PATH 3610 Lecture Notes - Lecture 3: Agranulocyte, Myelocyte, Endothelium
27 Jul 2016
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Unit 03
Cellular Events: Leukocyte Recruitment and Activation
Acute inflammation is characterized by the active emigration of inflammatory cells from the
blood into the area of tissue injury
The Inflammatory Cells
- Also known as white blood cells or leukocytes
- Derived from myeloid cell line w/n bone marroe
- Move into bloodstream when mature
- Myeloid cell line has two arms, mononuclear cells and granylocytes
- Mononuclear cells have smoothly outlined, rounded nucleus
- Granulocytes have multilobulated nucleus, contain cytoplasmic granules – also called
polymorphonuclear leukocytes
- Bone marrow = site of differentiation for most leukocytes, red blood cells and platelets
- Many bone marrow-derived cells are derived from common precursors
- Cell lineages respond to a bunch of different cytokines, colony-stimulating factors and
hormones to up or downregulate production of mature forms
Granulocytes
- Neutrophil. Basophil and eosinophil
- Neutrophil = most important/greatest role in acute inflammation
- Is the white blood cell seen in greatest numbers in the early stages of inflamation
- Actively motile, capable of phagocytosis and contain enzymes which can degrade
biologic material
- Main function = phagocytosis of microorganisms
- You are at risk of infection if you have low neutrophil numbers or have defectively
functioning neutrophils
- Eosinophils contain different repertoire of enzymes and granules than neutrophils
o Recruited to fight parasitic diseases
o Involved in hypersensitivity responses
- Neutropenia = low numbers of neutrophils
o Side effect of cancer therapy using cytotoxic drugs or radiation therapy
o Therapy directed at cancer cells but puts other cells at risk
o When total neutrophil counts are decreased sufficiently, patient at increased risk
of infection
Mononuclear cells
- Lymphocytes, plasma cells, monocytes and macrophages
- Greater role in more chronic or later stages of inflammation
- Lymphocytes can be attracted to inflammatory site by other cells
- May develop into antibody producing cells (plasma cells)
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- Monocyte/macrophage system
o Monocyte present in blood but can migrate into tissues
o Called macrophages or histiocytes and dendritic cells once they are in the tissue
- Macrophages are mononuclear cell type that have the greatest role in acute inflammation
o Ingest micro-organisms and help clean up debris
o Secrete substaances such as endogenous pyrogen and complement componenets
Leukocyte Recruitment
Margination, Rolling and Adhesion of Leukocytes
- Microvasculature dilates and becomes leaky (in acute inflammation)
- Rate of blood flow slows
- Causes normal laminar flow of blood constituents w/n vessels to become disorderd
- White blood cells tend to move out toward vessel wall from center
- Margination = increased contact between leukocytes and endothelium
- Marginated leukocytes roll along endothelial surface, sticking in place
- Mediated by selectins (receptors expressed on both the leukocyte and endothelial cell
surfaces)
- Receptors up regulated after stimulation by inflammatory mediators
- Pavementing or adhesion = endothelial cells become sticky, leukocytes adhere to vessel
wall
o Mediated by integrins on leukocyte surface
o Integrins interact with specific ligands on the endothelial cells
Transmigration of neutrophils
- Diapedesis
o After neutrophils are adhered to endothelium, they leave vessel by squeezing
between the intercellular junctions
o Made easier by enlarged pore size of endothelium
o They are focally degraded with secreted collagenases then they pass through
basement membrane and move into tissue spaces (interstitium)
o Occurs usually in venules in systemic circulation
- Diapedesis of neutrophils
o Movement of leukocytesis also through intercellular junctions and facilitated by
specific cell adhesion molecules
Chemotaxis
- Inflammatory cells are attracted to an injured area by this process
- Chemotaxis : process by which inflammatory cells are attracted to an area of injury by
direction migration along a chemical concentration gradient
- Chemical mediators of inflammation act as chemotactic signals to inflammatory cells
o Complement factors C3a and C5a, leukotriene and various cytokines
o Exogenous substances can be chemotactic
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- Chemotactic molecules bind to receptors on leukocyte surface
o leads to more intracellular calcium
o this triggers assembly of intracellular contractile elements
o this allows leukocytes to move by extending pseudopods
o also induce leukocyte activation
Leukocyte Activation
- leukocytes have different effectors that they can bring to fight foreign invadors within
tissues but they must be activated before they can use these
- Body has different ways it can recognize self from non-self
o Components of acquired immune system (antibodies) designed for this
- Pathogen-Associated Molecular Patterns or PAMPs – molecules associate with groups of
molecules that are recognized by innate immune system
o Toll like receptors – recognize various bacterial, viral and fungal components
o Recognition activates leukocytes and starts inflammatory response
- Introduction of pathogen in tissue can induce immediate response from leukocytes w/o
having to rely on recognition and upregulation of acquired immunity
- Initial activation of these leukocytes leads to several different changes including:
o Phagocytosis
o Upregulation of mechanisms for degradation and killing of microbes
o Production of inflammatory mediators
Phagocytosis and Pathogen Degradation
Phagocytosis – neutrophils and macrophages ingest and destroy particulate matter
- Phagocytic cells must first recognize and attach to the particle or agent
o Can be specific; occurs when particles are coated with antibody (IgG),
complement factor 3b, opsonization (IgG and C3b act as opsonins)
o Or nonspecific; large inert particles
- Collectins, carbohydrate-binding lectins found in plasma also bind to microbial walls as
opsonins
o Leucocytes have specific receptors for IgG, complement and collectins
o Opsonization = enhanced phagocytosis
- In early acute inflammation nonspecific phagocytosis will dominate
o As immune response develops, immune phagocytosis is more efficient
- Recognition and binding of opsonized particle occurs, particle engulfed by phagocytic
cell, forms membrane-bound vacuole w/n phagocytes cytoplasm
- Phagocytosis stimulates increase in oxygen dependent metabolism in leukocytes =
production of large amounts of reactive oxygen species
Inflammatory exudate also characterized by presence of inflammatory cells
- Give opaque or cloudy appearance
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Acute inflammation is characterized by the active emigration of inflammatory cells from the blood into the area of tissue injury. Also known as white blood cells or leukocytes. Derived from myeloid cell line w/n bone marroe. Myeloid cell line has two arms, mononuclear cells and granylocytes. Mononuclear cells have smoothly outlined, rounded nucleus. Granulocytes have multilobulated nucleus, contain cytoplasmic granules also called polymorphonuclear leukocytes. Bone marrow = site of differentiation for most leukocytes, red blood cells and platelets. Many bone marrow-derived cells are derived from common precursors. Cell lineages respond to a bunch of different cytokines, colony-stimulating factors and hormones to up or downregulate production of mature forms. Neutrophil = most important/greatest role in acute inflammation. Is the white blood cell seen in greatest numbers in the early stages of inflamation. Actively motile, capable of phagocytosis and contain enzymes which can degrade biologic material.
