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Lecture no. 9 Histology General Medicine Lymphatic/Immune System II Presenter: Lecturer Dr. Laura Chinezu“For internal use only! The unauthorized copy or distribution of this material is prohibited!” FACULTATEA DE MEDICINĂ LIMBA ENGLEZĂDISCIPLINA DE HISTOLOGIE 2023, May 26th

Organs of the Lymphatic system/ Immune system

The lymphatic system/immune systemoresponsible for the immunological defenseof the body, consists of>othe chief cellular constituents are the lymphocytesothe key elementsin an immune response olymphatic tissue -organized as odiffuse lymphatic tissueoaggregates of lymphatic follicles (nodules)oorgansof the lymphatic systemoconstitute the second line of defenseagainst invadersensuringthe immune response

Organsof the Lymphatic Systemoprimarylymphatic organs ohere, lymphocytes are ”educated” to recognize and destroy antigensothe site where undifferentiated stem(progenitor)lymphocytes develop/migrateand undergo proliferation anddifferentiationinto immunocompetent cellsothis initial proliferation and differentiation is antigen-independent othe resulting mature cells are able to recognize antigens but have not yet comein contact with the antigenmature and naïve Ly Histologyguide. com Fetal liver Red bone marrow Thymus

Organs of the Lymphatic Systemoprimary lymphatic organs oabsenceor incomplete development of the primary lymphatic organs oresults in a quantitative andqualitative disturbance (imbalance) of the immune functionothey are: othethymus, obone marrow and odiffuse lymphatic tissue and lymphatic nodules in the small intestine called GALT (Gut-associated lymphatic tissue) Histologyguide. com

Organs of the Lymphatic Systemosecondary (peripheral) lymphoid organsoprovidea proper environmentin which immunocompetent cells can react with: oeach otherowith antigens owith other cellsothe result is an immunological responseagainst invading antigens

Organs of the Lymphatic Systemosecondary (peripheral) lymphoid organsoorgans in which lymphocytes,othat have become“mature” cells in the primary lymphatic organs,obecome “effector” cells of the immune response omostof the activity of lymphocytes takes place in these organsoablationorfunctional impairment of one of the secondary lymphatic organs does not affect theimmune functionothey are: othe lymph node, spleen, MALT, and diffuselymphatic tissue

ØThymus

Thymus oit is the first lymphoid organ that develops during embryonic lifeoit developsbilaterally from the right and left 3. (and sometimes also the fourth) branchial(oropharyngeal) pouches,together with the parathyroidsofullyformedand functionalatbirth https://www. slideserve. com/xyla-thomas/development-of-thymus-from-the-three-primary-germ-layers

Thymus oit persists as a large organ until about the time of puberty when it reaches its top weight (about30-40 g)oafterpuberty, a progressive involutionoccurs o T cell differentiation and proliferation arereduced and omost of the lymphatic tissue (and the cortex in particular) is replaced by adipose tissue. oin the elderly, the thymus becomes a fibro-adipose tissue oinvolutionis under the controlof steroid hormones (sexual hormones)ohttps://www. researchgate. net/publication/230636244_Glucocorticoids_thymus_function_and_sex_hormone_in_human_body_growing https://www. medgadget. com/2018/05/thymus-cancer-market-2018

Thymus oit is a primary lymphoid organ, with two main roles:othe site of development and maturation of naïve TLy-omultipotent lymphatic stem cells proliferate and differentiate intoimmunocompetent T lymphocytes ocells that are able to distinguish the “self” from the “non-self”, todestroy the “non-self”, and to developself-toleranceoan endocrine organ: secretes hormoneswhichocontrol the proliferation, differentiation and maturation of TLyoregulate the TLyfunction in the peripheral tissues

Thymus ØGeneral organizationo Stromao Parenchymao T cells educationo Blood supplyo Roleo Involution

Thymusois situated in the upper part of the thorax behind the sternum oin the superior mediastinum, anterior to the heart and great vessels https://www. verywellhealth. com/thymus-anatomy-4800309 https://crev. info/2020/08/thymus-vestigial-not/

Thymusolobulated structureo2 lobesjoined by connective tissue oits structure-follows the general organization of the lymphatic organs:oconnective tissuecapsule at theperiphery, oseptathat divide the organ into lobes andlobules, ostroma, and oparenchyma https://www. canyons. edu/academics/biology/resources/lab107/thoracic/thymus. php

