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Lymphoid Organs Dr. Nabil Khouri MD, MSc, Ph.D Learning Objectives 1. 2. Understand the distinction between PRIMARY and SECONDARY lymphoid organs Be able to describe the general anatomical organization of: • lymph nodes • Spleen • Thymus • Mucosa-associated lymphoid tissue that include: Diffuse and nodular lymphoid tissue. regions of extensive lymphoid infiltration such as Peyer’s patches, appendix, and tonsils. Lymph Organs Free lymphocytes Mucosa-associated lymphoid tissue (MALT). Lymph nodes Tonsils Thymus Spleen What are Primary lymphatic organs? Primary lymphatic organs are where lymphocytes are formed and mature. They provide an environment for stem cells to divide and mature into B- and T- cells: There are two primary lymphatic organs: the Red bone marrow and the Thymus gland. The development of white blood cells (haemopoesis) was covered briefly in the section on blood. Both T-cell and B-cells are 'born' in the bone marrow. However, whereas B cells also mature in the bone marrow, Tcells have to migrate to the thymus, which is where they mature in the thymus. What are Secondary lymphatic organs? Secondary lymphoid tissues are arranged as a series of filters monitoring the contents of the extracellular fluids, i.e. lymph, tissue fluid and blood. The lymphoid tissue filtering each of these fluids is arranged in different ways. Secondary lymphoid tissues are also where lymphocytes are activated. These include: lymph nodes, tonsils, spleen, Peyer's patches and mucosa associated lymphoid tissue (MALT). Development LYMPH NODE DEVELOPMENT Except for the upper portion of the cisterna chyli, which persists, the lymph sacs are transformed into groups of lymph nodes during early fetal life, at about month 3. The surrounding mesenchymal cells invade each sac and break it up into lymphatic channels or sinuses. The mesenchymal cells give rise to the lymph node capsule and the connective tissue framework of the node The lymphocytes seen in the node before birth come from the thymus gland The lymph nodule and germinal centers of lymphocyte production do not appear in the nodes until just before or after birth Lymph nodes also develop along the course of other lymph vessels Development Other lymph organs THE SPLEEN develops from an aggregation of mesenchymal cells in the dorsal mesentery of the stomach THE PALATINE TONSILS form from the second pair of pharyngeal pouches THE TUBAL (pharyngo-tympanic) TONSILS develop from aggregations of lymph nodules around the openings of the auditory tubes THE PHARYNGEAL TONSILS (adenoids) develop from an aggregation of lymph nodules in the nasopharyngeal wall THE LINGUAL TONSILS develop from aggregations of lymph nodules in the root of the tongue General Lymphoid tissue “Description” Made up of free cells (Lymphocets, Macrophages and Plasma cells ) And rich network of reticular fiber Type III collagen Dense - Packed with cells Loose - more reticular fiber fewer cells Reticular cells produce the fibers Two Types of lymphoid organs NON ENCAPSULATED (Nodular) MALT (Mucosa Associated ENCAPSULATED Direct lymphoid organs Lymphoid Tissue) Solitary Nodules Aggregated nodules (Peyer’s patches) Lymphoid nodules in vermiform appendix Lymph node Spleen Thymus Tonsil Mucosa-associated lymphoid tissue (MALT) MALT is a lymphoid connective tissue located beneath mucous membranes in which the lymphocyte is the predominant cell type. Occur in the respiratory, gastrointestinal, urinary and reproductive tracts. The exact extent of these aggregations of lymphocytes mostly B and some T, and helper cells They have no distinct capsule like that of lymph nodes. MALT plays a role in regulating mucosal immunity. It may be the site of lymphoma, usually non-Hodgkin lymphoma. A specific entity is the MALT lymphoma linked to Helicobacter pylori in the stomach. LYMPHOCYTES IN CONNECTIVE TISSUE: MALT = mucosa-associated lymphoid tissue Diffuse lymphoid tissue within the Lamina propria (LP) of gut and can be found associated with mucosae anywhere in the GIT, Respiratory, and Genitourinary tracts. MALT: Intraepithelial lymphocytes: Shown here in The GIT – In which T-cells first to see antigens Intraepithelial lymphocytes Shown here in resp. epithelium. Nodular Lymphoid Primary Tissue Composition: oval concentrations of lymphocytes contained in meshwork of reticular cells. Not capsulated Presented within the lamina propria and mucosa of the organs Group of B-Lymphocytes arrange in spheres Called “lymphoid nodules” (Follicles) When activated by Antigaencarrying APCs and recognized by B lymphocytes they proliferate in the center called “germinative Center” This center contain follicular dentritic cells with processes LN contain follicular dendritic cells Nodule — A small solid collection of tissue, a nodule is palpable (can be felt). It may range in size from greater than 1.0 cm (3/8 inch) to somewhat less than 2 cm (13/16 inch) in diameter. A nodule may be present in the epidermis, dermis or subcutis Primary lymphatic nodule/follicle (LN) Aggregation of lymphocytes in lamina propria or submucosa Germinal center: high magnification Secondary follicles/nodules Composition: • Germinal center - a central region that contains large lymphocytes, mitotic figures, macrophages, and plasma cells. • An outer ring of small lymphocytes. • Arise when B-lymphocytes are presented with appropriate antigen, receive T-cell help, and then begin proliferating as lymphoblasts • Lymphoblasts differentiate into plasma cells or memory cells; aberrant lymphoblasts undergo apoptosis. • Function: morphologic indication of lymphatic tissue response to antigen that represents a cascade of events that includes proliferation of lymphocytes, differentiation of plasma cell, and antibody production. • After the antigen presentation and T-cell help, the activated B-cells set up germinal centers in secondary follicles The Appendix Blind sac extending from the caecum • primary and secondary follicles in lamina propria and submucosa • So, clearly a secondary lymphoid organ… • However, also a site of antigenINDEPENDENT differentiation • So, also it could be considered as primary lymphoid organ So, associated with just about any mucosa (GI, respiratory, genitourinary), you may see: • Intraepithelial lymphocytes (T-cells) • Diffuse lymphoid tissue: – B-cells – T-cells • Primary nodules • Secondary nodules – Germinal center with lymphoblasts and mphages Microfold, or “M” CELLS Are found in the gut-associated lymphoid tissue These cells are modified intestinal epithelial cells that assist in antigen presentation by conveying macromolecules from the intestinal lumen to underlying compartments housing lymphocytes and macrophages. M cells: TEM M cells are distinguished from other intestinal epithelial cells by their morphological differences. They are characterized by their short or no microvilli. When they present, the microvilli, they are short, irregular, and present on the apical surface or pocket-like invagination on the basolateral surface of these cells. Distribution of MALT • In the digestive system: • In the wall of the pharynx - tonsils (palatine, lingual, pharyngeal) • In the wall of the small intestine - aggregate lymphoid nodules (Peyer's Patches) or M cells • In the wall of the colon-aggregate lymphoid nodules • In the walls of the appendix • In the reproductive syst. • In the wall of the vagina Peyer patches are round or oval and are located in the mucous membrane lining of the intestine. They can be seen by the naked eye as elongated thickened areas, and their surface is free of the projections (villi) and depressions (Lieberkühn glands) that characterize the intestinal wall. Usually there are only 30 to 40 patches in each individual. In young adults they may be more numerous, and as a person ages they tend to become less prominent. Their full function is not known, but they do play a role in immunologic response and contain B and T cells similar to those found in peripheral lymph nodes. Peyer’s patches • Peyer’s patches are roughly egg-shaped lymphatic tissue nodules that are similar to lymph nodes in structure, except that they are not surrounded by a connective tissue capsule. They belong to a class of Non-Encapsulated lymphatic tissue known as lymphatic nodules, which include the tonsils and lymphatic tissue of the appendix Peyer’s patches Peyer’s patches are found throughout the ileum region of the small intestine known as aggregated lymphoid nodues, They form an important part of the immune system by monitoring intestinal bacteria populations and preventing the growth of pathogenic bacteria in the intestines. Summary Tonsils This lymphatic tissue belong to Mucosa-associated Lymphoid Tissue (MALT) group. They are considered organs because they are partially encapsulated Tonsils are covered by an epithelium depending on their location They include: 1. Palatine tonsils 2. Pharyngeal tonsils 3. Lingual tonsils 4. Tubal tonsils lymphoid organs Tonsils - A paired Lymphoid structure located in the Oropahrynx trap and destroy bacteria Palatine Tonsils •The non-capsulated surface is covered contains Dense lymphoid tissue (follicles) that forms a band of lymphatic nodules that lie below the stratified squamous epithelium lining the oral cavity in this region. • Subdivided into lobes by 10-20 crypts Palatine Tonsils Palatine tonsils • Overlying epithelium forms invaginations called multiple crypts that penetrate into the band of nodules. • These crypts act as collecting places for cellular debris