physio-leukocytes

The adult human being has about _______ WBCs per microliter of blood

Polymorphonuclear Neutrophils _____

Polymorphonuclear Eosinophils _____

Polymorphonuclear Basophils _____

Lymphocytes _____

Monocytes _____

2 IMPORTANCE OF WHITE BLOOD CELLS

These cells work together in two ways to prevent diseases:

1. phagocytosis

2. forming Antibodies and Sensitized lymphocytes

(destroy or inactivate the invader)

- Both ___ and _____ have a special ability to “SEEK OUT AND DESTROY” a foreign invader.

-WBC’s move through tissue spaces by __________

- Both neutrophils and macrophages can move through the tissues by ………. motion

WBCs are attracted to inflamed tissues by _______

When a tissue becomes inflamed at least a dozen different products that can cause chemotaxis toward the inflamed area are formed. (examples ?)

- The most important function of the neutrophils and macrophages are ____________, “cellular ingestion of the offending agent”

Whether phagocytosis will occur depends on this THREE SELECTIVE PROCEDURES

MONOCYTE-MACROPHAGE CELL SYSTEM aka

MONOCYTE-MACROPHAGE CELL SYSTEM (RETICULOENDOTHELIAL SYSTEM)

The total combination of monocytes, mobile macrophages, fixed (tissue) macrophages, and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes (various lymphoid tissues).

MONOCYTE-MACROPHAGE CELL SYSTEM (RETICULOENDOTHELIAL SYSTEM)

functions(?)

- Removal of foreign objects and toxins.

- Formation of new RBCs and WBCs.

- Destruction of senescent RBCs.

- Formation of bile pigments.

- Storage of iron.

- Clearance of heparin via heparinase

INFLAMMATION

- When tissue injury occurs, whether caused by bacteria, trauma, chemicals, heat or any other phenomenon, multiple substances are released by the bruised tissues and cause dramatic secondary changes in the surrounding undamaged tissues.

- The entire complex tissue changes is called INFLAMMATION.

- It is the body’s response to infection or injury. - Function: To destroy or inactivate foreign invaders and to set stage for tissue repair.

.PURPOSE OF INFLAMMATORY RESPONSE

1. Allows the body to defend itself from invading microorganisms.

2. Induces local blood clotting.

3. Promotes repair of injured tissue.

THE WALLING OFF EFFECT

- One of the first results of inflammation is to “wall off” area of injury from the remaining tissues.

- The tissue spaces and the lymphatics in the inflamed area are blocked by fibrinogen clots, so that after a while, fluid barely flows through the spaces. It delays the spread of bacteria or toxic products.

-This response helps to wall off infected area to further spread and allow the battle to focus at the inflammatory site.

FIRST LINE OF DEFENSE: TISSUE MACROPHAGES

Within minutes after inflammation begins, the macrophages already present in the tissues immediately begin their phagocytic actions. - Next, many of the previously sessile macrophages break loose from their attachments and become mobile, forming the first line of defense against infection during the first hour or so. - Examples of tissue macrophages:

VII. SECOND LINE OF DEFENSE: NEUTROPHIL INVASION OF THE INFLAMED AREA

- Within the first hour or so after inflammation begins, large number of neutrophils begin to invade the inflamed area from the blood. 1. They cause increased expression of adhesion molecules: selectins and intercellular adhesion molecule- 1 (ICAM-1) on the surface of endothelial cells in the capillaries and venule

2. They cause the intercellular attachments between the endothelial cells of the capillaries and small venules to loosen, allowing openings to be large enough for neutrophils to crawl through directly from the blood into tissue spaces by diapedesis

Neutrophilia - Within a few hours after the onset of acute, severe inflammation, the number of neutrophils in the blood increases 4-5 the normal (about 15 000 to 25 000 neutrophils per microliter). - Caused by products of inflammation that enter the bloodstream, transported to the bone marrow, and act on the stored neutrophils of the marrow to mobilize these into the circulating blood and makes even more neutrophils available to the inflamed area.

VIII. THIRD LINE OF DEFENSE: SECOND MACROPHAGE INVASION INTO THE INFLAMED TISSUE

IX. FOURTH LINE OF DEFENSE: INCREASED PRODUCTION OF GRANULOCYTES AND MONOCYTES BY THE BONE MARROW

• This action results from stimulation of the granulocytic and monocytic progenitor cells of the marrow. However, it takes 3 to 4 days before newly formed granulocytes and monocytes reach the stage of leaving the bone marrow. • If the stimulus from the inflamed tissue continues, the bone marrow can continue to produce these cells in tremendous quantities for months and even years, sometimes at a rate 20 to 50 times normal (specially in chronic inflammation).

Control of the Macrophage

• The cause of increased production of granulocytes and monocytes by the bone marrow is mainly the three colonystimulating factors, one of which, GMCSF, G-CSF and M-CSF. • Combination of TNF, IL-1, and colony-stimulating factors provides a powerful feedback mechanism that begins with tissue inflammation and proceeds to formation of large numbers of defensive WBCs that help remove the cause of the inflammation.

