17.0, 18.0 IMMUNE SYSTEM
a) Define and use properly the following words: Lines of defense, Primary lymphatic
organs, Secondary Lymphatic organs, Innate immune cells, Innate immune system,
Adaptive immune system, Immune system cells, Parenchymal cells, Antigen receptor
cells, Natural Killer Cells (NK), Antigen presenting cells, Macrophages, Dendritic cells,
Follicular dendritic cells, Interdigitating dentritic cells, Supporting stromal cells, Reticular
cells, Epithelial reticular cells, Primary lymphatic organs, Bone marrow, Thymus, Cortex,
Epithelial reticular, Blood-Thymus-Barrier, Medulla, Tingible body macrophages,
Epithelial reticular cells, Thymic corpuscles (Hassall’s corpuscles), Interdigitating
dendritic cells, Post capillary venules, Corticomedullary junction, Cloacal bursa,
Secondary lymphatic organs, Immune System Circulation, Lymphatics, Discontinuous
basal lamina, Afferent lymphatics, Efferent lymphatics, Diffuse Lymphatic Tissue, Dense
Lymphatic Tissues, Nodules, Tonsils, Lymph nodes, Spleen, Hemal nodes, Mucosa
associated lymphatic tissue (MALT), Nasal Associated Lymphatic Tissue (NALT), Gut
associated lymphatic tissue (GALT), Microfold (M) cells, Bronchiolar associated
lymphatic tissue (BALT), Lymph node, Capsule , Subcapsular sinus, Reticular cells and
fibers, Cortex, Lymphoid nodules, B-cell zone, Germinal center, Mantle, Cortical sinuses,
Subcapsular sinus, Paracortical zone, T-cell zone, Paracortical sinuses, Medulla,
Medullary cords, Medullary sinus, Afferent lymphatics, Efferent lymphatics, Spleen, Red
pulp, Capsule, Splenic sinuses, Splenic cords, Hemosiderin, White pulp, Lymphatic
nodules, B-cell zones, Germinal centers, Efferent lymphatics only, Periarterial lymphatic
sheaths (PALS), Diffuse lymphatic tissue, T-cell concentration, Marginal zone, Reticular
network, Circulatory pathways.
b) Describe and associate basic structure/function for the following: all structures listed
above.
c) Identify by microscopy: B-Lymphocytes, T-Lymphocytes, B-cell zones, Biological barrier,
Blood-thymus-barrier, Bronchus-associated (BALT), Cell-mediated immunity, Cortex,
Cortical sinuses, Dendritic cells, Dense Lymphatic Tissue, Diffuse Lymphatic Tissue,
Efferent lymphatics only, Follicular dendritic cells, Germinal center, Gut-associated
Lymphatic Tissue (GALT), Hemosiderin, Lymph nodes, Macrophages, Mantle, Marginal
sinus, Marginal zone, Mechanical barrier, Medulla, Medullary cords, Medullary sinus,
Mucosal Associated Lymphatic Tissues (MALT), Nodules, Paracortical sinuses,
Paracortical zone, Periarteriolar lymphatic sheaths (PALS), Phagocytosis, Primary
lymphatic organs, Peyer’s patch, Red Pulp, Reticular network, Secondary Lymphatic
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Organs, Secondary Lymphatic Tissues, Spleen, Splenic cords, Splenic sinuses,
Subcapsular sinus, T- Lymphocytes, Thymic corpuscles-Hassall’s corpuscles, Thymus,
Tingible body macrophages, Tonsils, Trabeculae, White Pulp.
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IMMUNE SYSTEM
I.
MAIN LINES OF DEFENSE:
A. Protective surface mechanisms
B. Organs
1. Primary lymphatic organs:
a. Bone marrow
b. Thymus
c. Cloacal bursa (birds)
2. Secondary Lymphatic organs
a. Diffuse Lymphatic tissues
b. Dense Lymphatic tissues
i. Mucosal associated lymphatic tissue
c. Lymph nodes
d. Spleen
e. Hemal nodes
C. Innate immune system = Cells:
1. Neutrophils,
2. eosinophils,
3. basophils,
4. macrophages,
5. histiocytes
6. mast cells.
