Lecture 2: Introduction to Innate Immunity Flashcards
PAMPs of Gram-Negative Bac
Lipopolysaccharide (LPS)
Porin
Lipoprotein
PAMPs of Gram-Positive Bac
Peptidoglycan
Lipoteichoic acid
Teichoic acid
PAMPs of Mycobacteria
Lipoarabinomannan
PAMPs of Fungi
Mannoproteins
General properties of PRRs
Specificity: For structures shared by classes of microbes (“molecular patterns”) Different microbes, identical mannose receptors
Receptors: TLRs, N-formylmethionyl receptor, Mannose receptor
Distribution of receptors: Nonclonal; identical receptors on all cells in same lineage
Discrimination of self vs nonself: Yes; host cells not recognized or express molecules that prevent innate immune rxns
TLR1:TLR2 heterodimer
Ligands: Lipopeptides & GPI
- Bacteria
- Parasites (trypanosomes)
Cells that carry receptor: Macrophages, DC, eosinophils, basophils, mast cells
Receptor on PM
TLR2:TLR6 heterodimer
Ligands: Lipoteichoic acid & Zymosan
- Gram (+) Bac
- Yeasts
- Fungi
Cells that carry receptor: Macrophages, DCs, eosinophils, basophils, mast cells
Receptor on PM
TLR3
Ligand: double stranded viral RNA
-Viruses (West Nile Virus)
Cells that carry receptor: NK cells
Receptor in endosomes
TLR4:TLR4 homodimer
Ligand: Lipopolysaccharides
-Gram (-) Bac
Cells that carry receptor: Macrophages, DCs, mast cell, eosinophils
Receptor on PM
TLR5
Ligand: Flagellin
-Motile bac having a flagellum
Cells that carry receptor: Intestinal epithelium
Receptor on PM
TLR7
Ligand: Single stranded viral RNA
-Viruses (HIV)
Cells that carry receptor: Plasmacytoid DCs, NK cells, eosinophils, B cells
Receptor in endosome
TLR8
Ligand: Single stranded viral RNA
-Viruses (Influenza)
Cells that carry receptor: NK cells
Receptor in endosome
TLR9
Ligand: Unmethylated Cpg-rich DNA
- Bac
- Virus (Herpes virus)
Cells that carry receptor: Plasmacytoid DCs,, B cells, eosinophils, basophils
Receptor in endosome
TLR2
Ligand: Peptidoglycan
-Gram (+) Bac
Receptor on PM
TLR4
Ligand: LPS
-Gram (-) Bac
Receptor on PM
Role of PRRs in Phagocytosis
Microbe binds to phagocyte receptors
- Mannose receptor
- MAC-1 integrin
- Scavenger receptor
Phagosome –> phagolysosome
Phagocyte oxidase used for O2 –> ROS
Nitric oxide synthetase (iNOS; inducible) converts Arg –> NO
Cytokines produced by immune cells
Mediate:
Inflammation
Hematopoiesis
Immunity
Pro-inflammatory or anti-inflammatory
Function of Chemoattractants
Trafficking immune cells
TNF
Source: Macrophages, T cells
Endothelial cells: Activation (inflammation, coagulation) Neutrophils: activation Hypothalamus: Fever Liver: Synthesis of APP Muscle: Fat catabolism Many cell types: Apotosis
IL-1
Source: Macrophages, endothelial cells, some epithelial cells
Endothelial cells: Activation (inflammation, coagulation)
Hypothalamus: Fever
Liver: Synthesis of APP
Chemokines
Source: Macrophages, endothelial cells, T lymphocytes, fibroblasts, platelets
Leukocytes: chemotaxis, activation
IL-12
Source: Macrophages, DCs
NK cells & T cells: IFN-y synthesis, increased cytotoxic activity
T cells: TH1 differentiation
IFN-y
Source: NK cells, T lymphocytes
Activation of macrophages
Stimulation of some Ab responses
Type I IFN (IFN-a & IFN-ß)
Source INF-a: Macrophages
Source IFN-ß: Fibroblasts
All cells: Antiviral state, increased class I MCH expression NK cells: activation
IL-10
Source: Macrophages, T cells (mainly TH2)
Macrophages: inhibition of IL-12 production, reduced expression of costimulators and class II MHC molecules
IL-6
Source: Macrophages, endothelial cells, T cells
Liver: synthesis of APP
B cells: proliferation of Ab-producing cells
IL-15
Source: Macrophages, others
NK cells: Proliferation
T cells: Proliferation
IL-18
Source: Macrophages
NK cells & T cells: IFN-y synthesis
