Immunology of the Lymphatic System

This is important for regulating the amount and the composition of fluids in circulation and within peripheral tissues. The second role is to absorb dietary fats in the intestine and transport them back into the blood stream. The third function is to facilitate the host's immune defenses. Lymphatic vessels are well recognized as the channels through which antigens and immune cells are transported to their draining lymph nodes for immune protection. When infectious microorganisms invade peripheral tissues, lymphatic vessels transport the pathogens, or the antigen presenting cells that had engulfed the pathogens, to the lymph nodes.

This initiates adaptive immunity that lead to production of cells and antibodies that will clear the pathogen and generate memory against it. Antigens and dendritic cells DCs reach the draining lymph node through afferent lymphatic vessels; they must then enter the lymph node and migrate deep into it to activate T cells. Lymph nodes are enclosed in a collagen-rich capsule, which is underlined with lymphatic endothelial cells forming the subcapsular sinus. This structure is directly exposed to the incoming lymph.

Lymphatic endothelial cells are also concentrated in the medullary area to form the medullary sinus Figure 1A. Macrophages are closely integrated between lymphatic endothelial cells in both the subcapsular sinus and the medullary sinus to sample antigens and pathogens present in the lymph [ 1 - 3 ]. Notably, the lymph and cells coming from the afferent lymphatics also maintain peripheral immune tolerance in the lymph node, which depends on the DC activation status and the lymph node stromal cell self-antigen expression [ 4 - 6 ].

We will discuss the potential roles of lymphatic endothelial cells in controlling the ultimate immune response. We will also discuss the involvement of these cells in shaping peripheral tolerance. Schematic figure of lymphatic system, including initial lymphatic vessels, collecting lymphatic vessel and the draining lymph node. Within the lymph node, fibroblastic reticular cells and high endothelial cells express CCL21 and CCL19 to attract T cells and dendritic cells at the paracortex area of lymph node.

The lymph node conduit system, composed of collagen fibers, forms a scaffold to support lymph node architecture and facilitate quick fluid trafficking within the lymph node. Initial lymphatic vessel and collecting lymphatic vessel. The initial lymphatic vessels have oak-leaves shaped cell junctions Button pattern. Collecting lymphatics have continuous junction molecules and basement membrane and organized smooth muscle cell coverage. Organized smooth muscle coverage in collecting lymphatics allows phasic lymphatic contractions to propel lymph through lymphatic vessels.

The button shaped cell junction form lymphatic portals between lymphatic endothelial cells, which allows easy access of fluid and cells. Chemokine CCL21 expressed on lymphatic endothelial cell attract cells to lymphatic vessels and facilitate cell trans-lymphatic endothelial cell migration. The initial lymphatic vessels are composed of single layer of overlapping, oak leaf-shaped lymphatic endothelial cells expressing the lymphatic vessel endothelial hyaluronan receptor 1 LYVE-1 , a typical initial lymphatic endothelial cell marker [ 7 ].

Thus, infectious pathogens, such as bacteria and virus particles, could directly enter lymphatic vessels via these portals. The collected lymph is composed of interstitial fluid from the surrounding tissue and contains a pool of self-antigens resulting from homeostatic tissue metabolism and cell turn over [ 9 ]. The self-antigens from the lymph may partially activate DCs and these semi-activated DCs play important roles in maintaining peripheral tolerance [ 10 ]. DCs are known to be the most potent antigen presenting cells. The peripheral DCs are constantly migrating to the draining lymph node during tissue steady state, carrying self-antigen to maintain peripheral tolerance.

They do so by causing self-reactive T cells anergy or clonal depletion [ 10 ]. Upon activation, DCs quickly sample and process foreign antigens, increase expression of co-stimulatory molecules and CCR7 and strikingly accelerate their migration speed towards lymphatic vessels.

DC migration through the interstitial area is integrin independent and relies on ameboid movement under chemotaxis of CCL21 [ 12 ]. CCL21 exhibits cluster pattern on lymphatic endothelial cell and attract DCs migration [ 13 ]. Once DCs reach a lymphatic vessel, they seek the endothelial cell portals Figure 1C , dock on lymphatic by interacting with CCL21 and squeeze through the portal into the lymphatic vessel lumen without any involvement of proteolysis or integrin interaction [ 12 , 14 ].