and bacteria as well as some living lymphocytes that have migrated into the crypts. • The band of lymph nodules is separated from underlying tissues by a partial capsule of dense connective tissue. Pharyngeal Tonsil Located in the Naso-pharynx Covered by ciliated Pseudostratified epithelium In Some areas of the covering epithelium may be stratified squamous. Form a thin sheet of lymphoid nodules and diffuse lymphocytes Diffuse lymphoid tissue and nodules, but no crypts. Thin partial capsule of dense connective tissue separates the lymphoid tissue from underlying tissue. Chronic inflammation = Adenoid Pharyngeal Tonsil -Tonsil that has nodules and covered by psedostratified epithelium with - No Cripts ⇒ Pharyngeal tonsil Lingual Tonsils They are multiple small collections of lymphoid tissue located at the base of the tongue Lingual Tonsil are Covered by Non keratinized stratified squamous epithelium One crypt for each tonsil Or without deep crypts ⇒ Lingual tonsil. • Along the course of lymphatic vessels there are numerous small Bean shaped structures called LYMPH NODES • Usually present in groups (will be presented for you in a separate session) • Lymph from any part of the body passes through one or more lymph nodes before entering the blood stream • Lymph nodes act as filter removing bacteria and other particulate matter from lymph • Provides necessary microenvironment for antigen-dependent differentiation • Lymphocytes are added to lymph in these nodes • Anatomy of lymph nodes: • • • • • Entire node is Bean shaped The concavity constituting a Hilum Usually a single lymph vessel leaves the node through its hilum. Several lymph vessels enter the node on its convex aspect Each lymph node consists of, – Connective tissue framework – Lymphocytes Lymph Node Structure The Capsule & Subcapsular sinus Send Trabeculae & trabecular sinuses Sinuses contain lymph, macrophages, and reticular cells The Cortex: •An Outer “superficial” Part (B-cells) contains: -primary follicles/nodules -secondary follicles/nodules •An Inner “deep” Part (T-cells, dendritic cells) - The Medulla: •medullary cords (B-cells, plasma cells) •medullary sinuses (lymph, more macrophages, plasma cells, and reticular cells) The Medulla • The medulla of a lymph node is composed of – medullary cords interspersed between medullary sinuses. • The medullary cords are composed of dense lymphoid tissue contain primary B lymphocytes their precursors plasma cells, macrophages and T helper cells. • The most prominent cell in the cord is the precursor to plasma cells or immunoblasts that came from the germinal centers of the lymphoid follicles in the cortex of the node. • The medullary sinuses are composed primarily of reticular fibers (RF) providing the support framework, reticular cells (fibroblast-like cells that secret the reticulin). • Contain lymph , lymphocytes and macrophages • Is composed of the cortical sinuses surrounded by dense accumulations of lymphocytes. • In the more superficial cortex the lymphocytes are arranged into spherical follicles, lymphoid follicles where B lymphocytes are activated and undergo proliferation. The cortex • GERMINAL CENTER (GC) contains pale-staining cells. • The open, pale-staining nature of the nuclei of these cells indicate that they are T and B lymphocytes undergoing active proliferation. • Other cells include: • Reticular cells = follicular dendritic cells that present antigen to the B Lymphocytes • Macrophages that engulfed dead B cells that have died by apotosis Para-cortical zone, Sub-capsullar and Radial sinuses • Subcapsullar regions of the cortex is made of loose lymphoid tissue with reticular cells and fibers • Radial sinuses of the cortex is placed between the nodules and Contain primarily T lymphocytes that do not form into follicles. • T lymphocytes enter the lymph node parenchyma reside in the Paracortical zone. • If activated, the T lymphocytes undergo active proliferation to produce expanded clones of activated T lymphocytes. Capsule Subcapsular sinuses Radial sinuses From the sub-capsular sinus, lymph percolates through trabecular sinuses, and finally into MEDULLARY SINUSES High magnification view of a sinus (subcapsular sinus shown here) M=macrophage, Ly=lymphocytes, RF/RC=reticular fiber (and associated reticular cell) Micrographs of lymph node of a cat showing medullary sinuses and cords. silver impregnation to visualize Reticular Fibers Special stain: •RF Form a delicate supporting framework for highly cellular tissues • found in lymph nodes, liver, bone marrow, spleen, smooth muscle). •Composed mainly of Type III collagen. •Thinner than type I collagen • Reticular cells. These are branched cells that contribute to the stroma (connective tissue framework) of the lymphatic organs and act as APCs in the thymus. Lymphatic Circulation Through a Lymph Node Lymph nodes filter lymph 1. Afferent lymphatic vessels drain lymph into the Subcapsular Sinus 2. Lymph then passes to the Trabecular sinuses 3. From there, the lymph goes to the Medullary sinuses. 