Organs of the Immune System: Lymph Nodes, Spleen

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Organs of the Immune SystemLymph Nodes, Spleen
Thymus

• Teresa Kraus MD
• Teresa-Kraus_at_ouhsc.edu

Modified from a lecture by Dr. William Kern
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Downloading any of the photographs, images or
diagrams from this presentation for any purpose
other than studying for the BHL course is
prohibited.
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Lymphatics

• Thin-walled vessels
• Drain interstitial fluid from tissues back into
  venous system
• Carry antigens to lymph nodes for processing and
  beginning of immune response

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Lymphatic System
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Lymphatic System Abdomen
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Function of Lymph Nodes

• Site where lymphocytes, macrophages and other
  cells can contact antigen and interact with each
  to generate immune response
• Trap malignant cells

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Structure of Lymph Nodes

• Fibrous capsule
• Cortex Outer portion
• Follicles Predominantly B-cells
• Germinal centers mantle zones
• Paracortical (interfollicular) areas
  Predominantly T-cells
• Medulla Center portion
• Medullary sinuses

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Structure of Lymph Node
Williams Hematology, 8th Ed.
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Lymph Node
Germinal center
Williams Hematology, 8th Ed.
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Secondary Follicle
Mantle zone
Germinal center
Jaffe Hematopathology
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Secondary Follicle B-cells vs. T-cells
B-cell stain
T-cell stain
(Brown is positive)
Jaffe Hematopathology
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The Germinal Center

• The GC is the primary site where B cell
  expansion, diversification, and affinity
  maturation occurs in response to antigen

Jaffe Hematopathology
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Cells Within the GC

• Centroblasts undergo division and somatic
  hypermutation in the dark zone of the GC before
  exiting the cell cycle, re-expressing surface
  immunoglobulin, and migrating to the light zone
• In light zones, clones with increased antigen
  affinity are preferentially selected by their
  interaction with antigen on follicular dendritic
  cells and survival signals provided by follicular
  helper T cells

Ki-67
CD23
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Extranodal Lymphoid Tissue

• Patches of lymphoid tissue located in GI tract,
  lungs, other extranodal sites
• Immunologic protection at areas vulnerable to
  potential invaders
• Important in IgA production

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GI Tract Lymphoid Nodules
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Lymph Node Enlargement

• Infections All types
• Drugs Phenytoin
• Metastatic malignancies
• Non-hematologic Carcinomas, others
• Hematologic Lymphomas, occasional myeloid
  malignancies
• Systemic diseases Sarcoidosis, systemic lupus
  erythematosus
• Miscellaneous

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Reactive Lymph Node
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Spleen

• Located in left upper quadrant of abdomen,
  beneath lower ribs
• Normal weight 100-150 grams (adults)
• Usually not palpable in adults
• Spleen tip may be palpable in a substantial
  number of children
• Spleen tip palpable in a small number of slender
  young adults
• Palpable splenomegaly is abnormal in older adults

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Spleen Blood Supply Venous Drainage

• Arterial
• Splenic artery Branch of celiac trunk primary
  supply
• Branches of gastric arteries Minor
• Venous drainage
• Splenic vein Joins with superior mesenteric vein
  to form portal vein
• Small veins draining to gastric veins
• Gets approximately 5 of cardiac output

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Arterial Supply of Spleen
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Spleen Venous Drainage
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Spleen Structure

• Fibrous capsule with trabecula extending into
  parenchyma
• Stroma composed of network of fibroblast-like
  reticular cells
• Splenic artery enters at hilum
• Gives off trabecular arteries ? central arteries
  ? penicilliary arteries

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Spleen Microanatomy

• White pulp
• Lymphoid zone
• Surrounds central arteries
• Periarteriolar lymphoid sheath (PALS) T-cells
• Follicles and marginal zones B-cells
• Red pulp
• Network of splenic (stromal) cords vascular
  sinuses

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Spleen Microanatomy
White pulp
Robbins Pathologic Basis of Disease, 8th ed.
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Spleen
From Hoffman et al Hematology Basic Principles
Practice, 5th Ed.
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Spleen
From Williams Hematology, 8th Ed.
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Spleen
White Pulp
Red Pulp
Ross Pawlina Histology A Text and Atlas, 5th
Ed.
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Spleen Red Pulp

