Transcript Present

Blood, Lymph and Immunity
Mosby items and derived items © 2008 by Mosby, Inc., an affiliate of Elsevier Inc.
Learning Objectives
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List and describe the functions of blood.
Describe the composition of blood plasma and the characteristics of mature
erythrocytes.
Describe the structure of the hemoglobin molecule. Explain the fate of
hemoglobin following intravascular and extravascular hemolysis.
Give the origin of thrombocytes. Describe their characteristics and
functions.
List the types of leukocytes and describe the functions of each.
Describe the formation of lymph fluid and its circulation through the
lymphatic system.
List the functions of the lymphatic system. Describe the structure and
function of the lymph nodes, spleen, thymus, tonsils, and GALT.
List the functions of the immune system. Differentiate between specific and
nonspecific immune reactions; cell-mediated and humoral immunity.
List the components of cell-mediated immunity. Explain the role of each.
List and describe the classes of immunoglobulins. Differentiate between
active and passive immunity.
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Functions of Blood
1.
Transportation
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2.
Regulation
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3.
Oxygen, nutrients ,waste products, hormones
Body temperature, tissue fluid content, blood pH
Defense System
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White blood cell phagocytosis, platelets, clotting
factors
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Composition of Blood
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Liquid portion:
Plasma
Cellular portion:
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Red blood cells
(erythrocytes)
White blood cells
(leukocytes)
Platelets
(thrombocytes)
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Plasma
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45% to 78% of a blood sample volume,
depending on the species of the animal
and the size of its red blood cells
93% water
Substances dissolved or suspended in
plasma
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Albumin, globulins, and fibrinogen
Oxygen, carbon dioxide, and nitrogen
Lipids, amino acids, metabolic wastes, and
electrolytes
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Cellular Components
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Erythrocytes - carry
oxygen
Thrombocytes - help
prevent leaks from
damaged blood
vessels
Leukocytes
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Granulocytic or
agranulocytic
Multiple functions
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Hematopoiesis
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Production of all blood cells
Occurs primarily in red bone marrow
Fetal hematopoiesis occurs in the liver and
spleen
Neonatal hematopoiesis occurs in red bone
marrow
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Hematopoiesis
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Older animals
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Some red bone marrow is converted to inactive,
yellow bone marrow
• Composed of fat cells that have replaced some
of the active red marrow
In a mature animal most red bone marrow is found
at the ends of long bones and in flat bones
Liver and spleen have a limited capacity to
participate in hematopoiesis
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Hematopoiesis
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Hematopoietic stem cell
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Pluripotent
 Can develop into any one of the blood cells
• Depends on chemical or physiological stimuli
• Involves numerous cell divisions
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Erythropoiesis
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Production of red blood cells
 Erythropoietin: hormone released from cells in
kidney in response to hypoxia
 Triggers stem cell to divide and differentiate
 Multiple maturation steps
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Red Blood Cells
Characteristics
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~65% water and 35% solids
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Primary solid - hemoglobin
Round, anuclear biconcave disks (most
mammals)
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Variable sizes
Uses plasma glucose for energy
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Hemoglobin
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Composed of heme and globin
Heme - pigment portion; produced in the
mitochondria; contains iron atoms (Fe++)
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Every heme group can carry one molecule of
oxygen.
Four heme groups attach to each globin
molecule.
Globin - protein portion; produced by
ribosomes
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Normal Hemoglobin Types
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Embryonic hemoglobin (HbE) - found in
developing fetuses.
Fetal hemoglobin (HbF) - found in fetal
blood during mid- to late gestation and up
to a couple months after birth
Adult hemoglobin - found in the red blood
cells of all animals beginning a couple of
weeks to a couple of months after birth
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Hemoglobin
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Oxyhemoglobin - hemoglobin that is
carrying oxygen.
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One oxygen molecule is associated with each
iron (Fe++) molecule
Deoxyhemoglobin - hemoglobin that has
released its oxygen
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Carbon Dioxide Transport
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CO2 diffuses into red blood cells and is
transformed into carbonic acid
Ionizes into hydrogen ions and
bicarbonate ions
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H2O + CO2 = H2CO3 = H+ + HCO3–
Deoxyhemoglobin accepts the hydrogen ion.
Bicarbonate diffuses back into the plasma.
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Red Blood Cell Life Span
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Varies with the species
