Blood, lymphoid tissues and haemopoiesis

Blood is an opaque fluid with a viscosity greater than that of water

(mean relative viscosity 4.75 at 18 °C).

• It has a specific gravity of 1.06 at 15 °C.

• Blood is bright red when oxygenated (in systemic arteries)

and dark red to purple when deoxygenated (in systemic veins).

• Blood is a mixture:

• Of a clear liquid (plasma)

• And of cellular elements (red blood cells, white blood cells, platelets).

• The hydrodynamic flow of blood in vessels is complex

and cannot be entirely predicted by simple Newtonian equations.

Plasma

• Plasma is a clear, yellowish fluid.

• It contains many substances in solution or suspension.

• Low-molecular-weight solutes cause a freezing-point depression of about 0.54 °C.

• Plasma contains:

• High concentrations of sodium and chloride ions

• Potassium, calcium, magnesium, phosphate, bicarbonate

• Traces of many other ions

• Glucose, amino acids, vitamins

• It also includes high-molecular-weight plasma proteins, such as:

• Clotting factors (e.g., prothrombin)

• Immunoglobulins and complement proteins (for immune defense)

• Glycoproteins, lipoproteins

• Peptide and steroid hormones

• Globulins for transporting hormones and iron.

Clinical Importance

• Plasma is responsible for transporting most molecules released or secreted by cells

in response to pathological or physiological stimuli.

• Therefore, routine chemical analysis of plasma is of great diagnostic importance.

• There is a growing interest in metabolomics:

• High-throughput analysis of small molecules or metabolites in serum

• As a tool to aid diagnosis and the understanding of diseases

(reference: Psychogios et al., 2011).

Blood Coagulation

• Fibrin is a protein that precipitates from plasma to form a clot.

• Clot formation is triggered by the release of materials from damaged cells and platelets, in the presence of calcium ions.

• When blood or plasma samples are left standing, they separate into:

• Clot

• Serum (clear, yellowish fluid)

• Prevention of clotting:

• Removal of calcium by adding agents such as:

• Citrate

• Oxalate

• Organic chelators (EDTA, EGTA)

• Heparin: prevents fibrin clot formation by interfering with the process.

Hemopoiesis (Blood Cell Production)

• Takes place in the bone marrow after birth.

• Produces:

• Erythrocytes (red blood cells)

• Leukocytes (white blood cells):

• Granulocytes:

• Neutrophils

• Eosinophils

• Basophils

• B lymphocytes

• Monocytes

• Platelets: cellular fragments derived from megakaryocytes.

• T lymphocytes develop in the thymus from bone marrow progenitors.

Circulation and Cell Migration

• Erythrocytes and platelets remain within the vascular system.

• Leukocytes can leave blood vessels and migrate into tissues, especially during:

• Inflammation

• Local infections

• Tissue damage

Lymphoid Tissues

• Main tissues:

• Thymus

• Lymph nodes

• Spleen

• Lymphoid follicles associated with:

• Gastrointestinal tract

• Respiratory tract

• Function: immune defense (populated by lymphocytes).

• Other cells present:

• Supportive stromal cells (non-hemopoietic origin):

• Thymic epithelium

• Follicular dendritic cells in lymph nodes and spleen

• Dendritic cells and macrophages (hemopoietic origin):

• Act as antigen-presenting cells (APCs).

• Also found in many tissues and organs.