D. Innate immune system = Proteins and peptides:
1. Complement,
2. acute phase proteins
3. cytokines
E. Adaptive immune system
1. Cellular response: T cell response
2. Humoral response: B cell response
II.
CELLS OF THE IMMUNE SYSTEM:
A. Parenchymal or functional cells
1. Antigen receptor cells
a. Can recognize by light microscopy
i. Look at nucleus; then cytoplasm
ii. Specific types require immunohistochemistry
b. T- Lymphocytes
i. Cell-mediated immunity
c. B- Lymphocytes
i. Humoral immune response; circulating antibodies
2. NK- Cells
a. Generally rare, more difficult to recognize
b. Use immunohistochemistry to recognize
c. Activated; can be larger with some granules, but round nucleus
d. Cytotoxic
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e. Target tumors; virus-infected cells; altered “self” molecules
B. Antigen presenting cells
1. Macrophages
a. Mononuclear phagocytes
b. Large nucleus; often folded; large cytoplasm; can have foamy
appearance
c. Process antigens; present to T cells; active in phagocytosis
d. Resident (Fixed)
i. Histiocyte (connective tissue)
ii. Osteoclast (bone)
iii. Sinusoidal (spleen)
iv. Microglial (neural tissue)
v. Kupffer cells (liver)
vi. Alveolar macrophages (lung)
2. Dendritic cells
a. Long cytoplasmic processes (not seen by light microscopy)
b. Look like T-cells within the epithelium
c. Follicular dendritic cells
i. Stromal cells within B-cell areas of lymphatic tissue
ii. Traps antigens
d. Interdigitating dentritic cells
i. Lymph nodes, thymic medulla, spleen
ii. Langerhans cells of the skin
iii. Present antigen to T-cells
C. Supporting stromal cells:
1. Reticular cells
a. Fibroblast-like
b. Reticular fibers
c. All lymphatic organs, except thymus and bursa
2. Epithelial reticular cells
a. Thymus and bursa only
b. No reticular fibers
III.
PRIMARY ORGANS AND TISSUES OF THE IMMUNE SYSTEM
A. Bone marrow
1. Stem cells for T and B-lymphocytes
2. B-lymphocyte differentiation
B. Thymus
1. Origin and Function
a. Outgrowth of epithelium (endoderm)
b. 3rd pharyngeal pouch
c. Lymphocyte stem cells migrate from bone marrow during fetal life
d. Stem cells produce T-cells
e. Lymphocyte graveyard
f. Regress (involution) after puberty
g. A school to educate immature immune system "T" cells.
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2. Cortex
a. Epithelial reticular
i. Large pale nuclei
ii. Long branching cytoplasmic processes
iii. Connected by desmosomes
iv. Form barrier
v. Surround lymphoblasts (committed stem cells)
3. Medulla
a. T-cells migrate to center for maturation
b. Tingible body macrophages
i. Eliminate dead T-cells
c. Epithelial reticular cells
i. Very large
ii. Thymic corpuscles (Hassall’s corpuscles)
a. Numerous cells that die and calcify
b. “2005 issue of Nature, researchers at The University of
Texas M. D. Anderson Cancer Center found that
Hassall's corpuscles produce chemical signals that
instruct dendritic cells in the thymus to induce
development of these regulatory T cells - the critically
important immune system cells that patrol the body
looking for "bad' T cells that can produce autoimmune
disease. These mysterious little structures in the thymus
are responsible for producing the T cell policemen that
our bodies depend so heavily on," Yong-Jun Liu.
d. Interdigitating dendritic cells
4. Blood supply, lymph and nerves
a. Arteries penetrate connective tissue septa
b. Form capillary network in cortex
c. Post capillary venules in corticomedullary junction
i. Site for T cell entry into blood
ii. T cells travel to lymphatic tissues
d. Blood-thymus-barrier
i. Continuous endothelium
ii. Perivascular connective tissue
iii. Epithelial reticular cell process sheath
iv. Decreases access of circulating antigens
C. Cloacal bursa
1. Birds
2. Original discovery of B-cells
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IV.