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Dogs ~ 110 days
 Cats ~ 68 days
 Horse and sheep ~ 150 days
 Cow ~ 160 days
 Mice ~ 20-30 days
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Senescence - process of aging
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Red Blood Cell Senescence
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Enzyme activity decreases
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Cell loses its deformability
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Becomes rounder; volume decreases
Extravascular hemolysis
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Macrophages (especially in the spleen)
remove senescent RBCs from circulation
RBCs broken down into components that can
be recycled in the body or eliminated as waste
material
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Red Blood Cell Senescence
Extravascular hemolysis
 RBC membrane is destroyed
 Iron is transported to the red bone marrow
 Amino acids from globin molecules are
transported to the liver for re-use
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Red Blood Cell Senescence
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Heme is converted to bilirubin, bound to albumin,
and transported to liver (unconjugated bilirubin)
Bilirubin is conjugated to glucuronic acid.
Conjugated bilirubin excreted as a bile pigment
into intestines
Converted into urobilinogen by bacteria
 Some is reabsorbed and eliminated in urine as
urobilin; some is converted to stercobilinogen
and excreted in stool as stercobilin.
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Red Blood Cell Senescence
Intravascular hemolysis
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RBCs in circulation subjected to stresses
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Can result in RBC fragmentation and/or
destruction
Hemoglobin released directly into the blood
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Red Blood Cell Senescence
Intravascular hemolysis
 Unconjugated hemoglobin attached to
haptoglobin
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Transported to macrophages in the liver
Processed as with extravascular hemolysis
Excess unconjugated hemoglobin in the
plasma (hemoglobinemia) is eliminated in
urine (hemoglobinuria)
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Anemia
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Results in decreased O2 carrying capacity of
the blood
Caused by:
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Low number of circulating mature red blood cells
(blood loss, increased RBC destruction,
decreased RBC production)
 Insufficient hemoglobin production (e.g., iron
deficiency)
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Polycythemia
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Increase in number of RBCs
Three types:
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Relative polycythemia - hemoconcentration due to
fluid loss (e.g., vomiting, diarrhea)
 Compensatory polycythemia - result of hypoxia
(e.g., high altitudes, congestive heart failure)
 Polycythemia rubra vera - rare bone marrow
disorder; cause unknown
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Platelets (Thrombocytes)
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Cytoplasmic fragments of bone marrow
megakaryocytes
Thrombopoiesis - production of platelets
Megakaryocyte undergoes incomplete
mitosis during maturation
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Nuclei divide, cytoplasm doesn’t
Results in multinucleated cell with abundant
cytoplasm
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Platelet Characteristics
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Circulating platelets are round with
numerous small, purple granules
Granules contain some of the clotting
factors and calcium
Platelets remain in peripheral blood until
they are removed by tissue macrophages
because of old age or damage.
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Platelet Functions
1. Maintain vascular integrity
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Release endothelial growth factor into blood
vessel endothelial cells
2. Formation of platelet plug
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Attracted to exposed connective tissue of
damaged blood vessel
Adhere to exposed connective tissue and
each other
3. Stabilize the hemostatic plug
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Fibrin strands form a netlike mesh around
and through the platelets.
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White Blood Cells (Leukocytes)
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Classifications:
Functions
2. Presence or absence of granules
3. Nuclear shape
1.
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Table 9-2. White Blood Cells
NAME
CYTOPLASMIC
GRANULES
NUCLEAR
SHAPE
FUNCTION
SITE OF
ACTION
Neutrophil
Don’t stain (usually
invisible)
Polymorphonuclear
Phagocytosis
Body tissues
Eosinophil
Stain red
Polymorphonuclear
Body tissues
Allergic reactions,
anaphylaxis, phagocytosis
Basophil
Stain blue
Polymorphonuclear
Initiation of immune and
allergic reactions
Monocyte
(Macrophage)
None
Pleomorphic
Phagocytosis and process Body tissues or
antigens
blood
B cell
None
Mononuclear
Antibody production and
humoral immunity
Lymphoid tissue
T cell
None
Mononuclear
Cytokine production and
cell-mediated immunity
Lymphoid tissue
and other body
tissues
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Body tissues
Leukopoiesis
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Occurs in red bone marrow
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Some lymphocytes develop further outside
bone marrow
Same pluripotent stem cell that produces
red blood cells and megakaryocytes
Each type of WBC has its own stimulus for
production
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Granulopoiesis
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Production of the neutrophils, eosinophils, and
basophils
Initially there are no cytoplasmic granules, then
non-specific granules are formed
Specific granules produced during maturation
 Granules contain different substances
depending on the cell’s function
