Cells of the Immune System — Veterinary Immunology Study Notes
Cells of the Immune System — Veterinary Immunology Study Notes
Hematopoiesis and Growth Factors
Hematopoiesis: Production of immune cells, red blood cells, and platelets. In healthy animals, the bone marrow generates from its hematopoietic stem cells (HSCs) the cells that enter circulation daily.
The key bone marrow cell: hematopoietic stem cell (HSC). From HSCs, multipotent and committed hematopoietic progenitors arise, which then differentiate into the blood cells that enter the circulation.
Daily production rate: 10^{11} to 10^{12} cells per day.
Three major lineages of hematopoiesis:
Erythroid (erythrocytes and platelets)
Myeloid
Granulocytes (neutrophils, eosinophils, basophils)
Mast cells
Monocytes
Macrophages
Myeloid dendritic cells
Lymphoid
Lymphocytes (T and B cells)
Hematopoietic Growth Factors (CSFs and interleukins):
Colony-stimulating factors (CSFs):
GM-CSF (granulocyte–monocyte CSF) ext{GM-CSF}
G-CSF (granulocyte CSF) ext{G-CSF}
Interleukins: ext{IL-}1, ext{ IL-}3, ext{IL-}4, ext{IL-}5, ext{IL-}6, ext{IL-}7
Key concepts in hematopoiesis:
Expression of specific cell receptors
Production of effector molecules
Changes in cell morphology
Maturation into fully functional cells
Major anatomical locations involved in hematopoiesis:
Bone marrow → Blood → Tissues (in steady state)
Differentiation and lineage commitment occur in bone marrow with progenitors giving rise to mature blood cells that circulate or populate tissues.
Overview of Hematopoiesis: Major Points and Locations
Diagrammatic flow of differentiation and anatomical sites (in healthy animals):
Bone Marrow → Blood → Tissues
From HSCs, differentiation yields:
NK Cells (from common lymphoid progenitor)
Common Lymphoid Progenitor → Lymphocytes (B and T cells) → Peripheral lymphoid organs
Common Myeloid Progenitor →
Common Erythroid/Megakaryocyte Progenitor → Erythrocytes, Platelets
Common Granulocyte Progenitor → Neutrophils, Eosinophils, Basophils; Mast cells (in tissues)
Monocytes → Macrophages and Dendritic Cells (myeloid lineage)
Dendritic Cells (Myeloid DCs)
Mature cell destinations include Blood, Tissues, and peripheral organs.
Cells of the Innate Immune System (Context)
Innate immune cells overviewed as background for the complementary adaptive system:
Early responders (non-specific) versus adaptive cells (specificity and memory).
Innate cells include neutrophils, eosinophils, basophils, monocytes/macrophages, dendritic cells, mast cells, natural killer (NK) cells, etc.
Cells of the Immune System: Morphology and Lineage Details
Neutrophils
Name: Neutrophils; Other names: polymorphonucleocytes; heterophils (in birds/reptiles)
Classifications: Granulocyte, phagocyte
Lineage: Myeloid
Appearance: Segmented nucleus, granular cytoplasm; diameter ≈ 10\,\mu m
Location in health: Blood
Lifespan in health: 48-72\,\text{hours}
Primary function: Antimicrobial effectors, especially in acute bacterial infection
Mechanism of action: Phagocytosis; degranulation; neutrophil extracellular trap formation (NETs)
Note: In many carnivores neutrophils constitute 60\%-75\% of blood leukocytes; in horses ~50\%; in cattle/sheep/rodents ~20\%!-!30\%.
