Histo(topic4)Lympathic

Lympha'c System

– Integral part of the immune and circulatory system

• In 1627-Gasparo Aselli ~ “lympha'c system “

• Hippocrates reported “white blood” in nodes

• Aristotle described fibers containing colorless fluid observed between blood vessels and nerves. (LYMPH)

• Science of lymphology : Lympha'c vascular biology

– early inves'ga'ons of the anatomy and physiology of the lympha'c system, its func'on, and implica'ons related to cancer have propelled technology and research to elucidate many of the enigma'c characteris'cs of the lympha'c system.

– Recent research has implicated the lympha'c system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflamma'on, atherosclerosis, hypertension, and myocardial infarc'on

Lympha'c System Development:

• parallels that of blood structures

Primordial LS : 6th wks in the form of lymph sacs

8th wks: cisterna chyli

Communica'ng channels connec'ng the lymph sacs (thoracic duct : 9th wk)

General Func'ons of Lympha'c System:

1. Returns Fluid from Tissues to Blood (2-4 liters of inters''al fluid /day) (preven'on & resolu'on of edema)

2. Returns Large Molecules to Blood (maintenenace of inters''al fluid homeostasis)

3. Absorb and Transport Fats

4. Hemopoiesis

5. Body Defense/Immunity

Organiza'on of the lympha'c vascular tree

The lympha'c vessels are found in almost every vascularized 'ssue except neural 'ssue and bone marrow.

Unidirec'onal lympha'c vascular system consists:

(1) lympha'c capillaries

(2) collec'ng lympha'c vessels

(3) lymph nodes,

(4) the thoracic duct and right lympha'c trunk

Factors that help in lymph flow

1. Tissue fluid pressure

2. contrac'on of sorrounding muscle (exercise,massage,pneuma'c compression)

3. Breathing movements (nega've intrathoracic pressure)

4. Rhythmic contrac'on of smooth muscle walls in vessels wall (pulsa'ons of adjacent arteries)

5. Presence of valves which prevent backflow

Organiza'on of the lympha'c vascular tree

, Lympha'c capillaries absorb inters''al solutes, macromolecules, and immune cells that extravasate from the blood vascular system. Lymph forma'on is facilitated by the discon'nuous basement membrane (red dashed line), and bufon-like endothelial junc'ons allow passive paracellular flow for lymph forma'on.

Lympha'c capillaries ( 30-80um)

Structural features:

• Lumen-filled with eosinophilic material (NO RBC)

• par'al basement membrane and not ensheathed by smooth muscles

• Anchoring filaments tethering the inters''al matrix to inters''al fluid

• Single layer of endothelium that are interconnected by discon'nuous junc'onal structures known as bufons – Very small 'ght junc'ons between endothelial cell

• Lympha'c capillaries are absent in: – All avascular structures • Epidermis • Cornea • Nail • Hair • Car'lage – Spleen and bone marrow – Alveoli and respratory bronchiole – Brain and spinal cord

Organiza'on of the lympha'c vascular tree

Collec'ng lympha'c vessels :

• con'nous junc'onal structures (zipper-like junc'ons lympha'c valves)

• contrac'le smooth muscle cells (SMCs) : pumping force for lymph movement

• unidirec'onal propulsion of lymph

Components of the Lympha'c system

• Circula'ng lymphocytes

• Lymph vessels

• Central (primary) lymphoid organs:

• bone marrow and thymus

• Peripheral (secondary) lymphoid organs:

• lymph nodes. spleen, tonsils, mucosa associated lymphoid 'ssues

Organiza'on of the lympha'c vascular tree

the lympathic vessels are found in almost every vascularized tissue except neural tissue and bone marrow

Unidirec'onal lympha'c vascular system consists:

(1) lympha'c capillaries

(2) collec'ng lympha'c vessels

(3) lymph nodes,

(4) the thoracic duct and right lympha'c trunk

Factors that help in lymph flow

1. Tissue fluid pressure

2. contrac'on of sorrounding muscle (exercise,massage,pneuma'c compression)

3. Breathing movements (nega've intrathoracic pressure)

4. Rhythmic contrac'on of smooth muscle walls in vessels wall (pulsa'ons of adjacent arteries)

5. Presence of valves which prevent backflow

Organiza'on of the lympha'c vascular tree

Lympha'c capillaries absorb inters''al solutes, macromolecules, and immune cells that extravasate from the blood vascular system.