 Example: neutrophil granules contain
lysosomal enzymes used in phagocytosis
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Neutrophil Characteristics
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Polymorphonuclear cells; segs
Most numerous WBC in circulation in the
dog, horse, and cat
Granules don’t stain with either the blue
alkaline stain or the red acid stain (neutral
staining).
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Neutrophils
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Mature neutrophils in circulation have two
to five nuclear segments joined by a strand
of chromatin.
Immature neutrophils have a horseshoe
nucleus without any segmentation (band
neutrophil).
Neutrophil function: phagocytosis
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Granules contain lysosomes capable of
destroying bacteria and viruses that have been
engulfed
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Neutrophil Characteristics
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In peripheral circulation for about 10 hours
Diapedesis - process used by neutrophils to go
from circulation into tissue spaces
Chemotaxis - process that attracts neutrophils to
inflammatory chemicals at a site of infection
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Neutrophil Action
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Outer membrane flows
around the
microorganisms and
encases them within a
membrane-bound
phagocytic vacuole
Cytoplasmic granules
move to the edge of the
vacuole and fuse with
its membrane
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Secrete lysosomes into
the vacuole
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Neutrophils
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Hydrogen peroxide - produced by
neutrophils during oxygen metabolism
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Bactericidal
Myeloperoxidase - released from
neutrophil granules
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Enhances the bactericidal action of hydrogen
peroxide
Capable of destroying the cell walls of
microorganisms
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Neutrophil Count
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Relatively stable range in peripheral blood
Controlled by
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Release of mature neutrophils from the storage
pool in bone marrow into the peripheral blood
 Rate of escape from peripheral blood into
tissue
 Entrance of increased numbers of pluripotent
stem cells into the neutrophil production line
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Intravascular Pools of Neutrophils
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Circulating pool - within lumen of blood
vessels
Marginal pool - line the walls of small
blood vessels mainly in the spleen, lungs,
and abdominal organs
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Eosinophil Characteristics
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Red granules in the cytoplasm of mature
cells
0-5% of the total white blood cell count
Produced in bone marrow from the same
pluripotent stem cell that gives rise to all
other blood cells
Segmented nucleus - usually two lobes
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Eosinophil Characteristics
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Granule shape varies
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Dogs: round granules of varying sizes; pale
staining
Cats: numerous small, rod-shaped granules
Horses: very large, round or oval-shaped
granules; stain intensely
Cattle, sheep, and pigs: round, small granules;
stain pink to red
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Eosinophil Pools
Bone marrow reserve
2. Circulating pool
3. Marginal pool
1.
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Migrate into tissue within a few hours of release
from bone marrow
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Eosinophil Functions
Anti-inflammatory: granules contain antiinflammatory substances
2. Immunity: can ingest substances
associated with the humoral immune
response
3. Phagocytosis: minimal phagocytotic and
bactericidal functions; usually large
organisms such as protozoa and some
parasitic worms
1.
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Eosinophilia
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Causes:
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Increased release of mature eosinophils
 Migration of eosinophils from marginal pool to
circulating pool
 Increased production
 Longer time in peripheral blood before entering
tissue
Accompanying leukocytosis may not occur
Eosinopenia (decreased numbers) - difficult to
detect because numbers are normally low.
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Basophil Characteristics
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Blue granules in the cytoplasm of mature
cells
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Not always visible on stained smear
May completely fill the cytoplasm
Least often seen WBC in circulation
Dog has fewer granules than the other
common domestic species
Nucleus usually has 2 to 3 lobes
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Basophils and Tissue Mast Cells
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Theories regarding the relationship between
mast cells and basophils:
Two different cell types with similar characteristics;
produced in different areas and don’t give rise to
one another
2. Mast cells are tissue basophils
1.
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Basophil Functions
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Granules contain histamine and heparin
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Histamine helps initiate inflammation and acute
allergic reactions.
Heparin acts as a localized anticoagulant to
keep blood flowing to an injured or damaged
area.
Eosinophils are attracted to site of an
allergic reaction by chemotactic factor
released from basophil granules
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Basophilia and Basopenia
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Basophilia - can be associated with an
