Information

Can lymph be in peripheral blood?


I read an argument that 1-3% of lymph is in peripheral blood. However, I am not sure if this lymph is about lymphocytes in peripheral blood; not lymph itself. Lymph gets exchanged between capillaries through Starling law powered by the heart and Frank-Starling mechanism. In this way, it makes sense that some lymph is leaking out from capillaries into the bolod.

Can lymph be in the peripheral blood?


Depends if your talking about interstitial fluid or lymph:

As per starling forces: the oncotic pressure of the late capillary plus hydrostatic pressure of interstitial space, would be higher than oncotic pressure of interstitium [though I dunno why since intertitial GAGs are very water hungry and they are responsible for the negative (hydrostatic?) pressures found in interstitium… Read lots of articles, still makes no sense to me] and hydrostatic pressure of the capillary… Thus there would be a net influx of interstitial fluid in the very ending part of the capillary, toward the venous side…

I say interstitial fluid, because it's not lymph yet since the interstitial fluid hasn't yet entered the adjacent lymph capillaries… if the interstitial fluid entered the lymph capillary then it would be stuck there, the mechanism of this one way flow is the junctions between the endothelial cells in these blind ended lymph capillary… These junctions which only opens up gaps between these endothelial cells when the interstitial pressure outside the lymph capillaries is higher than pressure inside the lymph capillaries…

The lymph then goes forward through lymphatic vessels/nodes because external pressure (pulsing of adjacent artery, contraction of adjacent skeletal muscle, changes in thoracic pressuring during breathing, etc) and there is little back flow because of valves (just like venous valves which prevent back flow in the low pressure venous system)… Ultimately the lymph returns by either thoracic duct (in the angle between left subclavian and left jugular vein) or right lymphatic duct (in the angle between right subclavian and right jugular vein)…

There are some sweet review articles from University of Bergen, Norway that go much more in depth on the physiology of interstitial fluid… Here is one of their more recent review articles: http://m.physrev.physiology.org/content/92/3/1005 it's free

IN SUMMARY: the starling forces bring interstitial fluid into the blood (the "peripheral part" right after the capillary)… The thoracic and right lymphatic duct drain lymph into the blood (I'm assuming this does not apply by your definition of peripheral, since this venous blood is about to be drained into the right atrium and is destined for the lungs)…

P.S. aqueous humor (in the eye), endolymph (cochlea aka inner ear) and CSF are also absorbed back into the blood… Also the brain has an interstitial fluid that is different from the CSF found in the subarachnoid spce of the meninges, i actually don't know how that drains… But anyway, the head is so special, I'm sure you weren't wondering about these specifics…


Biology

The causative agents of lymphatic filariasis (LF) include the mosquito-borne filarial nematodes Wuchereria bancrofti, Brugia malayi, B. timori An estimated 90% of LF cases are caused by W. bancrofti (Bancroftian filariasis).

Brugia Malayi Life Cycle

During a blood meal, an infected mosquito (typically Mansonia spp. and Aedes spp.) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound . They develop into adults that commonly reside in the lymphatics . The adult worms outwardly resemble those of Wuchereria bancrofti but are smaller. Female worms measure 43 to 55 mm in length by 130 to 170 &mum in width, and males measure 13 to 23 mm in length by 70 to 80 &mum in width. Adults produce microfilariae, measuring 177 to 230 &mum in length and 5 to 7 &mum in width, which are sheathed and have nocturnal periodicity (in some regions B. malayi may be sub-periodic, and note that microfilariae are usually not produced in B. pahangi infections). The microfilariae migrate into lymph and enter the blood stream reaching the peripheral blood . A mosquito ingests the microfilariae during a blood meal . After ingestion, the microfilariae lose their sheaths and work their way through the wall of the proventriculus and cardiac portion of the midgut to reach the thoracic muscles . There the microfilariae develop into first-stage larvae and subsequently into third-stage larvae . The third-stage larvae migrate through the hemocoel to the mosquito&rsquos proboscis and can infect another human when the mosquito takes a blood meal .

Wuchereria bancrofti Life Cycle

During a blood meal, an infected mosquito introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound . They develop in adults that commonly reside in the lymphatics . The female worms measure 80 to 100 mm in length and 0.24 to 0.30 mm in diameter, while the males measure about 40 mm by 1 mm. Adults produce microfilariae measuring 244 to 296 &mum by 7.5 to 10 &mum, which are sheathed and have nocturnal periodicity, except the South Pacific microfilariae which have the absence of marked periodicity. The microfilariae migrate into lymph and blood channels moving actively through lymph and blood . A mosquito ingests the microfilariae during a blood meal . After ingestion, the microfilariae lose their sheaths and some of them work their way through the wall of the proventriculus and cardiac portion of the mosquito&rsquos midgut and reach the thoracic muscles . There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae . The third-stage infective larvae migrate through the hemocoel to the mosquito&rsquos prosbocis and can infect another human when the mosquito takes a blood meal .

Hosts and Vectors

Wuchereria bancrofti, Brugia malayi, and B. timori are considered human parasites as animal reservoirs are of minor epidemiologic importance or absent felid species and some primates are the primary reservoir hosts of zoonotic B. pahangi.

The typical vector for Brugia spp. filariasis are mosquito species in the genera Mansonia and Aedes. W. bancrofti is transmitted by many different mosquito genera/species, depending on geographical distribution. Among them are Aedes spp., Anopheles spp., Culex spp., Mansonia spp., and Coquillettida juxtamansonia.

Geographic Distribution

W. bancrofti was once widespread in tropical regions globally but control measures have reduced its geographic range. It is currently endemic throughout Sub-Saharan Africa (excluding the southern portion of the continent), Madagascar, several Western Pacific Island nations and territories and parts of the Caribbean. Bancroftian filariasis also occurs sporadically in South America, India, and Southeast Asia.

