Immune/Lymphoid Histology 8/28

Question 1

Cells of the Lymphoid Organs

Answer 1

lymphocytes and their progeny, macrophages, APC’s, thymic epithelial cells, stromal cells (supporting cells), reticular cells, thymic epithelial cells

Question 2

B Lymphocytes

Answer 2

• produce and secrete Ig’s (antibodies)
• Ig’s bind specifically to antigens (Ag’s)
• humoral immunity

Question 3

T Lymphocytes

Answer 3

• produce T cell receptors

T cells act as :

• T Helper cells - assist other lymphocytes (CD4)
• T Cytotoxic cells - kills targets directly (CD8)
• T regulatory cells - regulate responses (CD25)
• cellular immunity

Question 4

Plasma Cells

Answer 4

• The real cells that produce antibodies. They are the instate B cell that is the actual producer of antibodies. They have a very large golgi/ER because producing so many proteins.

Question 5

Lymph Nodules

Answer 5

• Collections of lymphocytes in organ or tissue that is un-encapsulated
• primary lymph nodule: dense accumulations of lymphocytes, macrophages, denderitic cell in CT stroma
• secondary lymph nodule: central region known as germinal center, site of immunoblast activation, proliferation and differentiation
• seen in lymph nodes, spleen, bone marrow, thymus

Question 6

Peyer’s Patches

Answer 6

nodular collections found in intestine- lymphocytes in the mucosa of the gut.

• unencapsulated
• focused collection of lymphocytes.
• Peyer’s patches can also be called GALT= gut associated lymphoid tissue
• MALT = mucosal associated lymphoid tissue

Question 7

Tonsils

Answer 7

• do not have a complete capsule. They are a ring of tonislar tissue consisting of four parts: palantine, pharyngeal, lingual and tubal - “Waldeyer’s Ring”
• palantine tonsile: large, paired collections of lymph nodules, underlie stratified squamous non-keratinized epithelium. epithelial crypts/crevasses dip down allowing for increased surface area and exposure to infective agents.
• pharyngeal tonsil: further back, and up, associated with nasal passageways: underlies respiratory epithelium, possesses only small crypts- primarily composed of Collagen Type III
• lingual tonsil: smaller, more numerous collections of nodules at base of tongue. Underlies stratified squamous epithleium - no crypts.

Question 8

Lymph Nodes

Answer 8

• encapsulated collections of lymphoid tissue
• blood vessels/nerves enters base through the “hylum”

lymph = excess intracellular fluid that must be processed.

• Affarent lymphatics: enter on the outside surface
• Efferent lymphatics = leave through the hylum
• Cortex compused of: sinuses, nodules, diffuse lymphoid tissue, connective tissue trabeculae
• Medulla: medullary cords, medullary sinuses (draining place), medullary trabeculae

Question 9

Node Architecture

Answer 9

• Cortex: (nodular) affarent enter through the capsule and dump into the subcapsular sinus (immediately under the capsule), they then dump into the trabecular/cortical sinuses. – this area is not a distinct wall, when the sinus empities itself it is bathing all of the cells.
• In nodules, primarily B lymphocytes- (Cortex)
• Non-nodular areas = T lymphocytes (deep cortex/paracortex)
• deep cortex (Paracortex): where T lymphocytes are
• area of cortical tissue that is not nodule in nature
• in between cortex and medulla
• medulla: transport center: where B lymphocytes are
• medullary cords: diffuse lymphoid tissue (mostly B)
• medullary sinuses: irrecgular spaces similar in structure to cortical sinuses
• medullary trabeculae: like cortical trabeculae

Question 10

Lymph Node Function

Answer 10

• nodes filter lymph:
• trap and destroy immunogens by phagocytosis
• site of T and B proliferation, produce TCR’s and Ab’s
• T cells more numerous than B cells

Nodes recirculate T lymphocytes:

• T cells enter nodes through affarent lymphatic capillary, T cells leave nodes through effereent lymphatic capillary and enter venous system
• Where cells transit in and out of lymphatic tissue: T cells re-enter the node by transmigration through high endothelial venules (HEVs) in deep cortex. HEV’s also collecty lymph fluid
• HEV’s have loose tigh junctions, allowing cells to diapedise

Question 11

Spleen

Answer 11

1. filters blood (when spleen is absent, bone marrow takes up the role)
2. salvages Fe from RBC’s (older RBC’s can’t fit through the spleen filters and they explode, macrophages pick up Fe and recycle it, it is sent back to bone marrow)
3. site of generation of Ab’s by plasma cells (plasma cells migrate from white pulp to red pulp when mature)
4. resevoir for blood (RBC’s)
5. Site of erythropoeisis in fetus (moves to marrow around 7th month)

Question 12

Splenic Structure

Answer 12

• does not have an affarent lymphatic supply - all lymph gets there through vascular supply
• blood vessels and efferent lyjmphatics enter (arteries) or leave (lymphatics and veins) at the spleen hilum
• parenchyma composition: no cortex or medulla is present. instead the parenchyma is called “pulp”
• Red pulp: contains large [RBC]s
• White pulp: mostly small lymphocytes

Question 13

Splenic White Pulp

Answer 13

• composed mosly of aggregations of lymphocytes
• nodules: similar in structure to those in nodes
• splenic nodule has B cells in peripheral position, and T cells surround the central artery (arteriod situated eccentrically within the node)
• PALS = Peri-Arteriolar Lymphoid Sheath= name for the the T cell sheath that surrounds the central artieries of the splenic white pulp- this allows for the filtration of unwanted things - anything going through the spleen must pass through the PALS

