16: Lymphoid Tissues And Organs

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Properties of the Adaptive Immune System (Primary and Secondary Lymphoid Tissues/Organs)

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1) SPECIFICITY: antibodies and T cell receptors
2) DIVERSITY
3) MEMORY: secondary response stronger and faster than first response
4) SELF RECOGNITION: via glycoprotein cell surface markers called MHC molecles (present in all cells except RBC's)

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Humoral Immune Response

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production of antibodies

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Cell-Mediated Response

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production of special cells that directly attack foreign or infected cells

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Function of lymphoid organs and tissues

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production of lymphocytes for the purpose of protecting the body against harmful invasion of exogenous macromolecules

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Primary Lymphoid Organs

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FUNCTION: antigen INDEPENDENT proliferation --
precursor B or T lymphocytes undergo development, differentiations, and proliferation to generate populations of cells that respond to antigens

WHAT:
1) Thymus: primary organ for T cells
2) Bone marrow: B cells proliferation and development of immuncompetence (some also in GALT)
**no pure primary B cell organ

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Secondary Lymphoid ORgan

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WHAT:
1) MALT - Tonsils and Appendix
2) Lymph Nodes
3) Spleen

FUNCTION: antigen DEPENDENT proliferation
-where proliferation of B and T cells occur that occurs when an individual cell is stimulated by a specific antigen --> results in clone of cells that is responsive to that one antigen:
- Effector cells
- Memory cells

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Organization of Thymus

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Lobular Organization:
1) Cortex
2) Medulla - pale b/c of decrease packing density of parenchyma cells

Capsule: CT surrounding each lobule

Intralobular Trabeculae (Septa): from capsule projecting into cortex

Principal Cell: Thymocyte - developing T-cell

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Intralobular Trabeculae (Septae) of Thymus

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Project from capsule surrounding lobules into cortex

FUNCTION: provide route of entry and exit for blood vessels, efferent lymphatics, and nerves.

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Thymocytes (what, maturation pattern, and lifespan)

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maturing T Cells
- principal cell/most numerous cell of the thymus

- enters CORTEX and displaces older maturing thymocytes towards medulla
- can detect via CD proteins

MATURATION PATTERN:
from cortex -> medulla
- acquire:
1) surface markers (MHC molecules)
2) specific receptors for recognition of antigens (T-cell receptors)
-when reach MEDULLA = naive IMMUNOCOMPETENT T-LYMPHOCYTES

THYMOCYTE SURVIVAL:
- about 90% die via apoptosis before reaching medulla
-ones that survive are those that recognize alien antigens + have certain self MHC molecules

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Migration Pathway of Thymocytes:
1) Developing T-Cells -> Maturation
2) Gaining Competence
3) Naive Immunocompetent T-cells

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1) Developing T-Cells: from bone marrow to thymus via THYMOTAXIC FACTORS SECRETED BY EPITHELIORETICULAR CELLS
2) Gaining Competence: Cortex-> Medulla
3) Immunocompetent T-Cells: Medulla -> corticomedullary junction via 1. Venules and/or 2. lymphatic caps (in the inner medulla and pass into the septa)

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Stroma of Thymus

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Cytoreticulum - network of cells - comprised of epithelioreticular cells

- cells derived from embryonic epithelium

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Epithelioreticular cells: Morphology and Function

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MORPHOLOGY:
- large pale nuclei and relatively voluminous cytoplasm,
- stains lighter than than thymocytes

FUNCTION:
1) BARRIER: blood-thymic barrier - that isolates cortical thymocytes as they proliferate and undergo by encircling capsule, septa, and vessels
2) STROMAL SUPPORT
3) DEVELOPMENTAL SUPPORT: monitor thymocyte development & play role in immunological "education of thymocytes"
- Thymic Nurse Cells
- Hassall's corpuscles: found in medulla!
4) ENDOCRINE FUNCTION: thymic hormone-secreting cells
- secrete peptides that serve both paracrine and endocrine functions for differentiations of thymocytes and thh expression of their surface markers

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Hassall's Corpuscles: Function and Morphology

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FUNCTION:
- like thymic nurse cells in function: play immunological role in education of thymocytes
- unique to thymus' medulla!