SECONDARY LYMPHATIC ORGANS AND TISSUES OF THE IMMUNE SYSTEM
A. Introduction to Secondary Lymphatic Tissues
1. Immune System Circulation
a. Blood vessels carry antigens and cellular elements
b. Lymph vessels (lymphatics) carry intercellular fluid and WBCs
i. Capillaries (large, mold to the tissue)
ii. Larger vessels are like arteries with muscle
iii. Discontinuous basal lamina and sometimes absent
a. Absent or modified in tissues lacking ground substances
derived from Hyaluronic acid
i. CNS, eye, bone marrow, cartilage, red pulp of
spleen, liver lobules, tonsils.
iv. Afferent lymphatics carry lymph towards an organ
v. Efferent lymphatics carry lymph away from an organ
2. Activity includes antigen processing and antibody production
a. Antigen interaction with lymphocytes ONLY in secondary tissues
b. Antigen entry and exposure
i. Designed to be guarded by lymphoid tissue at entry points
ii. Oral, gut, respiratory
3. Diffuse Lymphatic Tissue
a. Network of reticular cells
b. Mixed in with nodules to provide filtering and antigen exposure to cells
c. associated with reticular fibers that enmesh White Blood Cells and
macrophages
d. Found in the following sites:
i. Between lymphatic nodules
ii. In medullary cords and deep cortex of lymph and hemal nodes
and lymphatic sheaths of spleen
iii. Scattered throughout loose connective tissues wherever
lymphocytes, plasma cells, macrophages accumulate.
4. Dense Lymphatic Tissues or Mucosal Associated Lymphatic Tissues (MALT) or
nodules
a. Tonsils
b. Bronchus-associated (BALT)
c. Gut-associated (GALT)
5. Lymph nodes
a. Filters interstitial fluids
b. Lymphatics drain all organs and skin
c. Infectious agents travel to lymph nodes for antigen interaction with
lymphocytes
6. Spleen
a. Filters the blood
7. Hemal nodes
a. Blood sinuses
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V.
DENSE LYMPHATIC TISSUE -MUCOSA ASSOCIATED LYMPHATIC TISSUE (MALT)
A.
B.
C.
D.
E.
F.
Similar to lymph node but no capsule; not organ
Sometimes called MALT (Mucosa Associated Lymphatic Tissue)
Primary lymphatic nodules, with specific epithelial (mucosal) covering
Tightly packed lymphocytes
No afferent lymphatic vessels, but have efferent lymphatics
Tonsils
1. Covered with stratified squamous or respiratory epithelium
G. Nasal Associated Lymphatic Tissue
1. NALT
2. Covered by stratified squamous or respiratory epithelium
H. GALT (gut associated lymphatic tissue)
1. Nodules, lymphoid cells, mucosa
2. Specialized cells form epithelial nodule associated epithelium
i. Microfold (M) cells
ii. Screen antigen in the gut
iii. Fewer goblet cells here
I. BALT (Bronchiolar associated lymphatic tissue)
1. Nodules and lymphoid cells; mucosa
2. Respiratory epithelium
VI.
