MONONUCLEAR PHAGOCYTIC SYSTEM

BY Tathagata Bhattacharjee 2nd year P.G. student

On December 11 1908, Elie Metchnikoff and Paul Ehrlich were jointly awarded the Nobel Prize in recognition of their pioneering work on immunity.

DEFINITION
The mononuclear phagocyte system (MPS) is

defined as a population of cells derived from progenitor cells in the bone marrow, which differentiate to form blood monocytes, circulate in the blood, and then enter tissues to become resident tissue macrophages.

DIFFERENT NAMES
Reticuloendothelial system

Tissue macrophage system

Mononuclear phagocytic system

CELLS OF MPS
Monoblasts-

Promonocytes-

CELLS OF MPS
Monocyte of blood-

Histiocytes of connective tissue-

CELLS OF MPS
Littoralcells-

Microglial cells-

CELLS OF MPS
Macrophages in pleura-

Dendritic cells of epidermis-

MONOCYTE MACROPHAGE LINEAGE

ORIGIN OF MONOCYTES/MACROPHAGES

THREE-MODEL

HIERARCHICAL MODEL
Hematopoietic stem cells
Common myeloid precursor common lymphoid precursor

Precursors of megakaryocytes, erythrocytes,granulocytes & monocytes/macrophages monoblast

precursors for T & B cells & NK cells

promonocyte

monocyte

STOCHASTIC MODEL

Hematopoietic precursors is stochastic, in

that it can occur at any time.

SEQUENTIAL MODEL
Hematopoietic stem cells progressively

express the potential for megakaryocyte, erethrocyte, granulocyte,monocyte,B cell, T cell, NK cell development.

GENETIC CONTROL
Differentiation of MPS is controlled by-

specific growth factor CSF-1,it binds to its cell surface receptor CSF-1R,that is encoded by csf1r gene or c-fms proto oncogene for cell receptor. Expression of csf1r gene is dependent on the expression of PU.1 transcription factor.

MACROPHAGES
End stage product of monocytes that enter

the tissue from the blood.

Activated by immune system.

DISTRIBUTION
Endothelial lining of vascular & lymph

channel.
Connective tissue & some organs.

CLASSIFICATION
Fixed reticuloendothelial cells.

Wandering reticuloendothelial cells.

FIXED RETICULOENDOTHELIAL CELLS- TISSUE MACROPHAGES

FIXED MACROPHAGES OF CONNECTIVE TISSUE

Reticuloendothelial cells of connective tissue

& in serous membranes like pleura, omentum & mesentery.

ENDOTHELIUM OF BLOOD SINUSOIDS

The endothelium of the blood sinusoid,

bonemarrow,liver,spleen,lymphnodes,adrena l glands & pituitary glands. eg.Kupffers cells.

RETICULUM
Reticulum of spleen, lymphnode & bone

marrow.

CENTRAL NERVOUS SYSTEM

Meningiocytes of meninges and microglia.

LUNG
Tissue macrophages are present in the alveoli

of lungs.

SUBCUTANEOUS TISSUE

WANDERING RETICULOENDOTHELIAL CELLS

-FREE HISTIOCYTES

FREE HISTIOCYTES OF BLOOD

Monocytes,which become macrophages &

migrate to the site of injury or infection.

FREE HISTIOCYTES OF SOLID TISSUE

During emergency,the fixed histiocytes from

connective tissue & other organs become wandering cells & enter the circulation

FUNCTIONS

PHAGOCYTIC FUNCTION
Macrophages The antigens liberated by macrophages

activate the B lymphocytes & helper T lymphocytes.

SECRETION OF INTERLEUKINS
Secrete IL-1,IL-6,IL-12. IL-1----- accelerates the maturation &

proliferation of specific B lymphocytes & T lymphocytes. IL-6------causes growth of B lymphocytes & production of antibodies. IL-12-----influences the T helper cells.

SECRETION OF TUMORNECROSIS FACTOR

Secrete TNF -alpha ,TNF beta. TNF-alpha----necrosis of tumor & activate

immune system.
TNF-beta-----stimulate immune system &

vascular response in addition.

SECRETION OF PDGF
PDGF accelerates repair of damaged blood

vessel & wound healing.

REMOVAL OF CARBON PARTICLE & SILICONE

Macrophages ingest the substances.

DESTRUCTION OF SENILE RBC

Reticuloendothelial cells those in spleen.

DESTRUCTION OF HEMOGLOBIN

HEMOPOIETIC FUNCTION
Anti hematopoietic related antibody-ERHR3

IMMUNO BIOLOGIC FUNCTION OF MACROPHAGES

Locomotion and chemotaxis Ingestion and killing of microorganisms and

clearance of cellular debris Antitumor activity Control of granulopoiesis Immune reactions

ROLE IN IMMUNE REACTION

Antigen presentation to T cells Intermediate role in the passage of signals to

and from lymphocyte subclasses Interactions with B cells Secretion of soluble factors Maintenance of lymphocyte viability and differentiation

ROLE IN IMMUNE REACTION

Recruitment into inflammatory

reaction of delayed hypersensitivity Secretion of soluble factors Phagocytic and biochemical reactions as a consequence of activation

DISEASE STATESMONOCYTE-MACROPHAGE CELL LINE

mild blood monocytosis-Infectious,inflammatory or collagen vascular diseases. neoplastic proliferation of histiocytes monocytic leukemia, malignant histiocytosis. histiocytic proliferation of unknown origin sarcoidosis, granulomatous vasculites and

Wegener granulomatosis.