Erythrocytes (RBCs):

• Make up 99% of blood cells

• Normal values:

• Males: 4.1–6.0 × 10⁶/μL

• Females: 3.9–5.5 × 10⁶/μL

Disorders:

• Polycythaemia: Too many RBCs (e.g. at high altitude, arterial hypoxia)

• Anaemia: Too few RBCs; causes vary (rarely structural)

Structure:

• Shape: Biconcave disc

• Diameter: ~7.1 μm (dry), ~7.8 μm (fresh)

• No nucleus

• Color: Pale red with lighter center (due to shape)

• Rouleaux: Cells stick in stacks

• Osmotic effects:

• Hypertonic: Crenated (shrink)

• Hypotonic: Swell, burst (haemolysis)

Membrane:

• Made of: 60% lipids, 40% proteins

• Main protein: Haemoglobin (33% of cell content)

Membrane Proteins:

• Glycophorins A & B: Carry negative charge (via sialic acid)

• Band 3 protein: Ion exchange (bicarbonate ↔ chloride)

Cytoskeleton:

• Key protein: Spectrin

• Forms tetramers → hexagonal lattice

• Other proteins: Ankyrin, actin, tropomyosin, protein 4.1

• Function: Shape maintenance, flexibility

• Defects cause: Hemolytic anemia

Fetal RBCs:

• Larger, nucleated, contain fetal hemoglobin (HbF)

• Replaced by adult RBCs after 4th month gestation

Haemoglobin (Hb):

• Globular protein, 67 kDa

• Composed of:

• Globulin + Haem group (contains iron)

• Iron binds oxygen (Fe²⁺ state maintained by glutathione)

• Tetramer: 4 polypeptide chains, each holds 1 haem

• Mutations → Hemoglobinopathies (e.g. sickle cell)

Lifespan of Erythrocytes:

• Live 100–120 days

• Ageing changes:

• Fragility increases

• Decrease in negative membrane charge (loss of glycoproteins)

• Lipid content reduces

• Old RBCs removed by spleen & liver macrophages

• Degradation process:

• Haemoglobin → globulin + porphyrin

• Globulin → amino acids

• Iron → reused (bound to transferrin) or stored (ferritin/haemosiderin)

• Haem → bilirubin, excreted in bile

• Free Hb binds haptoglobin → taken up by CD163 receptors

• Recognition signals for macrophages:

• Exposure of inner membrane phospholipids (e.g. phosphatidylserine)

• Loss of sialic acid

• Binding of autoantibodies

• Destruction rate: ~5 × 10¹¹ RBCs/day (~6 million/second)

• Replaced at the same rate by bone marrow

Blood Groups:

• 300+ red cell antigens

• 19 major blood group systems (e.g. ABO, Rhesus, Kell, Duffy, Kidd, etc.)

• Important in transfusion compatibility

• ABO & Rhesus = clinically most important

• Unmatched transfusion → agglutination & lysis

Leukocytes (White Blood Cells):

• 5 types (based on size, nucleus shape, cytoplasmic granules)

• Divided into:

• Granulocytes: contain visible granules

• Agranulocytes: no visible granules

Granulocytes:

• Eosinophils: stain with acidic dye (eosin)

• Basophils: stain with basic dyes

• Neutrophils: stain weakly with both

• All have multilobed nuclei

• Originate from myeloid series.

Neutrophils (Polymorphonuclear Leukocytes / Polymorphs):

• Named for their irregularly shaped, multilobed nuclei

• Belong to granulocytes; part of myeloid lineage

Haemoglobin Chains and Types:

• Five types of polypeptide chains:

• α, β, γ, δ, ε (ε only in early fetal life)

• Each Hb molecule = 2 α-chains + 2 others → various combinations:

• HbA (adult): 2 α + 2 β (major form)

• HbA₂: 2 α + 2 δ (~2% of adult Hb)

• HbF (fetal): 2 α + 2 γ (<1% in adults)

Haemoglobinopathies:

• Thalassaemia:

• One chain type underproduced or absent

• β-thalassaemia: Excess α-chains (α₄)

• α-thalassaemia: Excess β-chains (β₄)

• Sickle-cell disease:

• HbS: β-chain mutation (valine replaces glutamic acid)

• HbS polymerizes in low O₂ → RBC deformity

ABO Blood Group System:

• Determined by two allelic genes:

• AA → group A, BB → B, OO → O

• AB → AB, AO → A, BO → B

• Antigens = membrane glycolipids

• AB: No anti-A or anti-B antibodies → universal recipients

• O: No A/B antigens → universal donors

• ABO antibodies = IgM (do not cross placenta)

Rhesus (Rh) System:

• Controlled by three gene pairs: Cc, Dd (clinically most important), Ee

• D antigen defines Rh status:

• Dd or DD → Rh-positive, dd → Rh-negative

• Maternal sensitization:

• Rh-negative mother + Rh-positive fetus → anti-D (IgG) antibodies

• IgG crosses placenta, especially at birth → may destroy fetal RBCs

• First pregnancy: little/no damage

• Subsequent pregnancies: haemolytic disease of the newborn

• Causes of sensitization:

• Birth, miscarriage, abortion, amniocentesis

• Treatment/Prevention:

• Anti-D (Rh-immune globulin) given after first Rh⁺ pregnancy

• Exchange transfusion for newborn if needed.

Leukocytes and Their Functions

Eosinophils

• Have bilobed nuclei.

• Cytoplasm contains pink granules rich in major basic protein (MBP) and eosinophilic cationic proteins.

• MBP is cytotoxic: kills parasites and is involved in allergic reactions.

• Increase in parasitosis and allergies.

• Capable of chemotaxis, diapedesis, and phagocytosis.

Basophils

• Least abundant leukocytes in the blood.

• Nucleus is irregular, often obscured by coarse blue granules.

• Contain heparin (anticoagulant), histamine (vasodilator), and other inflammatory mediators.

• Active in allergic reactions and hypersensitivity.

• Precursors of mast cells.

• Not very phagocytic.

Monocytes

• Large cells with kidney-shaped nucleus.

• Cytoplasm is abundant and gray-blue.

• In tissues, they differentiate into macrophages.

• Involved in phagocytosis, antigen presentation, and inflammation modulation.

• Secrete cytokines, attract and activate other immune cells.

• Examples of tissue macrophages:

• Kupffer cells (liver)

• Alveolar macrophages (lungs)

• Microglia (brain)

Lymphocytes

• B lymphocytes:

• Produce antibodies.

• Differentiate into plasma cells after antigen stimulation.

• T lymphocytes:

• Helper T cells (CD4+): activate B cells and other immune cells.

• Cytotoxic T cells (CD8+): destroy infected or tumor cells.

• Natural Killer (NK) cells: part of innate immunity, attack virus-infected or abnormal cells.

• Fundamental in adaptive immune response.

PLATELETS – Study Notes in English

1. General Overview

• Platelets (thrombocytes) are small, oval or irregular discs, measuring 2–4 μm in diameter.

• Present in large numbers in blood: 200,000–400,000/μl.

• In fresh blood samples, they readily adhere to each other and to surfaces, unless treated with citrate or other calcium-chelating agents.

• They are anucleate cell fragments, derived from megakaryocytes in the bone marrow.

2. Structure

• Surrounded by a plasma membrane with a thick glycoprotein coat, which gives them adhesive properties.

• Just beneath the membrane: a band of 10 microtubules, associated with actin filaments, myosin, and other contractile proteins.

• The cytoplasm contains:

• Mitochondria

• Glycogen

• Scant smooth endoplasmic reticulum

• Tubular invaginations of the plasma membrane

• Three main types of granules:

• Alpha (α) granules (up to 500 nm): contain PDGF (platelet-derived growth factor), fibrinogen, and other proteins.

• Delta (δ) granules (up to 300 nm): contain serotonin (5-HT) taken up from plasma.

• Lambda (λ) granules (up to 250 nm): contain lysosomal enzymes.

3. Function: Hemostasis (Stopping Bleeding)

Activation

• When a blood vessel is damaged:

• Platelets become activated

• Form lamellipodia and filopodia (membrane extensions)

• Aggregate at the injury site, forming a temporary plug

Adhesion & Aggregation

• Platelets adhere to each other (agglutination) and to surrounding tissues.