Question 14

Splenic Red Pulp

Answer 14

• composed of blood vessels, macrophages, and extravasted blood
• it is free cells suspended in mesh of reticular fibers/cells
• filtration, turn over of dead and dying RBC’s is happening, where hemicidrin (iron in tissue) is being released and recovered by macrophages
• fenestrated capilaries have small holes (2-3 micron gaps between epithelial cells, allowing for entrance and exit) - old RBC’s cannot squeeze through these holes, resulting in release of iron.
• between venous sinusoids are blood-filled masses (pulp cords of Bilroth) - where Maacrophages destroy old RBC’s, where plasma cells produce and secrete antibodies, and where RBC’s /platelets are suspended in high density

Question 15

Splenic Circulation

Answer 15

• Spleen has a unique circulation: Two system of blood supply/delivery
• Closed: continuous channel: trabecular artery, pulp arteries, sinusoids, pulp veins, trabecular veins, splenic return.
• Open circulation: some capillaries don’t connect directly to venule, but dump from the pulp arteries into the red pulp cords - thus they have to filter through the red pulp to get into vascular circulation: way to filter our old Red Blood Cells.
• Cords of Bilroth: areas of red pulp, where the blood dumps into in open circulation

Question 16

Thymus

Answer 16

• thin connective tissue capsule consisting of two major lobes joined by thin isthmus. Lobulation is incomplete - lobules have cortex and medulla, but medulla is continuous from lobe to lobe.
• TEC: thymic epithelial cells - make up thymic stroma - do not produce fibers but instead form a network of cell processes that present antigens and secrete T cell-maturing agents
• This is the site of T cell bone maturation - thus it is similar to bone marrow
• There are many pro-thymocytes (immature T lymphocytes) in the Thymus

Question 17

Thymic Circulation

Answer 17

• vessles enter through capsule and go through thymic septa where they go through the cortico-medullary junction: either send vessles into the parenchyma (medulla) or they are sent toward the cortex where they encounter the Thymus-blood barrier.
• Blood thymus barrier: important in immune education: the capillaries here have continuous endothelium vessels that are sheathed by macrophages and by processes of Thymus Epithelial Cells. TEC’s and basal laminae for the blood-thymus barrier. TECs form “nests” for maturing thymocytes.
• T cell produced in cortex are directed toward medulla access blood via post-capillary venules in medulla called high endothelial venules (HEVs) - function with blood-thymus barrier so that only mature T lymphocytes are released into the blood.
• have an efferent lymphatic (no affarent though)

Question 18

Hassal’s Corpuscles

Answer 18

• TEC’s of medula for Hassall’s corpuscles
• have no known function, but are believed to be dead and dying TEC’s after assistinginthymocyte maturation.
• The number and size of corpuslces increases with age - thus thought to be a reason why people’s immune systems are weakened with age.

Question 19

Thymic Involution:

Answer 19

• thymus involutes (regresses) during later life
• this is largely due to loss of lymphocytes as they mature
• parenchyma gradually replaced by fat
• absolute size is not substantially deifferent from infants
• many T cell clones are now gone –> this is partly why older people get more sick more often

Question 20

T lymphocyte Maturation

Answer 20

• Prothymocyte migrate from marrow to thymus. The homing is based on prothymocyte expression of CD44 (leave bone marrow) and thymic production signals of CCL21 and CCL25 (causes them to stick in thymus.)
• T helper cells = CD4
• T regulatory = CD25 - important for runaway immune responses
• T cytotoxic cells = CD8

Maturing cells:

1. are CD4, CD8, CD25 negative (DN1)
2. expression of CD25 (DN2)
3. Lose expression of CD44 (DN3)
4. Lose expression of CD25 (DN4) - negative for everything (happens in thymic cortex)
5. develop expression of CD4 and CD8 (double positive DP)
6. DP’s lose expression of either CD4 or CD8
7. become either CD4 single positive (SP) or CD8 SP

• during this maturation process T cells undergo immune education, which involves positive and negative selection (learning to recognize self and non-self)

Question 21

Immune (Thymic) Education

Answer 21

• hemapoietic stem cell migrates out, a prothymocyte expresses CD44 and the immature T-cell moves into the thymus.
• in thymus it moves into the cortex, where circulation in thymus is important (first branches go into corico-medullary junction). In cortex it associates with TEC in cortex.

Positive Selection: Some prothymocytes won’t interact strongly with TEC’s - this is a problem, they don’t recognize self - cells that don’t bind well to TEC’s will be eliminated. They do not recognize the MHC complex 1.

• • If they bind too strongly to TEC’s they are also apoptosed (these are cells that won’t interact well with friends.)
• we are keeping cells that are positively communitcating.
• Now the cells that are kept are double positive and migrate into medulla of thymus where they encounter macrophages and dendritic cells:

Negative selection: Some will bind to thymic macrophage and thymic dendritic cells that have self-antigens - they want to attack self-recognizing proteins - if they bind they are apoptosed. (eliminating cells that bind)

• the cells are now single positive, and are function t lymphocytes that will recognize foreign antigens and respond to them.

Question 22

T lymphocytes and B lymphocytes

Answer 22

T cell independent: when B cells are activated directly (through bacterial toxin antigens)

T cell depended immune response (most common): most B cell responses depend onhelp from other cells- helper T-cells stimulate B-cells to profliferate and activate.

• T cells secrete lymphokines (IL4, IL5, IL13)

Helper T cells also stimulate other T-cells (cytotoxic T cells and regulatory T cells)

• HIV infects/inactivates helper T cells by binding to CD4 at the surface and thus rendering the individual immunocompromised.