Lecture 12 - Phagocytosis Flashcards
Roles of phagocytosis (5)
• Protection from pathogens.
• Disposal of damaged/dying (apoptotic) cells.
• Processing and presentation of antigens (ag).
o Activation of adaptive immune system.
o Links innate and adaptive immunity.
Innate immune system - Effector cells (3)
Phagocytes: neutrophils, macrophages, dendritic cells.
Identify, ingest, destroy pathogens.
Mast cells, eosinophils, basophils (myeloid lineage). Natural killer (NK) cells (lymphoid lineage; bone marrow)
Innate immune system - Effector cells - Phagocytes - Neutrophils (4)
PMN - Polymorphonuclear leukocytes.
Early response - inflammation.
Life span = Blood 8-10 hours. Tissue 4-5 days.
Enzymes: Lysozyme, Elastase, Collegenase.
Innate immune system - Effector cells - Monocytes/Macrophages (4)
Monocytes blood for 20-40 hours.
Macrophages in tissues
Killing of microbes
Secrete inflammatory factors e.g. cytokines
Innate immune system - Effector cells - Dendritic cells (3)
Skin, mucosa, tissue
Capture microbes.
Present Ag to T cells.
Phagocytosis - Steps - Just the names (4)
1) CHEMOTAXIS (MOBILISATION TO SITE OF INFECTION/INJURY)
2) RECOGNITION AND ATTACHMENT TO MICROBE/DEAD CELLS
3) ENGLUFMENT
4) KILLING/DIGESTION OF INGESTED MICROBE/DEAD CELLS
Phagocytosis - STEP 1 (5)
1) CHEMOTAXIS (MOBILISATION TO SITE OF INFECTION/INJURY)
• Movement of cells towards site of infection
• Guided by chemoattractants
• Released by:
• Bacteria fMLP/ N-formyl-methionine-leucine-phenylalanine peptides
• Inflammatory cells – chemokines (IL-8)
• Damaged tissues
Phagocytosis - STEP 2 (3)
2) RECOGNITION AND ATTACHMENT TO MICROBE/DEAD CELLS
• React to invading pathogens (foreign)
• No reaction to body’s own tissues (self)
• Pathogen Associated Molecular Patterns (PAMPs) – structures shared by groups of related microbes.
Phagocytosis - STEP 3 (5)
3) ENGULFMENT
Actin-cytoskeleton arrangement –> Phagosome formation –> Lysosome –> Phagolysosome –> Pathogen destruction
Phagocytosis - STEP 4 (6)
4) KILLING/DIGESTION OF INGESTED MICROBE/DEAD CELLS
Killing of pathogens: oxygen-independent:
• Lysosomes:
o Proteolytic enzymes (cathepsins): degrade microbes.
o Lysozyme: breaks bacterial walls.
o Lactoferrin: Binds iron - Not enough left for bacteria.
o Defensins: destroy bacterial walls.
STEP 2 - Pattern recognition receptors (PRRs) (5)
- Toll-like receptors (TLRs) – plasma membrane, endosomal membrane.
- C-type lectin receptors (CTLRs) – e.g. mannose receptor.
- NOD-like receptors (NLRs) - reside as free proteins in cytoplasm.
- RIG-like helicase receptors (RLRs) - cytosolic receptors for viral dsRNA.
- Scavenger receptors - various bacterial wall components (CD14 scavenges LPS-LBP).
STEP 2 - Pattern recognition receptors (PRRs) - TLRs (4)
- Essential roles in innate immunity.
- Conserved during evolution.
- Stimulate production of inflammatory cytokines.
- Human TLRs recognise PAMPs.
STEP 2 - Opsonisation (3)
Facilitates phagocytosis (recognition of microbes).
Coating of microbes with opsonins - complement system (C3b/C4b), antibodies (Ig).
Oponised microbes can be phagocytosed easier as they have a receptor that phagocytes bind to.
Sabotage by pathogens (4)
• Blocking phagocyte attachment
Streptococcus pneumoniae – encapsulated bacteria
• Blocking engulfment
Yersinia
• Blocking destruction
Salmonella – resistant to ROS
Mycobacterium – blocks phagosome-lysosome fusion
• Killing of phagocytes
Staphylococcus aureus – toxin damages membranes
What else do phagocytes target? (3)
Microorganisms.
Damaged/dying cells.
Apoptotic cells - release ‘eat-me’ signals, which promote engulfment.
