be ingested.

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• A scavenger receptor is an example that
  recognizes materials with charged molecules on
  their surface.
• These receptors allow cell to bind to certain
  molecular configurations on debris and foreign
  material for ingestion.
• Macrophages located in skin tissue destroy small
  amounts of bacteria in a wound
• Macrophages can produce cytokines to recruit
  additional phagocytes (neutrophils) for help.

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The Process of Phagocytosis

• A series of complex steps allowing phagocytes to
  engulf and destroy invading microorganisms.
• Most pathogens have evolved an ability to evade
  one or more of the steps (resistance).

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Step 1

• Chemotaxis- Phagocytic cells are recruited to
  site of infection or tissue damage by chemical
  stimuli (chemoattractants).

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Step 2

• Recognition Attachment- Receptors located on
  outside of phagocyte recognize and bind (directly
  or indirectly).
• Direct binding-receptors recognize and bind to
  patterns of compounds found on invaders
• Indirect binding-particle is opsonized, coating
  particle with antibody substance for easier
  ingestion

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Step 3

• Engulfment-Phagocytic cell engulfs invader,
  forming a membrane-bound vacuole called a
  phagosome.
• Cytoskeleton of phagocyte rearranges to form
  armlike extensions (pseudopods) that surround
  material being engulfed.
• 
  

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Step 4

• Fusion of the phagosome with the lysosome -within
  the phagocyte, the phagosome moves along the
  cytoskeleton to where it can fuse with lysosomes.
• Lysosomes-membrane bound bodies filled with
  various digestive enzymes like lysozyme and
  proteases.
• Fusion creates a phagolysosome.
• In neutrophils, membrane-bound bodies are
  granules.

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Step 5

• Destruction Digestion-Oxygen consumption
  increases, sugars metabolized (aerobic
  respiration), highly toxic oxygen products
  produced (superoxide, hydrogen peroxide, singlet
  oxygen, hydroxyl radicals).
• As available O2 in phagolysosome is consumed
  metabolic pathway switches to fermentation,
  producing lactic acid and lowering pH.
• Enzymes degrade peptidoglycan of the bacterial
  cell walls, and other parts of the cell.

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Step 6

• Exocytosis-membrane-bound vesicle containing
  digested material fuses with the plasma membrane.
  Material is expelled to the external environment.

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Macrophages

• Scavengers located in tissue
• Play essential role in every major tissue in the
  body
• Live for weeks to months
• Maintain killing power by regenerating their
  lysosomes

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• Characteristics
• Toll-like receptors-allow them to sense
  dangerous materials.
• Produce pro-inflammatory cytokines, alerting
  other cells in the immune system.
• Activated macrophages-increases killing power
  with assistance from certain T cells. This
  cooperation between innate and adaptive host
  defenses induces production of nitric oxide and
  oxygen radicals, helping to destroy microbes.

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• If activated macrophages fail to destroy
  microbes and chronic infection occurs, large
  numbers can fuse together forming giant cells.
• Granulomas- concentrated groups of macrophages,
  T cells, giant cells. Contain organisms and
  material that cant be destroyed by walling off
  and retaining the debris to prevent infection of
  more cells. Granulomas are commonly part of the
  disease process in TB, histoplasmosis, and other
  diseases.

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Neutrophils

• Characteristics
• Known as the rapid response team. Quickly move
  into an area to eliminate invaders.
• Critical role in first stages of inflammation.
• First cell type recruited from bloodstream to
  site of damage.
• More killing power than microphages.
• Short life span (1-2 days) in the tissue.
• Expend granules, then die.
• For every neutrophil in the circulatory system,
  there are 100 more waiting in the bone marrow.

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The End