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Organs of the Immune System: Lymph Nodes, Spleen

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Organs of the Immune System: Lymph Nodes, Spleen & Thymus Teresa Kraus MD Teresa-Kraus_at_ouhsc.edu Modified from a lecture by Dr. William Kern * The thymus is divided ... – PowerPoint PPT presentation

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Title: Organs of the Immune System: Lymph Nodes, Spleen


1
Organs of the Immune SystemLymph Nodes, Spleen
Thymus
  • Teresa Kraus MD
  • Teresa-Kraus_at_ouhsc.edu

Modified from a lecture by Dr. William Kern
2
Downloading any of the photographs, images or
diagrams from this presentation for any purpose
other than studying for the BHL course is
prohibited.
3
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

4
Lymphatic System
5
Lymphatic System Abdomen
6
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

7
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

8
Structure of Lymph Node
Williams Hematology, 8th Ed.
9
Lymph Node
Germinal center
Williams Hematology, 8th Ed.
10
Secondary Follicle
Mantle zone
Germinal center
Jaffe Hematopathology
11
Secondary Follicle B-cells vs. T-cells
B-cell stain
T-cell stain
(Brown is positive)
Jaffe Hematopathology
12
The Germinal Center
  • The GC is the primary site where B cell
    expansion, diversification, and affinity
    maturation occurs in response to antigen

Jaffe Hematopathology
13
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
14
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

15
GI Tract Lymphoid Nodules
16
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

17
Reactive Lymph Node
18
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

19
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

20
Arterial Supply of Spleen
21
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22
Spleen Venous Drainage
23
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

24
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

25
Spleen Microanatomy
White pulp
Robbins Pathologic Basis of Disease, 8th ed.
26
Spleen
From Hoffman et al Hematology Basic Principles
Practice, 5th Ed.
27
Spleen
From Williams Hematology, 8th Ed.
28
Spleen
White Pulp
Red Pulp
Ross Pawlina Histology A Text and Atlas, 5th
Ed.
29
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

30
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

31
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

32
Howell-Jolly Bodies
From Hoffman et al Hematology Basic Principles
Practice, 5th Ed.
33
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

34
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)

35
Splenomegaly Causes
  • Congestive splenomegaly
  • Reactive splenomegaly
  • Infiltrative diseases
  • Gaucher disease, others
  • Malignancies
  • Hematologic
  • Non-hematologic

36
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

37
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

38
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

39
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

40
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

41
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42
From Jaffe ES et al Hematopathology
43
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

44
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

45
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

46
Thymus
From Jaffe ES et al Hematopathology
47
Thymus Cortex
From Jaffe ES et al Hematopathology
48
Thymus Medulla
Hassalls corpuscle
From Jaffe ES et al Hematopathology
49
T Cell Maturation
Jaffe Hematopathology Fig 8-8
50
From Williams Hematology, 8th Ed.
51
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
52
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

53
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
54
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

55
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

56
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

57
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

58
Thymomas
  • Tumors of thymic epithelial cells
  • Three variants
  • Encapsulated (noninvasive) Majority
  • Invasive but cytologically benign 20
  • Thymic carcinomas (cytologically malignant) Rare

59
Thymoma
Robbins Pathologic Basis of Disease, 8th ed.
60
Thymoma
Robbins Pathologic Basis of Disease, 8th ed.
61
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

62
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

63
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

64
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
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