• Promoted by the release of ADP and calcium ions from the platelets.

• The glycoprotein coat aids in adhesion.

Coagulation

• Alpha granules release PDGF, fibrinogen, and other factors.

• Along with substances from damaged tissue, they trigger a cascade of chemical reactions → leads to formation of insoluble fibrin.

• Fibrin forms a 3D meshwork: the fibrin clot.

• More platelets bind to the clot, inserting filopodia into the fibrin network → strong attachment.

Clot Retraction

• Platelets contract via actin-myosin interactions, tightening the clot and pulling the vessel walls together to reduce blood loss.

Clot Resolution

• After vessel repair (aided by PDGF), the clot is dissolved.

• Done by plasmin, activated from plasminogen by plasma activators.

• Lysosomal enzymes from lambda granules may assist.

4. Lifespan

• Platelets circulate for about 10 days.

• Removed mainly by splenic macrophages

Lymphocytes and Lymphoid Organs

1. Location of Lymphocytes

• Lymphocytes are found in many parts of the body, especially in areas exposed to infection (e.g., oropharynx).

• They are concentrated in lymphoid organs, divided into:

• Primary lymphoid organs: where lymphocytes are generated (e.g., bone marrow, thymus).

• Secondary (or peripheral) lymphoid organs: where mature lymphocytes become activated and initiate the immune response.

2. Secondary Lymphoid Organs

• These are the meeting points for B cells, T cells, and antigen-presenting cells.

• Include:

• Lymph nodes

• Spleen

• Mucosa-associated lymphoid tissue (MALT) – e.g., tonsils, Peyer’s patches (in the small intestine), lymphoid nodules in the respiratory and urogenital tracts, and skin.

• Lymphocytes enter secondary lymphoid tissues from the bloodstream (via high endothelial venules – HEVs) and exit through the lymphatic system.

• Dendritic cells enter via lymphatic vessels, carrying antigens from peripheral infection sites.

• After activation, lymphocytes migrate to other body sites to fight the infection.

• In sites of chronic inflammation, organized lymphoid structures may form called tertiary lymphoid organs.

3. Lymph Nodes

• Encapsulated centers for antigen presentation and for lymphocyte activation and proliferation.

• Filter particles and microbes through the activity of phagocytic macrophages.

• A young adult has about 450 lymph nodes, including:

• 60–70 in the head and neck

• 100 in the thorax

• Up to 250 in the abdomen and pelvis

• Numerous in: neck, mediastinum, posterior abdominal wall, mesenteries, pelvis, axillary and inguinal regions.

Microstructure

• Oval or kidney-shaped (0.1–2.5 cm).

• Hilum: the site where blood vessels enter/exit and where the efferent lymphatic vessel exits.

• Capsule: receives multiple afferent lymphatic vessels.

• Internal structure includes:

• Subcapsular sinus

• Cortex (with primary lymphoid follicles)

• Paracortex

• Medulla (with medullary sinuses)

• Efferent lymphatic vessel

4. Lymphocyte Origin

• All lymphocytes derive from pluripotent hematopoietic stem cells in the bone marrow.

• B lymphocytes: develop entirely in the bone marrow and then migrate to peripheral tissues.

• T lymphocytes: precursors migrate from the bone marrow to the thymus, where they mature and undergo selection (only 1–3% survive).

• Mature T cells enter the bloodstream and travel to secondary lymphoid organs.

Lymphatic and Vascular Supply of Lymph Nodes

• Lymph circulation: Lymph enters through afferent lymphatic vessels → subcapsular sinus → cortical sinuses → medullary sinuses → exits via efferent lymphatic vessels at the hilum.

• Conduit system: Sponge-like collagen network with fibroblastic reticular cells transports antigens and signaling molecules (e.g. chemokines).

