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Monocyte-Macrophage Cell System

(Reticuloendothelial system)

By:Dr Asma Jabeen

The total combination of monocytes,

mobile macrophages, fixed tissue

macrophages and a few specialized

endothelial cells in the bone marrow,

spleen and lymph nodes is called the

Reticuloendothelial system.

It is a generalized phagocytic system

located in all tissues, especially in those

tissue areas where large quantities of

particles, toxins and other unwanted

substances must be destroyed.

Components of RES (Bone marrow, spleen and lymph nodes)

▪ Monocytes

▪ Mobile macrophages

▪ Fixed tissue macrophages

▪ Few specialized endothelial cells

Tissue macrophages in skin

▪ Histiocytes

▪ In broken skin, local tissue macrophages

on exposure to infectious agent attack

and destroys the infectious agent

Macrophages in lymph nodes

▪ If particles are not destroyed locally,

they enter lymph and flow to lymph

Nodes.

▪ Foreign particles are trapped in

lymph nodes in a meshwork of sinuses

lined by tissue macrophages

Alveolar macrophages in lungs

▪ Large number of tissue macrophages

are present in alveolar walls

▪ Phagocytize particles entrapped in

alveoli

▪ Small particles digested

▪ Large particle-as granuloma or

giant cell capsule until slowly dissolved

Macrophages in liver sinusoids

(Kupffer cells)

▪ Common route for entry of bacteria

▪ Portal blood before entering into

systemic circulation passes through liver

sinusoids

▪ Very effective filtration system

Macrophages of spleen and Bone marrow

▪ Act against the organisms that succeedin entering the systemic circulation▪ Foreign particles are phagocytized by macrophages

After a tissue injury , substances

released by injured tissues cause dramatic

secondary changes in the surrounding

uninjured tissues. This entire complex of

tissue changes is called Inflammation.

Role of WBC in inflammation

▪ Vasodilation of local blood vessels

▪ Increased permeability of capillaries

▪ Clotting of fluid in interstitial tissues b/c of

fibrinogen and other proteins

▪ Migration of large no of granulocytes and

monocytes into tissues

▪ Swelling of tissue cells

Tissue products causing Inflammation

➢ Histamine

➢ Bradykinin

➢ Serotonin

➢ Reaction products of complement

➢ Lymphokines released by sensitized T cells

“Walling off” effect of inflammation

The tissue spaces and the lymphatics of theinflamed area are blocked by fibrinogen clots so that fluid does not flow through spaces.

Importance:

▪ It delays the spread of bacteria or toxic products.

▪ More severe tissue destruction, more is the walling off effect

• Streptococcus & staphylococcal infection

Macrophage and neutrophils in inflammation

1. Tissue macrophages

2. Neutrophils

3. Macrophage invasion

4. Increased production by bone marrow

Tissue macrophages -1st line of defense

▪ Macrophages in the tissues begin phagocyticaction within minutes

▪ On activation by products of infection andinflammation:

• Rapid enlargement

• Sessile change to mobile macrophages

• Less number but lifesaving

Neutrophil invasion- 2nd line of defense

▪ Within the first hour, large number ofneutrophils begin to invade the inflamed area

▪ Products of inflamed tissues help for supply of neutrophils to inflamed area by:

• Margination

• Diapedesis

• Chemotaxis

Neutrophilia

Acute increase in number of neutrophils in blood is called neutrophilia.

➢ Occurs within a few hours after the onset of acute severe inflammation

➢ 4000 to 5000 to 15,000 to 25,000➢ Products of inflammation act on bone marrow

for mobilization of stored neutrophils

Second macrophage invasion into inflamed Tissue- 3rd line of defense

▪ Monocytes from the blood enter the inflamed tissues and enlarge to become macrophages

▪ Still immature cells, require 8 hrs or more to swell to larger size with great no of lysosomes

▪ After several days to weeks, macrophages dominate the phagocytic cells of inflamed area

Increased production of granulocytes and monocytes from bone marrow -4th line of defense

▪ Stimulation of the granulocytic and monocyticprogenitor cells of the bone marrow- takes 3 to 4 days

▪ If stimulus continues, bone marrow continuouslyproduce WBC at rate 20 to 50 times normal formonths or years

How bone marrow produces more cells?

Factors formed by activated macrophage cells in the inflamed tissues and by other inflamed tissue cells:

▪ GM-CSF▪ G-CSF▪ M-CSF▪ TNF▪ IL-1

Formation Of Pus

After several days of inflammation, a cavity is formed containing necrotic tissue, dead neutrophils, dead macrophages and tissue fluid. This mixture is called PUS

Over a period of days, end products are eventually absorbed into the surrounding tissuesand lymph.