Lymph forma'on is facilitated by the discon'nuous basement membrane (red dashed line), and bufon-like endothelial junc'ons allow passive paracellular flow for lymph forma'on.

Lympha'c capillaries ( 30-80um)

Structural features:

• Lumen-filled with eosinophilic material (NO RBC)

• par'al basement membrane and not ensheathed by smooth muscles

• Anchoring filaments tethering the inters''al matrix to inters''al fluid

• Single layer of endothelium that are interconnected by discon'nuous junc'onal structures known as bufons

– Very small 'ght junc'ons between endothelial cells

• Lympha'c capillaries are absent in:

– All avascular structures

• Epidermis

• Cornea

• Nail

• Hair

• Car'lage

– Spleen and bone marrow

– Alveoli and respratory bronchiole

– Brain and spinal cord

Organiza'on of the lympha'c vascular tree

Collec'ng lympha'c vessels :

• con'nous junc'onal structures (zipper-like junc'ons lympha'c valves)

• contrac'le smooth muscle cells (SMCs) : pumping force for lymph movement

• unidirec'onal propulsion of lymph

Organiza'on of the lympha'c vascular tree

Organiza'on of the lymph node with afferent lympha'c vessels and a single efferent lympha'c vessel

Organiza'on of the lympha'c vascular tree

Lymph drains into venous circula'on through 4 dis'nct lymphovenous valves located where the internal jugular vein (IJV) and external jugular vein (EJV) drain into the subclavian vein (SCV)

Immune System

• Func'ons:

– To protect organism (body) from INVASION and DAMAGE by microorganisms (bacteria, virus) and foreign substances (an'gen, protein molecules etc..)

Components of the immune system

1. Lymphoid organs – spleen, lymph nodes, tonsils, thymus, bone marrow

2. Lymphoid nodules – A network of re'cular fibers and spherical, nonencapsulated aggrega'ons of lymphocytes

3. Free cells – lymphocytes, granulocytes, mononuclear phagocytes present in blood, lymph and connec've 'ssue

4. An'gen presen'ng cells – In various 'ssues of the body heavily exposed to an'gen (langerhans cell in epidermis)

Components of the immune system

Elaborate surveillance and defense by:

1. Monitoring body surfaces and internal fluid compartment

2. Having the ability to dis'nguish self from non-self

3. Reac'ng to presence of an'genic substances

Types of Immune Response

• Innate immune response

– First line of defense – Phagocy'c func'ons :

• Ac'va'on of phagocytes : cytokines

– Fast, nonspecific

– No memory cells

• Adap've immune response

– specific defenses –

slower response, numerous memory cells

• produc'on of long-lived memory cells

– Two (2) specific responses:

1. Humoral immune response : – B cells , plasma cells, an'bodies

2. Cell-mediated immune response: – ac'va'on of phagocytes, an'gen specific cytotoxic T cells, cytokines – (+) surface receptors for an'gens

Cellular IR/ Cell - mediated IR

– mediated by T lymphocyes; provide immune protec'on w/out secre'ng an'bodies

– Immunocompetent cells react against and kill microorganisms, foreign cells and virus-infected cells

– T cells secrete cytokines : (+) other T cells, B cells, cytotoxic T cell

– specificity is determined by small pep'des associated with major histocompa'bility cells (MHC) in membrane an'gen-presen'ng cells (APC)

– Immunoglobulin-like receptor or T cells bind directly to foreign cells and induce :

• Cytotoxic killing

• Secre'on of signalling molecules (interleukins) that regulate immune response and ac'vate macrophages and granulocytes

Types of Immune Response (IR)

Humoral Immune Response:

