Monday, September 9, 2019 10:22 AM
Innate- responds right away
Adaptive- adapts to the specific pathogen
⚫ Target organisms of immune responses
➢ Pathogenic microbes - bacteria, viruses, parasites, fungi
▪ Microbiota outnumbers the # of cells in our body
➢ Macromolecules - bacterial toxins, foods, drugs, chemicals
➢ Cells- tumor cells, virally infected cells, donor cells from transfusions or tissue transplants
⚫ Composition of innate immune system
➢ Barriers - anatomical and chemical
▪ Acts first
➢ Cells- macrophages, natural killer cells, neutrophils, etc.
⚫ General overview of immune response
*don’t need to know specific hours, but know the order in which it happens
➢ Innate immunity (immediate)
▪ No lag time for innate immune response
➢ Early induced innate response
▪ PAMPs= Pathogen Associated Molecular Patterns
➢ Adaptive response
⚫ Innate immune response
• First wave of an immune response
• Ready for immediate action against pathogens
• Can initiate activation of adaptive immune system
⚫ Anatomical barriers
• Anatomical - skin, respiratory tract, GI tract, eyes, nose, mouth
• Sebaceous glands
▪ Hair covered areas
▪ Glands deposit sebum (made of fat and debris from fat-producing cells) on hair, which then comes to the surface
▪ Bacterial breakdown produces odors
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, ▪ Bacterial breakdown produces odors
⚫ Mucosal barrier protection
• IgA-secreting plasma cell - specialized B cells that function to neutralize bacteria that passes the epithelial barrier, makes antibodie
• Lymphocyte= B & T cells
⚫ Role of non-immune cells in innate immunity
• Epithelial cells constitutively secrete;
➢ Bacterial cell wall attack enzymes
Lysozyme-->cleaves PG
➢ Antimicrobial peptides
Defensins-->kill bacteria and some viruses
⚫ Lysozyme function
• Remember: gram + has thick PG layer, exposed on surface of bacteria ; gram - has thin PG membrane not on surface
• Lysozyme:
○ Secreted in tears, saliva and by phagocytes
○ Breaks specific bonds holding PG together
• Lysozyme more effective against gram positive bacteria due to exposed PG
⚫ Defensins
• Evolutionarily conserved class of peptides
• Amphipathic structures - distinct positively charged regions and hydrophobic regions
• Act within minutes to create a leaky membrane
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, Act within minutes to create a leaky membrane
⚫ Immune responses when microbe crosses anatomical barriers
➢ Inflammation
• Tissue redness (erythema)
• Tissue swelling (edema)
• Heat
• Pain
• Cytokines and chemokines released from macrophages and endothelial cells causing;
○ Attraction of other immune cells, ex: neutrophils and monocytes -->killing the microbe
○ Vasodilation
○ An increase in capillary permeability
⚫ Important cells in innate immunity
➢ Neutrophils
• First responders to infection
• Phagocytose bacteria - excellent killing of ingested microbes
• NETosis, killing of pathogens by extracellular traps
□ Spits out DNA acting as a net, killing bacteria
➢ Macrophages (found in tissue) and monocytes (found in circulation)
• Monocytes leaves circulation, goes into tissue and differentiates into macrophage
• Efficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation and immune cells
➢ NK (natural killer) cells
• Non-phagocytic, lysis of infected cells
⚫ Phagocytosis and intracellular killing of microbes
➢ Macrophages have phagocytic receptors that bind microbes and their components
➢ Process of phagocytosis
1. Attachment
2. Ingestion
3. Fusion
4. Digestion
5. Release
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, 5. Release
➢ Opsonization - coating microbe with macromolecules called opsonins that are recognized by surface receptors on phagocytes
○ Increases efficiency of phagocytosis
○ Ex: an antibody
⚫ Summary of phagocytosis
1. Bacterium becomes attached to membrane evaginations called pseudopodia
2. Bacterium is ingested, forming phagosome
3. Phagosome fuses with lysosome
4. Bacterium is killed and then digested by lysosomal enzymes
5. Digestion products are released from cell
⚫ Neutrophils and NETosis
• NET = Neutrophil extracellular traps
• Type of cell death where a lattice-work of DNA, histones and proteins is released from the cell
• The "webs" entrap and kill microorganisms
• Other cell types; eosinophils, mast cells, macrophages can also die by this mechanism
*neutrophils can undergo phagocytosis AND netosis
⚫ NK cell function
• NK cells can recognize infected cells
• Release cytotoxic granules which induce death/apoptosis of the infected cell
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