DISEASE STATESMONOCYTE-MACROPHAGE CELL LINE

reactive proliferation secondary to infection-

(tuberculosis), or chemical exposure (beryllium and zirconium salts)

MONOCYTE MACROPHAGE DYSFUNCTION SYNDROME

Neoplasia -

Chemotaxis

Chediak-Higashi syndrome -

Abnormal degranulation
Chronic granulomatous disease -

Abnormal oxygen metabolism

Hodgkin disease-

Neoplastic proliferation of macrophages

MONOCYTE MACROPHAGE DYSFUNCTION SYNDROME

Miliary tuberculosis-

Suppressor monocytes

Lepromatous leprosy- Suppressor monocytes

Disseminated fungal infection-

Chemotaxis, Suppressor monocytes

Glucocorticoid treatment-

Chemotaxis,Microbialkilling

IMMUNE MEDIATED THROMBOCYTOPENIA

Mechanism- antibody/complement coated

platelet can also be removed by mononuclear phagocytic system. Storage disorders

monogenetic defects of lysosomal

lipoprotein metabolism are associated with complex alterations of mononuclear phagocyte differentiation and extravasation.

MPS DISORDER IN AIDS

Impaired in vivo Fc receptor-specific

clearance.
The in vivo function of macrophage C3

receptors was also found to be abnormal.

The antibody-dependent cell-mediated

cytotoxicity of circulating mononuclear cells was significantly lower in AIDS patients than in healthy controls.

MPS DISORDER IN CARDIOVASCULAR DISEASE

Pleckstrin is an intriguing signaling protein that is only found in haematopoietic cells of lymphoid

and myeloid origins where it is expressed at high levels.

Defects in pleckstrin phosphorylation have been directly linked to cardiovascular disease

MPS DISORDER IN DIABETES

the level of pleckstrin phosphorylation in

mononuclear phagocytes of poorly controlled diabetics is greatly elevated.

MPS DISORDER IN ALZIMER DISEASE

Interaction of CCL2, with its receptor CCR2 regulates mononuclear phagocyte accumulation . ( CCL2- A major
monocyte chemokine)

Monocytes accumulate at sites of Abeta deposition in an initial attempt to clear these deposits and stop or delay their neurotoxic effects. CCR2 deficiency leads to lower mononuclear phagocyte accumulation . Higher brain Abeta levels

MPS DISORDER IN MALIGNANCY

Cell maturation- closed packed surface

microvilli is less in hodgkins & non hodgkins lymphoma.

Migration & chemotaxis-

disseminated carcinoma localised carcinoma

fewer macrophages increased monocyte mobilisation

MPS DISORDER IN MALIGNANCY

Phagocytosis,cytotoxicity-

Increased phagocytic activity in monocyte/macrophages--- untreated hodgkins disease. decreased phagocytic activity---stage iii &iv hodgkins disease

MPS DISORDER IN MALIGNANCY

Disorder in lysozyme secretion-

raised serum lysozymeneoplastic disorder. enhanced lysozyme secretionfavourable clinical condition. depressed lysozyme secretion--- poorer prognosis.

MPS DISORDER IN MALIGNANCY

Macrophages within malignant tumor---

Presence of macrophages

morenon metastasizing tumor.

lessMetastasizing tumor

RECENT STUDY
separate embryonic phagocyte lineage-use

of F4/80 markers.
No influence of acute alcoholism in the

phagocytic function in the liver, spleen and lungs .

Possible Failure of the Mononuclear

Phagocyte System after Total Splenectomy in rats.

RECENT STUDY
Colloidal thorium dioxide is used to block the

reticulo endothelial system.

BIBLIOGRAPHY
www.abcam.com

Textbook of medical physiology-Gyton &hall 11th edition.

Essential of medical physiology-

k.sembulingam 3rd edition Textbook of human histology-Inderbir Singh 4th edition. www.britannica.com www.bookrags.com

BIBLIOGRAPHY
Influence of acute alcoholism in the

phagocyticfunction of the mononuclear phagocyte systemin an experimental model--- Kelly Renata Sabino, Adriana Nunes Machado, Andy Petroianu, Luiz Ronaldo Alberti, Carlos Jorge Rodrigues Simal.
MononuclearPhagocyte System after Total Splenectomy in Rats--Ruy Garcia Marques, Andy Petroianu, Mrcia Betnia Nunes de Oliveira, MrioBernardo-Filho and Margareth Crisstomo Portela.

Evaluation of Possible Failure of the

BIBLIOGRAPHY
Recent development of the mononuclear

phagocyte system: in memory of Metchnikoff and Ehrlich on the 100th Anniversary of the 1908 Nobel Prize in Physiology or Medicine-Zong-Liang Chang. Ultrastructural Localization of Thorotrast in the Reticuloendothelial System--Trond Kluge and Torstein Hovig.

BIBLIOGRAPHY
Mononuclear Phagocytes:Immunological

Functions and Disease Implications. Blood Monocytes:Development, Heterogeneity,and Relationship with Dendritic Cells--Cedric Auffray, Michael H. Sieweke,and Frederic Geissmann. The mononuclear phagocyte system revisited David A. Hume, Ian L. Ross, S. Roy Himes, R. Tedjo Sasmono, Christine A. Wells and Timothy Ravasi.

THANK YOU