THE LYMPHOID SYSTEM IS THE PART OF THE IMMUNE SYSTEM COMPRISING A NETWORK OF

CONDUITS CALLED LYMPHATIC VESSELS THAT CARRY A CLEAR FLUID CALLED LYMPH (FROM

LATIN LYMPHA"WATER" [ 1 ]

Lymphoid system

Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated with the digestive system such as the tonsils.

The system also includes all the structures dedicated to the circulation and production of lymphocytes, which includes the spleen, thymus, bone marrow and the lymphoid tissue associated with the digestive system.

Lymphoid cell

Classification of lymphocytes

B cells (B = bone)T cells (T = thymus)NK cells (NK = Natural Killer)

B cells

Synthesizes IgM and IgDActivated and proliferated by helper T-

lymphocytesPerforms the role of antigen-presenting cells

(APC)Bone marrow

T cells

Cell-mediated immunity

Has T cells receptorsBone marrow

thymusFunction changes per

subset

NK cells

Produced in the red bone marrowReleases small cytoplasmic granules of

proteins Target cell = die

Apoptosis – programmed cell death

Recognizes general classes of cells Involved in innate immunity

Lymphatic tissue response and function

Lymphatic tissue Aggregation of lymphocytes and lymphocyte-rich

organs Thymus, spleen (white pulp), tonsils, loose CT of other

organs

Response: Layered defense

Innate immunity adaptive immunity

Primary and Secondary

Lymphoid Organs

PRIMARY LYMPHOID ORGANS

The central or primary lymphoid organs Generate lymphocytes from immature

progenitor cells. Includes thymus and bone marrow

THYMUS

Gk. “thumos”, meaning heart, soul, desire, life.

A specialized organ of the immune system.

A two lobed, glandular organ It is largest after birth and during

childhood. Is replaced by adipose (fat) tissue

when one gets older

THYMUS

THYMUS

pinkish-gray color, soft, and lobulated on its surfaces in children. It is yellowish in adults

At birth it is about 5 cm in length, 4 cm in breadth, and about 6 mm in thickness.

Consists of two lateral lobes

HISTOLOGY OF THYMUS

Each lateral lobe is composed of numerous lobules held together by delicate areolar tissue

Entire organ enclosed enclosed by a thin connective tissue capsule from which numerous septa extend into the thymus subdividing the two lobes into numerous lobule.

HISTOLOGY OF THYMUS

Primary lobules vary in size from that of a pin's head to that of a small pea, and are made up of a number of small nodules or follicles.

The follicles are irregular in shape and are more or less fused together, especially toward the interior of the organ.

The cells housed within the thymus are primarily white cells called T lymphocytes, along with smaller amounts of other lymphoid cells.

LOBULES AND INTERLOBULAR CONNECTIVE TISSUE

THYMUS

 Each lobulus is divided into a darker peripheral zone, the cortex, and a lighter, central zone, the medulla. 

The cortex and medulla play different roles in the development of T-cells

THYMUS: CORTICAL PORTION

The darker, peripheral zone Composed mainly of lymphoid cells

supported by a network of finely-branched epithelial reticular cells

Reticular cells and macrophages are present in addition to the lymphocytes, which are the dominant cell type within the lobules.

The cortex is the location of the earliest events in thymocyte development, where T cell receptor gene rearrangement and positive selection takes place.

LOBULES AND INTERLOBULAR CONNECTIVE TISSUE,CORTEX AND MEDULLA

RETICULAR CELLS

“Thymic epitheliocytes.” Quite abundant. Cytoplasm is eosinophilic, and their large,

ovoid and light nuclei may contain one or two nucleoli.

Their slender processes are connected with the processes of other reticular cells to form a cellular reticulum (or cellular network).

RETICULAR CELLS

Reticular cells sheathe the cortical capillaries; they form an epitheloid layer which delimits the cortical tissue from the connective tissue and secrete substances (hormones and other factors) important for thymic function.

They create and maintain the microenvironment necessary for the development of T-lymphocytes in the cortex.

CELLS IN THE CORTEX

MACROPHAGES AND LYMPHOCYTES

Macrophages occur in both cortex and medulla. They are

difficult to distinguish from the reticular cells Lymphocytes

are present in both cortex and medulla, but are more numerous in the cortex. Their sizes are variable (5 - 15 µm) in the cortex but generally small in the medulla. The vast majority of them will be developing T-lymphocytes. They are also called thymic lymphocytes or thymocytes.