Neutrophils

• Margination• Diapedesis• Phagocytosis• Secretory function: Enzymes(DNase, RNase)

Histamine, vitamin B12 binding globulin, leukocytepyrogen, Proteins ( that inhibit bacterial growth,cause monocyte chemotaxis and increase membrane permeability. Leukotrienes

Neutrophil Extracellular traps (NETs)

Neutrophils are capable of releasing a web of extracellular fibers called neutrophil extracellulartraps (NETs)• These fibers contain bacteria killing chemicals

enabling NETs to trap and destroy bacteria extracellularly.

NETosis- Activation & release of NET

Neutropenia:Decrease in neutrophil count. Caused by diseases like typhoid, viral infections, bone marrow depression, drugs( antiviral, anticancer)

Neutrophilia: Leukocytosis affecting neutrophils.• Acute bacterial infections• Hemorrhage, tissue injury, Myocardial

infarction, polycythemia vera

Eosinophils

▪ 2% of all white blood cells

▪ Weak phagocytes▪ Exhibit chemotaxis▪ Doubtful if help to protect against usual

infections

➢ Especially abundant in mucosa of

gastrointestinal tract, respiratory

and urinary tract.

➢ Specifically important in

• Parasitic infections

• Allergic reactions

Eosinophils in parasitic infections

➢ They attach to parasites by special surface molecules and release substancesto kill parasites

Substances released by eosinophils:

▪Hydrolytic enzymes from granules (modified lysosomes)

▪ Highly reactive lethal forms of oxygen▪ Larvicidal polypeptide called

Major Basic Protein is also released from granulocytes.

Eosinophils in allergic reactions

▪ Collect due to eosinophil chemotactic factor released by mast cells & basophilsespecially in lung tissue(asthma) & skin.

▪ Detoxify some of inflammation inducing substances released by mast cells and basophils

▪ Phagocytize and destroy allergen-antibody complexes , prevent excess spread of inflammatory process

Basophils▪ Similar to mast cells in

tissues▪ Release inflammatory

mediators:

• Heparin

• Histamine & slow reacting substance

• Bradykinin of anaphylaxis

• Serotonin

Basophil in allergic conditions

➢ The antibody IgE causing allergic reactions becomes attached to mast cells and basophils

➢ Binding of specific antigen to specificIgE antibody, cause basophil to ruptureand release chemicals

➢ These chemicals cause local vascular andtissue reactions that cause most of the allergic manifestations.

Leukopenia

A decrease in total

leukocyte count

below the normal

lower limit of 4000/µl

is called leukopenia.

Leukopenia…………..cont'd

Bone marrow produces very few white

blood cells leaving the body unprotected

against many bacteria and other agents

that might invade the tissues.

Causes:

▪ Non-pyogenic bacteria:▪ Typhoid and paratyphoid fevers▪ Malaria▪ Viral infections like influenza, mumps

small pox, AIDS ▪ X-rays▪ Gamma rays▪ Exposure to drugs and chemicals▪ Malnutrition & starvation

Decrease in WBCs immediately allows

invasion of adjacent tissues by bacteria that

are already present.

Effects:

▪ Within two days, ulcers may appear inmouth and colon or severe respiratory infection may occur.

▪ Bacteria from ulcers rapidly invade surrounding tissues and blood.

▪ Death occurs in less than a week.

Leukocytosis

It is an increase in TLC count above

11,000/mm3 irrespective of the types of

cells involved

➢ Infection ,tissue injury

➢ Count usually does not exceed

25,000/mm3

➢ No immature cells in circulation

The Leukemias

Characterized by greatly increased

numbers of abnormal white blood cells in

the circulation.

Cause:

Uncontrolled production of white blood

cells caused by cancerous mutation of a

myelogenous or lymphogeous cells

Types

▪ Lymphogenous leukemia

▪ Myelogenous leukemia

➢ TLC is generally above 50,000/mm3

➢ Uncontrolled production

➢ Both immature and mature WBCs are

released into circulation

➢ The leukemic cells are bizarre and undifferentiated, not identical to any of the normal white blood cells.

➢ More undifferentiated cell, more acute is leukemia, leading to death within a few months.

Leukemia

Effects of leukemia:

▪ Metastatic growth of leukemic cellsin abnormal areas of the body

▪ Infection

▪ Severe anemia

▪ Bleeding tendency

Displacementof normal marrowor lymphoid cells by leukemic cells

▪ Excessive use of metabolic substratesby growing cancer cells.

▪ As leukemic tissue grow, other tissuesbecome debilitated Metabolicstarvation

Effects of leukemia…….cont'd

Leukemoid reaction

It is an extreme elevation of TLC above50,000/mm3 as a resultof presence of

mature and/or immature neutrophils.Causes:▪ Severe chronic infections▪ Severe hemolysis▪ Malignant growths

( breast lung, kidney)

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