17. Lymphatics Histology

7/31/2019 17. Lymphatics Histology

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Esguerra, Espiritu, Eugenio, Falloria, Flores

Lymphatic Systemthe second circulatory system

one of the bodys primary defenses against invasion by

harmful organisms and chemical toxins

COMPONENTS OF THE LYMPHATIC SYSTEMCells:

-Lymphocytes of blood-Plasma cells and macrophages of connective tissue

Lymphoid (a.k.a. lymphocyte-containing) organs-Thymus-Spleen-Lymph nodes-Lymphoid nodules of the GIT

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Figure 1. Organs of the Lymphatic System

Figure 2. WBC differentiation

Leukocytes found in blood: lymphocytes, monocytes,neutrophilsSoft tissues: lymphocytes, plasma cells

The Story: IMMUNITYActors:1. APC: Macrophage, B cells, dendritic cells2. T helper cells3. T lymphocytes (cytotoxic lymphocytes)

4. B lymphocytesMHC MHC I

-all nucleated cells-binds T cell (cytotoxic) to CD8 receptor

MHC II-antigen presenting cells-binds T helper cells to CD4 receptors

Cells of the Immune SystemLYMPHOCYTES

Develop in the bone marrowComprise 20-50% of WBCs in the circulation; the secondmost abundant WBC

Most are small (~6-9m) while about 3% are large (~915m)Precursor cells develop into two types: T lymphocytes andB lymphocytesNull cells: small proportion of lymphocytes that cannot be

classified as T or B lymphocytes- Capable of destroying tumor cells spontaneously o

through an antibody-dependent cellular cytotoxicmechanism

1. T (thymus-dependent) LYMPHOCYTESArise from precursor cells that migrate from the bone

marrow to the thymus for further differentiation

Comprise about 70% of circulating lymphocytes

Antigen receptor: T cell receptor (TCR)

Initial function: seek, recognize and attach to antigensthat fit their surface receptors (lock and key mechanism)Ultimate function: cell-mediated immunity

Functional subsets (Sensitized T lymphocytes):a. T helper cells (TH)Interact with other T and B lymphocytes toenhance the immune response

help other cells to perform their effectorfunctions by secreting a variety of mediatorscalled interleukinsUpon activation, they secrete lymphokines,which increase activation of B cells, cytotoxic Tcells and suppressor T cells by antigens

Attract macrophages; promote more efficientphagocytosis

b. Cytotoxic T cells (TC)

a.k.a. killer cells

possess the ability to kill virus-infected cells andsome cancer cells directly

-by binding tightly to the invading cell,eventually swelling and releasingcytotoxic substances directly into theattacked cell

-capable of attacking and killing manyorganisms in succession without beingharmed

interaction with TH is required for their activationand proliferation to form clones of effector cells

PH 121- Gross and Microscopic Anatomy

Immune System Histology

September 5, 2012

Dr. Ryner Carrillo

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c. Suppressor T cells (TS)

Inhibit the immune response-suppress the action of TH and TC-regulator of other T cells, preventing themfrom causing excessive immune reactionsand severe tissue damageNOTE: Loss or destruction of TH (as inthe case of AIDS) leads to a relative excessof TS, which therefore inhibits immuneresponse and increases the susceptibility toinfection

d. Memory T cells

Develop from activated T cells to provide a rapidreaction force for a subsequent encounter with thesame antigen

*Further classification of sensitized T lymphocytes,according to specific antigens on their membranes:

a. CD4 lymphocytes- TH- account for ~70% of all T cells- activate cytotoxic cells to mature and stimulate

b. CD8 lymphocytes-TS and TC

-account for ~30% of all T cells A normal ratio of CD4 to CD8 lymphocytes isessential for proper immune function. (refer tothe case of AIDS in the previous section)

2. B (Bone marrow-dependent) LYMPHOCYTESDerived from precursor cells in the bone marrow andcontinue to mature there

Possess surface markers for recognitionAntigen receptor: surface immunoglobulin (sIg)

Initial function: synthesize and insert antibodies ontheir surfaceUltimate function: humoral immunity

Plasma cells: mature B cells that secreteantibodies (immunoglobulins: IgG, IgA, IgD, IgM,

