Title: Organs of the Immune System: Lymph Nodes, Spleen
1Organs of the Immune SystemLymph Nodes, Spleen
Thymus
- Teresa Kraus MD
- Teresa-Kraus_at_ouhsc.edu
Modified from a lecture by Dr. William Kern
2Downloading any of the photographs, images or
diagrams from this presentation for any purpose
other than studying for the BHL course is
prohibited.
3Lymphatics
- Thin-walled vessels
- Drain interstitial fluid from tissues back into
venous system - Carry antigens to lymph nodes for processing and
beginning of immune response
4Lymphatic System
5Lymphatic System Abdomen
6Function of Lymph Nodes
- Site where lymphocytes, macrophages and other
cells can contact antigen and interact with each
to generate immune response - Trap malignant cells
7Structure 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
8Structure of Lymph Node
Williams Hematology, 8th Ed.
9Lymph Node
Germinal center
Williams Hematology, 8th Ed.
10Secondary Follicle
Mantle zone
Germinal center
Jaffe Hematopathology
11Secondary Follicle B-cells vs. T-cells
B-cell stain
T-cell stain
(Brown is positive)
Jaffe Hematopathology
12The Germinal Center
- The GC is the primary site where B cell
expansion, diversification, and affinity
maturation occurs in response to antigen
Jaffe Hematopathology
13Cells 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
14Extranodal 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
15GI Tract Lymphoid Nodules
16Lymph 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
17Reactive Lymph Node
18Spleen
- 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
19Spleen 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
20Arterial Supply of Spleen
21(No Transcript)
22Spleen Venous Drainage
23Spleen 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
24Spleen 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
25Spleen Microanatomy
White pulp
Robbins Pathologic Basis of Disease, 8th ed.
26Spleen
From Hoffman et al Hematology Basic Principles
Practice, 5th Ed.
27Spleen
From Williams Hematology, 8th Ed.
28Spleen
White Pulp
Red Pulp
Ross Pawlina Histology A Text and Atlas, 5th
Ed.
29Spleen 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
30Functions 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
31Erythrocytes 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
32Howell-Jolly Bodies
From Hoffman et al Hematology Basic Principles
Practice, 5th Ed.
33Disorders 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
34Disorders 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)
35Splenomegaly Causes
- Congestive splenomegaly
- Reactive splenomegaly
- Infiltrative diseases
- Gaucher disease, others
- Malignancies
- Hematologic
- Non-hematologic
36Congestive 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
37Gastroesophageal 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
38Reactive 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
39Neoplasms 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
40Thymus
- 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(No Transcript)
42From Jaffe ES et al Hematopathology
43Thymus 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
44Thymus 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
45Thymus 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
46Thymus
From Jaffe ES et al Hematopathology
47Thymus Cortex
From Jaffe ES et al Hematopathology
48Thymus Medulla
Hassalls corpuscle
From Jaffe ES et al Hematopathology
49T Cell Maturation
Jaffe Hematopathology Fig 8-8
50From Williams Hematology, 8th Ed.
51Thymus 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
52Thymus 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
53Thymus 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
54Thymus Aplasia or HypoplasiaOther Variants
- Ataxia-Telangiectasia
- Autosomal recessive mutations in ATM gene
11q22-23 - Cerebellar ataxia, immunodeficiency
- Oculocutaneous telangiectasia
- Hypoplasia / agenesis of the thymus
55Thymic 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
56Thymic 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
57Neoplasms 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
58Thymomas
- Tumors of thymic epithelial cells
- Three variants
- Encapsulated (noninvasive) Majority
- Invasive but cytologically benign 20
- Thymic carcinomas (cytologically malignant) Rare
59Thymoma
Robbins Pathologic Basis of Disease, 8th ed.
60Thymoma
Robbins Pathologic Basis of Disease, 8th ed.
61Thymomas 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
62Hematologic 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
63T 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
64Primary 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