LYMPH NODE
A. Function
1. This is an ORGAN
2. Forms lymphocytes
3. In line filter of interstitial fluids or lymph
4. Phagocytosis of foreign material
5. Produce antibodies (Plasma cells)
B. Structure:
1. Capsule
a. Subcapsular sinus
b. Reticular cells and fibers
c. Capillary network surround nodules in cortex
2. Cortex
a. Lymphoid nodules
1. B cell zone
2. Germinal center
a. Large euchromatic lymphocytes
3. Mantle
a. Surrounds germinal center
b. Contains smaller dense lymphocytes
b. Cortical sinuses
1. Between lymphatic nodules
2. Continuous with subcapsular sinus
3. Paracortical zone
a. T-cell zone
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b. Paracortical tissue
1. Reticular cells, Antigen presenting and lymphocytes
2. Surrounds nodules
c. Paracortical sinuses
1. Extend from cortical into medulla
4. Medulla
a. Less cellular; lacks nodules
1. Exception is pig (nodules in medulla)
b. Medullary cords
1. Reticular cells, antigen presenting, lymphocytes
2. Plasma cells, macrophages
3. T-cell area
c. Medullary sinus
1. Reticular cells and fibers
5. Lymph flow
a. Flows through sinuses NOT blood
b. Afferent lymphatics
1. Bring lymph into the lymph node
2. Enter capsule
3. Empty into subcapsular sinus
4. Enter cortical sinus and Paracortical
5. Enter medullary sinuses
c. Efferent lymphatics
1. Lymph leaves node at the hilus
2. Should observe lymphatic valves
a. Prevent back flow
C. Species differences
1. Pig (porcine)
a. Lymph node of pig is inverted
b. Nodules are in the center of the lymph node.
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VII.
SPLEEN
A. General Information
1. Function: filters the blood
2. Thick connective tissue capsule
3. Cortex and Medulla areas
4. Two zones; Red and White Pulp
a. Can form RBCs
b. Destruction of old or damaged RBCs
c. Formation of WBCs
d. Blood storage
5. Species differences
a. Some horses have extra storage (50%)
i. Increases thickness of blood
ii. Stronger hearts
iii. Splenic contraction gives oxygen boost
b. Dogs and cats store RBC, too
c. Humans store platelets
B. Capsule
1. Thick connective tissue
a. Dense irregular
b. Smooth muscle layer
c. Trabeculae
i. Connective tissue
a. Collagen, elastin, smooth muscle
ii. Blood vessels, lymph, nerve
C. Red Pulp
1. Most of the parenchyma
2. Blood, Erythrocytes
3. Splenic sinuses
a. Wide channels
b. Long longitudinal endothelial cells, contractile
c. Slits form upon contraction
i. Allow RBCs to migrate (squeeze) into cords
d. Fenestrated basal lamina supported by reticular fibers
4. Splenic cords
a. Between sinuses
b. Network of fibers, reticular cells
i. RBCs, macrophages, lymphocytes, leukocytes
ii. Build up of iron from breakdown of old RBCs
a. ‘Hemosiderin’
i. brown pigment of hemoglobin breakdown
5. Filtration
a. Mechanical
i. by reticular fibers and endothelial cells
b. Biological
i. Macrophages and Neutrophils
6. Species differences
a. Ruminant and porcine
i. More smooth muscle
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b. Horse and dog
i. Myofibroblasts (contractile)
ii. Plus smooth muscle
D. White pulp
1. Lymphatic nodules and diffuse lymphatic tissue
2. Nodules
a. B-cell zones
b. Germinal centers +/c. Efferent lymphatics only
3. Periarterial lymphatic sheaths (PALS)
a. Diffuse lymphatic tissue
b. Line the white pulp arteries (can see in microscope)
c. T-cell concentration
d. Mixture of T and B as you near the nodules
e. Other cells
i. Macrophages, dendritic cells, reticular cells
4. Species differences
a. Cat, ruminant
i. Less nodules, short PALS; large macrophage sheaths
b. Horse, dog, pigs
i. Numerous nodules
ii. Numerous PALS
E. Marginal zone
1. Between white and red pulp
2. Flattened reticular cells form concentric layer
3. Reticular network
4. Marginal sinus formed
a. Drain slowly toward venous sinuses of red pulp
5. Numerous macrophages and B-cells
6. Extensive antigen and foreign body interaction with lymphocytes and
macrophages
a. Macrophages transport trapped antigens to the PALS
F. Circulatory pathways in the spleen:
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