Thymusoenclosed by a thincapsule (connective tissue)ofrom which trabeculae or septa extend into theparenchyma othecapsule and trabeculaecontain oconnective tissue with collagen fibers and fibroblasts, oa variable numbers of plasma cells, granulocytes, lymphocytes, mast cells, adipose cells, andmacrophages. oblood vessels, efferent (but not afferent)lymphaticvessels and nerves Histologyguide. com

Thymusothe trabeculae/septaestablish domains in the thymus called lobulesothey are not true lobules othe septadivide only the peripheral area-the cortex odarker peripheral zoneowhereas the central area forms a commoncore for several lobules-the medullaolighterperipheral zone

Thymusocell types in thymusoepithelioreticularcells-form the stroma of the thymusomacrophageso TLy-dominant cell type-thymocytes https://www. researchgate. net/figure/Thymus-histology-and-IHC-from-9-weeks-of-age-in-male-SD-rats-a-HE-stain-b-T-cells_fig2_223963289AE1/AE3

Thymuso General organization ØStromao Parenchymao T cells educationo Blood supplyo Roleo Involution

Thymus-stromaodiffers from that of other lymphatic organs because of its epithelial origin othe thymicstromal cells are called epithelioreticularcellsoform an extensivemeshwork-with spaces occupied by T lymphocytes Histology of the Tissues, A. Borda, 2017

Thymus-stromaothe epithelioreticular cells-stromal cellsoare larger cells, with cytoplasmic processes (stellate cells)ohavean abundant pale, eosinophilic cytoplasm and a large,centrally located hypochromaticnucleus, oas their name implies, they have featuresof both epithelial and reticular cells othey provide a framework for the developing T cells othey do not synthetize reticular fibers, the thymus being the onlylymphatic organ without reticular fibers in its stromaoexhibit certain characteristic featuresof epithelial cells, such as ointercellular junctions (desmosomes) and o CKs(cytokeratins)in the intermediatefilaments histologyguide. com

IHC-Cytokeratin AE1/AE3 positive cells IHC-CK14 positive cellshttps://journals. plos. org/plosone/article?id=10. 1371/journal. pone. 0230668

Thymus-stromaothe epithelioreticular cells-stromal cellsohave important functions:oprovide supportfor other cells of the thymus oare part ofthe blood-thymus barrierocreate and maintain the microenvironmentnecessary for the development of TLyin the cortex oform the Hassalbodies/corpusclesosecrete hormons: thymosin, thymopoietin, thymulinoon the basis of their function, six types are recognized, designated by roman numerals IVIothree in the cortex and three in the medulla https://histologylab. ctl. columbia. edu/lab08/thymus/Histology of the Tissues, A. Borda, 2017

Thymus-stroma in the cortexotype I, II and III epithelioreticular cellsomacrophages

Thymus-stroma-cortexo Type I epithelioreticular cells-located at theoboundary of the cortex and the connective tissuecapsule as well as obetween the cortical parenchyma and the trabeculaeoaround theadventitia of the cortical blood vessels https://vetmed. tamu. edu/peer/wp-content/uploads/sites/72/2020/08/17.-Structure-of-Lymphoid-System-Components. pdf

Thymus-stroma-cortexo Type I epithelioreticular cells-oserve to separatethethymic parenchyma from the connective tissue of the organo playingan important roleinthe formation ofthe blood-thymusbarrierodue to the occluding junctions between these cells that reflect theyfunction as a barrier oisolatingdeveloping T cells from the connective tissue of the organ (capsule, trabeculae, andperivascular connective tissue) https://vetmed. tamu. edu/peer/wp-content/uploads/sites/72/2020/08/17.-Structure-of-Lymphoid-System-Components. pdf

Thymus-stroma-cortexo Type II epithelioreticular cells-olocated within the cortex. odivide the cortex into isolatedareas for the developing T cells. ounliketype I cells, type II cells express MHC I and MHC II moleculeswhich are involved in thymiccell education. https://www. researchgate. net/figure/The-thymic-cortex-in-a-newborn-An-epithelial-cell-type-2-or-3-called-nurse-cell_fig5_380347751-ERC II, 2-processes, 3-T Ly https://www. histology. leeds. ac. uk/lymphoid/thymus. php