IgE) in response to antigensMemory cells: small long-lived circulatinglymphocytes that are able to respond quickly toany subsequent exposure with the same antigen

MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

a.k.a. Human Leukocyte Antigen (HLA)

set of genes that encode for the glycoproteins foundon the surface of all cellsClasses

MHC I (self-antigen)-all nucleated cells-binds T cell (cytotoxic) CD8 receptor

MHC II (T cell receptor)

-Antigen-presenting cells (macrophage, dendriticcells)-binds T helper cell CD4 receptor

ANTIBODY

Complex protein with antigen-binding and cell-binding sites

Figure 3. Antibody

Antigen Presentaition1. Antigen enters dendritic cell2. Enzyme inside cell breaks antigen to pieces3. Antigen pieces bind to MHC protein inside

endoplasmic reticulum4. The MHC antigen is transported to the cell surface via

the Golgi apparatus5. The MHC protein presents the antigen on the surface

of the cell membrane

Figure 4. The immune response

THE IMMUNE RESPONSE

Initiation requires contact between antigen and surfacereceptors on mature lymphocytes

Initiation requires contact between antigen and surfacereceptors on mature lymphocytesInitial phase involves lymphocyte and macrophage

interaction; both are widely distributed in the body and canrespond to a foreign substance wherever they encounteit.Macrophages ingest the foreign material, process itsantigens and present the processed material to thelymphocytes (antigen-presenting cells, APC)Lymphocytes then respond and transform into antibodyforming plasma cells and sensitized lymphocyteswhich proliferates rapidly to perform immune functions

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Following initial contact with an antigen, several weeksare needed for macrophages to process the antigen andfor lymphocytes to respond

After reaction to the antigen, memory cells retain theability to respond promptly to the same antigen onsubsequent exposure

Figure 5. Lymphocyte activation

A. Cell Mediated Immunity

Identification of antigen by T-cells

The bodys main defense against viruses,parasites, and some bacteria

Results from the function of sensitizedlymphocytes

Also eliminates abnormal cells that may ariseduring cell division (which if not destroyed,become tumors)

Also causes organ transplant rejection

Commonly associated with hypersensitivity tobacterial antigens or other foreignsubstancesCharacteristic reaction is an intenseinflammatory reaction at the site of contactwith the foreign substance

In this process, MHC molecules of infectedcells orAPCs present antigenic peptides tothe lymphocytes, thereby sensitizing the Tlymphocytes to that antigen; this allows Tlymphocytes (TH and TC) to destroy the antigenon subsequent exposure

B. Humoral or Antibody Mediated Immunity

The major defense against many bacteria andbacterial toxinsResults from the function ofB lymphocytesFormation of antibodies

B lymphocytes->plasma cells: response to antigen

stimulationAntibodies directly attack the invader or activatethe complement system, which destroys theinvader

In this process, macrophages present processedantigens to the lymphocytes; B lymphocytedifferentiation into plasma cells follows

antigen elimination

abnormal cells recognized bycytotoxic T-cells are

destroyed by apoptosis

sometimes, helper T-cellsrelease cytokines that

activate macrophages that

kills the organism (type IVsensitivity)

MHC-Ag complex contacts with a T-cell

If MHC class I, it is recognizedby TcR of cytotoxic T-cell

If MHC class II, TcR of helper T-

cells recognize for B-cellactivation

binds to MHC

becomes a processed antigen

taken up by APC

APC - antigen presenting cells such as macrophage, B-cells,dendritic cells and Langerhans cell of the skin

Antigen

antibodies eliminate antigen

antibodybinds to

surfaceantigens toblock entry

oforganisms

activatecomplimen

t system

facilitatesphagocytos

is viaopsonizatio

n

antibody-dependent

cytotoxicity

bindstoxin

causiinactiv

n anremovphagoc

plasma cells produce antibodies

clonal expansion

Some B-cells become memorycells for anamnestic response

Other B-cells mature to becoplasma cells to secrete

antibodies

activates other B-cells

T-cell helper cell also recognize process antigen to releaseinterleukins to mediate activation, clonal expansion and matura

of t-cells

Recognized by sIg (surface immunoglubulin) of B-cell

Antigen

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Lymphatic Tissues / Organs

A. ThymusLocated in the chest, behind the sternum, and anterior tothe heartFUNCTIONS:

site of precursor T lymphocyte selectionand maturation to T-helper and cytotoxic Tlymphocytes

retains non-self recognizing T cells

Development of immunological self-tolerance by initiating apoptosis topotentially harmful T cells

