Innate Immune System (Toll Like Receptors, Phagocytosis & inflammation ) - Immunology

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This video is part 2 of Innate immunity - Cellular Factors (Toll-like Receptors, Phagocytosis and Inflammation)

Content:
0:00 Introduction
0:20 Toll-Like Receptors
4:45 Phagocytosis
12:40 Immune System's Role in Inflammation

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All information in my immunology videos are from:
- Book: Immunology, Eighth Edition by David Male, Jonathan Brostoff, David Roth and Ivan Roitt
- Additional research in PubMed
- University lecture materials
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Toll Like Receptors:

Location:
- Epithelial Cells of mucous membrane
- Endothelial Cells
- Macrophages
- Dendritic cells
- Neutrophils

Membrane bound TLR:
TLR 1/2 and TLR2/6:
- Peptidoglycan/Lipotechoic acid
- Lipoproteins
TLR 4:
- Lipopolysaccharides
- Fungal Mannan
- Viral Envelope Protein
TLR 5:
- Bacterial flagellin

Intracellular receptors:
TLR 3:
- Double Stranded RNA from virus
TLR 7:
- Single Stranded RNA
TLR 8:
- Double stranded RNA from virus
TLR 9:
- Unmethylated CpG islands

Toll Like Receptors trigger:
1. Release of cytokines (TNF, IL1 and IL12)
2. Chemokines (IL8)
3. Antiviral Cytokines (IFN a/b)

Phagocytosis:

Professional Phagocytes:
- Neutrophils
- Macrophages/Monocytes
- Mast Cells
- Dendritic Cells

Steps in Phagocytosis:
Step 1: Binding
- Non specific surface receptors (Mannose Receptor, Toll Like receptor, CD14)
- Indirect Opsonization (C3b)
- Direct Opsonization: Fc receptor to antibody
Step 2: Engulfment
- Pseudopods around bacteria
Step 3: Phagosome
- Formation of phagosome
Step 4: Digestion
- Oxygen Dependent digestion (Reactive Oxygen Species)
- Oxygen independent digestion
- Lysosome (Cell wall breakdown)
- Enzymes (Proteolytic, Hydrolytic)
- Antimicrobial Peptides (Defensins)
- Acidic Reactions (Low pH)
- Lactoferrin (Neutrophils)
Step 5: Antigen Presentation
- Present on MHC class 1 or class 2
- Or release digested bacteria to Interstitial fluid. It’s then absorbed by the lymph vessels to the lymph node

Active macrophage release cytokines:
- Interleukin 8: Chemotaxis for Leukocytes
- Interleukin 1: Activate T-Ly and Macrophages
- Interleukin 6: Activate T- and B-Ly
- TNF-a: Activate Endothelium
- Interleukin 12: Activate Natural Killer cell

Interleukin 1, 6 and Tumor necrotic factor alpha: Endogenic Pyrogens (Cause Fever)
- Goes to Hypothalamus to release Prostaglandins E2
- Interleukin 6 goes to the liver to release acute phase proteins

Incomplete Phagocytosis:
Phagocytes can’t breakdown bacteria
- Listeria: release Listeriolysin
- Mycobacteria tuberculosis: catalase

Immune system in Inflammation:
- Swelling (Due to increase permeability of blood vessel)
- Pain (Due to diapedesis and edema pressing on pain receptors)
- Heat
- Redness