Thymus-stroma-cortexo Type III epithelioreticular cells-olocated at the boundary of the cortex and medullaoliketype I cells,they create a barrier-functional barrier-oin this case, between the cortex and medullaoliketype II cells, they opossess MHC I and MHC II molecules https://artnscience. us/lect-thy-m. gif

Thymus-stroma-cortexo Macrophages-oreside within the thymiccortex and oare responsible for phagocytosis of T cells that donot fulfill thymic education requirements othese cells(T cells)are programed to die before leaving the cortexo!!!macrophages in the cortex are difficult to identify in HE staining odifficult to be distinguished from epithelio-reticular cellsothe periodic acid-Schiff(PAS) reaction readily defines them because of the many lysosomesthey contain. oaccordingly, thesemacrophages are called PAS cells histologyguide. com https://labmedicineblog. com/2020/05/01/

Thymus-stroma in the medullacontains a large number of epithelioreticularcells type IV, V and VI epithelioreticular cellsand loosely packed T cells

Thymus-stroma-medullao Type IV epithelioreticular cells-olocated between the cortex and the medulla, close to type III-cellsothey possess sheet-like processes owith occluding junctions obetween adjacent cells as well as obetween them and type III cells oand create the barrier at the corticomedullaryjunction

Thymus-stroma-medullao Type V epithelioreticular cells-olocated throughout the medulla. olikethe type II-cells, they have animportant role in the maturation of the T lymphocytesodisplay on their surface, class I MHC and II MHC molecules

Thymus-stroma-medullao Type VI epithelioreticular cells-form the most characteristic feature of the thymicmedulla, the thymic Hassall's corpuscles oround or oval eosinophilic structures, owith a lamellarappearance, similar to an onion bulb on the histological slides. ocomposed ofclosely packed, concentrically arranged type VI epithelioreticularcells that exhibit flattened nucleiothe center may display evidence of keratinization(*being cells developed from oropharyngeal epithelium)+ calcification histologyguide. com

Thymus-stroma-medullao-Hassall's corpusclesotheir numberincreaseswith age until puberty when the thymus involution process beginsoalthoughtheirfunction is not fully understood, oit is thought that thymiccorpusclesproduce interleukins (IL-4 and IL-7) othat function in thymicdifferentiation and education of Tlymphocytes. Histologyguide. com https://en. wikipedia. org/wiki/Hassall%27s_corpuscles#/media/File:Thymic_corpuscle. jpg

Thymuso General organizationo Stroma ØParenchymao T cells educationo Blood supplyo Roleo Involution

Thymus-parenchymaocontains developing T cellsoit has two distinct areasocortex-darker, peripheral omedulla-paler, centrally located https://journals. plos. org/plosone/article?id=10. 1371/journal. pone. 0230668

Thymus-parenchymaocortex is omarkedly basophilic because of the closely packed developing T lymphocytes owithintensely stained nuclei and sparse cytoplasm. otheseimmature T lymphocytes are called thymocytes. (CD3+)omacrophages, ERCs are also dispersed among the cortical cells https://journals. plos. org/plosone/article?id=10. 1371/journal. pone. 0230668 https://www. researchgate. net/figure/Thymus-histology-and-IHC-from-9-weeks-of-age-in-male-SD-rats-a-HE-stain-b-T-cells_fig2_223963289

Thymus-parenchymaomedullaostains less intensely than the cortex becauseit contains loosely packed Tlymphocytesomostly large lymphocytesowithpale-stainingnuclei and abundant cytoplasm oa large number of epithelioreticularcells https://journals. plos. org/plosone/article?id=10. 1371/journal. pone. 0230668

Thymuso General organizationo Stromao Parenchyma ØT cells educationo Blood supplyo Roleo Involution

T cell education-Maturation and differentiation o During fetal life, othe thymus is populated by multipotent lymphatic stem cells othat originate fromthe bone marrow and oare destined to develop into immunocompetent T cellsostem cell maturationand differentiation into immunocompetent T cells is called thymiccell educationoprocesscharacterized by the expression and deletion of specific surface molecules, TCR and CDoin that the epithelioreticularcells play an important roleoit is a very complex process

T cell education-Maturation and differentiation o Lymphatic stem cells omigrate from the RBM (red bone marrow) into the thymusothrough postcapillary venules into the thymus into the medulla migrate into thecortex under the capsule Medulla Cortex LSCPostcapillary venule ERC IVERC IIIERC ILSC LSC-lymphatic stem cell ERC-epithelioreticularcells