B cells, plasma cells, an,bodies

• related to the presence of circula'ng an'bodies that bind to, inac'vate or destroy specific foreign substances

• An'bodies produced by plasma cells derived from B lymphocytes

• Ac'va'on and prolifera'on of B cells against an'gens requires the coopera'on of helper T cells : respond to the same an'gen and secrete cytokines

• Specificity is determined by small molecular domains:

– an'gen has epitopes >>>taken by T helper cells >>s'mulate produc'on of B lymphocytes >>plasma cell which produce an'bodies bind to an'gen

An'bodies

• Plasma glycoproteins that interact specifically with an'gen determinant that elicit their forma'on

• Signal other components of the immune system of the presence of foreign bodies

• Agglu'nate cells or precipitate soluble an'gen

• Bind an'gen and start ac'va'ng the complement system

Classes of An'bodies (5)

1gG

-structure

-presence in sites other than blood, ct, and lymphoid organs

-Known Fnxs:

-AB % in the plasma:

IgM

-structure

-presence in sites other than blood, ct, and lymphoid organs

-Known Fnxs:

-AB % in the plasma:

IgA

-structure

-presence in sites other than blood, ct, and lymphoid organs

-Known Fnxs:

-AB % in the plasma:

IgD

-structure

-presence in sites other than blood, ct, and lymphoid organs

-Known Fnxs:

-AB % in the plasma:

IgE

-structure

-presence in sites other than blood, ct, and lymphoid organs

-Known Fnxs:

-AB % in the plasma:

memory: quick response

Long lived cells

primary response: Ag+ exposure

memory lymphocytes are left behind after Ag+ clearance

A second exposure to the same Ag+ re-stimulates memory lymphocytes

reactivation yields faster, more significant, better response

insert slide 27 later

Lymphoid cells: T Lymphocytes and B lymphocytes

• Chief cellular cons'tuent of lympha'c 'ssue

– Round, centrally placed nucleus

– Cytoplasm: lack specific granules with varying degrees of basophilia

• Originate from precursor hemopoie'c stem cells in the bone marrow that divide to give rise to an expanding popula'on of uncommifed lymphocyte precursors and complete their differen'a'on either in bone marrow or thymus

Lymphocytes

• Loca'on:

1. Primary lymphoid organs

• B lymphocytes – leaves bone marrow as mature cell

• T lymphocytes – migrate to thymus to differen'ate and mature

2. Secondary lymphoid organs Lymph nodes, spleen, lymphoid nodules

B Lymphocyte

• B lymphocytes

– differen'ate to plasma cell : an'bodies

– have immunoglobulin as integral membrane proteins

• membrane surface : an'gen receptor complex

– Response of B cell to an an'gen is more intense when APC’s ( T helper cells) , present the an'gen-ac'vated B cells – T helper cells secrete a cytokine ( interleukin 2) :

• Induce prolifera'on and differen'a'on of an'gen-ac'vated

• B memory cells – react rapidly to second exposure

T Lymphocytes

• T cells mature, differen'ate, and acquire surface receptors and immunocompetence in the thymus gland

– populate lymph nodes, the spleen, and lymphoid aggregates or nodules in connec've 'ssue.

• On encountering an an'gen, T cells destroy the an'gen either by cytotoxic ac'on or by ac'va'ng B cells when s'mulated.

T Lymphocyte

• Helper T cells

– S'mulate differen'a'on of B cells to plasma cells

– assist other lymphocytes by secre'ng immune chemicals called cytokines, (interleukins)

• Cytokines are protein hormones that s'mulate prolifera'on, secre'on, differen'a'on, and matura'on of B cells into plasma cells, which then produce immune proteins called an'bodies ( immunoglobulins)

T Lymphocyte

• Cytotoxic cells

– virus-infected cells, foreign cells, or malignant cells and destroy them.