4. Lymphocytes and macrophages pass easily between these sinuses and the tissue of the lymph node. 5. Macrophages in sinuses monitor the fluids. Macs phagocytose the antigenic material and present it to T- and B-cells Lymphocytes develop in lymph nodes (after they are formed in the bone marrow) T cells develop in the thymus and then enter the circulation Macrophages and dendrite cells “present” antigen in the lymph nodes The slpeen • Located in the abdominal cavity, below the diaphragma, 150 gram • The spleen lies obliquely along the long axis of the 10th rib. Thus it is Axis is directed downwards, forward and laterally, making an angle of about 45 degrees with the horizontal plane. EXTERNAL FEATURES • The spleen has two ends ,three borders and two surfaces and 2 angles and hillum. • TWO ENDS1 -The anterior or lateral end is expanded and is more like a border. It is directed downwards and forwards, and reaches the mid-axillary line. 2-The posterior or medial end is rounded. It is directed upwards, backwards and medially. • Three bordersEXTERNAL FEATURES • 1-The superior border is charcteristically notched near the anterior end. • 2-The inferior border is rounded. • 3-The intermediate border is also rounded and is directed to the right. • Two surfaces1.The diaphragmatic surface is convex and smooth. 2.The visceral surface is concave and irregular. • Two Angles• 1.Anterobasal angle-It is the junction of superior border with lateral or anterior end. • 2.Posterobasal angle-junction of inferior border with lateral or anterior end of spleen. • Hilum : the hilum lies between superior and intermediate borders it is pierced by branches and tributaries of splenic vessels. *RELATIONS* (a)Peritoneal relations (b)Visceral relations The Peritoneal relations The spleen surrounded by peritoneum and is suspended by following ligaments. 1-Gastrosplnic ligament extends from the hilum of the spleen to the greater curvature of the stomach. 2-Lienorenal ligament extends from the hilum of the spleen to the anterior surface of the left kidney. 3-phrenicocolic ligament is not attached to the spleen, but supports its anterior end. Four impression present are visceral surface of spleen for abdominal organ and other structure1.Gastric impression 2.Renal impression 3.Colic impression 4.Pancreatic impression The Hilum lies on the inferomedial part of the gastric impression along the long axis of the spleen. ………….. Relations Visceral Relations Visceral surface- Diaphragmatic surface The surface separates the spleen from the costodiaphragmatic recess of pleura, lung and 9th ,10th ,11th ribs of the left side. The spleen clears the blood of aged blood cells and foreign particles and is the site of immune reactions to blood-borne antigens. • Monitoring antigens in blood • Proliferation of lymphocytes • Production of humoral antibodies Hematopoietic Functions Of the Spleen Immune Functions Of the Spleen • Formation of blood cells in fetal life • Removal and destruction of RBCs & platelets • Retrieval of iron from RBC hemoglobin • Storage of RBCs and platelets (more so in non-human species) http://www.lab.anhb.uwa.edu.au/mb140/CorePages/Lymphoid2/lymph2.htm The Spleen histology Divided into: Red Pulp (RBC/ hemoglobin recycling) White Pulp (responsible for immune functions) The Spleen The spleen general structure consists of : Connective tissue capsule and trabeculae Splenic pulp Blood vessels The connective tissue capsule consist of collagen and elastic fibres, fibroblasts and smooth muscle cells It sends off trabeculae into the splenic pulp The trabeculae, carrying the larger blood vessels, branch and anastomose, and are ultimately continuous with the branching reticular fibres and cells in the splenic pulp The splenic pulp involves two distinct types: WHITE AND RED PULP Organization of the spleen: white pulp and red pulp Only the white pulp has the character of true lymphoreticular tissue White pulp: lymphatic aggregations around “central” arteries: periarterial lymphatic sheath (PALS): T-cells lymph nodules: B-cells Red pulp: is arranged in cords and sinuses WHITE Pulp RED Pulp The white White Pulp The pulp consists of Peri-arterial lymphatic sheath (PALS) Lymphoid nodule surrounded by a Marginal zone Peri-arteriolar lymphoid sheath • The white bulb Is characterized by: • a parenchyma that have two types of lymphocytes • B cells and T cells located in two different areas of the spleen. • B cells are located in the lymphoid follicle scattered throughout the organ. • white pulp