The initial lymphatic vessels are critically required for migration of tissue DCs to the draining lymph node, and their absence leads to a deficient induction of immune response or tolerance [ 15 ]. However, even a very low density of initial lymphatic vessels is sufficient for DCs to efficiently traffic to the draining lymph node [ 16 ]. In addition to DCs, a population of effector-memory T cells also circulates from peripheral tissue to the draining lymph node. While tissue resident memory T cells lack CCR7 expression, the migrating memory T cells express it and enter lymphatic vessels, likely using the same cues as DCs [ 17 , 18 ].

However, it is not clear how CCR7 expression is induced in the migrating memory T cells. Neutrophils can also enter lymphatic vessels, the mechanism of neutrophil trafficking in lymphatic vessel remains to be clarified [ 19 - 21 ]. Although CCR7 was shown to be involved in neutrophil entry to lymphatic vessels [ 19 ], another study claimed that neutrophils rely on macrophage-1 Ag, LFA-1, CXCR4 and sphingosinephosphate receptor 4 for lymphatic trafficking but not on CCR7 [ 20 ]. This area of research has gained more attention in the past several years.

Initial lymphatic vessels merge into pre-collecting and collecting lymphatic vessels while extending to draining lymph node. Collecting lymphatic vessels gradually loose LYVE-1 expression, gain continuous basement membrane and acquire smooth muscle cell coverage. These morphological changes also contribute to the reduced permeability of collecting lymphatic vessels.

Lymphatic System: An Active Pathway for Immune Protection

It is obvious that this vessel morphology favors transport of lymph and cells rather than material collection from the surroundings However, it is not clear if antigens or cells are able to directly enter collecting lymphatic vessels from peripheral tissue. Collecting lymphatic vessels possess luminal valves, which are strategically distributed to prevent back flow, favoring lymph and cell movement towards lymph nodes Figure 1B. The vessel sections spanning between two valves is called lymphangion. The lymphangions along the large collecting lymphatic vessels display phasic contractions lymphatic pumping , which drive lymph transport [ 22 ].

Soluble molecules, solid particles and cells traveling through the lymphatic vessels are considered to be passively carried with the lymph to the lymph node sinus. Surprisingly, once they transmigrate into the lymphatic vessel lumen, DCs are found to actively crawl along the initial lymphatic vessel wall. This DC crawling appears to be random and sometimes even opposite to the direction of the lymph [ 13 , 23 ]. Eventually, DCs detach from the vessel wall, round up and sweep into collecting lymphatic vessels Figure 1C [ 13 , 23 ].

It is not yet clear why DCs linger around the initial lymphatic vessels or how they detach from the lymphatic endothelial cells. One possibility is that while they move deeper into the collecting lymphatic vessels, DCs are flushed away from the vessel wall by the higher lymph flow. It could also be because the CCL21 that attracts DCs docking on the vessel is diluted by the faster lymph flow in the collecting lymphatic vessels. Another speculation could be that collecting lymphatic vessels have different adhesion molecule or chemokine expression profile that favor DCs detachment.

DCs may also change their gene expression during their random movement and eventually detach from the lymphatic endothelial wall. However, we observed that even when exposed to higher lymph flow rate driven by the rhythmical lymphatic pumping, some DCs still tether to the lymphatic vessel wall S. Thus, DC intralymphatic migration may be more actively regulated than previously thought and further investigations are needed to have a deeper understanding of this process. Once soluble molecules, particles and cells reach the lymph node subcapsular sinus from afferent collecting lymphatic vessels, a number of complex steps take place in order to efficiently present antigen and induce adaptive immune responses.

First, when entering lymph node subcapsular sinus, the DCs need to transmigrate across the lymphatic endothelial cell layer to reach the lymph node T cell zone. The migration of DCs from the subcapsular sinus to the lymph node paranchyma mainly relies on chemokines CCL21 and CCL19 another ligand of CCR7 expressed by lymph node fibroblastic reticular cells and high endothelial venule cells Figure 1A [ 26 , 27 ].

The difference between DC and T cell transmigration in the lymph node sinus may be due to differences in the structure tightly lined by collagen, lymphatic endothelial cells, macrophages and other innate lymphocytes of the subcapsular and medullary sinuses. However this area requires further study.