Brugia spp. associated with LF are more geographically limited and occur only in Southeast Asia. Like W. bancrofti, control measures have reduced the occurrence and endemic range considerably. Brugia timori is restricted to the Lesser Sunda Islands of Indonesia.

Clinical Features

While severe manifestations do not develop in the majority of infections, LF is a potentially highly disfiguring and disabling disease. The most prominent clinical feature is the development of severe lymphedema of the limbs (&ldquoelephantiasis&rdquo) and occasionally genitalia (hydrocele) due to dysfunction of lymphatic vessels. Affected limbs become grossly swollen the skin may become thick and pitted, and secondary infection are frequent due to lymphatic dysfunction. Scrotal hydrocele is also seen in some infected males. Lymphangitis, lymphadenopathy, and eosinophilia may accompany infection in the early stages.

A chronic syndrome called &ldquotropical pulmonary eosinophilia&rdquo has been associated with W. bancrofti and B. malayi infections, involving eosinophilic pulmonary infiltrate, peripheral hypereosinophilia, wheezing, chest pain, splenomegaly, and bloody sputum. This has most frequently been documented in South and Southeast Asia.


Lymphoid Organs of Immune System | Immunology

Immature lymphocytes generated in hematopoiesis, the process of formation and development of blood cells, mature and become committed to a particular antigenic specificity within the primary lymphoid organs, namely, thymus, bursa of Fabricius (in birds) and bone marrow (in mammals). A lymphocyte becomes immuno-competent, i.e., capable of mounting an immune response only after it matures within a primary lymphoid organ.

1. Thymus:

Thymus is a greyish, flat, bilobed lymphoid organ situated above the heart and extending into the neck on the front and sites of trachea. It develops from the epithelium of third and fourth pharyngeal pouches and, on maturity, acts as the site of development and maturation of lymphocytes named thymus-derived lymphocytes or T-lymphocytes or T-cells.

The thymus reaches peak activity in childhood and attains its largest size at puberty. Thereafter, the thymus begins to atrophy without any apparent effect on T-lymphocyte function and is extremely small in old age.

For convenience, the average weight of the thymus is 70 g in infants and its age- dependent involution leaves the thymus with an average weight of 3 g in the old age. This is probably due to the fact that T-lymphocytes are very long-lived and can circulate in the resting state for long periods of time.

Each lobe of thymus is surrounded by a capsule and is divided into a series of lobules, which are separated from each other by strands of connective tissue called trabeculae. Each lobule is organized into two compartments-outer and inner. The outer component is called cortex, whereas the inner component is called medulla (Fig. 42.2).

The cortex is densely packed with thymocytes, whereas the medulla is sparsely populated with thymocytes. Thymocytes develop from prothymocytes. The latter are produced in bone marrow, migrate through blood stream, enter the cortex of the thymus, and act as thymocytes. Thymocytes divide rapidly in the cortex and give rise to T-lymphocytes.

Of the T-lymphocytes produced in thymus only 5% leave the thymus as viable cells. Though the reason for this apparent wasteful process is not known, some believe that it is the elimination of T-lymphocyte clones that react against self.

Both the cortex and the medulla of the thymus are criss-crossed by a three dimensional network consisting of epithelial cells, dendritic cells, and macrophages, which make up the framework of the organ and contribute to the growth and maturation, of thymocytes.

Some epithelial cells of the outer cortex possess long membrane extensions that surround as many as 50 thymocytes. These cells are called nurse cells. Other epithelial cells of the cortex have long interconnecting cytoplasmic extensions that form a network and have been found to interact with many of the thymocytes when they traverse the cortex.

The function of the thymus is to generate T-lymphocytes and to confer immunological competence on to them during their stay in the organ. T-lymphocytes so educated in the thymus become capable of mounting cell-mediated immune response against appropriate antigen.

This is effected under the influence of the thymic microenvironment and several hormones such as thymosin and thymopietin produced by the epithelial cells of the thymus. The competent T-lymphocytes immediately move from thymus to the secondary or peripheral lymphoid organs.

2. Bursa of Fabricius:

Bursa of Fabricius is a primary lymphoid organ in birds where stem cells from yolk sac, foetal lever, and bone marrow mature, proliferate, and differentiate into bursa-derived lymphocytes called B-lymphocytes or B-cells.

Bursa of Fabricius arises as a pouch from the dorsal part of cloaca (fluid gut) in birds, Bursa of Fabricius is sensitive to hormones: administration of testosterone at the early embryostage completely prevents its formation (hormonal bursectomy).

Surgical removal of bursa (bursectomy) from newly hatched chickens destroys their subsequent ability to produce antibodies. The B-cells mature, proliferate, and differentiate into bursa and then migrate from it and reach outer or superficial cortex of the germinal follicles and medullary cords of peripheral lymph nodes and lymphoid follicles of spleen where, following appropriate antigenic stimulation, transform into plasma cells and secrete antibodies. Like thymus, the bursal of Fabricius starts to shrink or atrophy at puberty.

3. Bone Marrow:

Bone marrow is the site of origin and development of B-lymphocytes or B-cells (bone marrow derived lymphocytes) in mammals particularly in humans and mice after birth. Before birth, the yolk sac, foetal lever, and total bone marrow are the major sites of B-lymphocyte maturation. Bone marrow, therefore, is the mammalian equivalent of the bursa of Fabricius in birds.

Development of B-lymphocytes (B-cells) begins with the differentiation of lymphoid stem cells into the earliest distinctive progenitor B cells (pro-B cell), which proliferate within the bone marrow filling the extravascular spaces between large sinusoids in the shaft of a bone.

Proliferation and differentiation of pro-B cells into precursor B cells (pre-B cells) requires the microenvironment provided by the bone marrow stromal cells.