functions much in the manner that lymphoid follicles of lymph nodes function, i.e., initiation of immune responses by B cells to foreign antigens in the blood. • T cells are located around the central arteries and form a kind of sheath. • This site is called the peri-arteriolar lymphoid sheath. The ‘White’ Pulp • Appears basophilic on H&E and red on silver stain • Site where immune response is mounted; formation of germinal centers • Germinal centers with B cells and B cell derivatives push the ‘central artery’ off to the side The central artery is found in the white pulp The central artery is surrounded T cells Branch from the central artery into the red pulp As the body is exposed to antigens and the immune system mounts an immune response in the form of antibody production, lymph nodules (w/ germinal centers) appear in the white pulp of the spleen. U-M Histology Collection sinusoids The Red Pulp • Appears Red on H&E • Composed of sinusoids and Cords of Billroth • The cords are the parenchyma of the red pulp; they are composed of reticular tissue w/ macrophages, red blood cells, and lymphocytes Cords of Billroth Histology: The red pulp is "red" due to the presence of large numbers of erythrocytes in blood vessels called sinuses and white pulp is "white" due to lack of these sinuses and consequently fewer erythrocytes. The red pulp surrounds the white pulp while the latter looks like lymphatic nodules. – The white pulp indicates that there is a "central arteriole", sometimes called a central artery, close to the center of each area of white pulp. • The red pulp of the spleen • Characterized by a parenchyma (PN) Splenic cords supported by reticular fiber. • Consists of macrophages of the sheathed capillaries as well as other macrophages and blood cells that have not yet entered the venous sinuses. • The rest of the red pulp is occupied by numerous venous sinuses. • Their lining consists of long endothelial cells oriented along the longitudinal axis of the vessel. • Large spaces occur between adjacent endothelial cells and the underlying basement membrane is discontinuous. Allowing blood cells to easily pass between the endothelial cells and gain access to the blood-stream on the venous side. • A continuous reticular network forms the framework that supports the macrophages and a few fibroblasts responsible for producing the reticulin fibers; special stains are required to visualize the reticular network. A B Splenic sinuses and cords A. Red pulp B. Venous sinus (VS) and Cords of Billroth (BC) C. Silver-stained section C Spleen (red pulp) at high power (40x) sinus cord cord sinus U-M Histology Collection Sinusoids Lumen of the sinusoid Lining of endothelial cells: apposed to one another, but remain separated Macrophages extend their processes into the lumen of the sinusoid (you can see the remains of RBCs in macrophages) Sinusoids See how the basal lamina is interrupted; evident with both stains Splenic Circulation 1. Blood enters via splenic artery at hilus 2. Splenic artery branches into trabecular arteries (which travel within connective tissue trabeculae). 3. Trabecular arteries give off branches known as central arteries which leave the trabecula and enter the substance of the spleen (covered by a peri-arterial lymphatic sheath). 4. Central arteries branch into penicillar arterioles that piece through the lymphatic sheath and spill into splenic cords. 5. Blood percolates through splenic cords and across walls of splenic sinuses. 6. Splenic sinuses drain into pulp veins. 7. Pulp veins drain into trabecular veins. 8. Trabecular veins drain into splenic vein at the hilus. SPLENIC CIRCULATION Sinuses drain into splenic pulp veins, which, in turn, drain into trabecular veins. Trabecular veins travel within trabeculae and drain into splenic vein at the hilus. red pulp white pulp lymphoid organs Thymus - site of maturation of T lymphocytes secretes hormones (thymopoietin and thymosins) critical role in childhood Thymus Gland The Young Thymus Surrounded by a CT capsule; cortex has a lot of lymphocytes, fewer in the medulla THERE ARE NO GERMINAL CENTERS IN THE THYMUS! Location Structure 1. 2. 