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What is the primary responsibility of the lymphoid system?
defense against invading pathogens (immunity)
What are the two types of immunity?
Innate and Adaptive
What are complement proteins?
- Plasma proteins produced in the liver
- Bind to lipids/carbohydrates on pathogens
- Bind to receptors on macrophages/neutrophils
When/where are complement proteins released?
Released into connective tissue due to blood vessel innjury
What is a toll like receptor?
- TLRs are found on the surface of macrophages and neutrophils
- Recognize various pathogen molecules non-specifically (classes of molecules are recognized as foreign) ie. LPS, glycoproteins, dsRNA
How is innate immunity mediated?
Complement and TLRs initiate the response, macrophages and neutrophils engulf foreign bodies
What are natural killer cells?
- NK cells recognize and bind to target cells with low specificity
- NK cells transfer pore-forming perforins to bound target cell membranes; kills target cell
- NK cells release interferon gamma, a cytokine that stimulates macrophages
What two factors mediate the recruitment of WBC's during inflammation?
- 1) Cytokines released by macrophages, neutrophils and NK cells
- 2) Dendritic/Monocytic cells = Antigen-Presenting Cells, present antigens from pathogens to lymphocytes that also exit the blood by diapedesis
Name the five steps of diapedesis.
Capture, Rolling, Slow Rolling, Firm Adhesion, Transmigration
Explain the role of selectins and integrins during diapedesis.
Selectins on the endothelium initially grab onto the leukocytes. Integrins on the endothelium then bind the leukocytes in a focal adhesion-like manner.
Where does diapedesis/extravasation occur?
- Occurs most often at post-capillary venules.
- Leukocytes can also go back into the blood vessels- intravasation.
What is the functional role of dendritic cells?
- They are the bridge between the innate and adaptive immune system by presenting antigens on their surface to lymphocytes.
- Derived from monocytes/macrophages in the connective/peripheral tissues
What are the primary lymphoid organs?
- Sites of lymphocyte production
- Naive, immunocompetent B lymphcytes are produced in the bone marrow
- Naive, immunocompetent T lymphocytes are produced in the bone marrow and the thymus
Summarize the development of B lymphoctyes.
- Lymphoblasts proliferate and become lineage restricted to generate many different clones of B-lymphoblasts which remain in the bone marrow.
- Each B-lymphoblast clone rearranges a single set of immunoglobulin (Ig) genes and inserts the Ig protein into the plasma membrane to produce a naive pre-B-cell.
- If the Ig of a naive pre-B-cell interacts with self-antigens in the bone marrow, this induces apoptosis (clonal deletion). This ensures that there is a tolerance to self antigens.
- Remaining naive, immunocompetent B-cells leave bone marrow via venous sinusoids. They are ready to recognize and be activated by foreign antigens to produce soluble Igs in secondary lymphoid organs.
Summarize the development of T lymphocytes.
- Lymphoblasts proliferate and become lineage restricted to generate many different clones of T-lymphoblasts which migrate to the thymus.
- Each T-lymphoblast clone rearranges a single set of T-Cell Receptor (TcR) genes inserts the TcR protein into the plasma membrane where they can recognize a single, specific antigen presented to them by APCs; now a naive pre-T-Cell.
- If the TcR of a naive pre-T-cell interacts with self-antigens presented by APCs in the thymus this induces apoptosis (=clonal deletion). This ensures that there is a tolerance to self antigens.
- Remaining naive, immunocompetent T-Cells leave the thymus by entering post-capillary venules at the corticomedullary junction and can be activated by APCs that present foreign antigens in secondary lymphoid organs.
What is clonal deletion?
- A process by which lymphocytes which recognize self-antigens are removed via apoptosis.
- B-lymphocytes are removed in the bone marrow, and T-lymphocytes are removed in the thymus.
Describe the location and structure of the thymus.
- Located immediately posterior to sternum in the thorax.
- The connective tissue portions (including outer capsule) are mesodermally derived.
- The reticular epithelial portion is endodermally derived.
Describe the inner structure of the thymus.
- The thymus is surrounded by a dense irregular connective tissue capsule. Radiating inward from the capsule are lobules of dense irregular CT separated by septae.
- Each lobule consists of an outer basophilic cortex with many developing T-cells and an inner medulla with eosinophilic Hassal's corpuscles- clusters of reticular epithelial cells in Medulla that produce cytokines for T-cell development
Describe the role of the epithelial reticular cells in the thymus.
- 1) Contribute to the blood-thymus barrier around continuous capillaries in cortex to immunoprotect developing T-cells.
- 2) Together with dendritic cells present antigens that regulate clonal deletion of pre-T-cells at cortico-medullary junction
- 3) Become concentrically arranged as Hassall's corpuscles in medulla; produce thymopoietin
What are the secondary lymphoid organs?
- Sites of lyphocyte activation
- 1) Lymph nodes
- 2) Mucosa-Associated Lymphoid Aggregates
- 3) Spleen
Describe the structure of lymph nodes.
- Lymph nodes are in the path of the lymph vascular flow
- Surrounded by a connective tissue capsule
- There are dense irregular CT trabeculae and a reticular CT stroma
- B-cells are located in the cortex while T-cells are located in the paracortex.
What are germinal centers?
Site of B-cell activation in lymph nodes
Describe the function of the lymph vascular system.
- Moves interstitial fluid (lymph) from connective tissues back to the venous system.
- Empties into subclavian veins in the root of the neck.
Describe the structure of the lymph vessels.
- Begin as lymph capillaries- blind-ended, one way flow, easy passage in/out
- Intercellular clefts between endothelial cells to facilitate movement in/out (no tight junctions)
- Tunica intima, media, and adventitia are all thin-walled
- Tunica intima can be folded to form one way valves in the direction of flow back to venous system
Explain the movement of lymph through the lymph node.
- Lymph moves through sinuses from outer cortex to inner medulla.
- Passes over cortex and paracortex
Describe the structure of mucosa-associated lymphoid tissue (M.A.L.T).
- ie tonsils in oral cavity
- Prominent in mucosal connective tissue
- Sites of B-Cell and T-Cell Activation
- No capsule or afferent lymphatics (not in the path of lymph vascular flow)
Describe the structure of the spleen.
- Dual function- lymphocyte activation (white pulp) and red blood cell destruction (red pulp)
- Surrounded by a connective tissue capsule- not in lymph vascular flow
- Contains a central arteriole which supplies blood to the venous sinusoids.
- The germinal center activates B-cells which the periarterial lymphatic sheath activates T-cells
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