– Ac'vated in the presence of APC’s

– Lysosomes with ly'c granules than contain pore-forming protein : • Perforins : pores in the membrane of targeted cell – Programmed cell death : apoptosis

• Memory T cell

– rapid reac'on to reintroduc'on of an'gen

– long-living progeny of T cells

– Ac'vate the immune system and direct afack an'gens

• Regulatory (suppressor) T cells

– Regulates (moderate or inhibit) immune response thru inhibi'ng ac'on of helper and cytotoxic cells

HIV cripples the patient’s immune system - by attacking the helper T cells

susceptible to opportunistic infection

AIDS is the commonest secondary immunodeficiency d/o

Major Histocompatibility Complex (MHC) or Human Leucocyte AnrtiAntige (HLA) CompleX

-clusters of genes located on short aRM OF CHROMOSOME 6 (6pQ)

MHC (specialized integral membrane protein complexes on cell surfaces)

bind peptide fragments of foreign proteins for presentation to antigen-specific T cells (helper and cytotoxic)

-Cytotoxic T cells/CD8+ T cells: MHC-I restricted

- Helper T cells/ CD4+ T cells: MHC –II restricted

IMMUNE RESPONSE/ HLA MATCHING

- The immune response is the primary determinant of graft viability.

- Human leukocyte antigen typing, for graft compatibility, is

important for renal, lung, cardiac, and pancreatic matching

- Loci typed are HLA-A, -B, and –DR

• 6 Ag match

o Positive crossmatch shows that preformed Abs are

present, leading to hyperacute rejection.

- Importance:

• Cluster of genes whose products play important role in the

development of immune response and discrimination between self

and non-self.

• Determine whether a grafted tissue will be accepted as self

(histocompatible) or rejected as non-self (histoincompatible) by

the host.

Types of Transplant:

self -

twins -

same species -

different species -

Immunosupressants are drugs or medicines that lower the body’s ability to reject a transplanted organ. Another term for these drugs is anti-rejection drugs.

There are 2 types of immunosuppressants:

induction drugs: powerful antirejection medicine used at the time of transplant

maintainance drugs: antirejection medications used for the long term

Other cells

• An'gen-presen'ng cells

– phagocytose and process an'gens, and then present the an'gen to T cells, inducing their ac'va'on.

– Most an'gen-presen'ng cells belong to the mononuclear phagocy'c system.

• Connec've 'ssue macrophages

• perisinusoidal macrophages in the liver (Kupffer cells),

• Langerhans (dendri'c) cells in the skin,

• macrophages within lymphoid organs

NK cells

• 3rd type of lymphocytes

• Gene'cally programmed to recognize and destroy altered cells – virally infected and cance cells

• Same as cytotoxic T cells func'ons

Lympha'c system

• Diffuse lymphoid 'ssue

– found in the internodal, deep cor'cal and medullary regions of lymph nodes, periarterial lymphoid sheaths (PALS) of spleen , internodal region of the tonsils, peyer’s patches

– sponge-like stroma with lymphocytes in its meshes

– stroma is made up of re'cular fibers and cells of mesechymal origin

– re'cular cells appear elongate or stellate elements with ovoid euchroma'c nucleus and scant acidophilic cytoplasm – Free cells are also present ( lymphocytes, plasma cells and macrophages)

Lympha'c system

• Lymphoid nodules (lymphoid follicles)

– Circumscribed closely packed collec'on of lymphocytes within areas of diffuse lymphoid 'ssue

– Not encapsulated

– Found in the cortex of lymph nodes, periphery of white pulp of spleen and lamina propia of GIT and RT

– Numerous in tonsils, Peyer’s patches and appendix

– NONE in thymus

Types of Lymphoid nodules

1. Primary lymphoid nodule/ follicle (inac've )

– Lack the light –staining germinal centers;

– Small immature B lymphocytes; closely packed and disorganized

– Difficult to see in light microscope

2. Secondary nodules

– Most common; primary become secondary nodules

– Pale staining central por'on : germinal center

– Site of B lymphocyte prolifera'on and differen'a'on to plasma cells following ini'al or secondary exposure to an'gen

• B cells predominate in nodules

• T cells are abundant in adjacent areas

Secondary lymphoid nodule

Parts:

• Dark region : mantle/marginal zone

– dark-staining nuclei, condensed chroma'n, and lifle or no cytoplasm.

