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45 Cards in this Set

  • Front
  • Back
Describe the myeloid and lymphoid pathways of haematopoesis.
Give an overview of the body's immune organs and tissues.
>Organs of immunological function are sites in the body where distinct structure-function relationships have evolved to ensure that the immune system is maintained and responds to and protects against injury.

>These are separated into:
Primary sites:
- Development and maturation e.g. bone marrow and thymus
Secondary sites:
- Maturation and effector to immune function (i.e. responses to environmental antigens) - e.g. lymph nodes, spleen;
Specialised sites:
- Associated with particular organs e.g. respiratory and alimentary tracts (NALT, BALT, GALT)
Describe the sites and roles of the primary and secondary tissues.
What is an immune reaction?
>Core component in the response to injury.
>Response to injury is not only physiological but also the key reaction in pathology.
>The immune reaction will take place not only at the local site of injury, but also in 'organs of immunological function', where immune homeostatic physiology is an intrinsic feature.
Describe the different types, locations and roles of dendritic cells.
Professional Antigen Presenting Cells:
1. Langerhans' cells - peripheral tissues. Interact with pathogen, migrate to draining lymph nodes.
2. Interdigitating dendritic cells, present in T cell areas of secondary lymphoid tissue and thymic medulla.

>Follicular dendritic cells (not produced via haematopoeisis) do not express MHC II therefore do not function as professional APCs but play a role in B-cell activation in lymph nodes.
Identify this organ, its embryological origin, gross structure and function.
>Thymus:
- Lympho-epithelial organ derived from the third and fourth pharyngeal pouches which fuse and lose their connection at approx. 8 weeks of life.
- Has cortical and medullary zones
- T-cell maturation and selection occur in both zones
Describe the pathway for T cells between the thymic cortex and medulla.
>Cortex of the thymus is seeded with stem cells from the bone marrow from about 9 weeks of foetal life onwards; lymphocytes contribute to the rapid increase in size during development as they can divide in situ.
>Thymic epithelial cells (medulla and subcapsular; including Hassall's corpuscles), macrophages and dendritic cells (cortex) provide the signals required for T cell selection and for differentiation into CD4+ or CD8+ T cells.
Draw and explain the function of the lymph node.
>Lymph nodes are focal aggregates of structured lymphoreticular tissue placed as regular intervals along the lymphatic vessels which return excess tissue fluid to the blood.
Describe the functional anatomy of the lymph node.
>Arrest, neutralise and eliminate antigen / microorganisms;
>Facilitate antigen presentation to T and B lymphocytes.
What volume of traffic do lymph nodes transmit?
>It's own weight of recirculating lymphocytes every 12 days.
>Blood flows through a lymph node at a rate of 1ml min/gm weight
>Antigen stimulation results in increased traffic; cardiovascular changes can also increase traffic.
Principles governing the cellular content of the lymph node include...
>None of the lymphomedullary cell types seen in a lymph node are found exclusively in the lymphoid tissues.
>Cells which have passed through a node are as important in immune function as those which are there at the the time of biopsy.
>Recirculation of lymphocytes takes 1-2 days, and is not random.
What is the structure and function of the peripheral lymph?
>Peripheral lymph drains into the peripheral lymph nodes via the afferent lymphatic.
- There are more afferent lymphatics per lymph node than there are efferent lymphatics.
>85% of the cells in the peripheral lymph are lymphocytes and 15% belong to the myeloid series with very few neutrophils and eosinophils among them.
- 10% of lymphocytes are B-cells
>Many myeloid cells express surface MHC II antigens.
- Amongst peripheral lymph myeloid cells there are the population known as veiled cells which are derived from dendritic cells.
What is the structure and function of intermediate lymph?
>Flows between the peripheral and deeper lymph nodes.
>There are more cells in the intermediate than the peripheral lymph, but few mononuclear phagocytes and other non-lymphoid cells.
>25% of the intermediate lymph cells are B-cells.
>24 hours after antigen stimulation the intermediate lymph will contain lymphoblasts as well as small round lymphocytes.
What is the structure and function of central lymph.
>Flows from the deep lymph nodes towards the thoracic duct and bloodstream.
>No further filtration will place.
What is the structure and function of the lymph node stroma?
>Extensive network of 'reticulin' fibres - chiefly collagen synthesised locally by fibroblasts - covered by mononuclear phagocytes and dendritic cells, which provide an antigen uptake surface.
What is the structure and function of sinuses in the lymph node?
>Subcapsular structures lying within the node
>Provide potential channels for cell migration within the node.
>If the lining macrophages are activated then the term used is 'sinus histiocytosis'.
What is the structure and function of the lymph node paracortex?
>This is the region between the cortex and the medulla where T cells enter via the endothelial lined post-capillary venules and are the predominant cell type.
>Antigen Presentation takes place here, the local APCs are interdigitating dendritic cells.
What is the structure and function of the lymph node cortex?
>The cortex extends from the sub-capsular sinus to the lymph sinuses.
>In resting cortex there are many small round lymphocytes sometimes forming clusters and called primary follicles.
>Reactive form of these primary nodules are the germinal centres.
What is the structure and function of lymph node germinal centres?
>Site of lymphocyte activation (NOT lymphopoiesis).
>These structures can be identified approximately 24 hours after the introduction of antigen.
>Phagocytic starry-sky macrophages and follicular dendritic cells are other important components.
What is the structure and function of the lymph node medulla?
>Consists of characteristic channels or cords lined by endothelium.
>These sinuses can become packed with plasma cells during immune responses, with monocytoid B cells (e.g. Toxoplasmosis) and by monocyte - derived histiocytes in 'sinus histiocytosis'.
What are the key (immune) cells present in lymph node tissue?
>T and B lymphocytes
>Monocytes/macrophages
>Interdigitating and Follicular Dendritic cells
What is the function and role of macrophages in lymph nodes?
>Bone marrow derived and travel to the node as monocytes.
>Increase in production occurs in inflammation, with:
- rapid efflux
- migration
- transformation in tissues
>Controlled by M-CSF and GM-GCSF.
>Activated macrophages exhibit an increase in any one or more functional activities; 'tissue localised' macrophages include starry sky' germinal centre cells; sinus histiocytosis; and at other sites alveolar macrophages; Kupffer cells (liver); and serous cavity - resident and elicited.
What is the difference between Interdigitating and Follicular Dendritic cells?
INTERDIGITATING DENDRITIC CELLS:
>Bone marrow derived
>Travel to node paracortex as monocytes
>Functionally different to FDCs
>Linked to Langerhans cells in the skin and veiled cells in peripheral lymph
>When activated act as potent APCs stimulating T cells