The conduit system extends from the sinus throughout the lymph node, providing a supporting structure and more importantly an efficient route to deliver small antigens deep into lymph node parenchyma Figure 2 [ 30 ]. The conduits consist of collagen bundles, fibrillins and basement membrane components surrounded by fibroblastic reticular cells in the paracortex zone [ 30 , 31 ]. The population of lymph node resident DCs which are in direct contact with the conduits quickly uptake and process antigens [ 30 , 32 ]. The conduits also facilitate small molecule delivery into the B cell zone [ 33 ] and access of lymph borne factors, such as chemokines, inflammatory cytokines, to the T cell and B cell zone [ 30 , 34 ].

Multiphoton microscopy and 3D re-construction images of second harmonic generation, to reveal collagen distribution in lymph node. Instead, they flow into the lymph node sinus where they are sampled by the macrophages that bathe in the incoming lymph. Lymph node sinus macrophages Figure 3 have gained more attention in the past several years because of their unique distribution in lymph nodes and their function of capturing antigens and preventing systemic spread of pathogens [ 35 , 36 ].

Macrophages are concentrated at the lymphatic endothelial cell area in the lymph node. According to their relative position along the lymph node lymphatic network, they can be divided into two subpopulations, the subcapsular sinus macrophages SSM and the medullary sinus macrophages MSM. Schematic illustration of the lymph node macrophages. The close interaction between lymphatic endothelial cells and lymph node macrophages illustrated by immune fluorescent staining with Lyve-1 Green and CD Red.

While these cells are extremely difficult to distinguish in single cell suspensions, they are relatively easy to be identified in tissue sections after staining with specific markers [ 2 ]. Given their location in the lymph node sinus, SSMs and MSMs are directly exposed to the incoming lymph and thus are in the front line to capture lymph borne antigens.

MSMs are more potent in phagocytosis and express higher endosomal degradation enzymes, while SSMs are more susceptible to virus [ 36 , 37 ]. The quick response of sinus macrophages provides the first layer of immune defense and prevents systemic spread of infectious pathogens [ 35 ]. Furthermore, macrophages capture the antigen and shuttle them to B cells in the underlying follicles to initiate adaptive immune response [ 33 , 38 , 39 ].

After travelling through the lymph node, lymph enters efferent lymphatic vessels, flows through the downstream lymph node s and eventually returns to the blood circulation via the subclavian veins. Lymphocytes enter lymph node via high endothelial venule cells and move to T cell or B cell areas. Immune cell egress from lymph node depends on sphingosinephosphate S1P expressed by lymphatic endothelial cells [ 40 ].

Lymphocytes recirculate in blood and lymphoid organs. These four lymphatic capillary networks carry many critical antigens to draining lymph nodes, and the villus lacteals also transport dietary fat that is packaged into chylomicrons 8. Thus, the mesenteric lymph node is subjected to periodic high loads of fat that filter through this space, and the lymph node has had to evolve mechanisms to prevent fatty acid—driven inflammation, for instance 8.

It is quite possible that microbial lipids, likely available to the host , are components of chylomicrons and regularly affect the mesenteric lymphatic corridor. This relationship caused us to wonder if significant remodeling of the fat-localized mesenteric collecting vessels occurred. We developed a method to better identify human mesenteric collecting lymphatic vessels, which only weakly stain for many lymphatic markers.

Remarkably, we find that the collecting vessels are interrupted by the development of B cell—rich tertiary lymphoid structures that obstruct the path to the usual draining lymph node Tertiary lymphoid structures are common features in many inflammatory diseases and in cancers , but until we were able to view them in three-dimensional analyses, it was unclear that the structures were connected to existing collecting lymphatic vessels and thus in a position to affect both lymph transport and which cells and molecules arrived to the draining lymph node.

It will be interesting to determine whether this is true in other inflammatory diseases. It is not possible to know what the consequences of such obstruction would be in humans. However, various studies in mice may offer a clue. One illuminating study arose from an analysis of the consequence of Yersinia pseudotuberculosis infection in mice. The explanation for the development of chronic inflammation and impaired immunity is that migratory DCs arising from the lamina propria failed to arrive in the draining lymph node, apparently because collecting vessels became excessively leaky, allowing for a spilling out of immune cells and chylomicrons within lymph into the adjacent fat However, the concept of leaking, or high permeability, of collecting vessels as the basis of disease deserves more attention.