MORPHOLOGY:
- multi-layered sphere of epithelioreticular cells
- filled with keratohyalin granules and keratin filaments

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Unique Characteristics of Thymus

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1) Hassall's Corpuscles
2) No lymphoid nodules (follicles)

**Site of antigen INDEPENDENT T-cell proliferation

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Secondarly Lymphoid Tissues and Organs
1) Encapsulated
2) Solitary
3) Incompletely Encapsulated
4) Diffuse Lymphoid System - not encapsulated and a part of other organs

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1) ENCAPSULATED
- Lymph Nodes

2) SOLITARY:
-Spleen

3) INCOMPLETELY ENCAPSULATED:
- Tonsils

4) DIFFUSE: MALT

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MALT: Mucosa Associated Lymphoid Tissue

1) Types
2) Epithelium
3) Capsule??

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2 TYPES:
1) DIFFUSE MALT: composed of immunosurveillance cells
2) ORGANIZED MALT: in nodules w/ proliferative centers for both B and T cells

EPITHELIUM:
1) M-Cells: Antigen transporting cells in GI
2) langerhan Cells: APC cells of the epidermis
3) Intraepithelial Lymphocytes: reticulated epithelium w/in stratified squamos nonkeratinized epithelium

CAPSULE?
NO CAPSULE!

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Reticulated Epithelium of MALT

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modified stratified epithelium - simple columnar in shape and much thinner epithelial tissue that ALLOWS LYMPHOCYTES TO TRAVERSE!

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Migration to/from/within MALT

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1) BASAL LAMINA: underlying epithelium has gaps
2) LANGERHAN CELLS/M-CELLS: antigen presenting/transporting cells
3) HEV: lymphocytes travel from blood to lymph tissue via homing receptor on lymphocytes
**diapedisis

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HEV (Function, homing receptor, Location, morphology)

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FUNCTION:
1) lymphocytes travel from blood to lymph tissue
2) **in lymph node: basal plasma membrane of HEV have aquaporins that draw tissue fluid out of tissue into systemic circulation

HOMING:
lymphocytes have SELECTINS (homing receptor) with affinity for a complementary vascular ADRESSIN on the HEV endothelium
**DIAPEDESIS: outward migration of lymphocytes across the wall of a blood vessel

LOCATION:
1) Lymph Nodes - Paracortex
2) MALT: interfolicular region

MORPHOLOGY:
-bulging cuboidal endothelial cells
- lymphocytes collected within the lumen, attached to surface, or caught traversing endothelium (diapedsis: lumen ->lymph tissue)

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Palatine Tonsil
- Organization

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- both diffuse and nodular arrangement of lymphoid tissue dispersed within a reticular CT

- tonsillar crypts: increase surface area of reticulated epithelium

- Lymphoid Nodules: germinal center + mantle zone (corona)
- Interfollicular lymphoid Tissue

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Lymphoid Nodules (Lymphoid Follicles) and Interfollicular Lymphoid Tissue

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LYMPHOID NODULES: site of B cell proliferation!
1) GERMINAL CENTER: pale staining center - site of activated, proliferating, and maturing B-Cells
2) MANTLE ZONE (CORNOA): surrounds germinal center and consists of small proliferated lymphocytes that are the products of germinal center

INTERFOLLICULAR LYMPHOID TISSUE:
- site of T Lymphocyte area - antigen DEPENDENT T-cell proliferation
- site of HEV

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Appendix

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EPITHELIUM OF NODULES: (no capsule surrounding nodules!)
- simple cuboidal epithelium overlying nodules:
- contains M-CELLS and INTRAEPITHELIAL LYMPHOCYTES that invades the modified follicle associated epithelium.

