Lymphoid Organs Flashcards

Question

Lymphoid Nodules (Follicles)

Answer 1

Found in LN and other secondary lymphoid organs. Areas to which B-cells preferentially migrate. Contains smaller numbers of: Follicular dendritic cells, macrophages, and few T-cells.

Answer 2

* Stains uniformly dark * Contains small inactive B-cells * Develop into secondary nodules when activated B-cells proliferate within them * Regress to primary nodules when immune response is over

Answer 3

* Sites where activated B-cells are dividing and maturing as part of a humoral immune response * Somatic hypermutation * Affinity maturation * Class switching * Maturation of _plasmablasts_ and memory B-cells * Have two components: * **_Germinal center_** * light-staining central region * site where B-cell proliferation and maturation occurs * **_Cap/Mantle/Corona_** * Dark staining peripheral region * Contains small inactive lymphocytes that get pushed to the edge of the nodule by rapidly dividing B-cells

Answer 4

Well-developed germinal centers can be subdivided into a dark zone and light zone. Activated B-cells move from dark zone to light zone. **_Dark Zone_** * Usually nearest to the T-cell region in paracortex * Site of intense proliferation of activated B-cells * Many mitotic figures * Dividing B-cells in the dark zone called **centroblasts** * Centroblasts undergo somatic hypermutation and Ab affinity maturation **_Light Zone_** * Centroblasts migrate into light zone and then known as **centrocytes** * Rate of mitosis decreases * Centrocytes interact with follicular dendritic cells (FDCs)

Answer 5

* Stromal cells of lymphoid nodules * Only found there * Have long cytoplasmic processes with a _beaded appearance_ * Are not derived from PHSC * Do not process Ag, therefore, are not technically APCs * FDCs bind _Ag-Ab complexes_ via _Fc receptors_ * Presents complexes to activated B-cells * Binding triggers FDCs to deliver a _rescue signal_ * T_H cells supply a second rescue signal * Important in B-cell selection and affinity maturation

Answer 6

Activated B-cells which survive selection develop into either **plasmablasts** or memory B-cells. * Plasmablasts are Ab-producing B-cells * Leave germinal centers and differentiate into plasma cells

Answer 7

* Produce Ab for several weeks then die * Within a lymph node, plasma cells are most abundant in medullary cords * Most plasma cells leave the node via efferent lymphatics * Are returned to the blood and distributed to tissues/organs * Old plasma cells may contain large eosinophilic Russel bodies = _Russel body cells_ * Russel bodies are swollen cisternae of RER filled with Ab

Answer 8

Afferent lymphatic vessels → subcapsular sinus → trabecular sinuses → medullary sinuses → efferent lymphatic vessel. * **Afferent lymphatics** * Carry lymph to the nodes * Lymph nodes are the only organs that have afferent lymphatics * Valve prevents backflow * **Subcapsular sinus** * One continuous space which lies just deep to the capsule * Seperates capsule from cortex * Receives lymph from afferent lymphatics * **Trabecular sinuses** (aka intermediate sinuses) * Receive lymph from subcapsular sinus * Each trabecular sinus surrounds a trabecula * Short, straight, and few in number * **Medullary sinuses** * Receive lymph from trabecular sinuses * Pass through the medulla of the node * Very numerous * Irregular in shape * Unite at the hilus to form the efferent lymphatic vessel * Surrounded by medullary cords * **Efferent lymphatic** * Leaves node at the hilus * Valves prevent backflow * The efferent vessel of one node typically becomes the afferent vessels of next node in the chain _Intra-nodular channels (subcapsular, trabecular, medullary):_ * Lack valves * Have discontinuous endothelium * Highly permeable * Have **stroma** within lumen which attaches to capsule and trabeculae * Composed of **reticular cells and reticular fibers** * Physically traps particulate Ag in the lymph * Also supports parenchymal cells * Have _fixed macrophages_ which adhere to the stroma and phagocytize Ag Efferent lymphatics gradually unite into _large lymphatic vessels_ that deliver filtered lymph back to blood by emptying into large veins at base of the neck.