FOLLICULAR DENDRITIC CELLS:
>Found in germinal centres
>Retain antigen in form of immune complexes
>Express Fc and C3 receptors but few macrophage markers
>Important in the generation / activation of B memory cells
What occurs following antigen stimulation in the lymph node?
>The 'decisive' event is the retention of antigen.
>Following antigen stimulation there is a shutdown phase within the node during which cells do not leave.
>This is followed by a phase of increased circulation through the node.
>These two phases coincide with the requirements for immunogenicity and subsequently for migration of responder cells to the site at which they function.
Describe the formation of a primary follicle.
Describe the structure of the spleen and its 'micro environments'.
The spleen is composed of red pulp and white pulp.

RED PULP:
>vascular sinuses lined by a single layer of endothelium on a thin connective tissue stroma
>blood flows from arteries to venous sinuses
>important role in clearance of antigens from the circulation
>lymphocyte entry is via venous sinuses
>up to 25% of lymphocytes are in spleen at any one time
>arteries enter and branch into trabecular, lobular and finally follicular or central arterioles
>about 5% cardiac output directed at the spleen

WHITE PULP:
>End branches of arteries are surrounded by periarteriolar lymphoid sheath (PALS)
>May be reactive with follicle formation.
>White pulp has two zones:
(i) Naive B cells, marginal zone macrophages and some memory B cells
(ii) follicle forming cells surrounding follicular dendritic cells
>Marginal zone is found at the interface between the white and red pulp.
>Endothelium of the marginal sinus expresses MadCAM-1 (mucosal addressing cell adhesion molecule 1) and is associated with the metallophilic macrophages.
What does the spleen's structure allow it to do efficiently?
>Morphological pattern of tissues allows:
- Filtration
- Recycling
- Reutilisation of blood components and reactivity.
What are MALT?
>Mucosal Associated Lymphoid Tissues
What are the different forms of MALT?
>Gut Associated (GALT)
>Bronchial Associated (BALT)
>Nasopharynx Associated (NALT)
What are the three micro environments of GALT?
Peyer's patches:
>Lymphocytes in prominent organised lymphoid aggregates, but with no afferent lymphatics
Intrapithelial lymphocytes:
>Lymphocytes in epithelium
Lamina propria:
>Lymphocytes here
What does NALT consist of?
>Waldeyers ring in pharynx
>Adenoids
>Palatine tonsils
>Scattered isolated lymphoid follicles are also seen in the nasal mucosa
What does BALT consist of?
>Similar to Peyer's patches in GALT
>Aggregates of lymphocytes organised into follicles that are found in all lobes of the lung and situated under epithelium along the bronchi
>Mainly B cells with antigen sampling carried out by M cells and epithelial cells lining the surface of the mucosa
What occurs in the MALT?
>Antigen is taken up via M cells;
- transferred to APC dendritic cells, activating CD4+ T cells;
- these regulate the isotype of Ab produced
>Plasma cells in lamina propria make and secrete IgA dimers containing joining peptide
- dimeric IgA attaches to poly-Ig receptor on epithelial cells;
- allowing it to be transported into the lumen
>Cleavage of poly-Ig receptor by protease acting at the luminal surface releases the dimeric secretory IgA;
- leaving behind a part of the receptor still attached to IgA, referred to as the secretory component
>Recirculating pathway via mesenteric lymph nodes and blood stream with homing of IgA+ B cells back to lamina propria and T cell blasts back to mucosal epithelium and lamina propria.
Compare the structure of secondary lymphoid organs.
Identify these cells, describe their function.
>Kupffer cells
- any of the stellate (star-shaped) cells in the linings of the liver sinusoids
- cells are phagocytic