• Most of blood goes directly into venous sinusoids
  Closed circulation
• Relatively fast
• Small amount goes into open splenic cords Open
  circulation
• Splenic cords lined by macrophages
• Erythrocytes screened phagocytized by
  macrophages
• Open circulation is very slow

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Functions of Spleen

• A major site of protection against blood-born
  pathogens
• Site of antibody production
• Screens and eliminates senescent or defective red
  cells
• Stores platelets and some granulocytes
• Normally 1/3rd of platelets sequestered in spleen
• Site of hematopoiesis in fetal life
• May be reactivated in severe anemia, MPNs

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Erythrocytes the Spleen

• Senescent RBCs phagocytized removed
• Spleen removes excess membrane lipids from young
  RBCs
• Spleen removes RBC inclusions Nuclei, nuclear
  fragments, iron granules
• RBCs must pass through narrow slit to enter
  vascular sinuses from splenic cords
• Requires flexibility

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Howell-Jolly Bodies
From Hoffman et al Hematology Basic Principles
Practice, 5th Ed.
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Disorders of Spleen

• Accessory spleen
• Common incidental finding
• Usually single hilum of spleen is common site
• Usually clinically insignificant
• Wandering spleen
• Abnormal positioning due to excessive mobility of
  splenic ligaments
• May present as abdominal mass, intermittent pain,
  or torsion with acute abdomen
• Splenogonadal fusion

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Disorders of Spleen

• Hypersplenism
• Splenic enlargement with sequestration of WBCs,
  RBCs and platelets
• Usually due to passive splenic congestion
• Hyposplenism
• Increased risk of severe bacterial sepsis
• Due to surgical splenectomy, autosplenectomy in
  sickle cell diseases, congenital asplenia (rare)

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Splenomegaly Causes

• Congestive splenomegaly
• Reactive splenomegaly
• Infiltrative diseases
• Gaucher disease, others
• Malignancies
• Hematologic
• Non-hematologic

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Congestive Splenomegaly

• Backup of venous blood flow through splenic vein
• Causes Cirrhosis of liver, right heart failure,
  thrombosis of portal or splenic veins
• May be associated with hemorrhage from
  gastroesophageal varices
• Congestion of spleen may also occur in chronic
  hemolytic anemias
• Hereditary spherocytosis, thalassemia, others

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Gastroesophageal Varices

• Backup of blood from portal vein through splenic
  vein to gastric veins may result in
  gastroesophageal varices
• Dilated veins near gastroesophageal junction
• May cause massive upper GI hemorrhage in patients
  with cirrhosis

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Reactive Splenomegaly

• Infections of many types
• Viral EBV and others
• Parasitic infections Malaria and others
• Bacterial, fungal, mycobacterial
• Chronic inflammatory disorders
• Felty syndrome, systemic lupus erythematosus
  (SLE), sarcoidosis, others
• Hemolytic anemias

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Neoplasms the Spleen

• Primary splenic neoplasms Rare usually vascular
  tumors
• Benign Hemangiomas, lymphangiomas
• Malignant Angiosarcomas
• Hematologic neoplasms
• Hodgkin and non-Hodgkin lymphomas
• Myeloproliferative neoplasms CML, P. vera,
  primary myelofibrosis, etc.
• Hairy cell leukemia
• Non-hematologic malignancies Rarely metastasize
  to spleen

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Thymus

• Located in superior mediastinum
• Bilobed irregularly pyramidal
• Derived predominantly from 3rd pair of pharyngeal
  pouches 4th pouches
• Parathyroid glands also derived from pharyngeal
  pouches
• Atrophies after puberty ? few small islands of
  epithelial cells in older adults

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From Jaffe ES et al Hematopathology
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Thymus Function

• Site of T-cell selection and maturation
• T-cells originate in bone marrow, but immature
  T-cells must migrate to thymus to mature
• Selected for ability to recognize self HLA
  antigens to allow antigen presentation
• T-cells with strong autoreactivity deleted
• Prevent autoimmune reactions

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Thymus Anatomy

• Two fused lobes
• Surrounded by a fibrous capsule
• Fibrous bands divide the thymus into lobules
• Predominantly consists of epithelial cells and
  immature T-cells