THYMUS: MEDULLARY LAYER

Lighter, central zone The reticulum is coarser than in the

cortex, the lymphoid cells are relatively fewer in number

Hassall's corpuscles are present  location of the latter events in

thymocyte development.

HASSAL’S CORPUSCLES

“Thymic corpuscles” Peculiar nest-like structures found in the

medulla of the human thymus  Composed of a central mass, consisting

of one or more granular cells, and of a capsule formed of epithelioid cells.

are rounded eosinophilic structures, which consist of concentrically arranged, flattened cells.

HASSAL’S CORPUSCLES

Thymic corpuscles are likely to be formed by reticular cells

Increases in size as one gets older The function of Hassall's corpuscles is

currently unclear

H CA OS RS PA UL S’S C

LE

INVOLUTION OF THE THYMUS

After puberty, much of the parenchyma of the thymus, cortical lymphoid in particular is replaced by adipose tissue

This process is called involution initially proceeds rapidly but slows down in adulthood.

It is under the control of steroid hormones It is a common feature of all lymphoid

tissues but most pronounced in thymus

FOETAL THYMUS THYMUS OF AN ADULT

VASCULATURE

The arteries supplying the thymus are derived from the internal mammary, and from the superior thyroid and inferior thyroids.

The veins end in the left brachiocephalic vein (innominate vein) , and in the thyroid veins.

The nerves are exceedingly minute; they are derived from the vagi and sympathetic nervous system.  Branches from the descendens hypoglossi and phrenic reach the investing capsule, but do not penetrate into the substance of the organ.

THYMUS The main function of the thymus gland is to

mature, or "educate" antibody producing white cells called T lymphocytes

In the two thymic lobes, hematopoietic precursors from the bone-marrow, referred to as thymocytes, mature into T-cells.

Loss of the thymus at an early age through genetic mutation (as in DiGeorge Syndrome) results in severe immunodeficiency and a high susceptibility to infection.

Its function is diminished in adults but still continues its endocrine function

BONE MARROW

BONE MARROW

 Flexible tissue found in the interior of bones.

 In humans, bone marrow in large bones produces new blood cells (hematopoiesis)

Produces lymphocytes and acts to prevent the backflow of lymph.

Constitutes 4% of the total body mass of humans

Cone marrow hematopoietic compartment produces approximately 500 billion cells per day

BONE MARROW

RED MARROW “Medulla ossium rubra” Consist mainly of hematopoietic tissue For formation of RBCs, platelets, and most

WBCs Found mainly in flat bones and cancellous

material at the epiphyseal ends of long bones

YELLOW MARROW Consist mainly of fat cells Found in the medullary cavity, the hollow

interior of long bones

BONE MARROW

Both types of bone marrow  contain numerous blood vessels and capillaries.

All bone marrow is red at birth In cases of severe blood loss, the body

can convert yellow marrow back to red marrow to increase blood cell production.

BONE MARROW IN FEMUR HEAD SHOWING RED AND YELLOW MARROW

BONE MARROW: STROMA

Stroma  are cells that support the function of the parenchymal cells of an organ.

The stroma of the bone marrow is composed of all the tissue not directly involved in the primary function of hematopoiesis.

It is indirectly involved in hematopoiesis because it provides the hematopoietic microenvironment that facilitates hematopoiesis by the parenchymal cells.

BONE MARROW: STROMA

Yellow bone marrow makes up the majority of bone marrow stroma

 Cells that constitute the bone marrow stroma are: fibroblasts macrophages adipocytes osteoblasts osteoclasts

BONE MARROW: BARRIER

Formed by blood vessels of bone marrow

Inhibits blood cells from leaving the marrow

Only mature blood cells contain the membrane proteins required to attach to and pass the blood vessel endothelium.

Hematopoietic stem cells may also cross the bone marrow barrier

BONE MARROW: STROMA

The bone marrow stroma contain mesenchymal stem cells (MSCs) (also called marrow stromal cells).

 multipotent stem cells that can differentiate into a variety of cell types. 

To osteoblasts ,chondrocytes , myocytes, adipocytes and beta-pancreatic islets cells. MSCs can also transdifferentiate intoneuronal cells.