The stromal cells within the bone marrow:

(1) Interact directly with the pro-B and pre-B cells and

(2) Secrete various cytokines that are required for development.

Bone marrow is not the site of origin and development of B-lymphocytes (B-cells) in all mammals. In cattle and sheep, the fietal spleen is the primary lymphoid tissue wherein the maturation, proliferation, and diversification of B-cells take place during early gestation.

During later gestation this function is performed by ideal Peyer’s patch, a patch of tissue embedded in the wall of the intestine. In rabbit, gut-associated tissues (e.g.. appendix) act as primary lymphoid tissue for maturation, proliferation, and diversification of B-cells.

Secondary or Peripheral Lymphoid Organs:

As stated earlier, the lymphocytes mature, proliferate, and differentiate in the primary or central lymphoid organs. These lymphocytes migrate therefrom via circulation to the secondary or peripheral lymphoid organs. Here they bind appropriate antigens and undergo further antigen-dependent differentiation.

Once in the secondary lymphoid organs, the lymphocytes do not remain there but move from one lymphoid organ to another through the blood and lymphatic’s. The passage of lymphocytes facilitates the induction of an immune response. Lymph nodes and the spleen are the most highly organized secondary or peripheral lymphoid organs, whereas mucosa-associated lymphoid tissue (MALT) is the less organized lymphoid tissue.

1. Lymph Nodes:

Lymph nodes are small, encapsulated, bean-shaped structures clustered at junctions of the lymphatic vessels which are distributed throughout the body. Lymph nodes contain a reticular network packed with lymphocytes, macrophages and dendritic cells, and filter out pathogenic microorganisms and antigens from the lymph.

As the lymph percolates through a lymph node, any pathogen or antigen that is brought in with the lymph is trapped by the phagocytic cells and dendritic cells.

A lymph node consists of three regions: the cortex, the paracortex, and the medulla (Fig. 42.3). Cortex is the outermost region and contains several rounded aggregates of lymphocytes (mostly B-lymphocytes), macrophages, and follicular dendritic cells arranged in primary follicles. Each follicle has a pale-staining germinal centre surrounded by small dark-staining lymphocytes.

The deeper region lying beneath the cortex is the paracortex. It is the zone between the cortex and the medulla. Paracortex possesses large number of T-lymphocytes and also contains inter-digitating dendritic cells thought to have migrated from tissues to the lymph node.

Because of the presence of large number of T-lymphocytes in it. the Para-cortex is also referred to as a thymus-dependent area in contrast to the cortex which is a thymus-independent area. Medulla, the inner most region of lymph node, is more sparsely populated with lymphoid-lineage cells. Of the lymphoid-lineage cells present, many are plasma cells actively secreting antibody molecules.

Each lymph node has a number of lymph vessels called afferent lymphatic vessels, which pierce the capsule of a lymph node at numerous sites and empty lymph into the sub-capsular sinus. The lymph now percolates slowly inward through the cortex, paracortex, and medulla, allowing phagocytic cells and dendritic cells to trap pathogens and antigens carried by the lymph.

The lymph then is drained into a single large lymph vessels called efferent lymphatic vessel that carries the lymph to the thoracic duct, which empties into a large vein in the neck.

2. Spleen:

The spleen, which is about 5 inches long and 200 g in weight in adults, is an ovoid encapsulated, and the largest secondary or peripheral lymphoid organ. Spleen is specialized for trapping blood-borne antigens and is present high in the left abdominal cavity and being encapsulated, its capsule extends a number of projections, called trabeculae, into the interior resulting in the formation of compartments.

These compartments are filled by two types of tissues, the red pulp and white pulp, which are separated by a diffuse marginal zone (Fig. 42.4). The red pulp consists of a network of sinusoids populated by large number of erythrocytes (red blood cells) and macrophages and few lymphocytes.

In fact, red pulp is the region where old and defective erythrocytes are destroyed and eliminated. The white pulp consist of the branches of the splenic artery that make a periarteriolar lymphoid sheath (PALS) populated heavily by T-lymphocytes.

Periarteriolar lymphoid sheath (PALS) is attached with primary lymphoid follicles that are rich in B-lymphocytes. The marginal zone separating the red pulp from white pulp is populated by lymphocytes and macrophages.

When the blood-borne antigens enter the spleen the B- and T-lymphocytes present in periarteriolar lymphoid sheath (PALS) are initially activated. Here interdigitating dendritic cells capture antigen and present it combined with class II MHC molecules (major histocompatibility molecules) to TH cells (T helper cells). Once activated, these TH cells can then activate B- lymphocytes (B-cells).

The activated B-lymphocytes, together with some TH cells then migrate to primary follicles in the marginal zone. When the primary follicles are challenged by antigen, they differentiate into characteristic secondary follicles.

The latter contain germinal centres (similar to those occurring in lymph nodes) where rapidly dividing B-lymphocytes and plasma cells are surrounded by dense clusters of concentrically arranged lymphocytes.

3. Mucosal-Associated Lymphoid Tissue (MALT):

The mucous membranes lining the alimentary, respiratory, and genitourinary systems have a very large combined surface area (about 400 m 2 nearly the size of a basketball court), which is constantly exposed to numerous antigens and is the major site of entry for most pathogens.

These vulnerable membrane surfaces possess a group of organized lymphoid tissues which defend it from pathogens and antigens. The group of organized lymphoid tissues is known collectively as mucosal-associated lymphoid tissue (MALT).

There are several types of MALT the most studied one is the gut-associated lymphoid tissue (GALT) which includes tonsils, Peyer’s patch, appendix, and loosely organised clusters of lymphoid cells in the lamina propria of intestinal villi.

