Lymphoid Organs Flashcards
Secondary Lymphoid Organs
- Lymph nodes
- Tonsils
- Spleen
Lymphoid Tissue
- Specialized CT made primarily of lymphocytes
- Predominant tissue in lymphoid organs
- Component of non-lymphoid organs
Blast Transformation
- Cell enlarges to become a large lymphocyte
- Form new daughter cells which become effector/memory
Thymus development
- 3rd pharyngeal pouch endodermal epithelium
- Consists of mainly TECs until 8-9 weeks gestation
- T cell precursors migrate into thymus and insert between TECs
Thymus Capsule
- Dense irregular connective tissue
- Collagen Type I
- Reticular fibers
CT Septa
- Trabeculae divide the thymus into lobules
- Extend inward from the capsule
Thymus Lobule
-Divided into cortex and medulla
Thymus Cortex
- Outside
- Contains more lymphocytes
Thymus Medulla
- Continuous throughout entire Thymus and each lobule
- More macrophages
- More TECs
Thymic Epithelial Cells
- Large, Pale staining, euchromatic nuclei
- Cytokeratin filmaents means that these are Epithelial cells
- Desmosomes link TECs
- Part of stroma (supportive function)
- Chemokines/cytokines
- Blood thymus barrier
- Selection process
- Hassal’s corpuscles
- Non phagocytic
Type I TECs
- Form sheets of cells connected by tight junctions
- Line inner surface of capsule
- Cover CT septa
- Part of blood-thymus barrier in cortex
Type II TECs (Thymic Nurse Cells)
- Long processes connected by desmosomes
- Form network throughout cortex
- Secrete factors that influence thymocyte development and migration
- Positive selection
Type III TECs
- Connected via tight junctions
- Form barrier between cortex/medulla
Type IV TECs
- Joined by tight junctions
- Form a layer beneath Type III TECs at cortico-medullary boundary
Type V TECs
- Stellate cells connected by desmosomes
- Form meshwork throughout medulla similar to type II TECs in cortex
Type VI TECs
- Form Hassal’s Corpuscles
- Center may be calcified, keratinized, necrotic
- Produce cytokines
- May help produce T-reg cells
Thymocyte migration path
1) Lead blood vessels at cortico-medullary boundary
2) Migrate to outermost part of cortex
3) Back to cortico-medullary boundary
4) Enter medulla
5) Leave via post capillary venules or via lymphatics
6) Leave as inactivated naive T lymphocytes and migrate to secondary lymphoid tissues/organs
Positive Selection
- Occurs mostly in the cortex
- Double positive thymocytes bind to MHC molecules on Type II TECs
- No binding means death by apoptosis
- Eliminates defective thymocytes that cannot bind self-MHC and cannot be activated in immune response
Negative selection
- Occurs most often in medulla, but also in cortex
- Cells that bind to Type V TECs will die b/c they adhere too strongly
- Cells must be exposed to a wide variety of self-antigens
- Medullary APCs synthesize “nonthymic” antigens such as PTH, insulin, AchR, etc.
Blood Thymus Barrier (Medulla)
-Leaky in the medulla and allows self-antigens to be present
Blood Thymus Barrier
Cortex
- Not leaky in the cortex
- Made of Type I TECs and capillary endothelial cells
- Each set has their own basal lamina and are joined by tight junctions
Thymic involution
- Loses efficiency as size decreases
- Affects the cortex most and forms cortical caps
- Cortex becomes discontinuous
- Old tissue becomes replaced by adipose tissue instead
- Accidental involution stimulated by steroid hormones, infections, illness, etc.
DiGeorge syndrome
- Congenital defects of pharyngeal pouches
- Very susceptible to infections
- Underdeveloped/absent thymus
- Stroma of thymus most affected
Macrophages
- Found in both cortex/medulla
- More in the medullar (relatively)
- Dark-staining apoptotic bodies (tingible bodies) from dead thymocytes
- Large lysosomes are PAS+
Thymic Dendritic Cells
- Found in medulla
- Large, pale staining with elongated cytoplasmic processes
- Difficult to distinguish from medullary TECs
- APCs
Lymph nodes
- Encapsulated organs (Dense irregular CT)
- Trabeculae are finger-like projections into organ
- Stroma made of reticular CT/fibers
- Afferent lymphatic vessels penetrate capsule at multiple sites
Lymph cortex
- Outermost region
- Stains darkly basophilic due to lymphocytes
1) Lymphoid nodules: B cells (thymus independent region)
2) Inter-nodular cortex: T cells
(thymus dependent region)
Lymph paracortex
- Lies deep to cortex
- No nodules
- Dark staining
- Contains mainly T cells (thymus dependent region)
- Contains HEV which deliver lymphocytes to a node
Lymph medulla
- Central portion of node
- Medullary sinuses (light staining)
- Medullary cords (dark staining)
- Lighter staining than cortex/paracortex due to lymphatic sinuses
High Endothelial Venules (HEV)
- Cuboidal/columnar epithelial cells
- Deliver lymphocytes to paracortex
- Diapedesis
Nodules
- Found at outer cortex separated by internodular cortex
- Macrophages, Follicular dendritic cells (FDCs), some Th Cells, B cells
Internodular Cortex
- Mostly T cells
- Between nodules in the outer cortex
Internodular Cortex
- Mostly T cells
- Between nodules in the outer cortex
Primary nodules
- Stain uniformly dark
- Small inactive B cells
- Develop into secondary nodules when B cells activate and proliferate during immune response
Secondary nodules
- activated B cells are dividing and maturing as part of humoral response
- Germinal center
- Cap (mantle, corona)
- Activated B cells proliferate/divide
Germinal center
- Light staining central region because activated B cells are large lymphocytes
- Activated B cells proliferate/mature
Cap/mantle/corona
- Inactive lymphocytes that get pushed to edge of nodule during rapid division of active B cells
- Dark staining peripheral region
Germinal center dark zone
- Site of intense proliferation of activated B cells
- Dividing cells are called centroblasts
- Somatic hypermutation of immunoglobulins
Germinal center light zone
- Centroblasts migrate into light zone and are then known as centrocytes
- Mitosis decreases
- Centrocytes interact with follicular dendritic cells
Lymphocyte entry into lymph node
- Enter via high endothelium venule
- Found in paracortex of the node
- Some enter via afferent lymphatics
Immune response in lymph node
1) Antigen arrives as free antigen, APC, or bound to Ab
- Langerhans cells; become IDCs in lymph node
2) Lymphocytes arrive via HEV in paracortex
3) Migrate to T/B cell territory
- T cells go to paracortex/internodular cortex
- B cells go to lymphoid nodules in the cortex
4) APCs activate naive T cells which then activate B cells
5) Activated B cells differentiate/proliferate and form secondary nodule and germinal center (pale staining)
6) Plasma cells migrate to the medulla to secrete Ab into medullary sinuses
Follicular Dendritic Cell
- Aid in selection process
- Interact in the light region with centrocytes
- Not antigen presenting
- Beaded processes due to inclusion bodies