Collecting vessels are known to have a basal level of permeability to proteins like albumin This permeability is sufficient to broadcast antigens to DCs and macrophages that closely associate with the muscular wall of the collecting vessel Indeed, the associated DCs appear to support collecting vessel integrity and lower permeability 80 , suggesting that high permeability might be associated with infection or inflammation-mediated loss or modification of these support DCs.

Although development of tertiary lymphoid structures was not reported in connection with the Y. The structures form within ten days after cessation of DSS administration. In this experimental model, as in humans, they are highly enriched in B cells The structures formed in the absence of lymphoid tissue inducer cells, and they functioned to contain bacteria and perhaps bacterial products transported from the DSS-damaged epithelial border However, they were also proinflammatory and drove immune pathology The study did not carry out three-dimensional imaging or look at the preexisting lymphatic network.

1. Overview

A number of research questions related to the lymphatic vasculature are ripe to be addressed. However, too little is known about the mechanisms at play to maintain normal physiology of the vessels at present. Some of these mechanisms no doubt relate to the properties of the vessels themselves and the response to local mediators; others may relate to the status of neighboring immune cells 73 , 80 , Still others may relate to mechanisms that operate at a distance—via neural communication, for instance. Why does the application of an inflammatory mediator like IL-1b in the vicinity of a collecting vessel cause markedly enhanced permeability in the analogous contralateral collecting vessel of the same experimental subject ?

Is there a neural cue? Many an experimental design would assume that the contralateral tissue is the ideal control, yet even such basic assumptions require close examination. Clearly, much remains to be learned. Some of the more straightforward tasks may include comprehensive profiling of lymphatic endothelium from different organs and parts of the network.

We have a hint, mostly derived from work in the lymph node, that lymphatic vessel diversity exists and peripheral lymphatic capillaries are distinct from those in the lymph node http: Indeed, such work highlights a number of genes relatively selectively expressed in the lymph node by lymphatic endothelium. Some of these selected genes have already been connected to lymphatic valve formation and maintenance Table 2 , yet lymphatic valves have not been described in lymph nodes.

Other genes suggest connections that might link lymph node lymphatics to osmolyte transport , and pacemaker activity Clearly, there are many new functional connections to be made as we explore lymphatic diversity in full. The tools to do so are at hand. Survey of gene expression profiling in the Immunological Genome Project identifies novel genes selectively expressed by lymphatic endothelial cells in lymph nodes. The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review. National Center for Biotechnology Information , U.

Author manuscript; available in PMC Aug Randolph , 1 Stoyan Ivanov , 1 Bernd H. Zinselmeyer , 1 and Joshua P. Louis, Missouri Find articles by Gwendalyn J. Louis, Missouri Find articles by Stoyan Ivanov. Louis, Missouri Find articles by Bernd H. Author information Copyright and License information Disclaimer. The publisher's final edited version of this article is available at Annu Rev Immunol. See other articles in PMC that cite the published article. Abstract The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity.

Open in a separate window. Table 1 Key functional molecules expressed on lymphatic endothelium. Molecule Function Reference s Prox-1 Transcription factor necessary for lymphatic development and maintenance. Also expressed by a subset of macrophages. Also expressed by many stromal cells and podocytes. Unique isoforms of CCL21 distinguish peripheral and lymph node lymphatic endothelia. Lymphatic Collecting Vessels Lymphatic capillaries, specialized for uptake of lymph as described above, coalesce into contractile vessels that are called collecting vessels.

Lymphatics and the Lymph Node Microenvironment A major factor in considering how inflammation affects immunity and antigen transport relates to the profound impact that inflammation can have on the arrangement of lymphatic vessels and sinuses in the lymph nodes, which directly drain the collecting lymphatic vessels.