BONE MARROW: LYMPHATIC ROLE

 one of the primary lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells.

performs a valve-like function to prevent the backflow of lymphatic fluid in the lymphatic system.

Granular leukocytesAgranular leukocytes

BONE MARROW: STEM CELLS

3 types of stem cells: HEMATOPOIETIC STEM CELLS

give rise to the three classes of blood cells that are found in the circulation: white blood cells (leukocytes), red blood cells(erythrocytes), and platelets (thrombocytes).

MESENCHYMAL STEM CELLS They have the capability to differentiate

into osteoblasts,chondrocytes, myocytes, and many other types of cells. They also function as "gatekeeper" cells of the bone marrow.

ENDOTHELIAL STEM CELLS

SECONDARY LYMPHOID

ORGANS AND TISSUES

SECONDARY LYMPHOID ORGANS “Peripheral lymphoid organs” Maintain mature naive lymphocytes and

initiate an adaptive immune response. sites where lymphocytes are most

active (activated by antigen)  Provides the environment for the foreign

or altered native molecules (antigens) to interact with the lymphocytes.

SECONDARY LYMPHOID ORGANS It is exemplified by the following:

lymph nodesTonsilsPeyer's  patchesSpleenSkinOthers that are associated with the mucosa-

associated lymphoid tissue (MALT).

LYMPH NODES Also known as lymph glands Small, flattened, oval or bean shaped

organs Situated in the course of the collecting

lymph vessels. Is an organized collection of lymphoid

tissue, through which the lymph passes on its way to returning to the blood. 

The three regions of aggregations of nodes in the body are the groin, armpits and neck

LYMPH NODES

LYMPH NODES Consists of an outer portion called the

CORTEX, which contains the lymphoid follicles, and an inner portion called MEDULLA which is surrounded by the cortex on all sides except for a portion known as the HILUM.HILUM is the slight depression on one side

of lymph nodes through which the efferent nodal artery enters and a nodal vein leaves the node

It is covered by a capsule made of fibrous connective tissue that extends into the node

LYMPH NODES

LYMPH NODES

Trabeculae – capsular extensions which divide the lymph node internally into a series of compartments that contain lymphatic sinuses or lymphatic tissue

LYMPH NODES  Afferent lymph vessels penetrate the

capsule and empty into the subcapsular space. The lymph continues thereafter through cortical and medullary sinuses towards the efferent lymph vessels, which emerge from the hilus of the lymph node. The walls of the sinuses can be traversed freely by all components of the lymph, which allows lymphocytes to enter/leave the lymphoid tissue (as part of their constant circulation) or to get in contact with antigens/antigen-presenting cells that may arrive with the lymph.

LYMPH NODES

LYMPH NODES In lymph nodes we find B- and T-

lymphocytes, macrophages and reticular cells.

Reticular cells form a delicate network between the

capsule and trabeculae.  The cytoplasm of reticular cells is only

weakly eosinophilic.  Lymphocytes and macrophages are housed

in the network of reticular cells and the reticular fibres formed by them.

LYMPH NODESMEDULLARY CORDS - cord-like extensions of

the lymphoid tissue into the medulla. It is where  Mature B-lymphocytes (plasma cells) are located

PARACORTEX – deep part of the cortex. It is where T-lymphocytes are located

LYMPH NODES: CELLS

1 - cortex 2 - paracortical zone 3 - medulla 

4 - medullary cords 5 - lymphoid follicle of the cortex 6 - capsule 

1 - cortex 2 - paracortical zone 3 - medulla 

7 - subcapsular sinus 8 - cortical sinus 9 - medullary sinus 

4 - medullary cords 5 - lymphoid follicle of the cortex 6 - capsule 

TONSILS Masses of lymphoid tissue embedded in

mucous membrane There are three groups of tonsils:

Palatine tonsilsPharyngeal tonsilsLingual tonsils

Tonsillar crypts Epithelium Capsule

TONSILS: PALATINE Palatine tonsils

Occasionally called the faucial tonsils Located on the tonsillar fossae between the

pharyngopalatine and glossopalatine arches on each side of the posterior opening of the oral cavity

Commonly removed in a tonsillectomy tend to reach their largest size near puberty,

and they gradually undergo atrophy thereafter.  can become enlarged

(adenotonsillar hyperplasia) or inflamed (tonsillitis) and may be surgically removed in tonsillectomy.

