Lymphoid System

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I. Components of the Lymphoid System

1. Lymphatic Vessels

• Structure: Composed of lymphatic capillaries, vessels, and nodes.

• Lymphatic Capillaries:

  • Resemble blood capillaries.

  • Have thin walls with a single endothelial cell layer.

  • Highly permeable—allow passage of fluid, proteins, and particulate matter.

• Larger Lymphatics:

  • Structurally similar to veins but with thinner muscle layers.

  • More numerous valves than veins.

• Function:

  • Drain excess tissue fluid (lymph).

  • Return lymph to the bloodstream.

  • Help in immune surveillance and transport of immune cells.

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2. Lymph Nodes (Normal Structure)

• Gross Anatomy:

  • Bean-shaped or oval.

  • 1–2 cm in length.

  • Covered by a fibrous capsule.

• Entry & Exit of Lymph:

  • Afferent lymphatics enter at convex surface.

  • Drain into subcapsular sinus → branches → exit via efferent lymphatic at the hilum.

• Internal Structure:

  • Cortex: Contains B-cell rich lymphoid follicles.

    • Germinal center: Pale, active site of B-cell proliferation.

    • Mantle zone: Dark-staining outer ring.

  • Paracortex: T-cell rich zone between cortex and medulla.

  • Medulla: Contains plasma cells and lymphocytes in medullary cords.

• Reticulin Framework: Supports the lymph node structure.

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3. Functional Zones

• B-cell Zones:

  • Found in follicles, mantle zone, interfollicular spaces.

• T-cell Zones:

  • Located mainly in the paracortex and medulla.

• Immune Functions:

  • Antigen presentation, lymphocyte activation, maturation, and antibody production.

  • Phagocytosis by mononuclear phagocytic cells.

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II. Lymphatic Disorders

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A. Lymphangitis

• Definition: Inflammation of lymphatic vessels.

• Types:

  • Acute: Commonly caused by β-hemolytic streptococci or staphylococci.

    • Gross: Red streaks on skin.

    • Microscopy: Dilated lymphatics, inflammatory exudate, neutrophils, oedema.

  • Chronic: Seen in tuberculosis, syphilis, actinomycosis.

    • Leads to fibrosis, obstruction, and chronic lymphoedema.

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B. Lymphoedema

• Definition: Swelling due to accumulation of lymph.

• Types:

  • Primary (Idiopathic):

    • Congenital:

      • Milroy’s disease: Autosomal dominant; one limb or extensive; associated with congenital anomalies.

      • Simple form: Non-familial; often seen in Turner’s syndrome.

    • Praecox:

      • Occurs in young females.

      • Begins in the foot, ascends; non-pitting oedema.

  • Secondary (Obstructive):

    • More common.

    • Causes: Tumour invasion, surgical removal, radiation fibrosis, filariasis (elephantiasis), post-inflammatory scarring.

    • May result in:

      • Chyloperitoneum

      • Chylothorax

      • Chylopericardium

      • Chyluria

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III. Reactive Lymphadenitis

A. Acute Nonspecific Lymphadenitis

• Causes: Infections (oral cavity, extremities, GI tract).

• Lymph Nodes Affected:

  • Cervical (oral)

  • Axillary (arm)

  • Inguinal (legs)

  • Mesenteric (appendicitis, enteritis)

• Clinical:

  • Enlarged, tender nodes.

  • Skin may be red and hot.

  • Usually resolves; may progress to chronic form.

• Microscopy:

  • Sinus congestion, oedema.

  • Neutrophilic infiltration.

  • Prominent follicles, possible abscess formation.

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B. Chronic Nonspecific Lymphadenitis (Reactive Lymphoid Hyperplasia)

• Causes: Chronic antigenic stimulation, infections, malignancy.

• Patterns:

  1. Follicular Hyperplasia (B-cell proliferation)

     • Seen in children, RA, AIDS, syphilis.

     • Large germinal centers, active mitosis, phagocytosis.

     • Plasma cells, histiocytes in medulla.

     • Castleman’s Disease: A variant.

       • Hyaline-vascular type: Hyalinised arterioles, vessel proliferation.

       • Plasma cell type: Plasma cell and vascular proliferation.

  2. Paracortical Hyperplasia (T-cell proliferation)

     • Causes: Drugs (Dilantin), viral infections (e.g., EBV), vaccines, autoimmune disease.

     • Histology: Enlarged paracortical area with activated immunoblasts.

  3. Sinus Histiocytosis

     • Dilated sinuses with macrophages and reticular cells.

     • Seen in draining lymph nodes near malignancies.

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IV. Summary of Lymphocyte Maturation in Lymph Nodes

Stage	Location	Description
Centroblasts	Follicular center	Large non-cleaved B-cells
Centrocytes	Follicular center	Small cleaved B-cells
Large cleaved/non-cleaved	Follicular center	Intermediate maturation
Immunoblasts	Paracortex	Activated large lymphocytes
Lymphoblasts	Paracortex	Precursor to plasma cells
Plasma cells	Medulla	Antibody production

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V. Clinical Correlations

• Reactive vs. Neoplastic: Reactive lymphadenitis is benign and often reversible, while neoplastic involvement (e.g., lymphoma) is persistent and progressive.

• Lymph node biopsy is crucial for diagnosis in persistent lymphadenopathy.

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THYMUS

Normal Structure

• Location: Lies in the mediastinum, behind the sternum.

