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LYMPHATIC SYSTEM, HEMATOPOIETIC & IMMUNE SYSTEM ORGANS

Comprehensive MBBS Notes - Basic to Advanced

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PART 1: THE LYMPHATIC SYSTEM

1.1 Overview and Definition

• Specialized vessels (lymphatics) that drain fluid from tissues
• Lymph nodes interspersed along those vessels
• Secondary lymphoid organs (spleen, tonsils, MALT)
• Primary lymphoid organs (bone marrow, thymus)

1. Fluid homeostasis - prevents tissue edema by returning interstitial fluid to the bloodstream
2. Immune surveillance - transports antigens and immune cells to lymph nodes where adaptive immune responses are initiated

"The lymphatic system represents an accessory route through which fluid can flow from the interstitial spaces into the blood. Most importantly, lymphatics can carry away proteins and large particulate matter that cannot be removed by absorption directly into blood capillaries - without which we would die within about 24 hours."

• Guyton & Hall Medical Physiology

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1.2 Components of the Lymphatic System

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1.3 Lymphatic Vessels - Four Types

• Rhythmic smooth muscle contractions in collector segments (peristalsis-like, 10-12 contractions/min)
• Musculoskeletal movement (external compression)
• Arterial pulsations transmitted to adjacent lymphatic vessels
• One-way valves prevent backflow at every level

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1.4 Drainage Routes - MUST KNOW

• Left side of head and neck
• Left arm
• Both legs
• Abdominal viscera (via cisterna chyli)
• Left thorax → Empties into junction of left subclavian vein and left internal jugular vein

• Right side of head and neck
• Right arm
• Right thorax → Empties into junction of right subclavian vein and right internal jugular vein

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1.5 Formation of Lymph

• Approximately 10% of capillary filtrate enters lymphatics (the other 90% is reabsorbed by venous capillaries)
• Total lymph returned to circulation: 2-3 L/day
• Protein concentration of lymph: ~2 g/dL in most tissues; up to 6 g/dL in liver lymph (liver is very protein-leaky)
• Intestinal lymph: 3-4 g/dL protein; after fatty meal, contains 1-2% fat as chylomicrons
• Thoracic duct lymph (mixture of all): 3-5 g/dL protein

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1.6 The Glymphatic System (Advanced)

• In the CNS, true lymphatic vessels exist only in the meninges
• Deeper brain tissue uses the glymphatic (glial-lymphatic) system:
  • CSF flows into perivascular spaces formed by astrocytic endfeet around cerebral arteries
  • Flows into brain parenchyma via aquaporin-4 water channels (AQP4) on astrocytes
  • Exits via perivenous spaces, carrying waste products (including amyloid-beta) into meningeal lymphatics
• Clinical relevance: Disruption of the glymphatic system is implicated in Alzheimer disease and other neurodegenerative conditions

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PART 2: LYMPH NODES

2.1 General Structure

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2.2 Follicles - Primary vs Secondary

• Dark zone - packed with proliferating centroblasts (hypermutation occurring)
• Light zone - centrocytes selected by FDCs for high-affinity antibody; low-affinity cells undergo apoptosis
• Output - memory B cells + long-lived plasma cells (migrate to bone marrow)

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2.3 T Cell Zone (Paracortex)

• Populated mainly by T lymphocytes and dendritic cells (DCs)
• Contains High Endothelial Venules (HEVs) - specialized postcapillary venules allowing lymphocyte trafficking from blood into the node
• Naive T cells express CCR7 receptor → binds CCL19/CCL21 produced by paracortical FRCs → directs naive T cells into T cell zone
• Naive B cells express CXCR5 → binds CXCL13 from B zone FRCs → directs B cells into follicles
• FRC conduits (0.2-3 μm diameter tubes of ECM) act as tracks along which T cells and DCs migrate

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2.4 Antigen Transport Through Lymph Nodes

1. DCs in skin/mucosa capture antigen → enter afferent lymphatics
2. Arrive at subcapsular sinus of draining lymph node
3. High-molecular-weight antigens → taken up by sinus macrophages → passed to FDCs in follicles
4. Soluble small antigens → travel via FRC conduits to T cell zone
5. DCs in T zone present antigen to T cells → adaptive immune response begins

