Lecture 5: Immune system- Phagocytosis

Process of Phagocytosis

1. Bacterium binds to the surface of phagocytic cell. Antibody or complement can aid binding 2. Phagocyte pseudopods extend and engulf the organism 3. Invagination of phagocyte membrane traps the organism within a Phagosome 4. Lysosome fuses and deposits enzymes into the phagosome. Enzymes cleave macromolecules and generate reactive oxygen, destroying the organism

Perforin mediated killing

1. monomers of peroferin are released from the NK cell and enter a host cell membrane that lacks MHC 1 2. Monomers oligomerizeto form a pore in the target cell membrane 3. NK cells release cytotoxic proteins such as granzyme that enter target cells through the perforin pores

Extracellular killing

2 innate immune cell types are capable of extracellular killing -Natural killer lymphocytes (NK cells) -Eosinophils

Surviving phagocytosis

Although very effective, some pathogens have evolved ways to prevent being killed by phagocytosis Some bacteria become intracellular pathogens: -coxiella- live in toxic phagolysosome -Shigella and listeria- escape from phagosome --can also enter a host cell and kill it by triggerin aptptosis before phagocytosis occurs -Salmonella stays in phagosome but secretes proteins that prevent fusion with lysosome

Natural killer lymphocytes (NK cells)

Can distinguish normal body cells from virally infected or tumor cells Recognize and kill virally infected or tumor cells by two different mechanisms -Missing self method -Antibody dependent cell-mediated cytotoxicity (ADCC)

Recognizing alien cells and particles

Fail-safe controls built into our immune defenses prevent Phagocytes from killing host cells in the absence of infection Macrophages and neutrophils must first "see" the surface of a particle as being foreign When phagocyte surface binds with the surface of another body cell, phagocyte becomes temporarily paralyzed so it can evaluate whether the other cell is alien or not CD47 Phagocytes express numerous receptors that directly recognize MAMPs and enhance phagocytosis Opsonization enhances phagocytosis

Eosinophils

Mainly attack parasitic helminths (worms) by attaching to their surface Produce proteins that weaken or kill the worm Eosinophilia, or elevated eosinophil levels is often indicative of a helminth infection

Antibody-dependent cell-mediated cytotoxicity (ADCC)

NK cells also contain antibody binding Fc receptors on their surface. The Fc receptor on the NK cell links to an antibody coated host cell which is then killed.

CD47

The "dont eat me" receptor Because invading bacteria lack CD47 surface molecules, they can be readily engulfed

Missing self fethod

When a NK cell binds to MHC 1 protein, it will not attack. If cell lacks MHC 1 molecules, NK cells will preceive the cell as foreign and insert a pore-forming protein called perforin into the membrane

Opsonization

coating of pathogens with C3b or antibodies, enhances activation of phagocytosis

Phagolysosome

subsequent phagosome-lysosome fusion permits both oxygen-independent and oxygen-dependent killing pathways Anaerobic pathways: -lysosome, lactoferrin, defensins Aerobic mechanisms: -oxygen radicals such as superoxide ion and hydrogen peroxide, hydroxyl radicals, and myeloperoxidase Reactive nitrogen intermediates: -nitric oxide, nitrite/nitrate ions