• Size:

  • At birth: 10–35 gm

  • At puberty: Maximum size

  • In elderly: Involuted; 5–10 gm

• Lobes: Right and left, encapsulated, connected by fibrous tissue.

• Lobules: Formed by connective tissue septa; each has:

  • Cortex: Outer, dense in lymphocytes (immature T-cells = thymocytes)

  • Medulla: Inner, less dense; contains mature T-cells

• Cell Types:

  • Epithelial cells: Network with elongated processes

  • Thymocytes: Immature T-cells (cortex), mature T-cells (medulla)

  • Macrophages

  • Hassall’s corpuscles: Concentric keratinized epithelial cells (in medulla)

• Function:

  • Maturation of T-cells

  • Secretes thymic hormones: Thymopoietin, Thymosin-α1

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Thymic Disorders

1. Thymic Hypoplasia and Agenesis

• Hypoplasia: Acquired (aging, malnutrition, cytotoxic drugs, steroids, irradiation, stress)

• Agenesis: Congenital (e.g., DiGeorge syndrome, SCID, Reticular dysgenesis)

2. Thymic Hyperplasia

• Failure of involution or actual enlargement

• Histological hallmark: Lymphoid follicles in medulla (thymic follicular hyperplasia)

• Causes:

  • Most common: Myasthenia gravis

  • Others: Addison’s disease, Graves’, RA, SLE, scleroderma, cirrhosis

3. Thymoma

• Most common anterior mediastinal tumour

• Derived from epithelial cells of thymus

• Usually in adults

• Clinical Presentation:

  • Asymptomatic (incidental)

  • Myasthenia gravis (common association)

  • Local symptoms: cough, dyspnoea, chest pain

• Gross Pathology:

  • Size: 5–10 cm, weight: ~150 gm

  • Lobulated, soft, yellowish; cystic, hemorrhagic or necrotic

• Microscopy:

  • Encapsulated with fibrous septa

  • Lobules with epithelial tumour cells + non-neoplastic lymphocytes

• Types:

  • Benign thymoma (medullary): Resembles normal thymic epithelium

  • Malignant thymoma:

    • Type 1: Benign histology, invasive

    • Type 2: Thymic carcinoma – true malignancy (squamous cell type common)

• Paraneoplastic syndromes:

  • Myasthenia gravis (most common)

  • Hypogammaglobulinemia

  • Pure red cell aplasia

  • T-cell leukaemia/lymphoma

  • Multiple myeloma, autoimmune diseases

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SPLEEN

Normal Structure

• Weight: ~150 gm in adults

• Location: Upper left quadrant, under 9th–11th ribs

• Capsule: Thin; sends trabeculae inside for support

• Blood Supply:

  • Splenic artery → trabeculae → central arterioles → sinuses and splenic veins

• Pulp Types:

  • Red pulp:

    • Thin-walled venous sinuses + splenic cords (cords of Billroth)

    • Contains blood cells, macrophages, lymphocytes

  • White pulp:

    • Lymphocytes around arteriole

    • T-cells: periarteriolar

    • B-cells: germinal centers surrounded by lymphocytes

Functions

1. Immune: Maturation and proliferation of B and T lymphocytes

2. Filtration: Removes abnormal/aged blood cells

3. Regulation: Controls portal blood flow

4. Haematopoiesis: Extramedullary in pathological states

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Splenic Disorders

1. Splenomegaly

• Definition: Enlargement of spleen

• Pathogenesis: Increased vascularity or cellularity

• Degrees:

  • Mild (≤5 cm): CHF, malaria, typhoid, RA, SLE, thalassemia minor

  • Moderate (to umbilicus): Cirrhosis, hepatitis, lymphoma, haemolytic anaemia

  • Massive (below umbilicus): CML, myelofibrosis, Gaucher’s, malaria, thal major

• Gross: Enlarged, firm, thickened capsule

• Microscopy:

  • Dilated sinusoids

  • Prominent red pulp

  • Atrophic white pulp

  • Long-standing: fibrosis, Gamna-Gandy bodies

• Special Type: Banti’s spleen = fibrocongestive splenomegaly

2. Hypersplenism

• Definition: Excess destruction of blood cells

• Mechanisms:

  • Sequestration due to altered blood flow

  • Autoimmune destruction

• Criteria:

  1. Splenomegaly

  2. Cytopenia (anemia, leukopenia, thrombocytopenia)

  3. Bone marrow is normal/hyperplastic

  4. Improvement post-splenectomy

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Effects of Splenectomy

• Red Cells:

  • Appearance of target cells, Howell-Jolly bodies, normoblasts

  • Increased osmotic fragility

• White Cells:

  • Transient leukocytosis with immature cells (myelocytes)

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Table 14.13: Causes of Splenomegaly

I. Infections

• Malaria, Leishmaniasis, Typhoid, Mono, TB, AIDS, Hepatitis, Septicemia

II. Immune Disorders

• RA, SLE, Autoimmune cytopenias

III. Altered Blood Flow

• Cirrhosis, Portal/splenic vein obstruction, CHF

IV. Lymphohaematogenous Malignancies

• Hodgkin's, NHL, Multiple myeloma, Leukaemias, Myeloproliferative disorders (CML, polycythemia vera, myelofibrosis)

V. Abnormal RBC Disorders

• Thalassemia, Sickle cell disease, Spherocytosis, Ovalocytosis

VI. Storage Diseases

• Gaucher’s disease, Niemann-Pick disease

VII. Miscellaneous

• Amyloidosis, Tumours (primary/metastatic), Idiopathic