Mucosal-associated lymphoid, tissue (MALT) is functionally very significant in immune system of the body because of the presence of large number of antibody-producing plasma cells in it. The number of plasma cells in MALT for exceeds that of the total of the number of plasma cells present in spleen, lymph nodes, and bone marrow.

There are three groups of tonsil present at three different locations: palatine, lingual, and pharyngeal (adenoids). Palatine group of tonsil occur at the sides of the back of the mouth lingual in the basal region of the tongue and pharyngeal (adenoids) in the roof of the nasopharynx (Fig. 42.5).

All the aforesaid tonsil groups are nodule-like and consist of a meshwork of reticular cells and fibres interspersed with lymphocytes, macrophages, granulocytes, and mast cells.

The B-lymphocytes are organised into follicles and germinal centres. The germinal centres are surrounded by regions showing T-lymphocyte activity. However, the tonsils protect against antigens that enter through the nausal and oral epithelial routes.

(ii) Peyer’s Patch:

Peyer’s patches occur in the sub-mucosal layer present beneath the lamina propria lying under the epithelial layer of intestinal villi. Each Peyer’s patch is a nodule of 30-40 lymphoid follicles. Like lymphoid follicles in other sites, those that compose Peyer’s patches can develop into secondary follicles with germinal centres (Fig. 42.6).

(iii) Lamina Propria:

Lamina propria occurs under the epithelial layer of intestinal villi (Fig. 42.6). It is populated with large number of plasma cells, macrophages, activated T helper cells (activated TH cells) in loose clusters. More than 15,000 lymphoid follicles have beer, reported within the lamina propria of a healthy child.


Approach to lymphocytosis

Lymphocytes are white blood cells that serve primarily as the body’s adaptive immune system, and provide humoral or cell-mediated immunity against a variety of bacterial, viral, or other pathogens. They are comprised mainly of T, B, and natural killer (NK) cells, and the body typically maintains the absolute lymphocyte count (ALC) in a range of less than 4,000 lymphocytes per uL. Elevation of the lymphocyte count above this level is most commonly due to a reactive lymphocytosis, the body’s normal response to an acute infection or inflammatory condition.

The mechanisms leading to an increased number of circulating lymphocytes include increased lymphocyte production, release of already formed lymphocytes into the blood, or decreased clearance of lymphocytes from the blood. A less common etiology of an elevated lymphocyte count is malignant lymphocytosis, where the lymphocyte count becomes elevated due to either an acute or chronic lymphoproliferative disorder.

An elevated lymphocyte count alone is unlikely to cause harm. Therefore, taking time to identify the underlying cause is essential, as treatment will differ substantially between reactive and malignant causes. For example, reactive lymphocytosis due to a viral infection, such as in infectious mononucleosis, requires no specific treatment other than supportive care. In contrast, acute lymphoblastic leukemia (ALL) may present with an elevated lymphoblast count which can easily be mistaken as a lymphocytosis. Recognizing an elevated white blood cell count that is due to ALL is important, as this disease requires expedient treatment with intensive chemotherapy.

Other causes of malignant lymphocytosis, such as chronic lymphocytic leukemia (CLL), exhibit a wide range of clinical behavior, and may or may not require expedient treatment depending on a variety of clinical and laboratory factors. Most often, however, chronic lymphoproliferative disorders do not require urgent therapy.

What features of the presentation will guide me toward possible causes and next treatment steps:

Even with highly elevated lymphocyte counts, it is unusual for patients to develop leukostasis or other signs and symptoms directly attributable to lymphocytosis. However, signs and symptoms resulting from the condition responsible for the elevated lymphocyte count may be important clues to help identify the underlying etiology. For example, a young patient with lymphocytosis in the setting of fever, pharyngitis, fatigue, and splenomegaly would raise concern for infectious mononucleosis. In contrast, an older patient with lymphocytosis in the setting of lymphadenopathy, anemia, and thrombocytopenia would cause suspicion for CLL.

The time course of lymphocytosis can be a key discriminating factor between different etiologies. In general, lymphocytosis due to an infectious etiology such as mononucleosis will increase rapidly, and peak in the second or third week of illness. Although it may persist for up to 2 months, reactive lymphocytosis is generally self-limited. Malignant lymphocytosis may develop acutely or more gradually, and although it can wax and wane, it does not tend to resolve without specific treatment. The rate of change of the lymphocyte count can influence treatment decisions. For example, a lymphocyte doubling time of less than 6 months is an important consideration in deciding when to initiate treatment of CLL.

Lymphocyte morphology, as evaluated on the peripheral blood smear, can also be an important clue as to the possible cause of the lymphocytosis. For example, atypical lymphocytes with generous cytoplasm and eccentric nuclei are often seen in infectious mononucleosis. Small, mature-appearing lymphocytes with sparse cytoplasm accompanied by damaged lymphocytes (“smudge cells”) are seen in CLL. An elevated white blood cell count due to ALL may exhibit heterogeneity in the size of the malignant cells, with smaller cells being easily mistaken for lymphocytes. The presence of large lymphoblasts with prominent nucleoli and pale blue cytoplasm suggests ALL and not true lymphocytosis.

What laboratory studies should you order to help make the diagnosis and how should you interpret the results?

A complete blood count with manual differential should be ordered to accurately quantify the total white blood cell (WBC) and absolute lymphocyte count (ALC). The ALC is calculated by multiplying the total WBC by the percentage of lymphocytes and dividing by 100 (ALC = WBC [cells/uL] x [% lymphocytes /100]). With patients in whom a reactive lymphocytosis is suspected, a thorough infectious work-up should be performed. This may include the heterophile antibody (or monospot) test, viral direct fluorescent antibody testing for influenza, RSV (respiratory syncytial virus), and other common viruses, HIV testing, and blood and throat cultures.