TONSILS: PALATINE

TONSILS: PALATINE

TONSILS: PALATINE

TONSILS: PALATINE Has an extensive system of crypts,

which result in a large internal surface.  Tonsillar crypts are long and branched Incompletely encapsulated Covered by non-keratinized stratified

squamous epithelium that extends into deep and partly branched crypts

TONSILS: PALATINE

TONSILS: PALATINE Tonsillar crypts greatly increase the

contact surface between environmental influences and lymphoid tissue

not merely a group of invaginations of the tonsillar epithelium 

Macrophages and other white blood cells concentrate by the tonsillar crypts  in response to the microorganisms attracted to the crypts. 

provide such an inviting environment to bacteria that may form solidified "plugs" or "stones" within the crypts.

TONSILS: PALATINE Tonsillar crypts

Chronic sinusitis or post-nasal dripTonsillolith

 also known as a tonsil stones clusters of calcified material that forms in

the crevasses of the tonsils Occur mostly in palatine tonsils but may also

occor in lingual tonsils have a foul smell and can contribute to bad

breath can obstruct the normal flow of pus from the

crypts, and may irritate the throat main substance is mostly collagen, but they have

a strong unpleasant odor because of hydrogen sulfide and methyl mercaptan and other substances.

TONSILS: PHARYNGEAL Also known as adenoids, tonsilla

pharyngea, Luschka's tonsil, nasopharyngeal tonsil

Collection of lymphoid nodules located along the roof and posterior wall of the nasopharynx (upper throat)

When it becomes swollen, it may interfere with

breathing Removed through

adenoidectomy

TONSILS: PHARYNGEAL Covered with ciliated pseudostratified

columnar ciliated epithelium Incompletely encapsulated No crypts

TONSILS: PHARYNGEAL

TONSILS: PHARYNGEAL

TONSILS: PHARYNGEAL Enlarged adenoids, or adenoid

hypertrophyPharyngeal tonsils may become nearly the

size of a ping pong ball and completely block airflow through the nasal passages

Adenoid faciesAn atypical appearance of the face due to

enlarged adenoidsOpen mouth/mouth breathing, Long

elongated face, prominent incisors, Hypoplastic maxilla, Short upper lip, Elevated nostrils, High arched palate,

TONSILS: LINGUAL Rounded masses of lymphatic tissue that

cover the posterior region of the tongue at its base.

Their lymphatic tissue are dense and nodular Covered with non-keratinized stratified

squamous epithelium Partially surrounded by connective tissue

placing them in the group of Partially-Encapsulated Lymphatic Organs

They have associated mucous glands which are drained by ducts directly into the single tonsillar crypt.

Tonsillar crypts are long and unbranched

1. Pharyngeal Tonsil2. Palatine Tonsil3. Lingual Tonsil

4. Epiglottis

TONSILS: LINGUAL

TONSILS: LINGUAL

WALDEYER‘STONSILLAR RING  Pharyngeal lymphoid ring An anatomical term describing

the lymphoid tissue ring located in the pharynx and to the back of the oral cavity.

PEYER’S PATCHES Also known as aggregated lymphatic follicles Found in the wall of small intestine more numerous in younger individuals and

become less prominent with age.  appear as elongated thickened areas lacking the

villi that are typical of intestinal membrane Their macrophages destroy bacteria that are

common in the small intestines and prevent them from infecting and penetrating the walls of the intestine

PEYER’S PATCHES

PEYER’S PATCHES The Peyer's patches contain high

concentrations of white blood cells (or lymphocytes) that help protect the body from infection and disease.

Detect antigens such as bacteria and toxins and mobilize highly specialized white blood cells termed B-cells to produce protein structures called antibodies that are designed to attack foreign entities.