allergic or hypersensitivity reaction in
tissue
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May occur in conjunction with eosinophilia
Basopenia - difficult to evaluate because
numbers are normally low
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Monocyte Characteristics
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5-6% of all circulating WBCs in common
domestic species
Largest white blood cells in circulation
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Abundant cytoplasm stains gray-blue
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May contain vacuoles of varying sizes
Cytoplasm may take on a fine granular
appearance
Nucleus - pleomorphic, non-segmented
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Monocyte Functions
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Important phagocytic cells
Known as tissue macrophages when in
tissue spaces
Found in organs that remove or contain
foreign invaders, damaged/old blood cells,
and cellular debris (liver, spleen, lung,
lymph nodes)
Tissue macrophages and monocytes are
known as the mononuclear phagocyte
system (MPS).
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Monocyte Functions
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Remove cellular debris that remains after
an inflammation and/or infection clears up
Process certain antigens, making them
more antigenic
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Present antigens to lymphocytes as part of
immune response
Ingest foreign substances
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Monocyte Functions
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Follow neutrophils into tissue (chemotaxis)
in response to tissue damage caused by
trauma or invading microorganisms
Remain at site of damage longer than
neutrophils
Function in circulating blood to
phagocytize damaged blood cells or
microorganisms found in the blood
(septicemia)
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Monocytosis and Monocytopenia
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Monocytosis
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Increased number of monocytes in peripheral
blood
Often associated with a chronic inflammatory
condition
Monocytopenia
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Decreased number of monocytes in peripheral
blood
Difficult to evaluate because numbers are
normally low
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Lymphocytes
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Primary circulating WBC in ruminants and
pigs
No phagocytic capabilities
Most reside in lymphoid tissues and
circulate between these tissues and blood
Thought to arise from the same pluripotent
stem cell in the bone marrow as other
blood cells
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Some lymphocytes leave the bone marrow and
mature in other central lymphoid organs
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Types of Lymphocytes
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Every lymphocyte has surface markers
that differentiate subsets of each type of
lymphocyte.
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Markers are not visible under light microscopy.
Three type of Lymphocytes:
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T-lymphocytes (T cells)
 B-lymphocytes (B cells)
 Natural Killer (NK) Cells
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T-Lymphocytes
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Processed in the thymus before going to
peripheral lymphoid tissue
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Pre-T cells in the thymus are thymocytes
Responsible for cell-mediated immunity
and for activating B cells
Most of the lymphocytes in peripheral
blood are T cells.
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B-Lymphocytes
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“Bursa equivalent” - refers to bone marrow
and other lymphoid tissue thought to be
the equivalent of a bird organ called the
bursa of Fabricius
Inactive B cells travel through lymph
nodes, the spleen, and other lymphoid
structures
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Rarely circulate in peripheral blood.
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B-Lymphocytes
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Responsible for
antibody production
Each B cell produces
only one specific
antibody type against
one specific antigen
(foreign protein).
Surface receptors
are shaped to fit only
one antigen shape
(epitope).
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B-Lymphocytes and Plasma Cells
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Humoral immunity: B cells recognize an
antigen and transform into plasma cells
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Activated B cells multiply by mitosis (blastic
transformation) to become plasma cells.
Plasma cells produce, store, and release
antibodies (immunoglobins).
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Natural Killer (NK) Cells
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NK cells don’t have to be activated by a
specific antigen.
Have the ability to kill some types of tumor
cells and cells infected with various viruses
Must come in direct contact with these
cells before they can destroy them
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Lymphocyte Characteristics
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Circulating lymphocytes are classified as
either large or small lymphocytes.
No cytoplasmic granules
Nucleus - round or oval, non-segmented
Large lymphocytes - abundant sky-blue
cytoplasm
Small lymphocytes -scant amount of
cytoplasm
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Memory Cells
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Both T cells and B cells can become
memory cells.
Clones of an original lymphocyte
Reside in lymphoid tissue until second
exposure to the same antigen encountered
previously
Quicker and mounts a greater response
than the initial immune response
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Lymphocytosis
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Lymphocytosis - increased number of
lymphocytes in peripheral blood