FORMATION OF PUS

 When neutrophils and macrophages engulf large numbers of bacteria and necrotic tissue, essentially all the neutrophils and many, if not most, of the macrophages eventually die.  After several days, a cavity is often excavated in the inflamed tissues.  This cavity contains varying portions of necrotic tissue, dead neutrophils, dead macrophages, and tissue fluid (the mixture is commonly called pus).  After the infection has been suppressed, the dead cells and necrotic tissue in the pus gradually autolyze over a period of day

-The whitish yellow or yellow brown or greenish color of the pus is because of the accumulation of dead neutrophils. Sometimes it appears green because neutrophil produces green antibacterial protein called myeloperoxidase). -Pseudomonas aeruginosa produces green pigment

. EOSINOPHILS

• Weak phagocytes, exhibits chemotaxis • Often produced in large numbers in people with parasitic infections and they migrate in large numbers into tissues diseases by parasites • They are produced in large number in people with parasitic infection. They kill parasites by:  Releasing hydrolytic enzymes (modified lysosomes)  Releasing highly reactive forms of oxygen that are especially lethal to parasites (hydrogen peroxide)  Releasing highly larvicidal polypeptide called major basic protein • Eosinophils also have a special propensity to collect in tissues in which allergic reactions • Both mast cells and basophils release an eosinophil chemotactic factor that causes eosinophils to migrate toward the inflamed allergic tissue.

BASOPHILS

The basophils in the circulating blood are similar to the large tissue mast cells located immediately outside many of the capillaries in the body.  Both mast cells & basophils liberate heparin (anticoagulant) into the blood which prevent coagulation  Both release histamine, smaller amt. of bradykinin and serotonin (allergic reactions, pain, emotions)  Both play an important role in allergic reactions  IgE has a special propensity to attach to mast cells & basophils. The resulting attachment of antigen to antibody causes the mast cell or basophil to rupture and release large quantities of histamine, bradykinin, serotonin, heparin, slow-reacting substance of anaphylaxis and a number of lysosomal enzymes. These substances cause a local vascular and tissue reactions that cause allergic manifestation.

BASOPHILS

 Bone marrow produces very few WBCs  This condition leaves the body unprotected against many bacteria and other agents that might invade the tissues.  Within 2 days after the bone marrow stops producing WBCs, ulcers may appear in the mouth and colon. Bacteria from the ulcers rapidly invade surrounding tissues and the blood. Without treatment, death often ensues in less than a week after acute total leukopenia begins.  Irradiation of the body by x-rays or gamma rays, or exposure to drugs and chemicals that contain benzene or anthracene nuclei, is likely to cause aplasia of the bone marrow. Some drugs such as Chloramphenicol (an antibiotic), Thiouracil (used to treat thyrotoxicosis) and even various barbiturate hypnotics on rare occasions cause Leukopenia

LEUKOPENIA

The bone marrow produces very few WBC. This condition leaves the body unprotected against many bacteria and other agents that might invade the tissues.  Within 2 days after the bone marrow stops producing WBCs, ulcers may appear in the mouth and colon, or some form of severe respiratory infection might develop. Bacteria from the ulcers rapidly invade surrounding tissues and the blood. Without treatment, death often ensues in less than a week after acute total leukopenia begins. -Any decrease in the number of WBC immediately allows invasion of the adjacent tissue by the bacteria.

LEUKEMIA

 a disease characterized by greatly increased numbers of WBCs in the circulating blood  Uncontrolled production of WBCs can be caused by cancerous mutation of a myelogenous or lymphogenous cell. -Cancer of the body’s blood forming tissue -Caused by mutation in the DNA or can be precipitated by environmental factors -ACUTE- cut off is 6 months -CHRONIC- more than 6 months of occurrence

TWO TYPES OF LEUKEMIA: A. LYMPHOCYTIC LEUKEMIA (ACUTE LL or CHRONIC LL) -caused by cancerous production of lymphoid cell, beginning in a lymph nodes or other lymphocytic tissue and spreading to other areas of the body. - affects the lymphoid cells/lymphocytes B. MYELOGENOUS LEUKEMIA (AML or CML) -begins by cancerous production of young and myelogenous cells in the bone marrow and then spreads throughout the body so that WBCs are produced in many extramedullary tissues especially in the lymph nodes, spleen and liver.

C. EFFECTS OF LEUKEMIA -The first effect of leukemia is metastatic growth of leukemic cells in abnormal areas of the body - Leukemic cells from the bone marrow may invade the surrounding bone, causing pain and a tendency for bones for fracture easily. -There’s development of infection, severe anemia, and bleeding tendency caused by thrombocytopenia. These effects result mainly from displacement of the normal bone marrow and lymphoid cells by the nonfunctional leukemic cells. - Another important effect of leukemia on the body is excessive use of metabolic substrates by the growing cancerous cells - The leukemic tissues reproduce new cells so rapidly that tremendous demands are on the body reserves for foodstuff, amino acids, and vitamins. - Consequently, the energy of the patient is greatly depleted, and excessive utilization of amino acids by the leukemic cells causes especially rapid deterioration of the normal protein tissues of the body. Thus, while the leukemic tissues grow, other tissues become debilitated. After metabolic starvation has continued long enough, this factor alone is sufficient to cause death