Answer 9

* Most lymphocytes enter LN via blood through **high endothelium venules** (HEVs) * Located in the paracortex * Have cuboidal to columnar endothelial cells * Some enter via afferent lymphatics

Answer 10

1. **_Arrival of antigen_** * Ag picked up by lymphatic capillaries and carried to nearby LN arriving via afferent lymphatic * 3 forms of Ag * Free antigen * As part of Ag-Ab complex * Bound to APC 2. **_Arrival of lymphocytes_** * Most arrive via HEV's and migrate from paracortex to T or B cell regions within LN * "Homing" occurs in response to chemokines secreted by stromal cells * IDCs in T-cell zones attract T-cells * FDCs in follicles attract B-cells * T-cells tend to remain in paracortex or internodular cortex * B-cells migrate to lymphoid nodules in cortex 3. **_Lymphocyte activation, blast transformation, and replication_** * Most responses start in paracortex where APCs activate naïve T-cells * Activated T_H cells divide and migrate towards cortex to B-cell zone * T_H cells activate B-cells with similar Ag specificity * Small foci of activated B-cells proliferate outside of nodules * After several days, activated B-cells migrate into primary nodules, divide rapidly, and form secondary nodule. * Activated B-cells differentiate into plasmablasts or memory B-cells * Activated lymphocytes remain within LN for several days due to loss of **sphingosine-1-phosphate (S1-P) receptors** during activation (shut-down phase) * S1-P receptors required for exit from LN & thymus * Lymphocytes migrate up gradient of S1-P which is higher in circulating lymph than in nodal parenchyma * Re-express receptors after several days and can exit * Plasmablasts migrate to medullary cords or exit node * Memory B-cells remain in mantle of GC or migrate with memory T-cells to medullary cords/efferent lymphatics * Lymphadenopathy occurs due to retention and replication of activated T & B cells

Answer 11

* Immature dendritic cell found in the skin * Within lymphatic vessels, develop sheet-like cytoplasmic projections called "veils" and are called **veiled cells** * Within lymph node, changes shape and becomes **interdigitating dendritic cells** (IDCs) * Localize in T-cell zones and helps activate T-cells

Answer 12

Most immune responses involve both cell-mediated (T-cells) and humeral responses (B-cells) but in some cases one type of response predominates. * _If Ab production predominates:_ * Node shows **follicular hyperplasia** * Minimal paracortex hypertrophy * Ex. Rheumatoid arthritis * _If cell-mediated response predominates:_ * Node shows **paracortical hyperplasia** * Few secondary nodules develop * Ex. Viral infections

Answer 13

* Microbial infection within the node * Yersinia pestis replicates within lymph nodes * Causes bubonic plague * Swollen, black LN called bubo * Primary malignancies of the lymphocytes of the node * Ex. cancers such as Hodgkin's lymphoma * Replication within the node of metastatic malignant cells * Malignant nodes are usually slow-growing and non-tender

Answer 14

Lymphocytes are the only type of leukocytes which recirculate via lymph and blood. * Leave LN via efferent lymphatics → large veins → secondary lymphoid organs and lymphoid tissues via arterial system * Naïve lymphocytes recirculate to any secondary lymphoid organ * Effector cells usually recirculate to site of infection/inflammation via chemokines * Memory lymphocytes return to the type of lymphoid tissue where they first encountered Ag

Answer 15

1. Filters Ag from blood and initiates immune responses * Occurs within the white pulp * Lymphoid region * Basophilic & darker in H&E due to lymphocytes * Paler in fresh sections due to fewer RBC's 2. Destroys senescent RBC's * Occurs in red pulp * Non-lymphoid region

Answer 16

* Covered in **mesothelium** d/t intraperitoneal location * Thick **capsule** of _dense irregular CT_ * Contains some contractile _myofibroblasts_ * **Trabeculae** of CT extends inward from capsule * **Stroma** consists of _reticular fibers_ and _reticular cells_ * Found in both red and white pulp * Provides support * Produces chemokines which attract T & B cells * **Hilus** where blood vessels enter and leave & _efferent lymphatics_ leave

