gen physio: leukocytes

Leukocytes

Mobile units of the body’s protective system

White blood cells

Aka leukocytes

Formation of leukocytes

Formed partially in the bone marrow (granulocytes and monocytes and a few lymphocytes) and the lymph tissue (lymphocytes and plasma cells)

Granulocytes formed in bone marrow

Neutrophils, eosinophils, basophils

Agranulocytes formed in lymph tissue

Lymphocytes and plasma cells, monocytes and macrophages

Transport of leukocytes

Transported to areas of serious infection and inflammation

Function of leukocytes

Provide a rapid and potent defense against infectious agents

Defense mechanisms of leukocytes

Ingest invading organisms (by phagocytosis) and release antimicrobial or inflammatory substances

Types of granulocytes

Neutrophil, eosinophil, basophil

Types of agranulocytes

Lymphocytes/Plasma Cells, Monocytes/Macrophages

Myelocytic lineage

Genesis of white blood cells formed exclusively in the bone marrow

Lymphocytic lineage

Genesis of white blood cells formed in various lymphogenous tissues (lymph glands, spleen, thymus, tonsils, Peyer’s patches)

Megakaryocytes

Formed in the bone marrow

Megakaryocyte function

Fragment to form platelets (or thrombocytes), important in the initiation of blood clotting

Life span of granulocytes in blood

4 to 8 hours

Life span of granulocytes in tissues

4 to 5 days

Life span of monocytes in blood

10 to 20 hours

Tissue macrophages life span

Can live for months unless destroyed while performing phagocytic functions

Life span of lymphocytes

Weeks or months

Neutrophils and macrophages defense

Defend against infections

Diapedesis

How neutrophils and macrophages enter the tissue spaces

Ameboid motion

How neutrophils and macrophages move through tissue spaces

Chemotaxis

How neutrophils and macrophages are attracted to inflamed tissue areas

Chemotactic substances

Include bacterial or viral toxins, degenerative products of the inflamed tissues, reaction products of the complement complex, and reaction products caused by plasma clotting in the inflamed area

Chemotaxis dependence

Dependent on concentration gradient of chemotactic substance

Chemotaxis effectiveness range

Effective up to 100um away from an inflamed tissue

Phagocytosis

Major function of the neutrophils and macrophages, the ingestion of the offending agent

Phagocytosis selectivity

A highly selective process

Factors preventing phagocytosis of self-antigens

Smooth surfaces of natural structures, protective protein coats of natural substances, and antibodies against infectious agents developed by the immune system

Phagocytosis by neutrophils capacity

A single neutrophil can phagocytize 3 to 20 bacteria before inactivation and death

Phagocytosis by macrophages capacity

Capable of phagocytizing as many as 100 bacteria and can engulf much larger particles

Digestion by phagocytes

Most particles are digested by intracellular enzymes

Lysosomes in phagocytes

Filled with proteolytic enzymes

Bactericidal agents in phagocytes

Kill most bacteria, even when lysosomal enzymes fail

Oxidizing agents in phagocytes

Include superoxide (O2−), hydrogen peroxide (H2O2), and hydroxyl ions (OH−)

Tuberculosis bacillus resistance

Resistant to lysosomal digestion

Monocyte-macrophage cell system

Aka reticuloendothelial system

Composition of monocyte-macrophage system

Monocytes, mobile macrophages, fixed tissue macrophages, and specialized endothelial cells in the bone marrow, spleen, and lymph nodes

Tissue macrophages in skin and subcutaneous tissues

Histiocytes

Macrophages in liver sinusoids

Kupffer cells

Inflammation triggers

Tissue injury and subsequent release of histamine, bradykinin, serotonin, prostaglandins, reaction products of the complement system, reaction products of the blood clotting system, and lymphokines

Characteristics of inflammation

Vasodilation of local blood vessels, increased capillary permeability, clotting of fluid in interstitial spaces, migration of granulocytes and monocytes into the tissue, and swelling of tissue cells

Walling-off effect of inflammation

Blockage of tissue spaces and lymphatics by fibrinogen clots, delaying the spread of bacteria or toxic products

First line of defense against infection

Tissue macrophages

Macrophage activation during inflammation

Rapidly enlarge, previously sessile macrophages become mobile

Second line of defense against infection

Neutrophil invasion of the inflamed area

Neutrophil invasion cause

Caused by inflammatory cytokines such as tumor necrosis factor and interleukin-1

Neutrophil invasion steps

Increased expression of adhesion molecules (selectins and ICAM-1) on endothelial cells, loosening of intercellular attachments, and chemotaxis of neutrophils

Neutrophilia

Acute increase in the number of neutrophils in blood, increases fourfold to fivefold (15,000 to 25,000 neutrophils/µl)

Neutrophilia source

Mobilization of stored neutrophils of the marrow into the circulating blood

Third line of defense against infection

Second macrophage invasion into the inflamed tissue

Source of second wave macrophages

Monocytes from the blood that enter the inflamed tissue and enlarge

Fourth line of defense against infection

Increased production of granulocytes and monocytes by bone marrow

Stimulation of granulocyte/monocyte production

Stimulation of granulocytic and monocytic progenitor cells of the marrow

Time for new granulocytes/monocytes to reach blood

3 to 4 days

Rate of granulocyte/monocyte production during infection

20 to 50 times normal

Feedback control of macrophage and neutrophil responses

Mediated by tumor necrosis factor (TNF), interleukin-1 (IL-1), granulocyte-monocyte colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and monocyte colony-stimulating factor (M-CSF)

Pus

A cavity containing necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid

Eosinophil percentage in leukocytes

About 2%

Eosinophils as phagocytes

Weak

Eosinophil production increase

Occurs in people with parasitic infections

Eosinophil function against parasites

Destroys parasites by releasing hydrolytic enzymes, reactive oxygen forms, and major basic protein

Eosinophil role in allergic reactions

Collect in tissues, detoxify inflammation-inducing substances from mast cells/basophils, and destroy allergen-antibody complexes

Basophil secretion

Heparin, histamine, bradykinin, serotonin

Basophil role

Play an important role in allergic reactions

Leukopenia

A clinical condition with very few WBCs produced by bone marrow

Consequence of leukopenia

Allows invasion of adjacent tissues by bacteria already present, often leading to death in less than 1 week

Etiology of leukopenia

Irradiation, exposure to benzene/anthracene containing drugs/chemicals, and certain medications (chloramphenicol, thiouracil, barbiturates)

Leukemias

Uncontrolled production of WBCs due to cancerous mutation of myelogenous or lymphogenous cell

Characteristics of leukemia

Greatly increased numbers of abnormal WBCs in circulating blood, WBCs produced in extramedullary tissues

Acute leukemia cell differentiation

The more undifferentiated the cell, the more acute the leukemia

Leukemic WBC function

Nonfunctional for normal protection against infection

Untreated leukemia outcome

Death within a few months

Effects of leukemia on the body

Invasion of bone tissues, bone pains, pathologic fractures, spread to organs, infection, severe anemia, bleeding tendency, excessive metabolic substrate use, rapid deterioration of normal protein tissues