– Lymphocytes contained within a cellular framework of stellate cells consists of smaller and mature lymphocytes

• Light region: germinal center

– cells are more loosely aggregated and the developing lymphocytes have larger and lighter

-staining nuclei with more cytoplasm “lymphoblast”

– contains less mature lymphocytes undergoing mito'c division ( ac've site of lymphocyte prolifera'on)

Lymph node

• Small bean shaped encapsulated organs

– Capsule: LCT traversed by lympha'c sinuses

• Func'ons: – Lymph filtra'on and phagocytosis of bacteria or foreign substances from the lymph

– It produce, store, and recirculate B cells and T cells

• B cells congregate in the lympha'c nodules of lymph nodes

• T cells are concentrated below the nodules in the deep cor'cal or paracor'cal regions.

– Sites of an'genic recogni'on and an'genic ac'va'on of B cells, which give rise to plasma cells and memory B cells.

Lymph node

1. Lymph cortex:

– parenchyma supported by re'cular fibers and associated re'cular cells

– high concentra'on of lymphocytes

– mesh filled with lymphocytes, plasma cells and macrophages

• Parts:

– Outer cortex

• B lymphocytes ; 10 and 20 lymph nodules

– Inner (paracortex)

• Diffuse lympha'c 'ssues

• populated with T lymphocytes

– enter the lymph nodes through the specialized post capillary venules (HEV’s)

B and T cells enter the LNs through the HEV in the paracortex Lined by tall cuboidal or columnar endothelium • specialized lymphocyte-homing receptors

• Sites of entry by diapedesis of lymphocytes to the lymph nodes

• circula'ng lymphocytes recognize the receptors in the endothelial cells and leave the bloodstream to enter the lymph node

• Peyer’s patches in the small intes'ne, tonsils, appendix, and cortex of the thymus : present

• Absent from the spleen

Lymph node

CORTEX

- B cells

1. Primary nodules

- Packed B cell; Ag+

2. Secondary nodules GC with mantle zone

- Site of B cell proliferation

-

PARACORTEX

- T cells

- Antigen-dependent T cell

- Differentiation and proliferation

-HEVs (High endothelial venules)

• Facilitate rapid translocation of lymphocytes from blood into the lymphoid tissue

Lymph node

2. Lymph sinus

– Lined with incomplete squamous epithelial cells with lumen bridged by meshwork of stellate re'cular cell connected with each other and to walls of sinus via slender processes

– 1. capsular/ (subcapsular or marginal sinus)

• Inverted bowl shaped cavity which separates capsule from cor'cal parenchyma

– 2. trabeculae/intermediate/cor'cal

• sinus which penetrates parenchyma along with trabeculae medullary

• Large tortous irregular channels that branch and anastomose repeatedly dividing parenchyma into medullary cords

Unilateral flow

• Afferent lympha'c vessels>>>Marginal / subscapular sinus>>>Trabecular sinus>>> Medullary sinus>>>Marginal sinus at the hilum>>> Efferent lympha'c vessels in hilum

The central region of the lymph node is the lighter-staining medulla.

A. dark-staining medullary cords

B. light-staining lympha'c channels, the medullary sinuses

MEDULLA

- Medullary cords

• Are branched cordlike masses of lymphoid tissue extending

from the paracortex.

• T& B lymphocytes, plasma cells

- Medullary sinuses

• Dilated spaces lined by discontinuous endothelium that

separate the medullary cords

• Final lymph filter

• Cortical sinuses and converge at the hilum as the efferent

lymphatic vessel

LN Parts

• 4. Blood vessels

– Nearly all enter hilus

– Larger arterial branches ini'ally running with trabeculae enter medullary cords before returning to the cortex where they supply capillary plexuses of diffuse lymphoid 'ssue

Thymus

• Bilobed organ located in superior medias'num anterior to the great vessels as they merge from the heart