 MUCOSA-ASSOCIATED LYMPHOID TISSUE (MALT) diffusion system of small concentrations

of lymphoid tissue found in various sites of the body, such as the gastrointestinal tract, thyroid, breast, lung, salivary glands, eye, and skin.

populated by lymphocytes such as T cells and B cells, as well as plasma cells and macrophages

SKIN A  mucosa-associated lymphoid

tissue (MALT) star-shaped cells found mainly in the

spiny layer  an anatomical barrier from pathogens

and damage between the internal and external environment in bodily defense

Langerhans cells in the skin are part of the adaptive immune system

SKIN: LANGERHANS CELLS In skin infections, the local Langerhans

cells take up and process microbial antigens to become fully functional antigen-presenting cells

SKIN: LANGERHANS CELLS

Langerhans cell

RESPONSES TO ANTIGEN

Antigen

a.k.a. Immunogens These are any substances that stimulate

an immune response (antibody production or activation of T cells) and reacts only with the product of response (antibody or activated T cells)

Types of Antigen

• T dependent antigen – antigens that requires T cell’s help to stimulate B cells for antibody production

• T independent antigen – antigens with large repetitive structurese.g. polysaccharide

• Hapten – incomplete immunogen; cannot initiate immune response but can be recognized by antibodies

• Superantigen – capable of stimulating up to 20% of the total T cells of an individual

Hypersensitivity (Response) a.k.a. Allergy A condition of exaggerated or

inappropriate reaction of the immune response, that are harmful to the hostFirst contact – sensitizationSecond contact – allergic reaction

Types of Hypersensitivity

• Type I – Immediate (Anaphylactic) Hypersensitivity– Occurs within minutes– Local or systemic reaction

• Local anaphylaxis - atopic “out of place”

example: Hay fever, bronchial asthma• Systemic anaphylaxis – caused by venom and usually

cured by penicillin• Hives – eruption on the skin after food intake

– Mediators of Anaphylactic Hypersensitivity• Histamine• Prostaglandin• Thromboxane• Cytokines

Types of Hypersensitivity (Cont.) Type II – Cytotoxic Hypersensitivity

Involves bonding of antibodies to cell surface, activation of complement and cell damage

Type III – Immune Complex HypersensitivityAffects the joints, kidneys, blood vessels, and

skin○ Arthus reaction (4-10 hrs) – localized immune

complex deposit○ Systemic immune complex disease – generalized

reaction

Types of Hypersensitivity (Cont.) Type IV – Cell-Mediated Hypersensitivity

ReactionT cell mediated immune response

○ Allergic contact dermatitisCaused by haptensErythmia, itching, eczema, or necrosis of skin

○ Transplant rejection

Cells at the Lymphatic System

T Cells and B Cells

Lymphocytes

Lymphocyte is one of the the five kinds of leukocytes circulating in the blood

There are many types of lymphocytes but the most common are:› B Lymphocytes› T Lymphocytes

B Lymphocytes and T Lymphocytes

• These cells are not uniformly distributed in the lymphoid system

• They occupy special regions in non-thymic lymphoid structures

• When stimulated by antigens, these cells produce large basophilic lymphoid cells called immunoblasts, which contains large numbers of polyribosomes. These cells go through several mitotic cycles and may differentiate in several ways.

B Lymphocytes

Also known as B Cells B Cells are the most abundant type of

lymphocytes representing 65% of the circulating lymphocytes

They are derived from the bone marrow and migrate to non-thymic lymphoid structures

Differentiated B Cells

When B Cells migrate to the non-thymic tissue, they nest, proliferate when activated, and differentiate into antibody-secreting plasma cells

Some B Cells do not differentiate when activated. Instead, they generate the B memory cells

T Lymphocytes

Also known as T Cells They represent 35% of the circulating

lymphocytes in the body T Cells precursor are also produced in

the bone marrow but they leave the bone marrow and migrate at the thymus

Differentiated T Cells

T Cells proliferate at the thymus gland and then migrate to the non-thymic tissues where they mature. They are differentiated into:› Helper T cells – stimulates the

differentiation of B cells into plasma cells› Suppressor T cells – regulates both cellular

and humoral immunity and inhibit the action of helper and killer cells

Differentiated T Cells (Cont.)› Killer T cells – (a.k.a. cytotoxic lymphocytes or

graft-rejecting cells) produce the protein perforins that open holes in foreign cell membranes with consequent cell lysis Cell lysis is a process in which a cell is

broken down or destroyed as a result of some external force or condition

› Memory T cells – react rapidly to the reintroduction of antigen and stimulate production of killer T cells

Differentiated T Cells (Cont.)

Helper and suppressor cells are also known collectively as regulator cells. Helper T cells are killed by the retrovirus that causes the disease AIDS. Their immune system are made susceptible to opportunistic infections. Usually these are microorganisms that do not infect healthy individuals.