• Dendritic cells: Sample antigens from lymph within conduits and present them to lymphocytes.

Blood Supply

• Arteries and veins enter at the hilum and branch throughout the cortex and medulla.

• Postcapillary high endothelial venules (HEVs) in the paracortex are key sites for lymphocyte entry from blood.

• Vessels become denser during immune activation due to increased lymphocyte activity.

Cellular Zones of the Lymph Node

1. Cortex

• Contains lymphoid follicles (mostly B cells and follicular dendritic cells).

• Primary follicles: Small, resting B cells.

• Secondary follicles: Contain germinal centers with activated, proliferating B cells.

2. Germinal Centers

• Dark zone: Rapidly dividing B cells (centroblasts) undergo antibody hypermutation.

• Light zone: Selection of B cells with high-affinity antibodies (centrocytes), interaction with FDCs and T cells.

• Tingible body macrophages: Phagocytose dying B cells.

3. Mantle zone: Surrounds germinal center, mostly resting B cells and a few helper T cells.

4. Paracortex (deep cortex)

• Rich in T cells (CD4+ and CD8+).

• Contains interdigitating dendritic cells, including Langerhans cells.

• Expands during T-cell immune responses.

5. Medulla

• Contains medullary cords with fewer lymphocytes, more macrophages, plasma cells, and some granulocytes.

Mucosa-Associated Lymphoid Tissue (MALT)

• Found in mucosal surfaces: gastrointestinal, respiratory, reproductive, urinary tracts, and skin.

• Includes tonsils, Peyer’s patches, and many microscopic lymphoid nodules.

• Mainly B cells, T cells, dendritic cells, and macrophages.

• Functions similarly to lymph nodes: lymphocyte activation and antigen presentation.

• No afferent lymphatics; lymphocytes enter via HEVs and exit through efferent vessels.

• After activation, lymphocytes travel to other mucosal sites to provide immune defense.

• Main role of B cells in MALT: Produce IgA antibodies secreted into mucosal linings.

HAEMOPOIESIS

• Definition: The formation of blood cells, primarily occurring in the bone marrow after birth.

• If bone marrow production is insufficient, the spleen and liver may resume haemopoietic activity.

BONE MARROW

• Location: Found in marrow cavities of all bones and in large Haversian canals.

• Forms:

• Red marrow: Active haemopoiesis.

• Yellow marrow: Mainly fat; inactive, but can revert to red marrow if needed.

• In old age: cranial bone marrow may become gelatinous.

Yellow Marrow

• Made of connective tissue and blood vessels.

• Contains many adipocytes.

• Small number of red marrow cells remain and may be reactivated.

Red Marrow

• Present throughout fetal skeleton and in children.

• After ~5 years: red marrow is gradually replaced by yellow marrow in long bones.

• In adults (20–25 years): red marrow is found in vertebrae, sternum, ribs, pelvis, clavicles, scapulae, and proximal femur and humerus.

• Structure:

• Stroma: loose connective tissue supporting haemopoietic cells (cords/islands).

• Rich vascular supply, with large sinusoids draining into large veins.

• No lymphatic vessels.

• Marrow = vascular + extravascular compartments, enclosed by bone and separated by endosteal cells.

STROMA

• Composed of type III collagen (reticulin) fibers from reticular cells (fibroblast-like).

• When haemopoiesis stops, stromal cells fill with fat (→ yellow marrow).

• Functions:

• Support haemopoiesis.

• Contain macrophages that:

• Remove debris (e.g. erythroblast nuclei).

• Transfer iron to erythroblasts.

• Help regulate cell differentiation/maturation.

MARROW SINUSOIDS

• Lined by endothelial cells with tight junctions and thin cytoplasm.

• Basal lamina is discontinuous.

• Blood cells pass into circulation via transient fenestrae in endothelium.