T cell education-Maturation and differentiation o In the early stages of differentiationoon the surface of T lymphocytes(precursorsof TLy) ocertainantigens can be identifiedo CD2 and CD7o-a stage also called double-negative stage,becauseoon the surface of T lymphocytesoboth CD4 and CD8 molecules are absent Medulla Cortex LSCPCVERC IVERC IIIERC ILSCCD2, CD7

T cell education-Maturation and differentiation o This early stage is followed by theoexpression of the CD1molecule, owhich indicates the middle stage of T cell differentiation. o As maturation progresses, the Tcells express o TCRs, CD3, and oboth CD4 and CD8 molecules. othis is the double-positive stage of T celldifferentiation. Medulla Cortex CLPPCVERC IVERC IIIERC ICLPCD2, CD7CD2, CD7CD1CD2, CD7, CD1CD3, TCRCD4, CD8ERC II

T cell education-Maturation and differentiation o T cells are then presented owith antigens (self-and foreign)oby type II and III epithelioreticularcells ocellsthat have type I and II MHC molecules on their surfaceoif the lymphocyterecognizes self-MHCmolecules and antigens oit will survive, a process called positive selection. oif notothecell will diethrough apoptosis and will be phagocytizedby the macrophages. Medulla Cortex LSCPCVERC IVERC IIIERC ILSCCD2, CD7CD2, CD7CD1CD2, CD7, CD1CD3, TCRCD4, CD8ERC II positive selectionpassdo not pass

T cell education-Maturation and differentiation o Cells that pass the positive-selectiontest oleave the cortex and oenter the medullaowhere, they undergoanother selection process, othis timea negative selection process. Cortex ERC IVERC IIIERC ILSCCD2, CD7CD2, CD7CD1CD2, CD7, CD1CD3, TCRCD4, CD8ERC II positive selectionpassdo not pass

T cells that recognize self-antigensdisplayed by self-MCH and oactivate themselves,in the presence of these antigens owill be eliminated. othat do not activate themselvesosurvive and become oeither cytotoxic CD8+ T lymphocytes (by losing CD4 and retaining CD8) or ohelper CD4+T lymphocytes (by losing CD8 and retaining CD4). othis stage is called the single-positive stage of T celldifferentiation. T cell education-Maturation and differentiation

o T cellsthat survived willleavethe thymus by passing from the medulla into the systemic circulation ovialymphatics(efferentlymphatic vessels) orovia the bloodstream(post-capillary venules). oas mature, immunocompetent, but naive cells; othey are naivebecause they have not yet come in contact with the antigens osubsequently, these T Lymphocytes owillpopulatethe secondary lymphatic organs in T-lymphocyte specific areas. ohere they will gain their fullimmunological maturity effector cells T cell education

Thymuso General organizationo Stromao Parenchymao T cells education ØBlood supplyo Roleo Involution

Thymus-Blood supplyoit is richly vascularized and this allows the migration of lymphocytes. otheblood vessels(arteries)penetrate the thymus through the trabeculae. othe finest ramifications enterinto thethymus parenchyma accompanied by a small amount of connective tissue. ocorticalcapillaries have acontinuous wall, whereas othose in the medulla are fenestrated. oat the corticomedullaryjunction, therearepost-capillary venules,ovenuleswith high endothelium, through which lymphocytes migrate intoand out of the thymusothe venous system is tributary to the arterial one. http://www. people. vcu. edu/~aszakal/course_syllabi/IMMSYST. I2. htm

Thymus-Blood supplyothe thymus has no afferent lymphatic vesselsobut only efferent lymphatics othat are formed in thecortico-medullary junction area and in the medulla. http://www. people. vcu. edu/~aszakal/course_syllabi/IMMSYST. I2. htm

Blood-thymus barrierothe vascular supply+ ERCellsform a very powerful blood-thymus barrier oto prevent developing T cellsfrom contacting antigenso It has the following componentso*endotheliumo**perivascular connective tissue spaceo***type I epithelioreticular cells

Blood-thymus barriero The endotheliumothat linesthe capillary wall +its basal laminaoit is of continuous type with occluding junctionsoit is highly impermeable to macromoleculesoperivascular connective tissue spaceotype I epithelioreticular cells