KILLE

R T

CELL A T Cell killing a cancer cell

T C

ELLS

AN

D B

CELLS This picture shows how an activated T cells stimulate the B cells

B C

ELLS

AN

D T

CELLS Found in the non-Hodgkin lymphoma

B C

ELLS Differentiation of the B cells

AN

TIB

OD

Y P

RO

DU

CIN

G B

CELLS

Lymphokines

Lymphokines

are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte.

They are protein mediators to direct the immune system response by signalling between its cells.

released by T cells that have been activated by antigens.

Powerful chemical substances secreted by lymphocytes. These soluble molecules help direct and regulate the immune responses.

Lymphokines (cont.)

Functions:1. function in the immune response through

stimulating the production of non sensitized lymphocytes and activating macrophages.

2. Chemical messengers that carry messages between the cells of the immune system

3. involved in cell-mediated immune responses that play a part in the body's defense system.

Lymphokines (cont.)Important Lymphokines Involved with T Cells IL-1 (Interleukin-1): has a variety of effects on various types of cells. It

acts as a growth regulator of T-cells and it induces other cells to produce proteins relevant to host defense. IL-1 forms a chemotactic gradient for neutrophils and serves as an endogenous pyrogen which produces fever.

IL-2 (Interleukin-2): stimulates the proliferation of T-cells. IL-4 (Interleukin-4): causes B cell proliferation and enhanced antibody

synthesis. IL-6 (Interleukin-6): has effects on T cell activation, growth, and

differentiation. Probably has a major role in the mediation of the inflammatory and immune responses initiated by infection or injury.

IL-8 (Interleukin-8): chemotactic attractant for neutrophils. Interferons:  Gamma-Interferon (gamma IFN). It is sometimes called

"immune interferon" Gamma-interferon has several antiviral effects including inhibition of viral protein synthesis in infected cells. It stimulates IL-2, and antibody production.

Lymphotoxins: (Tumor Necrosis Factor-Beta): (TNF-beta is produced by T cells; TNF-alpha is produced by T cells, as well as other types of cells.) TNF kills cells, including tumor cells (at a distance).

Colony Stimulating Factor (CSF): several, including GMCSF, cause phagocytic white cells of all types to differentiate and divide.

Interleukines

Interleukines

group of cytokines that were first seen to be expressed by white blood cells (leukocytes)

small protein known as a cytokine that functions as an important regulator of the immune system

A major group of lymphokines and monokines.

Interleukines (cont.)

Functions:1. induce growth and differentiation of

lymphocytes and hematopoietic stem cells.

2. interact to control the immune system of cells

3. act as messengers between leukocytes involved in either immunologic or inflammatory response

Large Lymphocyte

Large Lymphocyte

9-15 microns Oval/bulging nucleus, somewhat looser

chromatin structure than the small lymphocyte. No nucleoles

Plentiful colorless to light blue cytoplasm

Possible isolated bright violet granules

Large Lymphocyte (cont.) Description: Large lymphocytes are the minor part

of lymphocytes in the bloodstream. The cell has a large roundish and regular nucleus.

Size: 10-15 µm. Cytoplasm: Fairly abundant and sky-blue color;

there may be up to 10 azurophilic granules. They are approximately 0.5 µ in diameter.

Nucleus: Slightly eccentric located, round or oval, sometimes slightly indented; chromatin is arranged in compact blocks, separated by lighter zones without sharp demarcation, often there are unclearly divided clumps.

Nucleoli: Not visible.

Large Lymphocyte (cont.)

Type of white blood cell with a large nucleus, produced in the bone marrow.

Most occur in the lymph and blood, and around sites of infection.

B lymphocytes or B cells are responsible for producing antibodies. T lymphocytes or T cells have several roles in the mechanism of immunity.

Antigen-presenting Cell

•antigen-presenting cell (APC) or accessory cell •displays foreign antigen complexes with major histocompatibility complex (MHC) on their surfaces. •T-cells may recognize these complexes using their T-cell receptors (TCRs).• These cells process antigens and present them to T-cells.•T cells can only 'see' antigen that has been processed and presented by cells via an MHC molecule.

•T cells can only 'see' antigen that has been processed and presented by cells via an

MHC molecule. Most cells in the body can present antigen to  T cells via MHC class I

molecules and, thus, act as "APCs"; however, the term is often limited to those

specialized cells that can prime T cells (i.e., activate a T cell that has not been exposed

to antigen, termed a naive T cell). These cells, in general, express MHC class II as

well as MHC class I molecules, and can stimulate "helper"cells as well as

"cytotoxic" T cells, respectively.

