Blood Cells: Identifying Neutrophils

Neutrophils

• Identified in blood smears by their multilobulated nuclei
• Nuclei consist of lobules connected by very thin strands
• Also known as polymorphonuclear leukocytes (PMNs) or polymorphs due to their multilobulated nuclei
• Cells are dynamic, with nuclear shape changing frequently

Eosinophils

• Characterized by bilobed nuclei and abundant coarse cytoplasmic granules
• Cytoplasm contains brightly eosinophilic specific granules and some azurophilic granules

Basophils

• Distinguished by large, strongly basophilic specific granules
• Nucleus is often obscured by granules and has 2-3 irregular lobes

Lymphocytes

• Have a single nucleus that occupies most of the cell
• Thin rim of basophilic cytoplasm surrounds the nucleus
• Contain azurophilic granules

Monocytes

• Large agranulocytes that mature into macrophages and other cells of the mononuclear phagocyte system
• Nuclei are eccentric, indented, kidney-shaped, or U-shaped

Platelets

• Often found in aggregates
• Consist of a lightly stained hyalomere region surrounding a darker central granulomere containing membrane-enclosed granules

Lymphoid Organs

• Lymphoid organs are classified into two categories: primary and secondary lymphoid organs.

Primary Lymphoid Organs

• Thymus is a primary lymphoid organ.
• Bone marrow is a primary lymphoid organ.

Secondary Lymphoid Organs/Tissue

• Spleen is a secondary lymphoid organ.
• Lymph nodes are secondary lymphoid organs.
• Lymphoid tissue is also classified as a secondary lymphoid organ.

Components of Lymphoid Organs

• Lymphoid organs include lymphocytes.
• Thymus is a component of lymphoid organs.
• Mucosa associated lymphoid tissue (MALT) is a component of lymphoid organs.
• Lymph nodes are components of lymphoid organs.
• Spleen is a component of lymphoid organs.

Bone Marrow Structure

• Red bone marrow consists of trabeculae of cancellous bone, adipocytes, and blood-filled sinusoids.
• Sinusoids are located between hemopoietic cords or islands of developing blood cells.

Component Cells

• Sinusoidal endothelial cells have flattened nuclei.
• Hemopoietic cells are densely packed in the cords between sinusoids and adipocytes.
• Stromal cells and specific cells of the hemopoietic lineages are difficult to identify with certainty in routinely stained sections of marrow.

Thymus Structure

• The thymus is composed of vascularized connective tissue with a capsule that extends septa into the parenchyma, dividing the organ into many incompletely separated lobules.
• The thymus consists of two main parts: the cortex and the medulla.

Cortex of Thymus

• The cortex is composed of newly arrived lymphoblasts, macrophages, and thymic epithelial cells (TECs).
• TECs have characteristics of both epithelial and reticular cells and are morphologically and functionally diverse.
• The cortex is divided into three layers.

Medulla of Thymus

• The medulla contains fewer and larger, mature lymphocytes.
• The medulla has three related types of medullary TECs that form:
  • A second layer of the boundary between the cortex and medulla.
  • A cytoreticulum that supports less densely packed T lymphocytes, dendritic cells, and macrophages, and expresses many specialized proteins specific to cells of other organs.
  • Large aggregates of TECs, called Hassall corpuscles, sometimes arranged concentrically.

Characteristics of Young Thymus

• The young thymus is surrounded by a connective tissue (CT) capsule.
• The cortex has a large number of lymphocytes, while the medulla has fewer.
• The thymus does not have germinal centers.

Blood-Thymus Barrier

• The education of T-cells requires a highly controlled environment where antigens are presented exclusively by epithelial reticular cells.
• The Blood-Thymus Barrier is crucial to ensure the absence of other cells and free antigens in this environment.

Components of the Blood-Thymus Barrier

• The blood capillary wall consists of: • Endothelial cells • Endothelial cell basal laminae • Pericytes

Perivascular Connective Tissue

• Composed of: • Type III collagen • Macrophages

Epithelioreticular Cell Layer

• Consists of: • Basal lamina of the epithelial reticular cells (type I ERCs) • Epithelial reticular cells

Lymph Nodes

• Bean-shaped and encapsulated structures
• Human body has approximately 400-450 lymph nodes
• Each lymph node has three major regions:
  • Outer cortex containing nodules
  • Deeper paracortex region lacking nodules
  • Medulla with prominent draining sinusoids adjacent to the hilum

Lymphatic Circulation through a Lymph Node

• Lymph nodes filter lymph
• Lymph flow:
  • Afferent lymphatic vessels → Subcapsular Sinus
  • Subcapsular Sinus → Trabecular sinuses
  • Trabecular sinuses → Medullary sinuses
• Lymphocytes and macrophages can easily pass between sinuses and lymph node tissue
• Macrophages in sinuses monitor fluids, phagocytose antigenic material, and present it to T- and B-cells

Blood Circulation Through a Lymph Node

• Blood circulation into a lymph node begins with the entry of blood through an artery at the hilus.
• The hilar artery branches into arterioles, which then feed into capillary beds.
• The capillary beds are drained by high endothelial venules (HEVs), which are specialized sites where lymphocytes can leave the bloodstream and enter the lymph node tissue.