Blood-thymus barriero The perivascular connective tissue spaceooccupied by macrophages:othat may phagocytoseantigenic molecules othat escape from the capillary lumen into the cortical parenchymaotype I epithelioreticular cells

Blood-thymus barriero The type I epithelioreticular cells and their basal lamina:oprovide with their occluding junctionsfurther protection to the developing T cellsosurroundthe capillary wall in the cortexoself-macromolecules are permitted to cross the blood-thymus barrier (probably controlled by the epithelial reticular cells)

Thymuso General organizationo Stromao Parenchymao T cells educationo Blood supply ØRole o Involution

The function of the thymusoto produce mature lymphocytes(TH, TC, TReg)for the secondary lymphoid organs othe progenitorsof T cells invade the cortical regions of the thymus (postcapillaryvenules) othey divideand differentiateto form mature lymphocytes othis process entails the synthesis of unique internal and membrane proteinsoonly a small fraction (10-30%) of these cells leave the thymus othey enter the blood stream to populate the areas of TLyof secondary lymphoid organsocells which do not express the necessary receptors to recognize antigenspresented to them or whichreact incorrectly towards "self-antigens"dieand are removed by cortical macrophages

The function of the thymusoto ensure the proliferation of T lymphocytes clones that will cover the needs of T lymphocytes fromthe blood and from the secondary lymphatic organs;oto suppress immune response towards self-antigens (development ofself-tolerance);othe endocrine role: synthesis of the thymichormones (thymulin, thymosin, and thymopoietin). o ERCells secrete thymichormones the entire life, even after the involution of the thymus

Thymuso General organizationo Stromao Parenchymao T cells educationo Blood supplyo Role ØInvolution

Involution of the thymusothe thymus reaches the maximum weight at puberty oafter which it undergoes a process of gradualinvolution; oit can be hardly recognized in the elderlyo T cell depletionoand most of the lymphatic tissue is replaced by adipose tissue Presence of adipose tissue and a decrease in the amount of cortical and medullary thymictissue https://embryology. med. unsw. edu. au/embryology/index. php/Thymus_Development

Involution of the thymuso Lymphocyte depletion consists of oreduced T cell proliferation and differentiation agradual decrease in the number of lymphocytes, oso that at some point the epithelioreticularcellsbecome visible in HE staining. o It is not always complete. o In the remaining thymusparenchyma, oa small number of lymphocytes continue to differentiate and proliferate, providing the Tlymphocytes for the body. Presence of adipose tissue and a decrease in the amount of cortical and medullary thymictissue https://link. springer. com/chapter/10. 1007/978-3-319-98980-8_1

Involution of the thymusothe accumulation of adipose tissue in the thymus obegins immediately afterbirth and oaccelerates dramatically after puberty. ofirst, it involves the cortex, then the medullaoinvolution is under the control of steroid hormones (sexual hormones) https://link. springer. com/chapter/10. 1007/978-3-319-98980-8_1

ØLymph Node 63

Lymph Nodeosmall, oval or bean-shaped, grayish organs ointerposed along lymphatic vessels owidely distributed throughout the bodyothey are concentrated in certain regions such as the axilla,groin, and mesenteries

Lymph Nodeohave a diameter of1 mm up to several millimeters when they are inactive, obut can enlarge up to 1-2 cm in case of an immune response(even more)oe. g. inflammation, metastasiso They have a oconvexsurface-afferent lymph vesselsoconcavesurface, owith a depression, the hilum,which serves as the entrance and exit for blood vessels, efferent lymph vesselsand nerves. https://training. seer. cancer. gov/anatomy/lymphatic/components/nodes. html

Lymph Nodeo Role oare secondary lymphatic organs oand fulfill two main functions:ofiltering the lymph oin this way the lymph nodes retainand inactivatevarious antigens(microorganisms, other antigens)oprovidingan ideal placewhere lymphocytes ocan interact with antigens or with APCs, ocan activate,oproliferate(clonal proliferation), and ocan destroythe antigens.