• Extends from the root of the neck to the pericardial sac

• Develops from the endoderm of the 3rd and 4th pharyngeal pouches

• Lymphocytes arise from mesenchyme

• 1st organ to become lymphoid during embryonic life

– T cells: site of differen'a'on and matura'on

histology-thymus gland

Most ac've and prominent before puberty and undergoes involu'on with less ac'vity in adult

– Lymphocyte produc'on declines, and the thymic (Hassall’s) corpuscles become more prominent

– parenchyma or cellular por'on :

• replaced by loose connec've 'ssue and adipose cells

Thymus

Fibrous capsule gives off trabeculae (septa) : subdivide the gland into incomplete lobules

• Each lobule consists:

1. cortex

• dark-staining

• Thymic lymphocytes : dense aggrega'ons that do not form lympha'c nodules

– T lymphoblast, macrophages, thymic epithelial cells (TEC)

2. medulla

• light-staining

• only a few lymphocytes but more epithelial re'cular cells • Thymic (Hassall’s) corpuscles are oval structures consis'ng of round or spherical aggrega'ons (whorls) of flafened epithelial cells.

– It exhibit calcifica'on or degenera'on centers that stain pink or eosinophilic

• Blood vessels and adipose cells

– pass into the thymus gland via the connec've 'ssue capsule and the trabeculae

Thymus

• Thymic cortex

– Epithelial re'cular cells,(thymic nurse cells)

• surround the lymphocytes and promote their differen'a'on, prolifera'on, and matura'on

1. immunocompetent T cells

2. helper T cells 3. cytotoxic T cells

– acquire their surface receptors for recogni'on of an'gens • Blood-thymus barrier

• ( endothelial cells, epithelial re'cular cells and macrophages)

– Prevent developing lymphocytes from exposure to blood- borne an'gens

– Macrophages outside of the capillaries ensure that substances transported in the blood vessels do not interact with the developing T cells in the cortex and induce an autoimmune response against the body’s own cells or 'ssues.

• Aqer matura'on, the T cells leave the thymus gland via the bloodstream and populate the lymph nodes, spleen, and other thymus-dependent lympha'c 'ssues in the organism.

Thymus

Thymic nurse cells Types:

– 1. squamous TECs forrm a layer: blood-thymus barrier

– 2. stellate TECs form cytore'culum:

• ENDOCRINE gland

– (thymulin, thymopoie'n, thymosin, thymic humoral factor, interleukins, and interferon)

a. APCs w/ MHC I and II

b. Cytokines for T- cell development and other immune func'ons

– 3. squamous cor'cal TECs w/ MHC II

• Func'onal cor'comedullary barrier between each lobul

Thymus (medulla) Three (3) types of TEC’s

1. A second layer of the boundary of medulla and cortex

2. A cytore'culum

(a)supports T lymphocytes,dendri'c cells,and macrophages (b)expresses many specialized proteins specific to cells of other organs

3. Large aggregates of TECs,(Hassall'corpuscles)

• Secrete cytokine thymic stromal lymphopoe'n that control ac'vity of local dendri'c cells,including factors that promote development of regulatory T cells for peripheral tolerance.

ROLE OF THYMUS IN T CELL MATURAATION AND SELECTION

- The thymus is the site of T-lymphocyte differentiation and the

selective removal of the cells reactive against self-antigens, a key

part of inducing central self- tolerance.

- Thymocytes begin a stringent, two-stage selection process of

quality control, which ensures that mature T cells have TCRs that

are fully functional but do not recognize and strongly bind MHC

with self- antigens.

- Selection process:

• Pre–T lymphocyte begins in the cortex, ends in the medulla,

and lasts about 2 weeks

Matura'on and Selec'on of T cells in the Thymus

• Nega've selec'on

– T cells are presented with self & foreign an'gens by APCs – T cells that are unable to recognize self-an'gens or that recognize self-an'gens die and are eliminated by macrophages (95% of the total cells)

• Posi've selec'on

– T lymphocytes that recognize the foreign an'gens survive, reach maturity , enter the medulla from the cortex, and distributed in the bloodstream

- Positive selection occurs in the cortex and allows survival only of T cells with functional TCRs that recognize MHC class I and class II molecules.

