Macrophages

Question 1

Monocytes

Answer 1

Properties:

• Round with Kidney shaped nucleus
• Phagosomes/lysosomes for phagocytosis and killing
• Circuate 3 days then enter tissues

Location:

• Bone Marrow
  
  • Site of monocyte Production
• Blood

Function:

• Recruited to sites of tissues inflammation to become macrophages

Question 2

Macrophages (M₀)

Answer 2

Properties:

• Derived from Blood Monocytes
• Phagosomes contain killing chemicals and proteins

Location:

• see picture

Question 3

Macrophage (M₀) Function

Answer 3

Sentinels:

• Express PRRs
• Active Phagocytosis
• Trap and clear Particulate matter from circulation

Question 4

Bacteria/partivle clearance from blood

Answer 4

Differs among species

Kupffer celss and macrophages on spleen:

• Rodents
• Dogs

Lung Pulmonary intravascular Macrophages:

• Cats
• Horses
• Ruminants
• pigs

Question 5

Particle Capture by other routes

Answer 5

Aerosol Route:

• Nose
• Tracheal Cilia
• Bronchia & Bronchioles
• Alveolar macrophages in lung

Dermal Route:

• Antigen Trapped by macrophages/dendritic cells in skin
  
  • Migrate to the lymph nodes
    
    • Stimulate adaptive immunity

Question 6

M₁ Macrophage Polarization

Answer 6

Question 7

M₂ Macrophage Polarization

Answer 7

Question 8

Microbial Killing Mechanisms of M₁ Macrophages:

Oxygen Dependent

Answer 8

Phagosome:

• NADPH oxidase
  
  • Superoxide anion
  • Hydrogen peroxide

Phagalysosome:

• Nitric Oxide Synthase 2 (NOS)
  
  • Oxidizes arginine to citrulline and NO
  • NO combines with superoxide anion to produce NO free radicals

Question 9

Microbial Killing Mechanisms of M₁ Macrophages:

Oxygen Independent

Answer 9

Natural Resistance-associated macrophage protein (NRAMP)

• Transport divalent metals out of phagosomes

Lysozomes:

• Proteolytic enxyme degrades cell wall

Defensins:

• Make holes in pathogen cell walls

Acidic Pump:

• Add H+ ions and reduce the pH

Question 10

Role of M₂ Macrophages

Answer 10

Clean up dying/dead neutrophils

Produce Protease inhibitors neutralize neutrophil enzymes

Produce Growth Factors:

• Transforming growth Factor (TGF-b)
• Fibroblast growth Factor (FGF)

Question 11

Macrophage Major Surface Receptors

Answer 11

Question 12

Cytokine Productn by Macrophages

Answer 12

Question 13

Local Inflammation

Answer 13

IL-8: Chemotaxis of neutrophils

IL-1, TNF-a: Increase expression of selectins adn integrins

TNF-a: Enhance Killing of Virus/Bacterial infected cells and tumor cells by assembling NADPH oxidase

Question 14

Positive Acute Phase Proteins

Answer 14

Concentration in blood Increases

• Complement proteins
• Fibrinogen
• Serum Protease Inhibitors
• Iron Binding Proteins

Question 15

Negative Acute Phase Proteins

Answer 15

Concentration in the Blood Decrease

• Albumin
  
  • stabilizes osmotic pressure of the blood
• Transferrin
  
  • transport iron to tissue

Question 16

Chronic Local Inflammation

Answer 16

Persistent inflammatory responses:

• Recruit more monocytes
• Becom activated macrophages
  
  • form a call around stubborn organisms - Granuloma
• Neutrophils usually present
• May recruit T lymphocytes