Phagocytosis

Clathrin-mediated endocytosis

(receptor-mediated micropinocytosis) - Small (100 nm) vesicles containing protein. - Vesicles form "pits" below receptor specific for the molecule that needs to be internalized.

Caveolae (non-receptor mediated micropinocytosis)

- Very small (50 nm) pits in membrane with no clathrin. - Abundant in muscle, lung, fat, endothelium, and fibroblasts. - Used for uptake of extracellular molecules. Happens continuously

clathrin-receptor mediated endocytosis

A process by which cells internalize molecules by inward budding of plasma membrane vesicles, using receptors specific to the molecule being internalized. This is how nearly all eukaryotic cells internalize specific nutrients, growth factors, antibodies, antigens and small molecules that have their own receptors such as LDL, transferrin. Also allows downregulation of receptors.

Th clonal proliferation - Th cytokine production stimulates B-cells---> plasma cells--> secrete Abs induces cytotoxic T-cells to kill infected cells

Ag presentation to T-helper cells causes

Phagocytosis

Engulfment is facilitated by actin-myosin contraction.

antimicrobial proteins and peptides (defensins and cathelicidins) - low pH - acid-activated hydrolytic enzymes (lysozyme, proteases, elastase, cathepsin G, ...) - oxidative attack

How does the phagolysosome kill?

Caveolae nonreceptor-mediated endocytosis

Lipid rafts in endothelial cells, adipocytes etc; contain proteins & cholesterol, and are important in signal transduction and turnover of adhesive complexes. Internalization of membrane components (glycosphingolipids), albumin, folic acid, bacterial toxins, several non-enveloped viruses.

Fibroblasts Epithelial cells Endothelial cells Mesenchymal cells Immature cell types

Nonprofessional phagocytes

lack of phagocytic receptors (opsonin) do not produce ROS

Nonprofessional phagocytes defined by

Electrically charged proteins Lysozyme Lactoferrins from neutrophil Proteases and hydrolytic enzymes

O2-ind intracellular killing consists of:

monocytes and macrophages

Only these cells can use both reactive oxygen species and reactive nitrogen species

Macropinocytosis

Ruffle/invagination of cell membrane (0.5-5 µm diameter) with large volume of extracellular fluid; fuses with lysosome for digestion.

Grow in sites where phagocytes cannot reach - like surface of unbroken skin. Suppress inflammatory response Inhibit chemotaxis Trick phagocytes into thinking the bacteria are self (e.g., coat bacterial surface with self-proteins such as fibronectin)

Ways pathogens evade phagocytosis

Neutrophils Monos/macrophages/~dendritic cells Mast cells To a lesser extent other granulocytes (basophils, eosinophils) These are "professional" phagocytes (which means they have receptors for pathogens on them, vs. nonprofessional phagocytes who can phagocytose without receptors under certain circumstances).

Which cells perform phagocytosis?

Neutrophil extracellular traps-exocytosis

expels granule content and attaches to DNA strands to trap extracellular bacteria and kill them

macrophages

found more in chronic inflammation;are activated by helper T cells secreting IFN-gamma, which further activates _____ and inhibits viral replication. also serve as antigen presenting cells. also secrete pro-inflammatory cytokines to enhance adaptive immunity. Activated____ play a potent role in tumor destruction by producing TNF-alpha, IFN-gamma, nitric oxide, reactive oxygen, cationic proteins, & hydrolytic enzymes.

Neutrophils

fuse the phagosome with the lysosome in their cytoplasm and digest the pathogen

Mast cells

has TLR can phagocytose gram - bacteria can present Ag to t-helper cells produce cytokines that induce chemotaxis and acute inflammation salmonella is example of gram - bacteria phagocytosed

Neutrophils

left shift, live 6-8 hrs in blood; more segmented nuclei; do not return to the blood

Prevent fusion of phagolysosome Create protective vacuole inside the phagocyte Produce catalase and SOD to break down reactive oxygen species

pathogen can survive inside the phagocyte by

Enterocytes Dendritic cells M (microfold) cells

phagocytes present in the intestinal epithelium