Secretes thymulin, thymupoietin andthymosins to regulate T-cell maturation,proliferation and function

Stem cells (precursor T lymphocytes) migrate to thymus

Consist of two lobes covered by thin connective tissueand subdivided by septa into smaller lobules

Should atrophy in adulthood to be replaced by adiposecells and fibrous tissue but sometimes persist

STRUCTURES:1. Capsule

- beneath it is a continuous layer of epithelial reticular

cells2. Cortex (darker)

- deeply staining- abundant lymphocytes- site of proliferation and selection- has a loose three-dimensional network or atypical

epithelial cell called stellar reticular cell- spaces between the network of stellar reticular cell

are filled with maturing lymphocytes in differentstages

- in the corticomedullary boundary is wheremacrophages are most abundant.

3. Medulla (lighter)- pale staining central portion- less lymphocytes thus epithelial cells are easier

seen- maturation of self-tolerant T lymphocytes (retained

cells)

o Hassals Corpuscle: unique feature ofmedulla

> eosinophilic group of flat anucleated cells> filled with keratohyalin granules> unknown significance

Figure 6. Thymus showing lobules, medulla, and cortex

Figure 7. Reticular cells and Hassals Corpuscle

3 WAYS FOR NOT DEVELOPING AUTOIMMUNE TLYMPHOCYTES

1. Thymus Blood Barrier at the cortex self toxiccells contained; cannot go into circulation

2. Medullary post-capillary venules- allow self-tolerant t-cells to go into circulation

3. Antigen presenting cells (APC) which present selfantigen destroy autoimmune cells

NOTE: Autoimmune = immune system mistakenly attacksand destroys healthy body tissue

SUMMARY OF SELECTION OF T CELLS:

UTERUS(has a lot of T cells but is not differentiated)

FETAL LIVER

PRE T CELLS

THYMUS(selection of T cells)

NEGATIVE SELECTION POSITIVE SELECTION

APOPTOSIS CIRCULATION

PERIPHERAL LYMPHOIDORGANS

THYMIC BLOOD SUPPLY

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B. Lymph NodesSmall, encapsulated, kidney-shaped structuresinserted within the pathway of lymphatic vessels

Principal cell types: Lymphocytes and Reticular CellsFUNCTIONS:

filters lymph drains infections as well as cancer cells

distributed over the body:- prevertebral region- thorax and abdomen

- mesenteries of intestines- subcutaneous CT of neck and groin

Only structures in the body that have both afferentand efferent lymphatic vessels

Arranged in such a way as to bring together thenecessary elements for stimulation of the adaptiveimmune response

STRUCTURES:

1. Capsule- packed collagen and reticular fibers thatencloses the lymph node

- has trabeculae which extend into theparenchyma

- pierced by branches of afferent lymphaticvessels with valves to ensure one-way flow

Subcapsular / Marginal Sinus- narrow space / sinus beneath thecapsule

- continuous with different sinuses:trabecular, cortical and medullarysinuses

- contains macrophages, dendritic cells,lysosomes and endocytic vacuoles

2. Cortex- deeper-staining- has a greater concentration of lymphocytes

Superficial Cortex- contains lymph follicles / nodules whichare dense cellular aggregations with apale-staining germinal center;

Lymph Follicles / Nodules- consistent features of the cortexof lymph nodes- site of B lymphocyte activationand proliferation- has a darker staining outerMantle Zone / Corona whichcontains lymphocytes andplasma cells- pale-staining central part is theGerminal Center which is the siteof development

Paracortical Zone- deeper regions of the cortex; consistsmainly of T lymphocytes; may be greatlyenlarged in a T-cell dominated response

Cortical sinuses- surrounded by dense accumulations oflymphocytes- where lymph passes through

3. Medulla- less cellular central layer of the lymph node- consists of cords of lymphoid tissue and sinusescarrying the lymph fluid

Medullary Cords

- longitudinal clump of cells composed oflymphocytes, macrophages, and plasmacells.- supported by reticular fibers which canonly be seen using silver stain