Eosinophils
Name: Eosinophils; Other names: eosinophil granulocytes
Classifications: Granulocyte; Myeloid
Appearance: Characteristic eosinophilic granules (stain pink/red with eosin)
Location in health: Blood and tissues lining GI tract and airways
Lifespan in health: Days to weeks
Primary function: Antiparasitic effectors (especially helminth infection); some antiviral actions; roles in allergy
Mechanism: Degranulation; limited phagocytosis
Basophils
Name: Basophils; Other names: basophil granulocytes
Classifications: Granulocyte; Myeloid
Appearance: Characteristic blue-purple basophilic granules with basic dyes
Location in health: Blood
Lifespan: Days
Primary function: Mediator of inflammation
Mechanism: Degranulation
Monocytes
Name: Monocytes; Other names: mononuclear phagocytes
Classifications: Mononuclear phagocyte; Sentinel cell; Antigen-presenting cell
Lineage: Myeloid
Appearance: Large round to kidney-shaped nucleus; pale blue-gray cytoplasm; vacuoles common
Location in health: Blood
Lifespan: Days (in circulation)
Primary function: Precursors to macrophages and dendritic cells; limited antimicrobial function in blood
Macrophages
Location: Tissue macrophages; examples include Kupffer cells (liver), splenic macrophages, microglia (CNS), alveolar macrophages (airways), peritoneal macrophages
Name: Macrophages; Other names: —
Classifications: Mononuclear phagocyte; Sentinel cell; Antigen-presenting cell
Lineage: Myeloid
Appearance: Round nucleus, clear-vacuolated cytoplasm, irregular cell shape
Location in health: Peripheral tissue
Lifespan: Months
Primary function: Immune surveillance; moderate antimicrobial capacity; antigen presentation (limited)
Mechanism: Phagocytosis; detection of threats; release of inflammatory mediators
Dendritic Cells
Name: Dendritic Cells; Other names: Inflammatory DCs; Conventional DCs; Langerhans cells (DCs in skin)
Classifications: Mononuclear phagocyte; Sentinel cell; Antigen-presenting cell
Lineage: Myeloid
Appearance: Round nucleus, clear cytoplasm; irregular shape with long branched projections (dendrites)
Location in health: Tissue
Lifespan: Months
Primary function: Immune surveillance; antigen processing and presentation
Mechanism: Endocytosis and phagocytosis; antigen processing
Mast Cells
Name: Mast cells; Other names: —
Classifications: Sentinel cells
Lineage: Myeloid
Appearance: Round nucleus; cytoplasm densely packed with granules (purple)
Location in health: Tissue (connective tissue around vasculature and nerves; lamina propria of mucosa)
Lifespan: Weeks to months
Primary function: Immune surveillance; mediator and amplifier of inflammation and allergy
Mechanism: Degranulation with vasoactive amines; synthesis of lipid mediators and cytokines
Natural Killer (NK) Cells
Name: Natural Killer Cells; Other names: Null lymphocytes
Classifications: Lymphocyte
Lineage: Lymphoid
Appearance: Large lymphoid cell; round nucleus; azurophilic cytoplasmic granules
Location in health: Blood, spleen
Lifespan: Weeks to months
Primary function: Destruction of virally infected or abnormal host cells (including tumor cells)
Mechanism: Recognition of virally infected or abnormal cells; targeted release of cytotoxic granules
Lymphocytes: The Adaptive Arm
Lymphocytes are the only cells in the body that can specifically recognize and distinguish different antigens; responsible for the adaptive immune response, specificity, and memory. They include different subsets with distinct functions and protein products but are morphologically indistinguishable.
B Lymphocytes
Recognize extracellular antigens; produce antibodies; differentiate into plasma cells; main role in Humoral Immune Response
Maturation sites:
Birds: Bursa of Fabricius
Mammals: Bone marrow
Function: Antibody-mediated (humoral) responses
T Lymphocytes
Recognize intracellular antigens; do not produce antibodies; produce cytokines; differentiate into several types
Maturation sites:
Precursors arise from bone marrow; mature in the Thymus
Subsets: Helper T cells (Th); Cytotoxic T cells (Tc)
Function: Cellular immune responses
Lymphocytes (general) — Visual references:
A: Light micrograph of a lymphocyte in a peripheral blood smear
B: Electron micrograph of a small lymphocyte
C: Electron micrograph of a large lymphocyte
Lymphocytes in development and function:
Mature lymphocytes develop from bone marrow stem cells in the generative (primary) lymphoid organs; immune responses to foreign antigens occur in the peripheral (secondary) lymphoid tissues
Birds vs Mammals: Lymphoid Maturation and Avian Leukocytes
Birds:
B lymphocytes mature in the Bursa of Fabricius
Heterophils are the avian counterpart to mammalian neutrophils
Thrombocytes are nucleated platelet-like cells commonly found in birds
Mammals:
B lymphocytes mature in bone marrow; T lymphocytes mature in the thymus
Birds: Heterophils, Lymphocytes, Eosinophils, Monocytes, Basophils, Thrombocytes (Avian Leukocytes)
Heterophil; Lymphocyte; Eosinophil; Monocyte; Basophil; Thrombocyte (avian equivalents to several mammalian leukocytes)
Clinical Case: Canine Trapped Neutrophil Syndrome (Canine TNS)
Case: Eight-month-old female Border Collie; farm/working dog; history of vaccination-associated episodes; presents with inappetence, vomiting, diarrhea, lethargy, pain on walking; repeated episodes; pyrexia, conjunctivitis, joint pain; infections of eye, skin, respiratory tract; puppies die before 6 months of age; neutropenia episodes every 12–15 days with rebound neutrophilia between episodes.