Functions of the Spleen

• The spleen filters the blood.
• It destroys old red blood cells.
• It serves as an immune organ.
• The spleen is divided into two main parts: the Red Pulp and the White Pulp.

Red Pulp

• Responsible for RBC/hemoglobin recycling.

White Pulp

• Responsible for immune functions.

Splenic Circulation

• Blood enters the spleen via the splenic artery at the hilus
• The splenic artery branches into trabecular arteries, which are surrounded by connective tissue trabeculae
• Trabecular arteries give off central arteries, which leave the trabeculae and enter the spleen's substance, covered by a peri-arterial lymphatic sheath
• Central arteries branch into penicillar arterioles, which pierce the lymphatic sheath and spill into splenic cords
• Blood percolates through splenic cords and across the walls of splenic sinuses
• Splenic sinuses drain into pulp veins
• Pulp veins drain into trabecular veins, which then drain into the splenic vein at the hilus

Blood and Lymphoid Tissue

• Neutrophils: • Identified by their multilobulated nuclei, with lobules held together by very thin strands • Also called polymorphonuclear leukocytes, PMNs, or polymorphs • Dynamic cells with frequently changing nuclear shape
• Eosinophils: • Bilobed nuclei • Abundant coarse cytoplasmic granules • Cytoplasm filled with brightly eosinophilic specific granules and azurophilic granules
• Basophils: • Large, strongly basophilic specific granules • Granules usually obstruct the appearance of the nucleus, which has two or three irregular lobes
• Lymphocytes: • Single nucleus occupying most of the cell • Thin rim of cytoplasm with fine azurophilic granules
• Monocytes: • Large agranulocytes • Precursors to macrophages and other cells of the mononuclear phagocyte system • Eccentric nuclei, indented, kidney-shaped, or U-shaped
• Platelets: • Often found in aggregates • Individual platelets have a lightly stained hyalomere region surrounding a more darkly stained central granulomere containing membrane-enclosed granules

The Immune System and Lymphoid Organs

• Lymphoid organs: • Classified as primary and secondary (effector) lymphoid organs/tissues • Include thymus, bone marrow, spleen, lymph nodes, mucosa-associated lymphoid tissue (MALT)
• Primary lymphoid organs: • Thymus • Bone marrow
• Secondary (effector) lymphoid organs/tissues: • Spleen • Lymph nodes • Mucosa-associated lymphoid tissue (MALT)

Bone Marrow

• Sections of red bone marrow: • Trabeculae of cancellous bone • Adipocytes (A) • Blood-filled sinusoids between hemopoietic cords or islands of developing blood cells
• At higher magnification: • Flattened nuclei of sinusoidal endothelial cells can be distinguished • Variety of densely packed hemopoietic cells in the cords between the sinusoids and adipocytes

Thymus

• Vascularized connective tissue capsule • Extends septa into paranchyme, dividing the organ into many incompletely lobules
• Cortex: • Composed of newly arrived lymphoblasts, macrophages, and thymic epithelial cells (TECs) • TECs have both epithelial and reticular cell characteristics • Divided into three groups (layers)
• Medulla: • Contains fewer and larger, mature lymphocytes • Three related types of medullary TECs form a boundary layer, cytoreticulum, and Hassall corpuscles

Blood-Thymus Barrier

• Education of T-cells must occur in a controlled environment where antigens are only presented by epithelial reticular cells
• The blood-thymus barrier ensures that no other cells or free antigens are present
• Consists of: • Blood capillary wall (endothelial cells, endothelial cell basal laminae, pericytes) • Perivascular connective tissue (type III collagen, macrophages) • Epithelioreticular cell layer (basal lamina of the epithelial reticular cells, epithelial reticular cells)

Lymph Nodes

• Bean-shaped, encapsulated structures • Approximately 400-450 lymph nodes • Three major regions within each lymph node:
  • Outer cortex containing nodules
  • Deeper extension of cortex called the paracortex, which lacks nodules
  • Medulla with prominent draining sinusoids adjacent to the hilum

Lymphatic Circulation through a Lymph Node

• Lymph nodes filter lymph • Afferent lymphatic vessels drain lymph into the Subcapsular Sinus • Lymph then passes to the Trabecular sinuses • From there, the lymph goes to the Medullary sinuses • Lymphocytes and macrophages pass easily between these sinuses and the tissue of the lymph node

Blood Circulation through a Lymph Node

• Blood enters through an artery at the hilus • Arterioles branch from hilar artery to feed into capillary beds • Capillary beds are drained by high endothelial venules (HEVs) • HEVs drain into hilar vein • HEVs are sites where lymphocytes can leave the bloodstream to enter the lymph node tissue bed

Spleen

• Functions: • Filters the blood • Destroys old red blood cells • Serves as an immune organ • Divided into Red Pulp (RBC/hemoglobin recycling) and White Pulp (responsible for immune functions)