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PART 3: PRIMARY LYMPHOID ORGANS

3.1 Bone Marrow

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3.2 Hematopoiesis - Full Hierarchy

1. Pluripotency - one HSC generates all mature blood cell types
2. Self-renewal - HSCs can divide to produce exact copies of themselves; this maintains the pool throughout life

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3.3 B Cell Development in Bone Marrow

1. Pro-B cell - DJ rearrangement begins
2. Pre-B cell - VDJ rearrangement complete; cytoplasmic μ heavy chain expressed (cμ+)
3. Immature B cell - Complete IgM assembled on surface (sIgM+); leaves bone marrow
4. Mature naive B cell - Co-expresses sIgM and sIgD; enters blood
5. Activated B cell (antigen-dependent) - encounters antigen + T helper signals → enters germinal center
6. Plasma cell - secretes large amounts of antibody
7. Memory B cell - long-lived; rapid secondary response

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3.4 Thymus

• Bilobed organ in the anterior superior mediastinum
• Each lobe is subdivided into multiple lobules by fibrous trabeculae
• Largest in childhood; begins to involute (fatty atrophy) at puberty
• By adulthood: largely replaced by fat but retains functional tissue

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3.5 T Cell Development in the Thymus

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PART 4: SECONDARY LYMPHOID ORGANS

4.1 Spleen

• Location: Left upper quadrant (LUQ), between 9th-11th ribs
• Attachments: Gastrolienal ligament (to stomach) and lienorenal ligament (to kidney)
• Blood flow: ~150 mL/min through splenic artery; drained by portal circulation
• Weight: ~150 g in adults

1. Quality control of erythrocytes in red pulp - removal of senescent/defective RBCs
2. Synthesis of antibodies in white pulp
3. Removal of antibody-coated bacteria and blood cells from circulation
4. Storage of monocytes (released during infection/inflammation)
5. Site of extramedullary hematopoiesis in certain diseases

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4.2 Splenic Microarchitecture

• Blood from central arterioles flows into macrophage-lined sinuses AND cords
• Blood in sinuses re-enters circulation easily (via splenic venules)
• Blood in cords must squeeze through narrow slits (2-3 μm) in the sinus lining
• Young, deformable RBCs pass through → enter sinuses → circulation
• Old, stiff, or damaged RBCs cannot pass → retained in cords → destroyed by macrophages
• Inclusions (Howell-Jolly bodies = nuclear remnants; Heinz bodies = denatured Hb; malaria parasites) are "pitted" out during this squeeze

• Loss of marginal zone macrophages → inability to rapidly clear encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis)
• Risk: Overwhelming Post-Splenectomy Infection (OPSI) - mortality up to 50%
• Prevention: Vaccinate against pneumococcus, meningococcus, H. influenzae; lifelong prophylactic penicillin; patient education
• Blood film after splenectomy: Howell-Jolly bodies, target cells, thrombocytosis

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4.3 Tonsils and MALT

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PART 5: CELLS OF THE IMMUNE SYSTEM

5.1 Summary Table of Key Immune Cells

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5.2 Chemokine-Mediated Cell Homing (Advanced)

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PART 6: REACTIVE CHANGES & CLINICAL CORRELATIONS

6.1 Leukocytosis - Mechanisms

1. Size of marrow precursor pool
2. Rate of release from marrow storage pools
3. Marginal pool (cells adherent to vessel walls)
4. Rate of emigration into tissues

6.2 Lymphadenopathy - Pattern Diagnosis

6.3 Splenomegaly - Classification

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PART 7: EMBRYOLOGY SUMMARY

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QUICK REVISION TABLE - HIGH-YIELD FACTS

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What These Notes Cover

• Hematopoiesis hierarchy from HSC to all blood cells (with full diagram)
• B cell maturation stages with VDJ rearrangement
• Thymus histology (cortex/medulla, Hassall's corpuscles)
• T cell development: double negative → double positive → single positive, positive and negative selection, AIRE gene