IV. Monocytes and Macrophages

• Myeloid progenitor → CFU-GM

• GM-CSF and interleukins drive monocyte formation

• Monocytes develop in BM

• Circulate briefly in peripheral blood

  • Migrate into tissues → macrophages

• Macrophages function in infection defense

Importance of myeloid progenitor cell, CFU- GM, monocytes, macrophages

Macrophages are named on location in the body:

1. Monocytes: __

2. Kupffer cells: __

3. Microglial cells: __

4. Osteoclasts: __

5. Langerhans cells: __

6. Alveolar cells: __

1. Monocytes—peripheral blood

2. Kupffer cells—liver

3. Microglial cells—central nervous system

4. Osteoclasts—bone

5. Langerhans cells—skin

6. Alveolar cells—lung

Cell line of Monocytes

1. Monoblast: No cytoplasmic granules

2. Promonocyte

3. Monocyte

4. Macrophage

Monoblast

Earliest recognizable monocyte precursor
NO CYTOPLASMIC GRANULES

• 12-18 um: N:C = 4:1

• round/oval eccentric nucleus w/ fine chromatin; 1-2 nucleoli

• Dark blue cytoplasm

Promonocyte

• 12-20 um; N:C = 3:1

• Irregularly shaped, indented nucleus w/ fine chromatin; 0-1 nucleoli

• blue to gray cytoplasm; fine azurophilic granules

Monocyte

• 12-20 um

• Horseshoe or kidney-bean-shaped nucleus “Brainlike” onvolutions

• FIne, lacy chromatin

• Blue-gray cyto; may have pseudopods and vacuoles

• Many fine azurophilic granules → ground glass appearance

• Transitional cell bc it migrates into tissue and becomes fixed or free macrophage

Macrophage

TIssue Monocyte

• 15-80 um

• Indented, elongated, or egg shaped nucleus, w/ fine chromatin

• Blue-gray cyto w/ many vacuoles and coarse azurophilic granules; may contain ingested material

Monocyte Characteristics

RR = 2-10% peripheral blood

• granules are lysosomes that contain hydrolytic enzymes, including peroxidases and ACP

• Highly motile cells tht marginates against vessel walls and into tissues

Monocyte/Macrophage role

initiating and regulating the immune response

They process ingested material and also process _____ , which is relayed to the _____ lymphs

They process ingested material and also process antigenic information, which is relayed to the T helper (CD4) lymphocyte. The T helper lymphocyte coordinates the immune response to foreign antigens.

T lymphs coordinate what?

The T helper lymphocyte coordinates the immune response to foreign antigens.

Moncytes/Macrophages arrive at site of inflammation after neuts. What is the difference between neuts and monocytes in this process?

Unlike neutrophils, the phagocytic process does not kill the monocyte.

Monocytes/Macrophages are very efficient phagocytic cells w/ receptors for…?

IgG or complement-coated organisms

Why are Monocytes/Macrophages known as scavenger cells?

ability to ingest foreign material

Blood monocytes func.

 ingest Ag-Ab complexes and activated clotting factors, limiting the coagulation response

Splenic macros func.

remove old/damaged RBCs and conserve iron for recycling.

 Liver macros func.?

 remove fibrin degradation products

Bone marrow func.  

remove abnormal RBCs, ingest bare megakaryocyte nuclei or extruded RBC nuclei, and store and supply iron for Hgb synthesis

Monocytes secrete what?

cytokines/interleukins and tumor necrosis factor

Nonmalignant Monocytic Disorders include:

1. Monocytosis

2. Lipid storage disorders:

• Gaucher disease  (gaucher cells)

• Niemann-Pick disease (Niemann-Pick cells)

• Sea-blue histiocytosis

1. Monocytopenia

• APLASTIC ANEMIA

Monocytosis

Inc. in the abs. # of **monocytes** associated w/

1. Recovery stage from acute bacterial infections and recovery following

   marrow suppression by drugs

2. Tuberculosis, syphilis, subacute bacterial endocarditis

3. Autoimmune disorders (systemic lupus erythematosus - SLE, rheumatoid arthritis - RA)

4. Tay-Sachs and Fabry diseases

Lipid storage disorders: Gaucher disease

• most common lipid storage disorder and has an AUTOSOMAL RECESSIVE inheritance pattern

• Gaucher cellls more commonly seen in BM

• Glucocerebrosidase deficiency leading to accumulation of glucocerebrosides in macrophages of BM, spleen, and liver

Lipid storage disorders: Neimann-Pick Disease

• Autosomal recessive inhertiance patter

• Niemann-Pick cells in BM

• Sphingomyelinase def. causes sphingomyelin to accumulate in macrophages in multiple organs and BM

Lipid storage disorders: Sea-blue histiocytosis

unk defic. → sea-blue macrophages in spleen and BM

Other Lipid storage disorders: Tay-sachs vs Fabry diseases

Feature	Tay-Sachs Disease	Fabry Disease
Inheritance	Autosomal recessive	X-linked
Primary impact	Severe, early-onset neurodegeneration	Multisystem disease (vascular, cardiac, renal, skin)
Classic sign	Cherry-red spot	Painful skin lesions; kidney and heart involvement

Monocytopenia

dec in # of monos, associated w/ stem cell disorder: Aplastic Anemia