Splenic Circulation

• Blood enters via splenic artery at hilus • Splenic artery branches into trabecular arteries (which travel within connective tissue trabeculae) • Trabecular arteries give off branches known as central arteries which leave the trabecula and enter the substance of the spleen (covered by a peri-arterial lymphatic sheath) • Central arteries branch into penicillar arterioles that piece through the lymphatic sheath and spill into splenic cords • Blood percolates through splenic cords and across walls of splenic sinuses • Splenic sinuses drain into pulp veins • Pulp veins drain into trabecular veins • Trabecular veins drain into splenic vein at the hilus

Blood and Lymphoid Tissue

• Neutrophils: • Identified by their multilobulated nuclei, with lobules held together by very thin strands • Also called polymorphonuclear leukocytes, PMNs, or polymorphs • Dynamic cells with frequently changing nuclear shape
• Eosinophils: • Bilobed nuclei • Abundant coarse cytoplasmic granules • Cytoplasm filled with brightly eosinophilic specific granules and azurophilic granules
• Basophils: • Large, strongly basophilic specific granules • Granules usually obstruct the appearance of the nucleus, which has two or three irregular lobes
• Lymphocytes: • Single nucleus occupying most of the cell • Thin rim of cytoplasm with fine azurophilic granules
• Monocytes: • Large agranulocytes • Precursors to macrophages and other cells of the mononuclear phagocyte system • Eccentric nuclei, indented, kidney-shaped, or U-shaped
• Platelets: • Often found in aggregates • Individual platelets have a lightly stained hyalomere region surrounding a more darkly stained central granulomere containing membrane-enclosed granules

The Immune System and Lymphoid Organs

• Lymphoid organs: • Classified as primary and secondary (effector) lymphoid organs/tissues • Include thymus, bone marrow, spleen, lymph nodes, mucosa-associated lymphoid tissue (MALT)
• Primary lymphoid organs: • Thymus • Bone marrow
• Secondary (effector) lymphoid organs/tissues: • Spleen • Lymph nodes • Mucosa-associated lymphoid tissue (MALT)

Bone Marrow

• Sections of red bone marrow: • Trabeculae of cancellous bone • Adipocytes (A) • Blood-filled sinusoids between hemopoietic cords or islands of developing blood cells
• At higher magnification: • Flattened nuclei of sinusoidal endothelial cells can be distinguished • Variety of densely packed hemopoietic cells in the cords between the sinusoids and adipocytes

Thymus

• Vascularized connective tissue capsule • Extends septa into paranchyme, dividing the organ into many incompletely lobules
• Cortex: • Composed of newly arrived lymphoblasts, macrophages, and thymic epithelial cells (TECs) • TECs have both epithelial and reticular cell characteristics • Divided into three groups (layers)
• Medulla: • Contains fewer and larger, mature lymphocytes • Three related types of medullary TECs form a boundary layer, cytoreticulum, and Hassall corpuscles

Blood-Thymus Barrier

• Education of T-cells must occur in a controlled environment where antigens are only presented by epithelial reticular cells
• The blood-thymus barrier ensures that no other cells or free antigens are present
• Consists of: • Blood capillary wall (endothelial cells, endothelial cell basal laminae, pericytes) • Perivascular connective tissue (type III collagen, macrophages) • Epithelioreticular cell layer (basal lamina of the epithelial reticular cells, epithelial reticular cells)

Lymph Nodes

• Bean-shaped, encapsulated structures • Approximately 400-450 lymph nodes • Three major regions within each lymph node:
  • Outer cortex containing nodules
  • Deeper extension of cortex called the paracortex, which lacks nodules
  • Medulla with prominent draining sinusoids adjacent to the hilum

Lymphatic Circulation through a Lymph Node

• Lymph nodes filter lymph • Afferent lymphatic vessels drain lymph into the Subcapsular Sinus • Lymph then passes to the Trabecular sinuses • From there, the lymph goes to the Medullary sinuses • Lymphocytes and macrophages pass easily between these sinuses and the tissue of the lymph node

Blood Circulation through a Lymph Node

• Blood enters through an artery at the hilus • Arterioles branch from hilar artery to feed into capillary beds • Capillary beds are drained by high endothelial venules (HEVs) • HEVs drain into hilar vein • HEVs are sites where lymphocytes can leave the bloodstream to enter the lymph node tissue bed

Spleen

• Functions: • Filters the blood • Destroys old red blood cells • Serves as an immune organ • Divided into Red Pulp (RBC/hemoglobin recycling) and White Pulp (responsible for immune functions)

Splenic Circulation

• Blood enters via splenic artery at hilus • Splenic artery branches into trabecular arteries (which travel within connective tissue trabeculae) • Trabecular arteries give off branches known as central arteries which leave the trabecula and enter the substance of the spleen (covered by a peri-arterial lymphatic sheath) • Central arteries branch into penicillar arterioles that piece through the lymphatic sheath and spill into splenic cords • Blood percolates through splenic cords and across walls of splenic sinuses • Splenic sinuses drain into pulp veins • Pulp veins drain into trabecular veins • Trabecular veins drain into splenic vein at the hilus