In immunocompromised patients, peripheral blood can be sent for viral PCR (polymerase chain reaction) tests to rule out EBV (Epstein-Barr virus), CMV (Cytomegalovirus), HSV (herpes simplex virus), HHV (human herpesvirus)-8, and adenovirus. If this work-up is negative, or if a malignant etiology is suspected, peripheral blood flow cytometry should be performed to rule out a lymphoproliferative disorder. Generally, flow cytometry is definitive for the detection of blasts or B-cell disorders, though it should be noted that T-cell disorders can sometimes be difficult to characterize by flow cytometry. If the diagnosis remains in question, determining the clonality of the lymphocytes may be helpful. For example, identification of clonal rearrangement of the immunoglobulin genes, as seen in B-cell leukemias/lymphomas, or clonal T-cell receptor rearrangement in T-cell leukemia/lymphomas can help solidify a diagnosis.

Serum free light chains, if elevated and skewed toward kappa or lambda, may also provide evidence for lymphocyte clonality. In addition, FISH (florescent in-situ hybridization) cytogenetics can be performed on the peripheral blood to evaluate for markers typical of a lymphoproliferative disorder. For example, a case with flow cytometry results that are atypical but consistent with CLL may show del 13q14, which would further support the CLL diagnosis. If the above studies remain inconclusive, a bone marrow aspirate and core biopsy may be indicated to more definitively rule out a malignant etiology of the lymphocytosis.

What conditions can underlie lymphocytosis:

Reactive lymphocytosis

– Infectious mononucleosis (most commonly due to EBV, less commonly CMV, primary HIV-1 infection, adenovirus, or HHV-6).

– Infectious lymphocytosis (usually in children, can be extreme, with WBC counts occasionally greater than 100,000, thought to be due to enteroviruses, also associated with mild eosinophilia).

– Other viral illnesses (measles, mumps, rubella, hepatitis, influenza, varicella, HTLV-1 [Human T-cell Lymphotropic Virus]).

– Bacterial infection (well-described with Bordetella pertussis, Bartonella henselae [“cat scratch disease”], tuberculosis).

– Parasitic diseases (babesiosis usually causes atypical lymphocytes with normal WBC count, toxoplasmosis can cause atypical lymphocytes with elevated lymphocyte count).

– Stress-induced lymphocytosis (seen in trauma, where it may confer a poor prognosis, also seen after seizure, cardiac emergencies, sickle crisis).

– Persistent polyclonal B cell lymphocytosis (generally middle-aged female smokers, associated with HLA-DR7).

– Hypersensitivity reactions (for example, drug-related such as with phenytoin, serum sickness).

– Chronic NK cell lymphocytosis (may be associated with anemia and neutropenia).

– Post-splenectomy (morphology tends to be large granular lymphocytes, typically persists for years).

– Miscellaneous (inflammatory bowel disease, vasculitis, thyrotoxicosis, Addison’s disease).

Malignant lymphocytosis

Chronic lymphocytic leukemia (CLL)

– The most common leukemia among adults in Western countries, absolute B cell count must be greater than 5,000 per uL, and typically has a phenotype that is positive for CD19, CD5, CD23, CD20 (dim), and either kappa or lambda (dim).

Prolymphocytic leukemia (PLL)

– May be B or T cell-derived. B-PLL may evolve from CLL or present de novo. T-PLL carries a particularly poor prognosis.

Monoclonal B cell lymphocytosis (MBL)

– A premalignant condition with a phenotype identical to CLL and similar chromosomal abnormalities but less than 5,000 B cells per uL. About 1% of patients per year develop progression to CLL that requires treatment.

Lymphoproliferative disease of large granular lymphocytes (LGL)

– Varied clinical behavior, usually indolent but can develop other cytopenias and systemic symptoms.

– Sezary syndrome, lymphocytes typically with “cerebriform” nuclei.

– Characteristic hair-like projections, positive for CD25, CD11c, CD103.

Non-Hodgkin lymphoma (NHL)with marrow involvement

– Leukemic phase seen more commonly in follicular, mantle-cell, marginal zone, and Burkitt lymphoma, but can occur with almost any NHL subtype.

When do you need to get more aggressive tests:

Any patient presenting with lymphoctyosis should have an aggressive work-up to rule out a malignant etiology. Patients who should generate particular concern include those with a markedly elevated lymphocyte count (for example, above 20,000 per uL), those with malignant-appearing lymphocytes, and/or persistent lymphocytosis of greater than 3 weeks.

If the initial work-up is unrevealing for a reactive cause, or if a malignant etiology is highly suspected, the following additional tests should be pursued:

Peripheral blood flow cytometry

Peripheral blood cytogenetics

– With interphase FISH for common cytogenetic abnormalities, including del 17p, del 11q, del 13q14, and trisomy 12 seen in CLL, and t[1114] seen in mantle cell NHL).

Immunoglobulin or T cell receptor gene rearrangement studies

Bone marrow biopsy and aspirate

Lymph node biopsy may also be indicated in select cases

What imaging studies (if any) will be helpful?

Imaging is rarely required in the evaluation and management of lymphocytosis. Exceptions include patients whose lymphocytosis is thought to be most likely due to non-Hodgkin lymphoma, patients with palpable lymphadenopathy, patients with CLL and unfavorable cytogenetic abnormalities such as del 17p or del 11q who may have bulky intra-abdominal lymphadenopathy not appreciated on physical exam, and patients with a suspicion of T-ALL, to rule out the presence of a mediastinal mass.

What therapies should you initiate immediately and under what circumstances – even if root cause is unidentified?