Medullary Sinuses- thin-walled structures that allow passageof lymph fluid, lymphocytes, and plasmacells out of the lymph nodes-converge to form the efferent lymphaticchannels

Figure 9. Lymph Node

NOTES:o B-lymphocytes migrate to area between germina

center and subscapular sinuso T-lymphocytes migrate to inner cortex between

germinal center and medullao Activated lymphocytes migrate to medulla and

differentiate into plasma cells

LYMPH FLOWAfferent lymphatic vessels

Subcapsular sinus

Cortical sinuses which passes towards the medulthrough the cortical cell mass.

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Medullary sinuses

Hilum(concavity on one side)

Efferent lymphatic vessels

It then joins the blood stream via the thoracic duct or

right lymphatic duct.

LYMPH NODE BLOOD SUPPLY:

Derived from one or more small arteries which enter atthe hilum and branch in the medulla.

This gives rise to extensive capillary networkscorresponding to the cortical follicles, paracortical zoneand medullary cords.

Lymphocytes enter lymph nodes mainly via the arterialsystem, gaining access by migrating across the walls ofspecialized postcapillary venules (high endothelialvenules (HEV)

The HEV drain into small veins that leave the node viathe hilum.

Figure 10. Blood supply of lymph node

Figure 11. Distribution of lymph nodes in the body

-------------------------------------------------------------NICE TO KNOW:

B Lymphocytes and other cells (Germinal Center)

Resting B cells

- Exposed to antigen to which they would react and entercycle of blast transformation

Centroblasts- Large, mitotically active cells with round nuclei that are

found in the darker zone of the germinal center(differentiates into centrocytes)- Undergo increased mutation of the immunoglobulin genes

(somatic hypermutation), thus creating further variations inimmunoglobulin structure- Differentiate into plasma cells or memory cells.

Centrocytes- Found in the pale midzone of the germinal center- Are of variable size; have folded, irregular (cleaved

nuclei. Mitotic figures are absent in this area.- Migrate towards the paler capsular zone of the germinacenter where they go through further division to produceeitherimmunoblastsI or memory B cells

Immunoblasts

- Move to the medullary cords where they complete theidifferentiation into plasma cells capable of secreting largeamounts of antibody.

Follicular Dendritic Cells- Major antigen presenting cells of the follicles.

- Found in all areas of the germinal center and alsoform a meshwork in the mantle zone and in primaryfollicles.

- Can retain antigen on their surface for many months andmay have a role in maintaining the activity of memory cellsas well as stimulating a primary immune response.

Tingible Body Macrophages- Easily seen in routine sections in active germinal centers.- Contain within their cytoplasm numerous apoptotic bodies

derived from B lymphocytes that have not been successful ingenerating a high affinity antibody.

T Lymphocytes (Paracortical Zone)- Enlarge to form immunoblasts

Interdigitating Dendritic Cell- Cytoplasmic processes form a meshwork in the paracortex

and are in close contact with the naive T cells circulatingthrough this zone.- Derived from macrophage precursors including the

Langerhans cells of the skin.

**Paracortical reactiongreat expansion of the paracortical zone in aT cell-dominated immunological response**Addresins lymphocyte binding molecules that allow lymphocyte tobind to the endothelium as the first step of migration into the tissue.

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C. Mucosa-associated Lymphoid Tissue (MALT)aggregates of lymphoid tissue found in the digestiveand reproductive systemsTonsils (palatine, lingual, pharyngeal)AdenoidsSmall Intestines: aggregate lymphoid nodules

which were known as Peyers PatchesAppendixVagina

composed mostly T lymphocytes but also have Bcells and plasma cells.

functions as lymph nodes

lymphocytes exposed in this regions go throughregional lymph nodes then back to the region afteractivation

secretes immunoglobulins:

IgA - protect against pathogens that maygain access to underlying tissues

IgG- majority of antibody-basedimmunity against invadingpathogens

IgM- eliminates pathogens in the earlystages of B cell mediated immunitybefore there is sufficient IgG

- secreted into lamina propria

D. TonsilsPALATINE TONSILS- stratified squamous epithelium due to abrasion- tonsil crypts

Figure 12. Tonsil with SS Epithelium and Crypt

E. Spleenlargest lymphoid organ in the body

situated in the left upper quarter of the abdomenbetween fundus and diaphragm

Receives a rich blood supply via a single artery, thesplenic artery, and is drained by the splenic vein intothe hepatic portal system

Covered by the visceral peritoneum, which consists of asingle layer of squamous epitheliumFUNCTIONS: Production of immunological responses against

blood borne antigens

Removal of particulate matter and aged odefective blood cells, particularly erythrocytefrom the circulation.