Supporting laboratory findings (example report):
PCV: 32.2\% (reference 35-55\%)
Hemoglobin (Hb): 10.9\text{ g/dL} (ref 12-18\text{ g/dL})
Red blood cells (RBC): 4.64\times 10^{12}/L (ref 5.4-8.0\times 10^{12}/L)
MCV: 69.4\fL (ref 65-75\fL)
MCHC: 33.7\text{ g/dL} (ref 34-37\text{ g/dL})
MCH: 23.4\text{ pg} (ref 22-25\text{ pg})
Platelets: 295\times 10^{9}/L (ref 170-500\times 10^{9}/L)
WBC: 2.57\times 10^{9}/L (ref 5.5-17\times 10^{9}/L)
Neutrophils: 0.05\times 10^{9}/L (ref 3-11.5\times 10^{9}/L)
Lymphocytes: 0.77\times 10^{9}/L (ref 0.7-3.6\times 10^{9}/L)
Monocytes: 0.72\times 10^{9}/L (ref 0.1-1.5\times 10^{9}/L)
Eosinophils: 0.0\times 10^{9}/L (ref 0.2-1.4\times 10^{9}/L)
Basophils: 0.0\times 10^{9}/L (ref 0-0.1\times 10^{9}/L)
Interpretation: Marked neutropenia with reduced overall WBC count; consistent with Canine Trapped Neutrophil Syndrome (a disorder of neutrophil storage and release from bone marrow) and predisposition to recurrent infections.
Note: The disorder often presents as recurrent infections and periods of neutropenia with subsequent rebound neutrophilia.
Summary: Bone Marrow Organization and Diagnostic Context
Bone marrow aspirate and blood smear reflect zonation and cell development:
Erythroid Zone: erythroid precursors and megakaryocytes
Myeloid Zone: neutrophil precursors, monocytes, macrophages, mast cells, etc.
Lymphoid Zone: lymphoid precursors and associated stromal cells
Structural elements noted in diagrams: venous sinusoid networks within bone marrow; stromal or reticular cells; megakaryocytes; erythrocyte precursors; neutrophils; platelets; lymphocytes
Clinical relevance: bone marrow status (production, maturation, and release of cells) underpins immune competence; disorders can present as cytopenias or cytoses with infectious susceptibility or inflammatory abnormalities.
Key Concepts and Recurrent Themes
Hematopoietic hierarchy: HSCs → multipotent progenitors → lineage-committed progenitors → mature blood cells.
Distinct lineages produce specific cell types with specialized functions (erythroid, myeloid, lymphoid).
Growth factors steer lineage commitment and maturation (GM-CSF, G-CSF, IL-1, IL-3, IL-4, IL-5, IL-6, IL-7).
Innate vs. adaptive immunity: innate cells provide immediate but non-specific defense; lymphocytes (B and T) provide antigen-specific, memory-based responses.
Lymphocyte maturation and trafficking: B cells mature in primary lymphoid organs (bone marrow or Bursa of Fabricius in birds); T cells mature in thymus; both migrate to peripheral secondary lymphoid tissues to mount responses.
Avian leukocyte differences: heterophils as neutrophil analogs; Bursa of Fabricius as B cell maturation site; thrombocytes as nucleated platelets in birds.
Clinical correlations: neutropenia or abnormal neutrophil dynamics can indicate primary immunodeficiency (e.g., Canine Trapped Neutrophil Syndrome) or other marrow disorders; interpretation requires complete blood counts and marrow evaluation.
References in the lecture slides include: overview of the innate immune system, differentiation diagrams for hematopoiesis, and the organization of bone marrow with respect to erythroid, myeloid, and lymphoid zones.