Table 2 Survey of gene expression profiling in the Immunological Genome Project identifies novel genes selectively expressed by lymphatic endothelial cells in lymph nodes. Gene Functions Reference s Xlr5a X-linked lymphocyte related; unknown function. Known to be expressed on subset of human lymph node lymphatic endothelium. In the Immgen database www. Previously associated with neurite growth and guidance. Quantifying Memory CD8 T cells reveals regionalization of immunosurveillance.

Preferential localization of effector memory cells in nonlymphoid tissue. Visualizing the generation of memory CD4 T cells in the whole body. Roozendaal R, Mebius RE. Stromal cell—immune cell interactions. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Bronte V, Pittet MJ. The spleen in local and systemic regulation of immunity.

Lymphatic transport of high-density lipoproteins and chylomicrons. Specific calcineurin targeting in macrophages confers resistance to inflammation via MKP-1 and p Steady-state fluid filtration at different capillary pressures in perfused frog mesenteric capillaries.

Microvascular fluid exchange and the revised Starling principle. LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans. The diaphragms of fenestrated endothelia: Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability.

Iijima N, Iwasaki A. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help. Wiig H, Swartz MA. Interstitial fluid and lymph formation and transport: Secretion of adipokines by human adipose tissue in vivo: Negrini D, Moriondo A. Lymphatic anatomy and biomechanics. Direct measurement of interstitial convection and diffusion of albumin in normal and neoplastic tissues by fluorescence photobleaching. Interstitial flow as a guide for lymphangiogenesis. Dendritic-cell trafficking to lymph nodes through lymphatic vessels.

Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling. Modest hyperglycemia prevents interstitial dispersion of insulin in skeletal muscle. Time lag of glucose from intravascular to interstitial compartment in type 1 diabetes.

Estimating plasma glucose from interstitial glucose: Metabolic competition in the tumor microenvironment is a driver of cancer progression. Lymphatic and interstitial flow in the tumour microenvironment: Endothelial nitric oxide synthase regulates microlymphatic flow via collecting lymphatics. Functionally specialized junctions between endothelial cells of lymphatic vessels. Plasticity of button-like junctions in the endothelium of airway lymphatics in development and inflammation. Clement CC, Santambrogio L. The lymph self-antigen repertoire. Rapid leukocyte migration by integrin-independent flowing and squeezing.

Lammermann T, Sixt M.

Lymphatic System: An Active Pathway for Immune Protection

Pflicke H, Sixt M. Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels. In vivo treatment with anti-ICAM-1 and anti-LFA-1 antibodies inhibits contact sensitization-induced migration of epidermal Langerhans cells to regional lymph nodes. The role of ICAM-1 molecule in the migration of Langerhans cells in the skin and regional lymph node. An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium. The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes.

CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Lymphoid aggregates remodel lymphatic collecting vessels that serve mesenteric lymph nodes in Crohn disease. Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues. Interstitial dendritic cell guidance by haptotactic chemokine gradients.

Normal dendritic cell mobilization to lymph nodes under conditions of severe lymphatic hypoplasia.

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Fluid flow regulates stromal cell organization and CCL21 expression in a tissue-engineered lymph node microenvironment. The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. D6 as a decoy and scavenger receptor for inflammatory CC chemokines. Cytokine Growth Factor Rev. The chemokine receptor D6 constitutively traffics to and from the cell surface to internalize and degrade chemokines.

Increased inflammation in mice deficient for the chemokine decoy receptor D6. The lymphatic system controls intestinal inflammation and inflammation-associated colon cancer through the chemokine decoy receptor D6. D6 facilitates cellular migration and fluid flow to lymph nodes by suppressing lymphatic congestion. Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis. Protection against inflammation- and autoantibody-caused fetal loss by the chemokine decoy receptor D6.

Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium. Immunological functions of hyaluronan and its receptors in the lymphatics. Hyaluronan digestion controls DC migration from the skin. Hyaluronan in tissue injury and repair.

Hyaluronan contributes to bronchiolitis obliterans syndrome and stimulates lung allograft rejection through activation of innate immunity. Lymphatic neoangiogenesis in renal transplants: Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection. Normal lymphatic development and function in mice deficient for the lymphatic hyaluronan receptor LYVE Rapid lymphatic dissemination of encapsulated group A streptococci via lymphatic vessel endothelial receptor-1 interaction.