HAEMOPOIETIC TISSUE

• Cords/islands contain clusters of blood cell precursors.

• Each cluster has a central macrophage:

• Transfers iron for hemoglobin.

• Helps regulate cell development.

CELL LINEAGES

Haemopoietic Stem Cells (HSCs)

• Very rare (~0.05%).

• Pluripotent and self-renewing.

• Can differentiate into all blood cell types.

• Identified by surface markers like CD34.

• Found near endosteum or sinusoidal endothelium (niches).

• Also present in peripheral blood after cytokine treatment.

Progenitor Cells

• Arise from HSCs.

• More lineage-specific (not self-renewing).

• Examples:

• CFU-GM → granulocytes + monocytes.

• CFU-E → erythrocytes.

• Mature in marrow before entering circulation (except monocytes, which mature in tissues).

• Full blood regeneration from a single HSC takes months.

Bone Marrow Transplantation

• Requires pluripotent stem cells to succeed.

• Only 5% of normal HSCs are needed to repopulate marrow.

• T lymphocyte recovery is slower due to thymic involution with age.

Mesenchymal Stem Cells

• Also found in marrow and circulation.

• Can differentiate into non-haemopoietic cells (e.g. bone, cartilage).

• Investigated for use in organ repair.

Haemopoietic Stem Cells

• Stem Cells in Adult Bone Marrow: Very small population (~0.05%); self-renewing and pluripotent — give rise to all blood cell types including lymphocytes.

• Identification: Not visible morphologically; detected by surface markers like CD34.

• Location: Found in specific niches near the endosteum or sinusoidal endothelium; microenvironment regulates self-renewal vs differentiation.

• Peripheral Blood Presence: Found in low concentrations, especially after cytokine treatment.

Progenitor Cells

• Lineage-Restricted: Arise from stem cells; called colony-forming units (CFU).

• CFU-GM → granulocytes & monocytes.

• CFU-E → erythrocytes.

• Maturation: Occurs in the marrow; some cells mature in blood (e.g., erythrocytes), others in tissues (e.g., monocytes → macrophages).

Timeframe and Therapy

• Development Time: Full blood cell set from one pluripotent cell takes months.

• Later progenitors: Faster maturation but not self-renewing → important in bone marrow transplants.

• Success of Transplant: Requires pluripotent stem cells (only ~5% needed).

• T-cell Recovery: Slower due to thymus involution with age.

Mesenchymal Stem Cells

• Also present in marrow; can become non-haemopoietic cells.

• Also found in the bloodstream; investigated for tissue repair applications.

Lymphocytes

• Arise from a lymphoid progenitor cell (separate from myeloid).

• First identifiable form: lymphoblast, then prolymphocyte.

• B Cells:

• Develop entirely in the bone marrow.

• Undergo gene rearrangement for a unique antigen receptor.

• ~25% complete development; autoreactive ones are eliminated.

• Leave marrow as naive B cells with IgM and IgD receptors.

• Class switching occurs in peripheral tissues post-activation.

• T Cells:

• Require thymus for development.

• Progenitors migrate to thymus during fetal/early life.

• Undergo gene rearrangement of TCR.

• Recognize peptides presented with MHC molecules:

• CD8 T cells: MHC I.

• CD4 T cells: MHC II.

• MHC restriction: T cells only recognize peptides with self-MHC.

• Selection in thymus:

• Positive (moderate affinity to self-MHC) in cortex by epithelial cells.

• Negative (eliminates self-reactive cells) by dendritic cells and epithelial cells.

• ~95% of T-cell progenitors undergo apoptosis.

• Mature naive T cells exit thymus and go to peripheral tissues.

Thymic Environment

• Crucial for T-cell development.

• Stromal cells (epithelial, dendritic, fibroblasts) express MHC and secrete cytokines, chemokines, neuropeptides, and thymic hormones (e.g., thymulin).

• Apoptotic cells are removed by macrophages.