It is unusual for immediate therapy to be required, and time should be taken to establish a definitive diagnosis prior to initiating treatment. One exception is in patients with aggressive lymphomas with circulating disease, such as Burkitt lymphoma, who may undergo spontaneous tumor lysis syndrome. In patients with these metabolic derangements, aggressive electrolyte management, early administration of intravenous fluids, allopurinol, and, when required, rasburicase, are all important interventions to stabilize the patient while they are being worked up.

What other therapies are helpful for reducing complications?

What should you tell the patient and the family about prognosis?

The prognosis of patients with lymphocytosis depends on the etiology of the condition, and discussions about prognosis with the patient and family should be postponed until a definitive diagnosis is established.

“What if” scenarios.

If an identifiable cause of reactive lymphocytosis such as infectious mononucleosis is found, supportive care with observation is appropriate. However, should the lymphocytosis persist longterm (for example, greater than 2 months), a re-evaluation must be performed, with a low threshold for pursuing studies to rule out an underlying malignant lymphocytosis.

If lymphocytosis is found to be intermittent, it should not be ignored, and further evaluation may be necessary. For example, patients with early stage CLL or indolent NHL may have borderline elevations of lymphocyte counts that wax and wane, and although these patients may not require immediate treatment, monitoring and definitive diagnostic evaluation should be performed.

Pathophysiology

The pathophysiology of lymphoctyosis varies widely, and depends on the underlying etiology driving the condition, as described in more detail in the topics covering these conditions. In both reactive and malignant lymphocytosis, the mechanisms leading to an increased number of circulating lymphocytes may include increased lymphocyte production, release of already formed lymphocytes into the blood, or decreased clearance of lymphocytes by the reticulo-endothelial system.

What other clinical manifestations may help me to diagnose lymphocytosis

What other laboratory studies may be ordered?

What’s the evidence?

Deardon, C. “B- and T-cell prolymphocytic leukemias: antibody approaches”. Hematology Am Soc Hematol Educ Program. 2012. pp. 645-51. (Overview of PLL with focus on monoclonal antibody therapies.)

Paul, S, Kantarjian, H, Jabbour, EJ. “Adult Acute Lymphoblastic Leukemia”. Mayo Clin Proc. vol. 91. 2016. pp. 1645-1666. (Review of current pathologic and molecular classifications of ALL and broad discussion of treatment approaches using chemotherapy and targeted agents.)

Luzuriaga, K, Sullivan, JL. “Infectious mononucleosis”. N Engl J Med. vol. 362. 2010. pp. 1993-2000. (Practical guide to evaluation and management of infectious mononucleosis.)

Macintyre, EA, Linch, DC. “Lymphocytosis: is it leukaemia and when to treat”. Postgrad Med J. vol. 64. 1988. pp. 42-7.

Quantz, MC, Robinson, JB, Sachs, V. “Lymphocyte surface marker studies in the diagnosis of unexplained lymphocytosis”. CMAJ. vol. 136. 1987. pp. 835-8. (Report on using immunophenotyping to distinguish reactive from malignant lymphocytosis.)

Strati, P, Shanafelt, TD. “Monoclonal B cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification”. Blood. vol. 126. 2015. pp. 454-62. (Comprehensive overview of the biology and clinical management of MBL.)

Shiftan, TA, Mendelsohn, J. “The circulating "atypical" lymphocyte”. Hum Pathol. vol. 9. 1978. pp. 51-61. (Classic pathological characterization of atypical lymphocytes.)

Benschop, RJ, Rodriguez-Feuerhahn, M, Schedlowski, M. “Catecholamine-induced leukocytosis: early observations, current research, and future directions”. Brain Behav Immun. vol. 10. 1996. pp. 77-91. (Characterization of the lymphocytosis induced by acute stress.)

Scarfo, L, Ferreri, AJ, Ghia, P. “Chronic lymphocytic leukemia”. Critic Rev Oncol Hematol. vol. 104. 2016. pp. 169-82. (Helpful overview of CLL biology and treatment.)

Bailey, NG, Kojo, S, Elenitoba-Johnson, G. “Mature T cell leukemias: Molecular and clinical aspects”. Current Hematologic Malignancy Reports. vol. 19. 2015. pp. 421-448. (Thorough description of the biology of LGL and related disorders.)

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To Galen: the fluid transported by the lymph vessels is lymph, which is returned to the cardiovascular system. The small organs associated with lymph vessels are lymph nodes. Hope this helps, good luck. anon177755 May 19, 2011

I want to ask what is the relation between the lymph vessels and edema. Thanks a lot. anon152339 February 13, 2011

The lymphatic system is made up of lymph (a fluid that resembles plasma), lymphatics vessels, and lymphoid organs. Lymph can be thought of as "leftover" fluid in the tissues because it is derived from blood passing through the capillaries.

How is lymph produced you might ask? Blood flowing slowly through capillaries is under enormous hydrostatic pressure. This pressure causes much of the plasma to become forced, into the surrounding tisssues to supply them with oxygen and nutrients. Once the fluid has delivered its "cargo" to the surrounding tissues, it is forced back into the capillaries and the venous system via capillary osmotic pressure.

Of the approximately 24 L of fluid that leave the capillaries daily, pressure in the blood vessels can return only 20.4 L to the circulatory system. The 3.6 L of fluid remaining in the tissues is lymph.

Hi -- thanks for all this information. I just wanted to ask you a little more about the lymphatic system in general.

I have recently become very interested in lymph drainage after experiencing a serious lymph node swelling in my neck a few weeks ago. Thankfully it went down after treatment, but my doctors are still trying to figure out exactly what caused it, so I'm doing my own research while waiting for results.

Could you perhaps point me to some more information about the lymphatic system in general, especially things that can cause swollen lymph nodes? Thank you! EarlyForest January 12, 2011

Lymphatic drainage is one of those things that is kind of gross to think about, but much, much worse if you have to think about it because it stops functioning.