Mucus membranes lining the respiratory, digestive, urinary, and reproductive tracts secrete mucus that forms another barrier. Physical barriers are the first line of defense. When microorganisms penetrate skin or epithelium lining respiratory, digestive, or urinary tracts, inflammation results. Damaged cells release chemical signals such as histamine that increase capillary blood flow into the affected area causing the areas to become heated and reddened. The heat makes the environment unfavorable for microbes, promotes healing, raises mobility of white blood cells, and increases the metabolic rate of nearby cells.

Clotting factors trigger formation of many small blood clots. Finally, monocytes a type of white blood cell clean up dead microbes, cells, and debris. The inflammatory response is often strong enough to stop the spread of disease-causing agents such as viruses, bacteria, and fungi. The response begins with the release of chemical signals and ends with cleanup by monocytes. If this is not enough to stop the invaders, the complement system and immune response act. Protective proteins that are produced in the liver include the complement system of proteins.

The complement system proteins bind to a bacterium and open pores in its membrane through which fluids and salt move, swelling and bursting the cell. The complement system directly kills microbes, supplements inflammatory response, and works with the immune response. It complements the actions of the immune system. Complement proteins are made in the liver and become active in a sequence C1 activates C2, etc. The final five proteins form a membrane-attack complex MAC that embeds itself into the plasma membrane of the attacker. Salts enter the invader, facilitating water to cross the membrane, swelling and bursting the microbe.

Complement also functions in the immune response by tagging the outer surface of invaders for attack by phagocytes. The complement system of proteins and their functioning. Image from Purves et al.

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Interferon is a species-specific chemical produced by cells that are viral attack. It alerts nearby cells to prepare for a virus. The cells that have been contacted by interferon resist all viral attacks. The immune system also generates specific responses to specific invaders. The immune system is more effective than the nonspecific methods, and has a memory component that improves response time when an invader of the same type or species is again encountered.

Immunity results from the production of antibodies specific to a given antigen antibody-generators, located on the surface of an invader. Antibodies bind to the antigens on invaders and kill or inactivate them in several ways. Most antibodies are themselves proteins or are a mix of protein and polysaccharides.

Immunology of the lymphatic system

Antigens can be any molecule that causes antibody production. White blood cells known as lymphocytes arise from by mitosis of stem cells in the bone marrow. Some lymphocytes migrate to the thymus and become T cells that circulate in the blood and are associated with the lymph nodes and spleen. B cells remain in the bone marrow and develop before moving into the circulatory and lymph systems.

B cells produce antibodies. This image is copyright Dennis Kunkel at www. Antibody-mediated humoral immunity is regulated by B cells and the antibodies they produce. Cell-mediated immunity is controlled by T cells. Antibody-mediated reactions defend against invading viruses and bacteria. Cell-mediated immunity concerns cells in the body that have been infected by viruses and bacteria, protect against parasites, fungi, and protozoans, and also kill cancerous body cells.

Human T-lymphocyte SEM x12, The cell-mediated immune responses. Images from Purves et al. Macrophages are white blood cells that continually search for foreign nonself antigenic molecules, viruses, or microbes. When found, the macrophages engulfs and destroys them. Small fragments of the antigen are displayed on the outer surface of the macrophage plasma membrane. The role of macrophages in the formation of antibodies.

Helper T cells are macrophages that become activated when they encounter the antigens now displayed on the macrophage surface. Activated T cells identify and activate B cells. The display path of an antigen as accomplished by a macrophage. B cells divide, forming plasma cells and B memory cells. Plasma cells make and release between and 20, antibody molecules per second into the blood for the next four or five days.

B memory cells live for months or years, and are part of the immune memory system. The activation of T cells by the action of macrophages and interleukin Antibodies bind to specific antigens in a lock-and-key fashion, forming an antigen-antibody complex. Antibodies are a type of protein molecule known as immunoglobulins. There are five classes of immunoglobulins: The five classes of Ig antibodies. Antibodies are Y-shaped molecules composed of two identical long polypeptide Heavy or H chains and two identical short polypeptides Light or L chains.

Function of antibodies includes: Structural regions of an antibody molecule. A unique antigenic determinant recognizes and binds to a site on the antigen, leading to the destruction of the antigen in several ways. The ends of the Y are the antigen-combining site that is different for each antigen.