Aims

• Introduction to inflammation

• Introduction to white blood cells (Leukocytes)

• leukocyte extravasation

• Readings: Robbins, Chapter 2; Abbas & Lichtman, Chapter 2

Cardinal Signs of Inflammation

• Rubor

• Tumor

• Calor

• Dolor

• Functio laesa ?

Robbins’ Basic Pathology 2-1

Cells and TissuesConnective Tissue Cells Connective Tissue Blood Vessel

Ganong’s Review of Medical PhysiologyErythrocyte leukocytes

Leukocytes, platelets and erythrocytes are all derived from the same progenitor stem cells.

Wheater’s Functional Histology

Wheater’s Functional Histology

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

Eosinophils

• Involved in type I hypersensitivity reactions (allergies)

• Involved in immunity from parasites– hydrolytic enzymes– oxygen radicals– specific agents

Wheater’s Functional Histology

Lymphocytes• Smallest leukocyte

– T cells (Helper, Cytotoxic)• cell mediated immunity

– B cells• make antibodies

• humoral immunity

– Natural Killer cells

Lymphocytes

Abbas & Lichtman’s Basic Immunology 1-11

Wheater’s Functional Histology

Monocyte

• Largest and longest lasting leukocyte.

• Differentiate into Macrophages in tissues.

• Phagocytes

Monocyte Differentiation

Abbas & Lichtman’s Basic Immunology 2-4

Wheater’s Functional Histology

Platelets

• Platelets– Non-nucleated– derived from megakaryocytes– Clot formation

Leukocyte Extravasation• AKA

– Diapedesis

– Emigration

– Egress/ingress

• Four step process– Rolling– Firm adhesion– Transmigration– Chemotaxis

Robbins’ Basic Pathology 2-5 7th Ed.

Robbins’ Basic Pathology 2-7 7th Ed & 2-4 8th Ed.

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.

Firm Adhesion– Adhesion Molecules

• The leukocytes become activated by cytokines and chemokines and increase the avidity of leukocyte 2 integrins for ICAM-1 and VLA-4 (41)integrin for VCAM-1

– The _________________________________________ in leukocyte extravasation.