I'm not even talking about finding cancer in lymph nodes -- I'm talking about all the crazy swelling and pain that you can get if your lymph system gets out of whack.

The one that I think would be the worst is elephantiasis. Not only do you swell up like a balloon, but your skin gets thick and painful too.

So the next time you're stuck counting your blessings, give thanks for your well-functioning lymphatic collecting vessels! galen84basc January 11, 2011

Hi -- I am in desperate need of some biology homework help. this first year seminar is really embarrassingly difficult!

Can anybody help me out with a few questions? Here they are:

"The fluid transported by the lymphatic vessels is called. "

Is it just lymph? I have looked at a few different sites, and I can't find a common answer.

OK, next one: "Small organs associated with lymphatic vessels are termed. "


Abstract

Background: Lymph nodes (LNs) are positioned strategically throughout the body as critical mediators of lymph filtration and immune response. Lymph carries cytokines, antigens, and cells to the downstream LNs, and their effective delivery to the correct location within the LN directly impacts the quality and quantity of immune response. Despite the importance of this system, the flow patterns in LN have never been quantified, in part because experimental characterization is so difficult.

Methods and Results: To achieve a more quantitative knowledge of LN flow, a computational flow model has been developed based on the mouse popliteal LN, allowing for a parameter sensitivity analysis to identify the important system characteristics. This model suggests that about 90% of the lymph takes a peripheral path via the subcapsular and medullary sinuses, while fluid perfusing deeper into the paracortex is sequestered by parenchymal blood vessels. Fluid absorption by these blood vessels under baseline conditions was driven mainly by oncotic pressure differences between lymph and blood, although the magnitude of fluid transfer is highly dependent on blood vessel surface area. We also predict that the hydraulic conductivity of the medulla, a parameter that has never been experimentally measured, should be at least three orders of magnitude larger than that of the paracortex to ensure physiologic pressures across the node.

Conclusions: These results suggest that structural changes in the LN microenvironment, as well as changes in inflow/outflow conditions, dramatically alter the distribution of lymph, cytokines, antigens, and cells within the LN, with great potential for modulating immune response.


Physical Examination

All patients with LAP should undergo a complete and systematic physical examination. Any palpable lymph node should be evaluated for its location, size, consistency, fixation, and tenderness.

Determining whether LAP is localized or generalized makes the differential range narrower. An enlarged node in a lymphatic-rich region mostly presents a local disease. The presence of a red lymphangitic streaking (lymphangitis) may be detected in a localized infection. 33

Nodes that are associated with malignancy tend to involve several groups of nodes. 34

LAP in the supraclavicular area has the highest risk of malignancy this risk is 90% in patients more than 40 years old and 25% in those under 40 years old. 12 The Virchow node, in the left supraclavicular area, suggests intra-abdominal malignancies (e.g., gastric carcinoma), while in the right side suggests intra-thoracic malignancies.

It is suggested that palpable supraclavicular, iliac and popliteal nodes, epitrochlear greater than 0.5cm, and inguinal nodes larger than 1.5 cm are abnormal. 16 The nodes in other areas are considered as abnormal if their diameter exceeds one cm. 2 However, there is no uniform nodal size at which the greater diameter can raise suspicion of a neoplastic etiology.

Pain and tenderness on a lymph node is a non-specific finding. It is typically due to infection. In some cases, pain is induced by hemorrhage into the necrotic center of a neoplastic node, immunologic stimulation of pain receptors, or rapid tumor expansion. 12

Acute inflammation by infiltrating the node may make it more consistent, with concomitant tenderness due to the tension on the capsule. Chronic inflammation also leads to fibrotic changes, making the node hard in palpation. Stony-hard and painless nodes are usually signs of metastatic cancer or granulomatous disease. Firm and rubbery nodes can imply lymphoma. Matted lymph nodes are described when a group of nodes are conglomerated. They can be either due to benign (mycobacterial infection and sarcoidosis) or malignant (lymphoma and metastatic carcinoma) disorders. 1 , 16 , 35

LAPs resulting from infections and collagen vascular diseases are usually freely movable in the subcutaneous region. Rubbery mobile nodes are associated with lymphoma. Nodes that are associated with malignancy are often fixed to the skin or surrounding tissues. 36 , 37

Organomegaly (especially splenomegaly) is sometimes associated with LAP, as in infectious mononucleosis, acute lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, and sarcoidosis. 29

Skin should also be examined for unusual lesions suggesting malignancy such as melanoma, and for traumatic lesions that potentially can be an inoculation site for microbial germs.


Lymphatic System

The lymphatic system is a network of tissues, vessels and organs that work together to move a colorless, watery fluid called lymph back into your circulatory system (your bloodstream).

Some 20 liters of plasma flow through your body’s arteries and smaller arteriole blood vessels and capillaries every day. After delivering nutrients to the body’s cells and tissues and receiving their waste products, about 17 liters are returned to the circulation by way of veins. The remaining three liters seep through the capillaries and into your body’s tissues. The lymphatic system collects this excess fluid, now called lymph, from tissues in your body and moves it along until it ultimately returns it to your bloodstream.

Your lymphatic system actually has many functions. Its key functions include:

  • Maintains fluid levels in your body: As just described, the lymphatic system collects excess fluid that drains from cells and tissue throughout the body and returns it to the bloodstream, which is then recirculated through the body.
  • Absorbs fats from the digestive tract: Lymph includes fluids from the intestines that contain fats and proteins and transports it back to the bloodstream.
  • Protects your body against foreign invaders: The lymphatic system is part of the immune system. It produces and releases lymphocytes (white blood cells) and other immune cells that monitor and then destroy the foreign invaders — such as bacteria, viruses, parasites and fungi — that enter the body.
  • Transports and removes waste products and abnormal cells from the lymph.

What are the parts of the lymphatic system?