- also store hemosiderin so that it is available for the production of haemoglobin
Where are the stem cells for lymphocytes located?
>In the bone marrow
Describe the differences between the primary and secondary lymphoid organs.
Primary lymphoid organs:
>Critical in differentiation and maturation of lymphocytes (e.g. bone marrow and thymus)
Secondary lymphoid organs:
>Important in development of the immune response (e.g. lymph nodes, spleen)
Where do the terms T-cell and B-cell come from?
T cell = Thymus dependent
B cell = Bursa of Fabricius
What events occur as T-cells pass through the thymus?
>Cortex of thymus packed by numerous T-lymphoblasts
1. Pre T cells first occupy outer cortex and differentiate as they move towards the medulla
2. Thymus contains meshwork of epithelia which are critical in:
- negative selection of self-reacting T-cells
- positive selection of T-cells which have differentiated successfully
Outline the immunological events that take place when an organism gains entry into the body via the cutaneous route.
1. Antigen carried into the lymph node by APCs such as dendritic cells, or in free form through the afferent lymph vessels which drain the skin
2. Antigen first occupies marginal sinuses, then moves into the cortex of the lymph node
3. Cortical APCs (IDCs) present the foreign antigens to the T-cells in the T-cell zone
- whereas most free antigen is retained by follicular dendritic cells in the B-cell follicles
>Following generation of the immune response, antigen specific T-cells activated by APCs move into the follicles and provide help for differentiation of B cells in the follicles into antibody secreting plasma cells in the medulla.
>Lymph containing the secreted antibody collected by medullary sinuses which drain into the efferent lymphatic vessels and finally join the blood to act on the foreign antigen at the peripheral site.
What are the differences between follicular versus interdigitating dendritic cells?
>FDCs:
- Present in follicles of lymphoid tissues;
- Do not express MHC II but markers for B cells

>IDCs:
- Express high level of MHC II for antigen presentation to T cells
Compare the histological features of the lymph nodes and mucosa-associated lymphoid tissue.
>Lymph nodes are defined encapsulated bean-shaped structures situated along the course of the lymphatics
- outer part of lymph node is highly cellular and is known as the cortex (outer cortex = follicles); central area (medulla) is less cellular (i.e. segmented structure)
>MALT is distributed along the GI, respiratory and GU tracts;
- diffuse, un-encapsulated aggregation
Why are the lymph nodes enlarged during an immune response?
>When stimulated by antigen the lymph nodes become enlarged with germinal centres
- Follicles are composed mainly of B cells and FDCs with some Th called T-follicular cells
- Paracortical region contains increased numbers of T-cells interspersed with IDCs
Compare the histology and function of red and white pulp in the spleen.
>White pulp - highly organised tissue, forms islands within a meshwork of reticular fibres containing red pulp, red blood cells, and plasma cells.
>RP = parenchyma removes particulate matter and aged / abnormal erythrocytes from the bloodstream
>WP = T or B cell (5-20% splenic mass) similar function to lymph node paracortex and superficial cortex
- APCs sample blood for antigens; lymphocytes exit circulation; monocytes enter lymphocytes + dendritic cells come into contact
What is splenomegaly and in what situations does it occur?
>Enlargement of the spleen:
- frequent clinical finding that can occur in a number of different disorders
>Causes include:
- Haematological e.g. lymphoma / haemolytic anaemias
- Infectious: mononucleosis, toxoplasmosis
- Portal hypertension: liver cirrhosis
- Immunological: rheumatoid arthritis
- Storage diseases e.g. Gaucher's disease
- Cysts