3. Capsule and lobules Cortex (T-Cell precursor, Reticuoepithelial cells, Macrophages) Medulla ( T-Cells, Hassall corpuscles) Located posterior to the sternum in the anterior part of the mediastinum, the thymus is a bi-lobed nodular organ that is very large in the first year or two of life reaching maximum size at puberty then becoming smaller in a process called Involution. Thymus :• In the elderly, the thymus is replaced almost entirely by fibrous and fatty tissue and is barely distinguishable from the surrounding tissues. • Reticular epithelial cells secrete hormones called thymosins, thymulin, and thymopoietin, which promote the development and action of T cells. • If the thymus is removed from newborn mammals, there will be lack of immunity development. The Thymus is a Primary Lymphoid (Immune) Organ Responsible For the Education of T-Cells Located over the great vessels of the heart in the area of the mediastinum Develops from an invagination of EPITHELIUM of the 3rd pharyngeal pouch, so it is called to be an endodermal organ. Made of : Specialized epithelial cells (called epithio-reticular cells) that are joined to one another by long processes with desmosomes on the extremities of the cells (like starfish joined together at the tips) make up the bag-like support for: Lymphocytes that, when the organ is young, fill this “bag”. The Thymus undergoes a process called THYMIC INVOLUTION, as T cells leave the thymus to populate other Lymphoid effector organs, the organ shrinks, leaving only the epithelioretucular cells NOTE: There are generally no B cells in the Thymus. The thymus with two tissue components • Parenchyma and Stroma. • The parenchyma is composed mostly of T lymphocytes in various stages of development into mature T cells • The stroma is composed of special thymic epithelial cells. • The stroma consists of sparse, delicate epithelial cells obscured by all of the lymphocytes. These epithelial cells form the support structure for the developing T cells but also play an important role in isolating the T cells from foreign anitgens during their development. Each lobule has an outer, darker staining cortex and an inner, paler staining medulla. In the cortex, (the parenchyma), consists mostly of the developing T lymphocytes and reticular cells . Epiytelial cells are called thymic nurse cells in the cortex contain maturing lymphocytes In the medulla • The stroma consists of prominent epithelial reticular cells that have large, pale-staining nuclei and substantial amounts of eosinophilic (pink-staining) cytoplasm. • There many T cells because most of them have entered the blood stream via vessels at the cortico-medullary junction. • Thymic corpuscles or Hassal corpuscles • Antigen presenting cells (APC) are also found in the medulla where they are called Thymic interdigitating cells. • T cells that recognize these self-antigens Cells and are removed by a process called apotosis. High mag view of medulla T-cells that survive selection process allowed to cross venule endothelium to enter circulation. Free lymphocytes • can be found in the lamina propria of the mucosa of organs of the digestive, respiratory, urinary and reproductive tracts. • Plasma cells: – Are derived from B lymphocytes that left the blood stream in connective tissue. – Usually the round to oval nucleus is eccentrically located in the cell due to the presence of a large Golgi apparatus. The predominant staining pattern of the cytoplasm is bluish to purple (basophilic) due to the large amount of rough endoplasmic reticulum , ribosomes. And packed with rough ER. – The nucleus has the appearance of being "spoked" or having a "clock face". Hassall’s corpuscles Type VI ERCs; function not very well known, but produce interleukins (such as IL-4 and IL-7) and so likely influence T-cell differentiation Source Undetermined Tertiary lymphoid organs/tissues • Ectopic or tertiary lymphoid tissues develop at sites of inflammation or infection in peripheral, non-lymphoid organs. • These tissues are architecturally similar to conventional secondary lymphoid organs, with separated B and T cell areas, specialized populations of dendritic cells, well-differentiated stromal cells and high endothelial venules. • Most important of these sites are those tissues with direct contact with the “external” environment, primarily the skin and mucosal lining of the gastrointestinal, pulmonary, and genitourinary tracts. PRIMARY IMMUNE RESPONSE •B-lymphocyte – antigen contact induces mitosis (plasma cells) for more antibody carrying cells. Antibodies released to circulatory systems. SECONDARY IMMUNE RESPONSE •Some “activated B-lymphocytes” become plasma cells. •Some remain smaller, but retain antigen-recognition ability. (B memory cells) •Next time similar antigenis encountered, response is MUCH FASTER due to resident and waiting memory cells. T-LYMPHOCYTES •Do not produce antibodies. •Function in “cell-mediated immunity.” •“NATURAL KILLER” cells destroy viruses. •Secrete “lymphokines” which attract phagocytic cells. •Secrete “perforin” which eats holes in the cells membrane or viral coat of invaders. •“Helper T cells”: •Induce macrophages to destroy other antigens •STIMULATE B-LYMPHOCYTES TO PRODUCE ANTIBODIES. (Can help hundreds of B-lymphocytes mature by releasing “B-cell growth factor.”) •“Suppressor T Cells” prevent overreaction of the system. (Inhibit B-lymphocye production.)