Lymph nodeo General organizationo Stromao Parenchyma o Sinuseso Blood supply

Lymph Nodes-general organizationothey have a oconnective tissue capsuleat the periphery, ocomposed of dense connective tissueotrabeculaeextend from the capsule into theparenchyma and divide only the periphery of the organostroma, and oparenchyma

Lymph nodeo General organizationo Stromao Parenchyma o Sinuseso Blood supply

Lymph node-stromaocomposed of a reticular connective tissue: oreticular cells and reticular fibersthat form a fine supporting meshwork throughout the organoprocessesof reticular cells and the reticular fibers extend into and crisscross within the lymphatic sinuses(lymphatic channels)oby IHCand EM-different types of stromal cells have been identifiedoreticular cellsomacrophagesodendritic cellsofollicular dendritic cells

Lymph node-stromaotypical reticular cells:oare indistinguishable from typical fibroblasts;oelongated cytoplasmic processes

Reticular cells (red arrow),with long processes that link with processes of neighboring cells and form a network. Lymphocytes

Lymph node-stromaotypical reticular cells:osynthesizeand secrete type III collagen fibers;otheir processes wrap around the bundles of reticular fibers,oeffectively isolating these structural components from the parenchyma of the lymphatic tissueand organs;

Lymph node-stromaomacrophages:obothphagocytic and antigen presenting cellsothat express MHC I, MHC II, and co-stimulatory molecules.

Lymph node-stromaodendritic cells DCor i DC:obone marrow-derived APCsomonitorthe local environment for foreign substances othat they then fagocytose, processand present to antigen specific T cells ousually localized in T lymphocyte-rich areasovery efficient in antigen presentation ocan present virtually any form of protein antigen on both MHC I and MHC II molecules https://www. cancer. gov/news-events/cancer-currents-blog/2019/in-situ-vaccine-non-hodgkin-lymphoma

Lymph node-stromaofollicular dendritic cells:oare localized in the germinal centers; owhere their cytoplasmic processes interdigitatebetween B lymphocytes ofound in B lymphocyte-rich areasodue to their properties, they are also called accessory immune cells (see below). Fresh FDC cells with clustered lymphoid cells 24 h after isolation NOT TRUE APCs!!!

https://escholarship. org/content/qt5d0808rm/qt5d0808rm. pdf?t=nsnwgm CD21+

Lymph nodeo General organizationo Stromao Parenchyma o Sinuseso Blood supply

Lymph node-parenchymaodivided into:othe cortex is the outer partothemedulla is the inner part https://slideplayer. com/slide/4767037Histology of the Tissues, A. Borda, 2017

Lymph node-parenchymaothe cortex oforms the outer portion of the lymph node except at the hilumoit consists of a dense massof lymphatic tissue and lymphatic sinuses, the lymph channels; oit is divided into two parts: othe outer, superficialcortex and othe inner cortex or paracortexothemedulla-the inner part of the lymph node containsolymphatic tissue (cords) and sinuses

Lymph node-parenchyma-outer (superficial) cortexois a B cell rich region,oconsisting of numerous lymphatic follicles (nodules)ooccasional, lymphatic follicles can also be found in deeper areas. https://www. nature-microscope-photo-video. com/en/photos/animal-histology/comparative-histology-of-vertebrates/other-systems/lymphatic-system/mammals/mammals/010505c0207050101b-mammal-lymph-node-transverse-section-32x. html

Lymph node-outer (superficial) cortexolymphatic follicles are round or oval structures with variable sizes and appearances:obefore birth, the lymphatic follicles are small, with a homogenous appearance, consisting chieflyof small “naive” lymphocytes that have not yet come in contact with the antigens; othese follicles arecalled primary lymphatic follicles; https://slideplayer. com/slide/10279532/

Lymph node-outer (superficial) cortexothe secondary lymphatic follicles odevelop after birth, following the contact with the antigens; ohave distinctive features that include the following:oa germinal centerolocated in the central region of the follicle and oappears lightly stained inhistological sections:omantle zone orcorona osurrounds the germinal center; oappears darkerstained http://www. meddean. luc. edu/lumen/Med Ed/Histo/frames/h_fram12. html

Lymph node-outer (superficial) cortexothe germinal center -of secondary lymphatic follicles-odevelops when alymphocyte that has recognizedan antigen returnsto a primary nodule and undergoes activation and proliferation;oit contains large lymphocytes (centro-follicular cells)-with abundant basophilic cytoplasm, surrounding a pale,hypochromaticnucleus, with a prominent nucleolusohence the lighter staining of the germinal centreothe presence of a germinal center represents a cascade of eventsthat includes oactivationand proliferation of lymphocytes, odifferentiation of plasma cells, and oantibodyproduction;o is a morphological indication of lymphatic tissue response to antigen https://act. downstate. edu/courseware/web_path/histhtml/normal/histquiz/hist2frm. htm