Macrophages

• Function: Phagocytose (engulf and digest) microorganisms, apoptotic cells, and tissue debris.

• Immunologically Silent: Uptake of apoptotic cells does not trigger antigen presentation or immune activation.

• Locations and Roles:

• Lungs: Alveolar macrophages (dust/heart failure cells) patrol respiratory surfaces, remove inhaled particles.

• Connective tissues: Kill invaders, clean up damaged cells.

• Pleural & peritoneal cavities: Act as scavengers.

• Lymph nodes: Line sinuses, filter lymph.

• Spleen & liver: Destroy old RBCs, recycle hemoglobin (iron, amino acids).

• Phagocytosis Enhancement:

• Increased by opsonization (coating with antibodies or complement).

• Uses Fc and C3 receptors.

• Fuses phagosome with lysosomes (contains hydrolases, bactericidal systems).

• Activated by cytokines like IFN-γ.

• Cytotoxic Role: Can release enzymes onto cell surfaces if targets are too large (e.g., parasites).

Macrophage Secretions

• Cytokines: IL-1 (stimulates lymphocytes), TNF-α (kills tumor cells, causes cachexia).

• Enzymes and Factors: Plasminogen activator, complement factors, clotting factors, lysozyme.

• Pathology: Can damage healthy tissue in diseases like rheumatoid arthritis.

Dendritic Cells

• Two Main Types:

• Myeloid (Classical) DCs: Professional antigen-presenting cells (APCs), from myeloid lineage.

• Plasmacytoid DCs: Also from lymphoid/myeloid origin, role in innate immunity.

• Locations:

• Immature DCs found in:

• Epidermis (Langerhans cells)

• Oral mucosa

• Dermis & most tissues (interstitial DCs)

• Functions:

• Immature DCs: Capture antigens, respond to chemotactic signals (e.g., defensins).

• Pattern Recognition: TLRs detect PAMPs (e.g., LPS, bacterial DNA).

• DAMPs Recognition: Respond to ATP, HMGB1 from damaged cells.

• Migration: Upon activation, DCs move to lymph nodes via lymphatics.

• In lymphatics: Called veiled cells.

• In lymph nodes: Become interdigitating DCs.

• Main Role: Present processed antigen to naive T cells, initiating immune responses.

Langerhans Cells

• Type: Immature dendritic cells.

• Location: Epidermis (especially in the stratum spinosum).

• Morphology: Irregular nucleus, clear cytoplasm, and Birbeck granules (specialized vesicles).

• Function: Capture and process antigens via endocytosis; mature into antigen-presenting cells (APCs).

• Activation: Upregulate MHC I & II, co-stimulatory, and adhesion molecules.

• Migration: Travel to lymph nodes to activate T lymphocytes.

Interdigitating Dendritic Cells

• Origin: Mature from immature dendritic cells found in peripheral tissues and blood.

• Location: T-cell zones of secondary lymphoid tissues:

• Paracortex of lymph nodes

• Interfollicular areas of MALT

• Periarteriolar sheath in spleen

• Function: Present antigen via:

• MHC I to CD8+ T cells

• MHC II to CD4+ T cells

• T cell activation requires:

• Antigen-MHC complex recognition (via TCR)

• Co-stimulatory signals

• Cytokine signaling (influences Th1/Th2 differentiation)

Follicular Dendritic Cells (FDCs)

• Origin: Non-haematopoietic (likely stromal).

• Location: Follicles of secondary lymphoid tissues (e.g., tonsils).

• Do not: Migrate, endocytose/process antigen, or express MHC II.

• Have: Fc receptors and complement receptors (CD21, CD35).

• Function:

• Retain antigen-antibody complexes on surface.

• Present unprocessed antigen to B cells in germinal centers.

• Support B cell selection and maturation (plasma cells & memory B cells).

• Interact with CD4+ helper T cells and B cells for high-affinity antibody production.