Lecture 03: Inflammatory Response PDF

## Lecture 03: Inflammatory Response **Question:** How does immunity respond to tattoo ink? * Resident skin macrophages phagocytize ink particles. * Why isn't all ink phagocytized? * All macrophages are killed. * Macrophages express diphtheria toxin receptor (CD96+ cells). * When macro...

## Lecture 03: Inflammatory Response **Question:** How does immunity respond to tattoo ink? * Resident skin macrophages phagocytize ink particles. * Why isn't all ink phagocytized? * All macrophages are killed. * Macrophages express diphtheria toxin receptor (CD96+ cells). * When macrophages are released, ink continues to cycle. **No Immune Response** * No DAMPS, no microbial patterns. * Cytokine response is low. * Phagocytosis enzymes don't work. * Resident macrophages don't move. **Inflammatory Response** **Before/No Injury** * Monocytes and macrophages move and travel in the body through capillaries. * Resident macrophages and dendritic cells wait in tissues. **(1) When Injured:** * Localized tissue damage/pain. * Bacteria entry. * Innate immune cells activated. **Maintain/Fix?** * New macrophages move in. * Engulf the invaders. **No DAMPS?** * No microbial pattern. * Cytokines/chemokines, histamine, bioactive lipids (IFN, IL-6, IL-1, histamine) **Damaged cells release (neutrophils/cytokines):** **(3) Effects on Capillaries:** * **Step 1:** * Mast cells and histamine, responding to tissue damage. * Vasoactive. * Vasodilation = capillaries and venules. * Capillaries becoming permeable > swelling (edema). * Blood volume flow velocity slows down. * Inflammatory rep esc the micro-blood. * Fluid exits and enters the tissues. * **Step 2:** * Plasma proteins enter the tissue. * Causing edema (swelling), redness, heat, pain. * **Step 3:** * Extravasation. * 1. **Rolling:** * Endothelial cells activated to express cell adhesion molecules (eg selectins [rectins]) on terminal (male). * Selectins bind w/ sugar molecules on neutrophil surface. * Leukocytes weakly attach and roll. * 2. **Activation:** * Neutrophils/rec. bind. * Monocytes enter. * Cytokines (TNF, IL-1) cause endothelial cell to express ICAMs. * Chemokines cause WBC to express high affinity integrin. * ICAM interaction is very strong. **(3) Arrest:** * WBC adhere strongly to endothelial cells and spread. * Diapedesis: * Endothelial junctions broken. * WBC crosses into tissue. * Neutrophils indicate infection. * Neutrophil emigration = the removal of neutrophils. **Immune Response:** * **1st responders:** * Neutrophils. * Monocytes/macrophages provide protection. * DC/Macrophages travel to lymph nodes to present antigens. **Dendritic cells:** * Resident in tissues. * To sense danger and release cytokines. **Mast cells:** * Resident in skin and mucosal tissue. * Activated by PAMPS, (glucans & antibodies). * Release histamine and cytokines. * Vasodilation. * Permeability & stimulate inflammation via cytokine production. * Linked w/ allergic reactions. * Histamine causes inflammation to allergens. **Inflammatory Cytokines:** * Leukocytes use cytokines to communicate. * Cytokines act on cytokine receptors. **Main functions:** * Change cell adhesion. * Activate enzyme activity. * Gene expression. * Determines when a cell survives/dies. ## Cytokine Family: * Called interleukins as well. * Binds on cytokine receptors. * **Chemokines:** type of cytokine that are chemoattractants: affect mobilization of cells: * TNF: * Epithelial cells. * Released by macrophage & cells. * Binds to TNF receptor. * Pro-Inflammatory. * Released by macrophages. * Binds to TNF receptor. * **Chemokines:** a subgroup of cytokines. * **Chemoattractants:** Affect cell movement. * **Self Cell Adhesion:** affect cell movement. * **Eg:** IL-8 recurs to activate neutrophils. **2 Main Classes:** * **CC:** attract monocytes and macrophages. * A single cysteine in amino termini. * **CXC:** attract neutrophils. * CC are separated by an amino acid.