Aims

1. Aims • Introduction to inflammation • Introduction to white blood cells (Leukocytes) • leukocyte extravasation • Readings: Robbins, Chapter 2; Abbas & Lichtman, Chapter 2

2. Cardinal Signs of Inflammation • Rubor • Tumor • Calor • Dolor • Functio laesa ?

3. Cells and Tissues Connective Tissue Cells Connective Tissue Blood Vessel Robbins’ Basic Pathology 2-1

4. Erythrocyte leukocytes Leukocytes, platelets and erythrocytes are all derived from the same progenitor stem cells. Ganong’s Review of Medical Physiology

5. Wheater’s Functional Histology

6. Neutrophil/PMN/Poly • Most common leukocyte • “Marines” • Note drumstick chromosome “Barr body” • Phagocytes Basophils • Least common leukocyte • Similar to a tissue mast cell • full of histamine and bradykinin • Involved in allergic reaction Wheater’s Functional Histology

7. Eosinophils • Involved in type I hypersensitivity reactions (allergies) • Involved in immunity from parasites • hydrolytic enzymes • oxygen radicals • specific agents Wheater’s Functional Histology

8. Lymphocytes • Smallest leukocyte • T cells (Helper, Cytotoxic) • cell mediated immunity • B cells • make antibodies • humoral immunity • Natural Killer cells Wheater’s Functional Histology

9. Lymphocytes Abbas & Lichtman’s Basic Immunology 1-11

10. Monocyte • Largest and longest lasting leukocyte. • Differentiate into Macrophages in tissues. • Phagocytes Wheater’s Functional Histology

11. Monocyte Differentiation Abbas & Lichtman’s Basic Immunology 2-4

12. Platelets • Platelets • Non-nucleated • derived from megakaryocytes • Clot formation Wheater’s Functional Histology

13. Leukocyte Extravasation • AKA • Diapedesis • Emigration • Egress/ingress • Four step process • Rolling • Firm adhesion • Transmigration • Chemotaxis Robbins’ Basic Pathology 2-5 7th Ed.

14. Rolling • Leukocyte rolling upon activated endothelium • Endothelial adhesion molecules • Inflammatory mediators upregulate the expression of E- and P-selectin on endothelial cells. • L-selectin ligand • Leukocyte adhesion molecules • Sialyl-Lewis X (CD15) • Bound by E- and P-selectin. • L-selectin • L-selectin binds L-selectin ligand on endothelial cells. Robbins’ Basic Pathology 2-7 7th Ed & 2-4 8th Ed.

15. Firm Adhesion • Adhesion Molecules • The leukocytes become activated by cytokines and chemokines and increase the avidity of leukocyte b2 integrins for ICAM-1 and VLA-4 (a4b1)integrin for VCAM-1 • The _________________________________________ in leukocyte extravasation. Robbins’ Basic Pathology 2-7 7th Ed & 2-4 8th Ed.