Antigen-Presenting Cell

1. Macrophage2. B Cells3. Dendritic Cells

Macrophages

“histiocyte” Largest cells in our immune system Location: connective tissue and lymphoid organs First line of defense against infection Processes and presents antigen to lymphocytes to

produce antibodies Arise from monocytes which develops from bone

marrow Extend and retract in their locomotion Have many short microvilli and thin undulating folds

of their surface, called “lamellipodia” Selective in the kind of particles that they ingest

Role of Macrophages in the Immune Response

Macrophage

Digest pathogen

Presents Antigen to helper T cells

Production of antibodies

Opsonisation

LYMPHATIC VESSELS

Functions:

1. Act as a reservoir from plasma and other substances including cells that leaked from the vascular system

2. Transport and carry lymph fluid back from the tissues to the circulatory system.

3. It is the garbage collector, the internal vacuum cleaner sucking up metabolic garbage, toxins and excess fluid from the extracellular fluid of every organ.

*Note: Without functioning lymph vessels, lymph cannot be effectively drained and edema typically results.

General Structure

Layer Composition Functio

nSeen in

Innermost : simple squamous epithelium which is composed of  endothelial cells

mechanically transport fluid

Large capillaries and Small capillaries

Middle :  smooth muscles that are arranged in a circular fashion 

by shortening (contracting) or relaxing alter the diameter (caliber) of the lumen.

Large capillaries

Outermost : adventitia consists of fibrous tissue

bind the lymph vessel to the surroundings

Large capillaries

General Structure As they proceed forward and in their

course are joined by other capillaries, they grow larger and first take on an adventitia, and then smooth muscles.

Lymphatic system is not closed and

has no central pump.

Lymph movement occurs despite low pressure due to peristalsis (propulsion of the lymph due to alternate contraction and relaxation of smooth muscle), valves, and compression during contraction of adjacent skeletal muscle and arterial propulsion.[2]

Lymphocyte Circulation Lymphocyte

-a type of agranular white blood cell in the vertebrate immune system.-originate from stem cells in the bone marrow.

Three major types of lymphocyte  1. Thymus (T) cells -  involved in cell-mediated immunity . 2. Bone (B) cells -  responsible for humoral immunity or antibody-mediated. 3. Natural Killer (NK) cells -  play a major role in defending the host from both tumors and virally infected cells.

Actual Process

Lymph Capillaries

Begins with lymph capillaries which are blind-ended, highly permeable and superficial.Formed by endothelial cells with button-like junctions between them that allow fluid to pass through them when the interstitial pressure is sufficiently high. These button-like junctions consist of protein filaments.

Semilunar valves prevent back-flow of lymph along the lumen of the vessel.A valve system that prevents the absorbed lymph from leaking. Lymph capillaries have many interconnections or anastomoses between them and form a very fine network.

If tissue fluid builds up the tissue will swell; this is called edema.

As the circular path through the body's system continues, the fluid is then transported to progressively larger lymphatic vessels culminating in the right lymphatic duct (for lymph from the right upper body) and the thoracic duct (for the rest of the body); both ducts drain into the circulatory system at the right and left subclavian veins. The system collaborates with white blood cells in lymph nodes to protect the body from being infected by cancer cells, fungi, viruses or bacteria. This is known as a secondary circulatory system.

Lymph Capillaries

Lymph Vessels The lymph capillaries drain the lymph to

collecting lymphatics. These are larger contractile lymphatics, which have valves as well as smooth muscle walls.  

As the collecting lymph vessel accumulates lymph from more and more lymph capillaries in its course, it becomes larger and is called the afferent lymph vessel as it enters a lymph node.

Here the lymph percolates through the lymph node tissue and is removed by the efferent lymph vessel. An efferent lymph vessel may directly drain into one of the (right or thoracic) lymph ducts, or may empty into another lymph node as its afferent lymph vessel.[4]

 Both the lymph ducts return the lymph to the blood stream by emptying into the subclavian veins.

