Cellular Innate Immunity: Granulocytes and macrophages

What are phagocytes? Which cells are professional phagocytes?

Cells that can phagocytize (uptake of large materials into pocket of the cell membrane)

Neutrophils and macrophages are professional phagocytes

Where do they originate and how do they function?

Pluripotent hematopoietic stem cells

Signals to migrate from blood into tissue, eat into cell from cell membrane

Why do neutrophilia and monocytosis often occur simultaneously?

Share common precursors and GF (G-CSF)

Are they part of innate or adaptive immune system? Why?

Innate

It’s an innate immune cell

Compare and contrast polymorphonuclear vs. mononuclear phagocytes. Where do they reside? How long do they survive?

Granulocytes (polymorphonuclear) and monocytes (mononuclear)

Reside in bone marrow until released in blood

Neutrophil (poly): BLOOD (5-10 hrs) TISSUE (24-48 hrs)

Macrophages (mono): BLOOD 2-4 days

What is opsonization and why is it important in phagocytosis? Name the opsonins you learned about.

Bacteria coat w/ complement proteins or antibodies to bind to WBC receptors and ingested

IgG, IgA, C3b

How do neutrophils recognize antigens for phagocytosis?

Surface receptors such as antibody receptors, pattern recognition receptors, CAM, complement receptors

How are neutrophils activated?

The binding to the receptors ON SURFACE OF BACTERIA

Describe two intracellular mechanism by which neutrophils ingested organisms?

Lyric enzymes/other antimicrobial compounds + respiratory burst - reactive oxygen species from NOX (bleach result)

NETs- enhances killing pathogens without host cell damage (TRAPS)

What are NETs and how do they work? What are the benefits of using NETs?

Neutrophils Extravascular Traps

Sticky DNA + antibacterial molecules extend arms from the neutrophil in high concentration and traps (fatal to neutrophil)

What are Chediak-Higashi syndrome? How would you diagnose this syndrome in a cat?

Rare autosomal recessive mutation in LYST: Lysosomal granules prevent phagolysosome/bacterial lysis

Diagnose: platelet increased clotting time, albinism, neurological abnormalities

What are some examples of specialized tissues macrophages?

SKIN: langerhans cells

LIVER: Kupffer cells

LUNG: ALveolar macrophages

Brain: microglial

How do M1 and M2 macrophages differs?

M1: aggressively kill (NOS, pro-inflammatory cytokines

M2: trigger wound repair and healing

Name the function that macrophages perform?

-tissue repair and wound healing

-antigen presentation

-phagocytosis/bacterial destruction

-cytokines, enzymes, CF (clot/complement) secretion

How do macrophages recognize antigens for phagocytosis?

Opsonization and FcR receptors

Also Ab receptors, transport receptors, cytokines receptors

How are macrophages activated in general? What is required for M1 and M2 activation?

Phagocytosis and chemotactic factors (DYING NEUTROPHILS, c5A ANAPHYLATOXINS

Products (TNF, IFN-gamma, LPS)

M1: *IFN-gamma*

M2: IL4,13,10*

What are the results of macrophage activation?

M1: increased size, movement, activity, lysosomal enzymes, bacterial abiding, phagocytosis, MHC Class 2 expression

M2:increased tissue repair, MHC class 2, reduce microbial killing

What is a granuloma and why do they form?

Macrophages gather in large numbers and fibroblasts surround if can’t be removed

Chronic infections, chemical insults

Lymphocytes and granulocytes join in