Haemopoiesis in the normal fetus and in adulwith certain diseases; as well as storage of 1/3 thbodys platelets and as reservoir of mature RBCs

STRUCTURES:1. Capsule

- fibroelastic outer layer- forms trabeculae that extend into the

parenchyma- thickened at the hilus and is continuous with

supporting tissues that sheath the larger bloodvessels entering and leaving the organ.

2. Splenic Parenchyma- not subdivided into a cortex and medulla- consists of red and white islands of cells

Red Pulpcords (cords of Bilroth) of reticular

cells and splenic sinuses- highly vascular tissue that forms the

bulk of the organ- sinuses are abundant in RBCs

White Pulp discrete 0.5 - 1mm white nodules

- consists of B and T cells which make up5-20% of the total mass of the spleen.

- consist of lymphoid tissue; scatteredthrough red pulp

Perilymphoid/Perifollicular Zone- zone of the red pulp immediatelysurrounding the white pulp.-devoid of sinuses; sparse reticulinmeshwork and contains a largenumber of red and white blood cells inthe same proportion as that of blood.

Mantle Zonenarrow zone of small lymphocytes at

the follicular periphery. Marginal Zone

- broader zone of less densely packedmedium-sized lymphocytes supportedby a framework of reticulin fibers.

Central Artery- surrounded by a periarterial

sheath of diffuse and nodular lymphoidtissue

Figure 13. Splenic parenchyma

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SPLENIC CIRCULATION

Blood enters the spleen in the splenic artery, whichbranches within the parenchyma. The larger arteries aresurrounded by central arteries surrounded by periarteriolarlymphoid sheath PALS which consists mainly of TH cell

The central artery branch at right angles to form penicilliaryarteries PA, and these terminate in two to three sheathedcapillaries SC. These vessels do not have endothelial lining

but surrounded by macrophages.

The blood arriving from a sheathed capillary traverses the SCbefore entering the red pulp RP.

The sheathed capillaries, form the first part of the filteringmechanism of the spleen.

NOTE: There are two theories regarding thetermination of blood vessels

CLOSED CIRCULATION OPEN CIRCULATION(favored)

- the blood vessels enteringthe red pulp becomeconfluent with the sinuses ofthe red pulp

- the blood vessels open attheir ends, into theextracellular space of theparenchyma, permitting theextravasation of RBCs- blood goes back tocirculation by going throughclefts in the walls of thesinuses

From the sinuses, blood drains to short pulp veins

Trabecular veins

Splenic vein

Figure 14. Visualization of splenic closed and open circulation

SPLENIC LYMPHOID TISSUE- Lymphoid tissue (T and B cells) is situated in thwhite pulp. The NFA (non-filtering area) of the red puis considered to be part of the splenic lymphoid tissuebut its immunological function remains to be unclear.

T cells mass of these cells form eccentrcylindrical sheath around the central arter(mainly helper T cells)

B cells form follicles at the vicinity of a

arteriole which exhibits germinal center withe function similar to the ones in the lympnodes

END

References: Sir Carrillos LectureBloom and Fawcett

NOTE: Bloom and Fawcett daw ang main reference ni Sir.

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Lab Checklist (From Sir):

1. Lymph Node

a. Regions and Zones

b. Structures

c. Circulation

2. MALT

3. Thymus

a. Regions

b. Structures

c. Circulation

4. Spleen

a. Regions

b. Structures

c. Circulation

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Laughinglowers levels of stresshormones and strengthens the immune systemSix-year-olds laugh an average of 300 times aday. Adults only laugh 15 to 100 times a day.

Isang anat exam na lang after this!!!!! Good lucksa combo natin this coming Monday andTuesday, 2014!

- Team 7

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17. Lymphatics Histology

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