The functional unit of a lymph vessel is known as a lymphangion, which is the segment between two valves., It can act either like a contractile chamber propelling the fluid ahead, or as a resistance vessel tending to stop the lymph in its place.[5]

DIFFUSE LYMPHATIC TISSUE

AND LYMPHATIC NODULE

Diffuse Lymphatic Tissue

The alimentary canal, respiratory passages and genitourinary tract are guarded by accumulations of diffuse lymphatic tissue, which are not encapsulated.

Cells of this tissue are found in the lamina propria of these tracts.

They are strategically placed to intercept the entry of antigens, travel to regional lymph nodes, and undergo proliferation and differentiation, with effector lymphocytes, plasma cells and memory cells returning.

Large numbers of plasma cells and eosinophils can be found in the lamina propria of the GIT.

 The diffuse lymphatic tissues and their aggregations of the alimentary canal form the gut associated lymphatic tissue (GALT).

Features of a lymphatic nodule include:1. A germinal centre. This region develops when a lymphocyte has recognised an antigen, and is an indicator of lymphatic tissue response to antigen. It stains less intensely than;2. The marginal zone containing smaller lymphocytes.

Spleenhistology and function

Spleen

largest accumulation of lymphoid tissue in the body

The only one that interposed in the blood circulation

Important defense against antigens and site of destruction of aged erythrocytes

Important blood filter and antibody forming organ(activated lymphocytes)

Composed of reticular tissues with reticular cells, macrophages and APC’s.

General structure

Capsule-dense CT that surrounds the spleen.Trabeculae- emerge from the capsule that

divides parenchyma or splenic pulp -Large trabeculae originates from

the hilum. -carries nerves and arteries into

the splenic pulp as well as veins that bring blood back to circulation

Hilum- medial surface of the spleen. -where lymphatic vessels leave.

Splenic Pulp

Has 2 component: White pulp- consists of periarterial lymphatic

sheath and lymphoid nodulesRed pulp- splenic cords( Billroth’s cords) and

blood Sinusoids.

White Pulp

Trabecular arteries follows the course of the connective tissue trabeculae.

Periarterial lymphatic sheaths (PALS) – Sheaths of T-lymphocytes that envelopes the trabecular arteries.

Central arteries or White Pulp ArteriesPALS receive large collection of Lymphocytes (B

cells) forming Lymphoid nodules. ( arterioles-occupies Eccentric Position)

Marginal Zone- surrounds the lymphoid nodules -consists of many blood sinuses and

loose lymphoid tissue. - few lymphocytes but many

macrophages found here.

-contains abundant of blood antigens, thus plays a major role in the immunological activities of spleen.

After leaving the white pulp, the PALS slowly thins and the central artery/arteriole subdivided to form Penicillar Arteries.

- outside diameter of approximately 24um. - Near their termination, surrounded by a thick sheath of reticular cells, lymphoid cells and macrophage.

Red Pulp

Composed of:-Splenic Cord -Sinusoid Splenic Cord- contains network of reticular cells supported by

reticular fibers. -contains B lymphocytes, macrophages, plasma

cells and many blood cells (erythrocytes, platelet and granulocytes)

-separated by irregularly shaped white sinusoids.Sinusoid- lined by endothelial cells with a long axes parallel to

the long axes of sinusoid.Endothelial cells, developed in reticular fibers set primarily in

transverse direction like a hoop on a barrel. - an incomplete basal lamina. -lumen of the red pulp may be very narrow.

Closed circulation- the capillary opens directly into the sinusoid. - blood always remain inside the vessels.

Open circulation- prolongation of penicillar arteries open into the splenic cords, and the blood passes through the space between the cells to reach the sinusoid.

From the sinusoid, blood proceeds to the red pulp veins that joint together and enter the trabeculae forming trabecular vein.

Trabecular Vein- splenic vein originates and emerge from the hilum. - do not have individual muscle walls. - channels hollowed out in the trabecular CT and lined by endothelium.

Function of SpleenFilter, phagocytose, and mount immunological

response against blood-borne antigens.Important production site of lymphocytes . (White

Pulp)Macrophages in the splenic cords engulf and digest

the erythrocytes. The hemoglobin that they contain is broken down to several parts. The protein,globin, is hydrolyzed to amino acids that are reused in protein synthesis. Iron is released from heme and joined transferrin,is transported in the blood to the bone marrow, where it reused in erythropoiesis. Iron-free heme is metabolized to bilirubin, which is excreted by the liver cells.