Can result from leukemia, chronic infection,
epinephrine release
 Can be significant enough to cause a
leukocytosis
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Lymphopenia
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Lymphopenia - decreased number of
lymphocytes in peripheral blood

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Can result from decreased production,
corticosteroids, immune deficiency diseases,
acute viral diseases
Can result in a leukocytopenia
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Lymphatic system
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Series of vessels/ducts
Carry excess interstitial tissue fluid to
blood vessels near the heart where fluid is
put back into the bloodstream
Also includes lymph tissue scattered
throughout the body (lymph nodes, spleen,
thymus, tonsils and gut associated lymph
tissue [GALT])
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Lymph
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Consists of:
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Blood cells - mostly lymphocytes
Nutrients (proteins, fats, etc.)
Hormones
Some T cells circulate from blood to
interstitial fluid to lymph and back to blood.
B cells are found primarily in lymph tissues
and rarely recirculate.
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Lymph Formation
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
Excess interstitial
tissue picked up by
small lymph
capillaries that start
blindly in the
interstitial spaces of
soft tissue
Fluid enters/leaves
tissues spaces due to
blood pressure and
osmotic pressure
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Lymph Circulation
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Lymph capillaries join together to form
larger and larger lymph vessels.
Many contain one-way valves that prevent
lymph from flowing backwards.
Body movements propel lymph toward the
heart.
Lymph vessels eventually join to form the
thoracic duct that empties lymph into the
vena cava just before it enters the heart.
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Lymph Circulation
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
Lymph vessels pass through at least one
lymph node and pick up lymphocytes.
Any microorganisms in the lymph are
removed by macrophages found in the
lymph nodes.
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Lymph Characteristics
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Transparent or translucent liquid
containing varying numbers of cells,
primarily lymphocytes
More water, sugar, and electrolytes than
plasma
Fewer of the larger proteins found in
plasma
Chyle - Lymph from the digestive system

Chylomicrons cause lymph to appear white or
pale yellow and cloudy.
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Lymphatic System Functions
1. Removal of excess tissue fluid
2. Waste material transport

Interstitial fluid contains some of the waste
materials from the tissue cells
3. Filtration of lymph

Removal of microorganisms, cellular debris,
and other foreign matter
4. Protein transport
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Lymph nodes
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Small kidney-bean-shaped structures
located at various points along the lymph
vessels
Connective tissue capsule sends branches
(trabeculae) into the body of the lymph
node
Afferent lymph vessels empty fluid just
beneath the capsule.
Efferent vessels exit the lymph node in the
indented hilus area.
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Lymph nodes

Cortex - location of
resident lymphocytes


Lymph nodules:
clusters of
lymphocytes around
periphery of the node
Medulla - contains
tissue macrophages
embedded in a
coarse fibrous mesh
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Spleen

Tongue-shaped organ located on the left
side of the abdomen



Near the stomach in simple-stomached
animals
Near the rumen in ruminants
Largest lymphoid organ in the body
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Spleen

Covered with a fibrous connective tissue
capsule and smooth muscle




Capsule sends branches (trabeculae) into the
soft tissue of the spleen
Trabeculae contain blood vessels, nerves,
lymph vessels, and smooth muscle cells.
Trabeculae are very muscular in carnivores.
When the smooth muscle cells contract, they
squeeze blood out of the spleen and back into
circulation.
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Spleen