- NO INTESTINAL VILLI

- GALT

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Lymph Node Organization and stroma

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CORTEX:
Cortical Nodules - B cells
- Germinal Center
- Mantle zone
**size and number of lymph nodules depend/vary on disease state/health condition

PARACORTEX
- HEV and T cells

MEDULLA:
- medullary cords: B cells, plasma cells
- medullary sinus

INTERNAL SINUSOIDAL SYSTEM: provide route for lymph and lymphocytes to traverse the node
1) Subcapsular sinus
2) Intermediate (peritrabecular) sinus
3) Medullary sinuses - between medullary cords of densely packed cells

STROMA:
-reticular fiber (Type III collagen) and the reticular cells that produce them
- sinusoidal endothelial cells
- macrophages: phagocytes and APC's (move via diapedesis)

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Germinal Center of Lymph Node Cortical Nodule

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mix of proliferating B cells and cells supporting proliferation (ie. APC, antigen binding cells, T helper cells, macrophages and reticular cells)

- B cells --> 1) effector cells, 2) memory cells as they go towards medulla
- antibody production begins!

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Lymph Node: Function and Pathway of movement

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1) filter lymph (tissue fluid)
2) mount immune response to potentially harmful lymph-borne materials

AFFERENT AND EFFERENT LYMPHATICS (cortex -> sinusoidal system -> medulla -> hilus

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Spleen: Function

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1) monitor blood and mount immune response to blood-borne antigens (white pulp)
2) cleanse the blood and eliminate effete RBC's, platelets and other blood borne debris (red pulp)

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Spleen: Organization of cells - red and white pulp

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1) WHITE PULP: lymphocytes/lymphoid tissue of spleen
- surrounds central artery
1) PALS
2) splenic nodules: w/ germinal center/B lymphocytes
3) marginal zone: macrophages, APCs, plasma cells and lymphocytes
- site of vascular sinuses!

2) RED PULP: RBC's (all peripheral blood)
- nearly 80% of spleen volume
- spongy mass w/ macrophages and reticular cells from reticular fibers (stroma)
1) Splenic Cords - cords of Billroth
2) Splenic Sinus

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Spleen: General Orientation/organization

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Capsule: dense CT that surrounds spleen

NO CORTEX, MEDULLA, LOBULES, OR HEV

Splenic Nodules:
1) germinal center
2) mantle zone

Trabeculae: stain pale pink like the dense CT capsule that surrounds spleene

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Unique Features of the Spleen

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1) Red Pulp
2) central arteries (in white pulp!)

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Blood Vessels of the Spleen

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1) Trabecular Arteries/Trabecular Veins: surrounded by pale stained trabeculae
- branch into central artery in white pulp

2) vascular sinuses: within marginal zone in white pulp of spleen

3) Central arteries: adventitia of artery surrounded by lymphocytes
- branch of trabecular artery
- carry blood to lymphoid tissue where the immune response to blood borne materials can be initiated
(flows from white pulp central artery -> red pulp)

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Splenic Cords

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spongy mass of tissue filled with:
1) reticular cells
2) macrophages
3) RBC's
4) other blood elements

FUNCTION:
site where platelets and other blood cells can be stored

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Splenic Sinuses

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MORPHOLOGY:
lined by atypical elongate endothelial cells (STAVE CELLS) separated from each other by narrow clefts
- reticular fibers surrounded sinus CIRCUMFERENTIALLY, overlying the LONGITIDUNAL stave cells.

*old or damaged RBCs have a hard time passing through sinus --> ie) sickle cell anemia!

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Red Pulp

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spongy mass of macrophages and reticular cells that ramify the sinusoids

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Open Circulation of Spleen:

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trabecular artery -> central artery -> penicillar or radial artery -> CORD OF BILLROTH -> splenic sinus -> trabecular vein

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Closed Circulation of spleen:

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trabecular artery -> central artery -> penicillar or radial artery > splenic sinus -> trabecular vein

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Marginal Zone:

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narrow zone between red and white pulp characterized by many macrophages and small blood sinuses (vascular sinuses)

- blood flow through marginal zone is large and slow:

- FROM BLOOD SINUSES IN MARGINAL ZONE: new lymphocytes arrive and enter back into the PAL
- RBC's use marginal zone sinuses to move back into red pulp

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PALS = periarterial lymphoid sheath

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- sleeve of lymphoid tissue surrounding small arteries or arterioles

-composed mainly of T cells

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Splenic Nodules

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mantle zone + prominent germinal centers = site of mainly B lymphocytes