Answer 17

* Many seperate areas of white pulp scattered throughout spleen * Each organized around a central artery * Has two structural components: 1. **Periarteriolar lymphatic sheath (PALS)** * Forms cylindrical sheath of lymphocytes around each central artery * Composed mainly of T-cells * Thymus-dependent region * Contains dentritic cells which activate T-cells 2. **Lymphoid nodules** 1. Embedded in the PALS 2. B-cell region 3. Primary vs secondary 4. Nodules often push central artery to edge of white pulp * Often not possible to see exact boundary between PALS and nodule

Answer 18

Has 2 structural components: 1. **Splenic sinuses** (aka venous sinuses or sinusoids) * Highly permeable sinusoidal capillaries * Contains blood, not lymph 2. **Splenic cords** (Bilroth's cords) * Regions of parenchyma that surrounds splenic sinuses * Sites where old RBC's destroyed

Answer 19

* Several layer of **reticular fibers** and **flattened cells** that surrounds each area of white pulp * Acts as interface between red and white pulp * Mixed cell population (T-cells, B-cells, DCs, several types of macrophages) * **Marginal zone B-cells** * Seperate subpopulation of B-cells specialized to detect blood-borne viruses and bacteria * Rapidly become IgM-producing plasma cells without T-cell help * Supplied by side braches arising from central arteries * Traps antigens and presents to lymphocytes

Answer 20

Spleen has both open and closed circulatory systems. **splenic artery** (enters hilus) → **capsular arteries** → **trabecular arteries** → **central artery** (WP) with side branches which open in marginal zone → **splenic cord** (red pulp) → **penicillar arterioles** → aquires a sheath of macrophages = **sheathed capillary** → _open circulation_ in **splenic cords** of red pulp → cells re-enter between endothelial cells of **splenic sinuses** → **pulp veins** → **trabecular veins** → **capsular veins** → **splenic vein** (exits hilus) → hepatic portal vein

Answer 21

* Main type of vessel in red pulp * Wide & highly permeable * **Spindle-shaped endothelial cells** * Long axis parallel to vessel * Large lateral gaps common * Easy for most blood cells to cross sinusoidal wall * Old RBCs less flexible and get stuck * Discontinuous **basement membrane** organized into **hoops** * Encircles the sinus * Stains with silver stain or PAS * **Reticular cell processes** form an incomplete layer around each sinus * Make reticular fibers which are part of basement membrane hoops * No stroma

Answer 22

* Side branches of central arteries open into marginal zone delivering blood with: * T & B lymphocytes * T-cells migrate from MZ into PALS * Follicular B-cells migrate from MZ into lymphoid nodules * APCs carrying processed Ag * APCs migrate into white pulp especially PALS * Soluble Ag * Naïve T and B cells leave via efferent lymphatics and recirculate * APCs activate T-cells in PALS * Activated T-cells migrate to edge of nodule and help activate follicular B-cells * Activated B-cells undergo blast transformation producing germinal center of secondary nodule * Plasmablasts leave nodules and differentiate into plasma cells * Plasma cells most abundant in splenic cords

Answer 23

1. **_Destruction of old RBCs_** * Senescent RBCs lose flexibility and tend to fragment as they are pushed between endothelial cells of splenic sinuses * Macrophages can also recognize changes in RBC membranes * Binding of auto-Ab to band 3 * Transfer of PS from inner to outer leaflet * Cleavage of sialic acid from carbohydrate side chains of membrane glycoproteins exposing terminal mannose 2. **_Breakdown of hemoglobin:_** * Macrophages break down hemoglobin into AA, iron, and heme * Heme converted to _biliverdin_ and iron * Biliverdin converted to _bilirubin_ and carried to liver * Liver converts bilirubin to _bilirubin glucuronide_ and secretes into duodenum as part of bile * Iron bound to transferrin and carried to bone marrow

Answer 24

Enlarged spleen Has many diverse causes including: * Diseases with excessive RBC destruction * Hereditary spherocytosis * Sickle cell anemia * Spleen enlarges due to congestion of splenic cords with defective blood cells * Certain lysosomal storage diseases * Phagocytic cells throughout the body accumulate indigestible substrates due to lack of a normal lysosomal enzyme