Interior of the spleen
is divided into white
pulp and red pulp
White pulp: localized
areas of lymphoid
tissue
Red pulp: blood
vessels, tissue
macrophages, and
blood sinuses
(storage)
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Spleen Functions
Blood storage in the red pulp
2. Removal of foreign material from
circulation by the tissue macrophages in
the red pulp
3. Removal of dead, dying and abnormal
red blood cells by the tissue
macrophages in the red pulp
4. Lymphocyte cloning in the white pulp
during an immune response
1.
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Thymus



Lymphoid organ located in the caudal neck
and cranial thoracic region on either side
of the trachea.
Most prominent in young animals
Processes thymocyctes and T-cells
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Tonsils



Nodules of peripheral lymphoid tissue
Not covered with a capsule
Found close to mucosal surfaces all over the body



Pharynx, larynx, intestine, prepuce, and vagina
Tonsils in pharyngeal region prevent spread of
infection into the respiratory or digestive systems
Located at the beginning of the lymph drainage
system, not along the lymph vessels like lymph
nodes
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Gut Associated Lymph Tissue
(GALT)



Lymphoid tissue found in the intestinal
mucosa and submucosa
Largest lymphoid organ in the body
GALT is classified as both central and
peripheral lymphoid tissue.
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The Immune System
Actions:
 Phagocytosis and destruction of foreign
cells
 Lysis of foreign cell membranes
 Inactivation of pathogenic organisms or
chemical substances
 Precipitation or agglutination of cells or
molecules
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Nonspecific Immunity




Mechanical barriers - skin and mucous
membranes
Chemical barriers (e.g., hydrochloric acid
in the gastric mucosa)
Inflammatory response - tissue damage
provokes release of chemical mediators
(e.g., histamine) and other chemotactic
factors
Phagocytosis by neutrophils, monocytes
and tissue macrophages
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Nonspecific Immunity


Natural Killer cells - come in direct contact
with tumor cells and tissue cells that have
been invaded by viruses and destroy them
Interferon – protein produced by a cell
after it has been infected by a virus;
inhibits further development and spread of
the virus
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Nonspecific Immunity


Complement - group
of enzymes in
plasma that can be
activated by the
attachment of an
antibody to an
antigen
Complement fixation
- cascade of
reactions that results
in antigen lysis
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Specific Immunity




B cells that produce antibodies or direct
other cells to attack the antigen
T cells that attack more directly
Response is initiated as a reaction to the
epitope on the invading cell’s wall
Lymphocytes primarily involved but may
depend on the actions of other cells for
activation
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Table 9-3. Humoral Immune Response versus Cell Mediated Immune
Response
Humoral Immune
Response
Cell-Mediated Immune
Response
Cell type involved
B cell that transforms into a
plasma cell after antigenic
stimulation
T lymphocyte that
transforms into cytotoxic T
cell, helper T cell or
supressor T cell after
antigenic stimulation
Substance produced
Immunoglobulins
(antibodies)
Lymphokines
Cellular mobility
B cells and plasma cells stay T cells can enter circulation
in the lymphoid tissue.
and travel to the site where
Antibodies are released into an antigen entered the body
plasma.
Memory cells
produced?
Yes
Yes
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Types of Immunoglobulins (Ig)
1.
2.
3.
4.
5.
IgG - first Ig made during first exposure to
an antigen
IgM - made when animal exposed to an
antigen for a long time or when exposed
to the antigen for the second time
IgA - can leave blood and enter tissue
fluids; plays a role in protecting mucosal
surfaces (e.g., intestinal tract and lungs)
IgE - associated with an allergic response
IgD - function is unknown
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Passive Immunity

Animal receives preformed antibodies




Antibodies produced by a mother that are
passed to a fetus transplacentally
Ingestion of colostrum (antibody-rich first milk
produced)
Antibodies produced by another animal and
given to a sick animal (e.g., administration of
tetanus antitoxin)
No memory cells produced
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Active Immunity



Exposure to antigen that triggers animal’s
own immune response
Memory T- or B cells are produced
Immunization: activate animal’s own
immune systems


Vaccines contain epitope of the antigens
Killed or live-but-weakened (attenuated)
antigens
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