Phagocytosis (Mechanism and steps involved)

  • Special form of endocytosis in which the cell engulfs solid particles such as cellular debris, whole microorganism, parasites, dead host cell etc via large endocytic vesicles known as phagosomes.
  • Only few cells in our body can carry out phagocytosis. They are termed as phagocytes.
  • In mammals two main types of phagocytes are present. They are macrophages and neutrophils
  • In protozoan’s phagocytosis is a method of nutrient uptake (phagotrophic nutrition). They will take up large food particles into phagosomes which will later fuse with Lysosome. The products formed after digestion are passed into the cytosol and is utilized as food.
  • In metazoans, phagocytosis plays a major role during development, tissue remodeling, immune response and inflammation
  • Phagocytosis is a vital defense mechanism that protects our body from disease.

Two major events occur before the actual phagocytic process.

1) Activation of the phagocyte

 Inflammatory mediators play important role in activating resting phagocytes

Examples of inflammatory mediators: bacterial products like bacterial proteins, capsules, LPS complement proteins, prostaglandins and inflammatory cytokines.

1) Activated phagocytes express glycoprotein receptors on their surface that will increase their ability to adhere to the inner surface of capillary walls. This will also helps them to squeeze out from the capillaries (diapedesis) into the site out infection.

2) Activation also enables phagocytes to produce endocytic pattern-recognition receptors. These receptors are involved in the recognition and binding of microbial PAMPs (so that microbes attached to the surface of phagocyte)

2) Chemotaxis

In this step macrophages are attracted by the chemical substance generated at the site of infection or cell damage as a result of immune response. Once they got the chemical signal they will move to the site of damage or infection and this chemical stimulated movement is known as chemotaxis.

Chemicals that attract phagocytes might come from invading microbes, damaged tissue cells or activated complement proteins or white blood cells

How these chemical signals help in the movement of phagocytes to the site of infection?

  • Signals from the infection cause the endothelial cells that line the blood vessels to synthesize a protein called selectin. Neutrophils stick to this protein when they pass through the blood to the site of infection.
  • Other signals called vasodilators which will loosen the junctions connecting endothelial cells. This will allow the phagocytes to pass through the wall.

Steps involved in phagocytosis

Step 1: Recognition and adherence of antigen/microorganism to phagocytic cell membrane

Attachment of microbe or other foreign material to the plasma membrane receptor on the phagocyte is necessary for ingestion to happen.

Phagocytic cells use two basic molecular mechanisms for the recognition of microorganisms:

1) Opsonin dependent recognition – enhanced adherence

2) Opsonin independent recognition – unenhanced adherence

Opsonin dependent recognition

  • The phagocytic process can be greatly enhanced by a process called opsonization.
  • IgG antibody, complement proteins C3b and C4b, acute phase proteins such as mannose-binding lectin (MBL) and C-reactive protein (CRP) etc involved in the enhancement of adherence of a pathogen to phagocyte.
  • These serum components function as a bridge between the microorganisms and the phagocyte.
  • They will bind to the surface of the microorganism at one end and to specific receptors on the phagocyte surface at the other end.
  • Coating of microorganism with these serum components will prepare them for easy recognition and ingestion by phagocytic cells.

 Examples 

  • Mannose-binding lectin (MBL) found in bloodstream and tissue fluids will bind to mannose containing microbial carbohydrates on their cell walls and to mannose receptor on macrophage membrane
  • CRP (C reactive protein) in the bloodstream and tissue fluid binds to phosphatidyl choline on microbial membrane and to CRP receptor on macrophage membrane.

Opsonin Independent recognition

  • Uses specific and non specific receptors expressed on phagocytic cell membrane for the recognition of distinct molecular patterns expressed on the surface of different microorganisms.
  • Opsonins are not involved in this type of recognition

 Examples

  • Scavenger receptors (SRs) on macrophage membrane: Binds to oxidized or acetylated LDL on microorganism.
  • TLR4 on macrophage/dendritic cell membrane: Binds to LPS on microorganism
  • TLR5 on macrophage membrane: Binds to flagellin of microorganism

Other Pathogen associated molecular patterns (PAMPs) like teichoic acid, peptidoglycan etc are also recognized by pattern recognition receptors on phagocytic cells

Step 2: Ingestion of the microbe by the phagocyte and phagosome formation

Once the recognition had happened, it will send signal for membrane remodeling and cytoskeletal rearrangement

  • Adherence of pathogen to the macrophage membrane induces the formation of membrane protrusions called pseudopodia (meaning false feet). Pseudopodia formation is by actin polymerization.
  • Pseudopodia extend around the attached microbe or particle and engulf the microbe in a process called ingestion.
  • When the pseudopods meet, they fuse and enclose the microorganism within a membrane bound sac called a phagosome (also called phagocytic vesicle).
  • The membrane of a phagosome has enzymes that pump protons (H+) into the phagosome. As result pH inside the phagosome is reduced to ~4 and hydrolytic enzymes are activated. They can either kill or inactivate the pathogen present.

(After the formation of phagosome, respiratory burst can happen. It is the rapid release of reactive oxygen species from the phagocytic cells like neutrophils. Lysosome fusion is not necessary for respiratory burst to happen. The toxic oxygen products produced are effective in killing invading microorganisms)

Step 3: Formation of phagolysosome

  • The phagosome pinches off from the plasma membrane and enters the cytoplasm of the phagocytic cell.
  • In the cytoplasm it fuses with one or more lysosomes (contain bactericidal substances and digestive enzymes) to form a single larger structure called a phagolysosome.

Step 4: Killing and digestion of the ingested material/microorganism

  • Within the phagolysosome, the bacterial cell is killed and digested through the activity of lysosomal enzymes and other toxic products generated as a result of various reactions occurring inside.
  • Any undigested materials in the phagolysosome remain in these vesicles and are called residual bodies.

Refer the bactericidal mechanism of phagocytic cells for more details.

Step 5: Exocytosis

  • The digested contents of the phagolysosome are eliminated by a process called exocytosis.
  • Residual body moves toward the cell boundary and discharges its wastes outside the cell.
Figure 1: Steps involved  in phagocytic process

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