PHAGOCYTOSIS

1. PHAGOCYTOSIS Chapter 15

2. 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.

3. 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.

4. 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).

5. Step 1 • Chemotaxis- Phagocytic cells are recruited to site of infection or tissue damage by chemical stimuli (chemoattractants).

6. 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

7. 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.

8. 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.

9. 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.

10. Step 6 • Exocytosis-membrane-bound vesicle containing digested material fuses with the plasma membrane. Material is expelled to the external environment.

11. 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

12. 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.

13. ~ 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 can’t 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.

14. 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.

15. The End