Lecture 32 Flashcards
3 layers of immune defense
- Physical & Chemical Barriers (skin, mucosal membranes)
- The Innate Immune System
- The Adaptive Immune System
What is the inflammatory response stage 1
Chemical signals from tissue-resident cells act to attract more cells to the site of injury or infection
What is The inflammatory response stage 2
Neutrophils enter blood from the bone marrow
The inflammatory response stage 3
Neutrophils cling to the capillary wall
The inflammatory response stage 5
Chemical signals from tissue-resident cells dilate blood vessels and make capillaries ‘leakier’
The inflammatory response stage 6
Neutrophils squeeze through the ‘leaky’ capillary wall and follow the chemical trail to the injury site
What is the theory of phagocytosis
In 1886-87 Elie Metchnikoff discovered the cells in the blood could ingest and destroy microbes — a process called phagocytosis
What is Phagein
Ancient Greek “to devour”
Stages of phagocytosis
1 Phagocyte adheres to pathogens or debris.
2: Phagocyte forms pseudopods that eventually engulf the particles, forming a phagosome.
3: Lysosome fuses with the phagocytic vesicle, forming a phagolysosome.
4: Toxic compounds and lysosomal enzymes destroy pathogens.
5: Sometimes exocytosis of the vesicle removes indigestible and residual material.
How do u Killing and digestion of phagocytosed microbes
• Low pH - acid environment
• Reactive oxygen (hydrogen peroxide) and reactive nitrogen intermediates (nitric oxide)
- Enzymes
Proteases
Lipases
Nucleases
The Complement Cascade
• Complement - 9 major proteins/ protein complexes (C1-9) act in sequence to clear pathogens from blood and tissues
• Label pathogens (opsonisation)
• Recruit phagocytes (chemotaxis)
• Destroy pathogens (lysis)
3 Complement Pathways
CLASSICAL
Antibody bound to pathogen binds complement
ALTERNATIVE
Pathogen binds complement to surface/pathogen component
LECTIN
Carbohydrate components of microbes bind complement
Complement pathways converge
Triggers: classical, alternative and lectin
Amplification: C3 convertase (enzyme complex)
Outcomes: label, destroy, recruit
3 outcomes from the complement cascade
Label:
Opsonisation (labels pathogens which bind to complement receptors on phagocytes) C3b
Destroy:
Membrane Attack Complex formation: pores in bacterial cells → death C9
Recruit:
Complement proteins act as peptide mediators of inflammation and recruit phagocytes C3a and C5a
Label (Opsonisation)
Opsonisation = coating of a microbe with:
Antibody and/or
Complement fragment C3b