- Negative selection occurs in the medulla and allows survival only of T cells that do not tightly bind self- antigens presented on dendritic cells there.

Thymus

• Involutes aqer puberty , replaced by adipose 'ssue, produc'on of T cells decreased.

• T lymphocytes progeny is established, immunity is maintained without new T cell produc'on

DiGeorge syndrome (Thymic aplasia)

- Failure of development of the third and fourth pharyngeal pouches

- Absence of the parathyroid glands and the thymus

- Loss of T cell-mediated immunity

• Recurrent fungal and viral infection

- Short stature, learning difficulties

DiGeorge syndrome (Thymic aplasia)

mnemonic

MUCOSA-ASSOCIATED LYMPHOID TISSUE

- GIT, Respiratory, GUT mucosal linings consist of:

• Large and diffuse collections of lymphocytes

• IgA-secreting plasma cells

• APCs

• Lymphoid nodules

- One of the largest lymphoid organs, containing up to 70% of all

the body’s immune cells.

• (B cells, Helper T cells)

RED BONE MARROW

- Soft, loosely organized, highly vascular material separated from

osseous tissue by endosteum of bone

• Vertebrae, ribs, sternum, cranium, ends of humerus/femur

- As blood cells mature, they push their way through the reticular

and endothelial cells to enter the sinusoids and flow away in the

blood stream

- Functions:

• Hemopoiesis

• Source of lymphocytes

Most of the immune cells in MALT are dispersed diffusely in the connec've 'ssue; others are found in aggregates that form large, conspicuous structures such as the tonsils, the Peyer patches in the ileum, and the appendix.

Reach their maximum development in childhood Involu'on begins at the of 15

Tonsils

• Pala'ne tonsils

– Two (2) large ovoid accumula'ons of lymphoid 'ssue beneath mucous membrane ; posteriorly located on the soq palate

– Stra'fied squamous nonkera'nized epithelium

– 10-20 deep invagina'ons or tonsillar crypts in which the epithelial lining is densely infiltrated with lymphocytes and other leukocytes

• The lymphoid 'ssue is filled diffusely with lymphocytes, with many secondary lymphoid nodules around the crypts. – Par'ally encapsulated : dense connec've 'ssue

• Acts as a barrier for spreading tonsillar infec'on

Tonsil

• Pharyngeal tonsil (single)

– posterior wall of the nasopharynx

– adenoid

– pseudostra'fied ciliated columnar epithelium, and has a thin underlying capsule

• The mucosa with diffuse lymphoid 'ssue and lymphoid nodules is invaginated with shallow infoldings but lacks crypts.

All the formed elements of blood must reenter the

vasculature by passing through narrow slits

between the stave cells into the sinusoids.

• S'ff or effete, swollen RBCs at their normal life

span of 120 days are blocked from passing

between the stave cells and undergo selec've

removal by macrophages

Immune component of the spleen

• Lympha'c 'ssue

• Lympha'c cells that surround the central arteries of the white pulp are primarily T

cells

• Lympha'c nodules mainly B cells

• APC’s and macrophages

• detect trapped bacteria and an'gens and ini'ate immune responses against them.

Macrophages in the spleen also break down hemoglobin of worn-out erythrocytes..

Iron recycled

Aqer surgical removal of the spleen (splenectomy), the number of abnormal erythrocytes in the circula'on increases although most such cells are then removed by macrophages in sinusoids of the bone marrow and liver.

Trauma : rela'vely thin capsule

Splenomegaly:

Lymphoma or other malignant growth, infec'ons such as mononucleosis, or sickle cell disease and other types of anemia.

Lympha'c system • Lymphoid nodules (lymphoid follicles) – Circumscribed closely packed collec'on of lymphocytes within areas of diffuse lymphoid 'ssue – Not encapsulated – Found in the cortex of lymph nodes, periphery of white pulp of spleen and lamina propia of GIT and RT – Numerous in tonsils, Peyer’s patches and appendix – NONE in thymus