Module 2 - Topic 4 - Monophages and Macrophages

What are monocytes?

Circulating leukocytes that differentiate into macrophages in tissues.

What is monocytopoiesis?

The process by which monocytes are produced in the bone marrow from granulocyte-monocyte progenitors.

What stimulates monocytopoiesis?

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) and Macrophage Colony-Stimulating Factor (M-CSF).

What percentage of total leukocytes do monocytes comprise?

2-10% of total leukocytes in peripheral blood.

What are the primary roles of macrophages?

Phagocytosis, antigen presentation, and cytokine secretion.

How do monocytes differ from macrophages?

Monocytes are circulating precursor cells, while macrophages are tissue-resident, differentiated effector cells.

What triggers the activation of monocytes?

T lymphocyte-derived cytokines (e.g., IFN-g) and endotoxins (e.g., lipopolysaccharide from Gram-negative bacteria).

What is the lifespan of monocytes in circulation?

Short-lived, typically hours to days.

What are the major types of leukocytes?

Granulocytes (e.g., neutrophils, eosinophils, basophils) and agranulocytes (e.g., monocytes, lymphocytes).

What is the role of macrophages in iron recycling?

Macrophages help recycle iron from dead cells and pathogens.

What is the function of pattern recognition receptors (PRRs)?

They recognize pathogen-associated molecular patterns (PAMPs) to initiate immune responses.

What is the lifespan of lymphocytes?

Weeks to years, contributing to long-lasting immunity.

What is leukocytosis?

An increase in leukocytes or total WBC count greater than 11.0 x10^3/uL.

What is leukopenia?

A decrease in leukocytes or total WBC count less than 4.0 x10^3/uL.

What is the primary role of innate immunity?

The first response to invading pathogens, providing immediate defense.

What is the primary role of adaptive immunity?

A slower, highly specific response that provides long-lasting immunity.

What percentage of total leukocytes do neutrophils comprise?

55-70% of total leukocytes in peripheral blood.

What are the key cells involved in innate immunity?

Granulocytes, monocytes, and natural killer (NK) cells.

What are the key cells involved in adaptive immunity?

B cells and T cells.

What is the significance of MHC in immunity?

Major Histocompatibility Complex (MHC) is crucial for antigen presentation to T cells.

What is the role of eosinophils?

Typically elevated in allergic reactions and parasitic infections, comprising 0-5% of total leukocytes.

What are the main functions of macrophages?

Perform phagocytosis, antigen presentation (increased MHC class II), and cytokine secretion.

What is hematopoiesis?

The production of all blood cells from hematopoietic stem cells (HSCs).

Where do all leukocytes originate?

From hematopoietic stem cells (HSCs) in the bone marrow.

What are the two major progenitors derived from HSCs?

Common Myeloid Progenitor (CMP) and Common Lymphoid Progenitor (CLP).

What does the Common Myeloid Progenitor (CMP) give rise to?

Granulocyte-Macrophage Progenitor (GMP), granulocytes, and monocytes.

What does the Common Lymphoid Progenitor (CLP) give rise to?

Lymphocytes, including B cells and T cells.

What is myelopoiesis?

The process of producing myeloid lineage blood cells.

What is lymphopoiesis?

The process of producing lymphoid lineage blood cells.

What are the stages of monocyte maturation?

Monoblast, Promonocyte, Monocyte (circulation), Macrophage (tissue).

How can monoblasts and myeloblasts be distinguished?

Monoblasts cannot be differentiated from myeloblasts in normal bone marrow.

What are the microscopic features of a monoblast?

Size: 12-20 μm, pale blue to purple nucleus, abundant blue-gray cytoplasm.

What is a promonocyte?

The first morphologically recognizable precursor in the monocytic lineage.

What are the characteristics of a mature monocyte?

12-20 μm diameter, kidney-shaped nucleus, blue-gray cytoplasm, vacuoles frequently seen.

What happens to monocytes when they enter tissues?

They mature into macrophages.

What are the key characteristics of macrophages?

Long-lived, derived from monocytes, do not typically reenter circulation.

What specialized names do macrophages adopt based on location?

Osteoclasts (bone), Kupffer cells (liver), Microglia (CNS), Alveolar macrophages (lung), Langerhans cells (skin).

What are the core functional identities of macrophages?

Maintain tissue homeostasis, provide innate immune defense, link innate and adaptive immunity.

What are the innate effector functions of macrophages?

Phagocytosis, microbicidal killing, clearance of debris.