Lymph node-outer (superficial) cortexothe germinal center-in secondary lymphatic follicles/nodules-osurrounding the germinal center, reticular cellsform a capsule-likestructureothat controlsthe cells that enter and exit the germinal center; othese cells are called bordering cells ofthe germinal center. Histology of the Tissues, A. Borda, 2017

Lymph node-outer (superficial) cortexothe mantle zone or corona oit represents an outer ring-surounds the germinal centreomade up of smalllymphocytes with hyperchromatic nucleus and littlecytoplasm

Lymph node-outer (superficial) cortex-cellso B lymphocyteso THlymphocyteso NK lymphocyteso Accessory immune cells (macrophages, follicular dendritic cells)

Lymph node-outer (superficial) cortex-cellso B lymphocytesoare the most numerous oin the cortex-several types of B lymphocytes are present othe corona containsosmall, naive B lymphocytes and omemory B lymphocytes. owhich expresscharacteristic immunohistochemicalmarkers: CD20, CD22, and CD24, as well as Ig M and Ig Goin thegerminal center, oactivated B lymphocytes, or centro-follicularcells, are foundotheyexpressthe same CD antigens and Ig M on their surface, but not Ig G!!

Lymph node-outer (superficial) cortex-cellso B lymphocyteso The contact with theantigen oleads to the activation and differentiation of small lymphocytes from the marginal zone owhich transform into activated B lymphocytes in the germinal center; othey first turn into centrocytes(largeand small cleaved cells), othen into centroblasts(large and small uncleavedcells) oand leave the germinalcenter as immunoblasts.

Lymph node-outer (superficial) cortex-cellso B lymphocytes-activated into immunoblastsomigrateintothe paracortexor in the medulla, owhere the immunoblastsdifferentiate oeitherinto antibody-producing plasma cells oor memory B lymphocytesowill retainthe memory of the antigen they came in contact with, oand will be able to activate themselves rapidlyat a new contact with the same antigen.

Lymph node-outer (superficial) cortex-cellso THlymphocytesoin the lymph node corona; otheir role is to activate B lymphocytes;otheir passageinto the germinal center is preventedby the bordering cells of the germinal center

Lymph node-outer (superficial) cortex-cellso NK lymphocytesoare present in small number in the cortex and in the lymph node in general; otheirrole is to identify and to destroymalignant cells and virus infected cells

Lymph node-outer (superficial) cortex-cellso Accessory immune cellso Macrophages oor, tingiblebody macrophages,omacrophages with phagocytized lymphocytes and cellular debris (tingiblebodies) inside their cytoplasmothat are antigen presenting cells (APC) https://link. springer. com/referenceworkentry/10. 1007%2F978-3-319-95309-0_3860https://www. arppress. org/v/vspfiles/assets/images/Chapter1T25Lymph Nodes. pdf

Lymph node-outer (superficial) cortex-cellso Accessory immune cellso Follicular dendritic cells otheirembryological origin-is still controversialohave multiple, thin, hair-like branching cytoplasmic processesothatinterdigitate between B lymphocytes in the germinal centers; https://link. springer. com/referenceworkentry/10. 1007%2F978-3-319-95309-0_3860

Lymph node-outer (superficial) cortex-cellso Accessory immune cells o Follicular dendritic cells othe antigens adhere to the dendritic cytoplasmic processes othe cell can retain theantigens on its surface for weeks, months or years and present it directly to the B lymphocytes. othey are antigen-bearing cellsothey do not phagocytose the antigenothey lack type II MHC molecules. othusthey arenot true APCs!https://link. springer. com/referenceworkentry/10. 1007%2F978-3-319-95309-0_3860

Lymph node-(inner/deep cortex)-paracortexobetween the medulla and superficial cortex ofree of lymphatic follicles

Lymph node-(inner/deep cortex)-paracortexoperinatal thymectomyin animals results in a poorlydeveloped deep cortexo zone dependenton the thymusothus-the deep cortex is called thymus-dependentcortex https://link. springer. com/referenceworkentry/10. 1007%2F978-3-319-95309-0_3860