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Thymus Microanatomy

• Divided into cortex and medulla
• Medulla contains Hassalls corpuscles (islands of
  squamous cells)
• The most immature T-cells are located in
  superficial cortex
• T-cells move down into medulla as they mature

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Thymus
From Jaffe ES et al Hematopathology
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Thymus Cortex
From Jaffe ES et al Hematopathology
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Thymus Medulla
Hassalls corpuscle
From Jaffe ES et al Hematopathology
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T Cell Maturation
Jaffe Hematopathology Fig 8-8
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From Williams Hematology, 8th Ed.
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Thymus Aplasia or Hypoplasia DiGeorge Syndrome

• Related to abnormalities of 3rd 4th pharyngeal
  pouches
• Absent or hypoplastic thymus ? immunodeficiency
• Aplasia or hypoplasia of parathyroid glands ?
  hypoparathyroidism ? hypocalcemia

Continued
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Thymus Aplasia or Hypoplasia DiGeorge Syndrome

• Variable congenital cardiac anomalies
• Mild facial dysmorphism
• Subset of chromosome 22q11.2 deletion syndrome
• Confirmatory test Fluorescence in situ
  hybridization (FISH) looking for deletion of
  chromosome 22q11.2

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Thymus Aplasia or HypoplasiaOther Variants

• Wiskott-Aldrich syndrome
• Abnormalities of gene producing WAS protein
• X-linked recessive inheritance
• Hypoplastic thymus, recurrent infections, eczema,
  thrombocytopenia with small platelets

http//emedicine.medscape.com/article/137015-overv
iewa0101
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Thymus Aplasia or HypoplasiaOther Variants

• Ataxia-Telangiectasia
• Autosomal recessive mutations in ATM gene
  11q22-23
• Cerebellar ataxia, immunodeficiency
• Oculocutaneous telangiectasia
• Hypoplasia / agenesis of the thymus

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Thymic Follicular Hyperplasia

• Presence of lymphoid follicles with germinal
  centers in thymus
• Lymphoid follicles not normally found in thymus
• Thymus size often normal
• Often associated with autoimmune diseases
  especially myasthenia gravis
• Muscle weakness due to antibody against
  acetylcholine receptor on muscle cells

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Thymic Follicular Hyperplasia Autoimmune Disease

• Thymic follicular hyperplasia found in 65-75 of
  patients with myasthenia gravis
• Myasthenia gravis also found in patients with a
  thymic tumor called thymoma
• Thymic follicular hyperplasia may also be found
  with other autoimmune diseases
• Graves disease (autoimmune thyroiditis with
  hyperthyroidism), systemic lupus erythematosus,
  others

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Neoplasms of Thymus

• Thymomas Tumors of thymic epithelial cells
• Most common tumors of thymus
• Hematologic neoplasms
• T lymphoblastic leukemia/lymphoma
• B-cell lymphomas
• Germ cell tumors Rare

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Thymomas

• Tumors of thymic epithelial cells
• Three variants
• Encapsulated (noninvasive) Majority
• Invasive but cytologically benign 20
• Thymic carcinomas (cytologically malignant) Rare

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Thymoma
Robbins Pathologic Basis of Disease, 8th ed.
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Thymoma
Robbins Pathologic Basis of Disease, 8th ed.
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Thymomas Autoimmune Diseases

• Thymomas may also be associated with autoimmune
  diseases
• Myasthenia gravis Not as often as thymic
  follicular hyperplasia
• Pure red cell aplasia
• Graves disease
• Others

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Hematologic Neoplasms of the Thymus

• T lymphoblastic leukemia/lymphoma Most common
• Formerly called precursor T-cell
  ALL/lymphoblastic lymphoma
• Most common in adolescent males
• Present with large mediastinal mass
• May have respiratory compromise, pleural effusions

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T Lymphoblastic Leukemia/Lymphoma

• Majority of precursor T-cell neoplasms present as
  lymphoma Tissue mass without blood or bone
  marrow involvement
• Minority of cases have blood and bone marrow
  involvement
• Distinction (lymphoma vs. leukemia) based on
  whether bone marrow involved
• Treatment and prognosis similar

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Primary Mediastinal Large B-Cell Lymphoma

• Uncommon neoplasm of thymus
• Derived from thymic B-cells
• Histologic variant of diffuse large B-cell
  lymphoma
• Typically occurs in young women