Immunology Chapter 4

==Phagocytosis==

1. chemotaxis and adherence of microbe to phagocyte
2. ingestion of microbe by phagocyte
3. formation of phagosome
4. phagosome + lysosome = phagolysosome
5. digestion of ingested microbe by enzymes
6. ingestion of residual body containing ingestible material
7. discharge of waste material

• @@Recognition@@ = receptor binds to pathogen
• @@Internalization@@ (endocytosis) = pathogen in cell into phagosome
• @@Phagosome-lysosome fusion@@= forms phagolysosome with enzymes inside
• @@Destruction@@ (exocytosis) = enzymes destroys pathogen

^^Receptors for Recognition^^

1. %%dectin-1%%

• binds to glucan

1. %%mannose receptor%%

• binds to mannose
• clears host glycoprotein

1. %%scavenger receptors%%

• binds to anionic (-) polymers and acetylated low density lipoproteins
• shielded by sialic acid
• becomes uncovered as cell dies → activates phagocytosis

1. %%lipid receptor%%

• binds to lipids

1. %%fMLF receptor%%

• bind to fMLF (protein)
  • activates second messenger = chemoattraction
  • production of reactive oxygen species (ROS) in phagolysosome

1. %%TLR%%

• recognizes peptidoglycan, LPS, lipoteichoic acids, flagella, lipoarabinomannan, double stranded RNA, and particular antigens from parasites and fungi
• binding on surface = phagocytosis
• binding anywhere = signal cell to produce chemokines and cytokines
• binding in professional phagocytes = release of cytokines

^^Internalization^^

• when a molecule binds to receptor, internal signal is produced
• internal signal triggers cell to internalize the bound pathogen
• phagocytosis = endocytosis
• process requires ATP

^^Phagosome-lysosome Fusion^^

• phagosome + lysosome = phagolysosome
• acidic enzymes help kill pathogens

==Mechanisms of Killing Pathogens==

1. @@Acidification@@

• proton pump @ phagolysosome
• increase protons = decrease pH (acidic)

1. @@Antimicrobial peptides and other enzymes from lysosome@@

• lysosome carries many antimicrobial peptides in phagolysosome

1. @@Respiratory Burst@@

• phagocyte activated (increase oxygen) = respiratory burst
• phagocyte can be activated by:
  • cytokines
  • binding to TLR, fMLF receptor, Fc receptor, and complement receptor for C3
• toxic ROS:
  • activate phagocyte = NADPH oxidase
  • phagolysosome → phagocytosis → binding to fMLF, C5a, or cytokine = ==activates Rac2==
• NADPH oxidase produces superoxide
• superoxide dismutase (SOD) = O2 → H2O2
• myeloperoxide = H2O2 → OCl- or OBr- or OH-

1. @@Toxic nitrogen derived products@@

   a.) bind to TLR with IFNy = phagocytes produces NOS

   • nNOS or NOS1 = in neuronal tissue
   • iNOS or NOS2 = phagocytes
   • eNOS or NOS3 = endothelial cells

   b.) NOS = arginine → NOHLA → citulline and nitric oxide

   c.) nitric oxide diffuses into phagolysosome

   d.) superoxide produces peroxynitrite radicals = kills microbes