What is the role of macrophages in adaptive immunity?

Antigen presentation and cytokine regulation.

What is the significance of lineage commitment in hematopoiesis?

It leads to the morphological identity and functional specialization of blood cells.

What is the hallmark of mature erythroid cells?

Anucleate biconcave red blood cells.

What is the hallmark of mature granulocytic cells?

Segmented nucleus.

What is the hallmark of mature monocytic cells?

Kidney/horseshoe-shaped nucleus with loose linear chromatin.

What is the hallmark of mature megakaryocytic cells?

Large cells that produce platelets.

What is the role of macrophages in tissue maintenance?

Remove aged RBCs, clear antibody-coated cells, eliminate damaged tissue.

What are the activation signals for macrophages?

IFN-g (from Th1 cells) and direct activation via LPS (TLR4).

PMNs =

multilobed nucleus

- aka granulocytes

Neutrophils

1. most abundant

2. bacterial defense

eosinophils

allergy, parasitic infections

basophils

1. histamine release

2. inflammation

agranulocytes

1. monocytes

2. lymphocytes

monocytes

differentiate into macrophages

- in circulation

lymphocytes

1. NK cells

2. B and T cells

NK cells

inname immunity

B and T cells

1. adaptive immunity

2. immune memory

% of neutrophils

55-70%

% eosinophils

0-5%

% Basophils

0-1%

% monocytes

2-10%

% lymphocytes

20-40%

% bands

0-5%

we need a total ____ and ___ for a clinical diagnosis

WBC, differential

innate immunity

1. first responder

2. uses PRRs

3. PAMPS (LPS, viral RNA)

Adaptive Immunity

1. slow

2. antigen-specific recognition

3. antigen presentation via MHC (T cells)

monocyte =

circulating precursor cells

- innate immunity

macrophages =

tissue-resident

- Antigen presentation (↑ MHC class II)

- innate immunity

monocytes are derived via

CMP

monocyte activation triggers

1. PRRs via PAMPs

2. T cell derived cytokines

monocytopoiesis

The process by which monocytes are produced in the bone marrow from the

granulocyte-monocyte progenitor (GMP), enter the circulation, and later migrate

into tissues where they differentiate into macrophages or dendritic cells

macrophages antigen present via

MHC class II.

monocytes primary role

1. host defense

2. circulate in the blood

3. Differentiate into macrophages in the tissue

What cytokine upregulates MHC class II expression on macrophages, and what is the effect?

IFN-γ upregulates MHC class II on macrophages, enhancing antigen presentation to CD4⁺ T cells and promoting classical (M1) macrophage activation for improved microbial killing.

Monocytes are derived from

myeloid progenitor cells in the bone marrow

Monocytes are stimulated by

1. GM-CSF

2. M-CSF

macrophages preform

1. phagocytosis

2. antigen presentation (MHC 2)

3. cytokine secretion

monocyte and macrophages activation triggers

PRRs that recognize PAMPs

CMP gives rise to

1. Neutrophils

2. Eosinophils

3. Basophils

4. Monocytes → macrophages / dendritic cells

CLP gives rise to

lymphocytes

primary granules are first found in

promyelocyte

MPO

Myeloperoxidase

what is the enzyme found in primary granules

MPO

morphology of primary granules

large and purple

what cells have primary granules

all granulocyte lineages

what is the function of primary granules

1. intracellular killing

2. phagolysosome

3. ROS

Secondary granules are first found in

myelocyte

what key contents are found in secondary granules

1. EOS = MBP

2. BAS = 1. Histadine 2. Heparin

Major Basic Protein (MBP)

Eosinophils release this, which puts holes in a helminth body, allowing it to then be phagocytosed

morphology of secondary granules

1. neurophils = pale

2. eosinophils = pink/red

3. basophil = purple/blue

What cells have secondary granules

neutrophils

what is the function of secondary granules

inflammation

Tertiary granules are first found in

metamyelocyte

Tertiary granules key components

1. Collagenase

2. MMPs

what is the morphology of tertiary granules

no stain

what cells have tertiary granules

neutrophils

what is the function of tertiary granules in neutrophils

migration

monoblasts cannot be differentiated from the

myeloblast in normal bone marrow

stages of monocyte maturation

1. monoblast

2. promonocyte

3. monocyte

4. macrophage

monoblast

1. immature monocyte

2. indistinguishable from myeloblast

3. lacy chromatin

4. nucleoli present

promonocyte

first morphologically recognizable precursor in the monocytic lineage

- lumpy