The lymphatic system consists of many parts. These include:

  • Lymph: Lymph, also called lymphatic fluid, is a collection of the extra fluid that drains from cells and tissues (that is not reabsorbed into the capillaries) plus other substances. The other substances include proteins, minerals, fats, nutrients, damaged cells, cancer cells and foreign invaders (bacteria, viruses, etc). Lymph also transports infection-fighting white blood cells (lymphocytes).
  • Lymph nodes: Lymph nodes are bean-shaped glands that monitor and cleanse the lymph as it filters through them. The nodes filter out the damaged cells and cancer cells. These lymph nodes also produce and store lymphocytes and other immune system cells that attack and destroy bacteria and other harmful substances in the fluid. You have about 600 lymph nodes scattered throughout your body. Some exist as a single node others are closely connected groups called chains. A few of the more familiar locations of lymph nodes are in your armpit, groin and neck. Lymph nodes are connected to others by the lymphatic vessels.·
  • Lymphatic vessels: Lymphatic vessels are the network of capillaries (microvessels) and large network of tubes located throughout the body that transport lymph away from tissues. Lymphatic vessels collect and filter lymph (at the nodes) as it continues to move toward larger vessels called collecting ducts. These vessels operate very much like your veins do: they work under very low pressure, have a series of valves in them to keep the fluid moving in one direction.
  • Collecting ducts: Lymphatic vessels empty the lymph into the right lymphatic duct and left lymphatic duct (also called the thoracic duct). These ducts connect to the subclavian vein, which returns lymph to your bloodstream. The subclavian vein runs below your collarbone. Returning lymph to the bloodstream helps to maintain normal blood volume and pressure. It also prevents the excess buildup of fluid around the tissues (called edema).

The lymphatic system collects excess fluid that drains from cells and tissue throughout the body and returns it to the bloodstream, which is then recirculated through the body.

  • Spleen: This largest lymphatic organ is located on your left side under your ribs and above your stomach. The spleen filters and stores blood and produces white blood cells that fight infection or disease.
  • Thymus: This organ is located in the upper chest beneath the breast bone. It matures a specific type of white blood cell that fights off foreign organisms.
  • Tonsils and adenoid: These lymphoid organs trap pathogens from the food you eat and air you breathe. They are your body’s first line of defense against foreign invaders.
  • Bone marrow: This is the soft, spongy tissue in the center of certain bones, such as the hip bone and breastbone. White blood cells, red blood cells, and platelets are made in the bone marrow.
  • Peyer’s patches: These are small masses of lymphatic tissue in the mucous membrane that lines your small intestine. These lymphoid cells monitor and destroy bacteria in the intestines.
  • Appendix: Your appendix contains lymphoid tissue that can destroy bacteria before it breaches the intestine wall during absorption. Scientists also believe the appendix plays a role in housing “good bacteria” and repopulating our gut with good bacteria after an infection has cleared.

What conditions affect the lymphatic system?

Many conditions can affect the vessels, glands, and organs that make up the lymphatic system.

Some happen during development before birth or during childhood. Others develop as a result of disease or injury. Some common and less common diseases and disorders of the lymphatic system include:

  • Enlarged (swollen) lymph nodes (lymphadenopathy): Enlarged lymph nodes are caused by infection, inflammation or cancer. Common infections that can cause enlarged lymph nodes include strep throat, mononucleosis, HIV infection and infected skin wounds. Lymphadenitis refers to lymphadenopathy that is caused from an infection or inflammatory condition.
  • Swelling or accumulation of fluid (lymphedema): Lymphedema can result from a blockage in the lymphatic system caused by scar tissue from damaged lymph vessels or nodes. Lymphedema is also often seen when lymph nodes are removed in persons who have had surgery and/or radiation to remove a cancer. The buildup of lymphatic fluid is most commonly seen in the arms and legs. Lymphedema can be very mild or be quite painful, disfiguring and disabling. People with lymphedema are at risk for serious and potentially life-threatening deep skin infections.
  • Cancers of the lymphatic system: Lymphoma is cancer of the lymph nodes and occurs when lymphocytes grow and multiply uncontrollably. There are several different types of lymphoma, including Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Cancerous tumors can also block lymphatic ducts or be near lymph nodes and interfere with the flow of lymph through the node.
  • Lymphangitis: This is an inflammation of the lymph vessels.
  • Lymphangioma: This is a condition that you are born with. It’s a malformation in the lymphatic system. Lymphangiomatosis is the presence of multiple or widespread lymphatic vascular malformations.
  • Intestinal lymphangiectasia: This is a condition in which loss of lymph tissue in the small intestine leads to loss of protein, gammaglobulins, albumin and lymphocytes. This is a condition in which there is a higher-than-normal amount of lymphocytes in the body.
  • Lymphatic filariasis: This is an infection caused by a parasite that causes the lymphatic system not to function correctly. Castleman disease involves an overgrowth of cells in the body’s lymphatic system. This is a rare lung disease in which abnormal muscle-like cells begin to grow out of control in the lungs, lymph nodes and kidneys.
  • Autoimmune lymphoproliferative syndrome: This is a rare genetic disorder in which there is a high number of lymphocytes in the lymph nodes, liver and spleen. This is an inflammation of the lymph nodes in the abdomen. This is an inflammation and infection of the tonsils.

How can I keep my lymphatic system healthy?

To keep your lymphatic system strong and healthy, you should:

  • Avoid exposure to toxic chemicals like those in pesticides or cleaning products. These chemicals can build up in your system and make it harder for your body to filter waste.
  • Drink plenty of water to stay hydrated so lymph can easily move throughout the body.
  • Maintain a healthy lifestyle that includes regular exercise and a healthy diet.

When should I call my doctor about an issue with my lymphatic system?

Call your doctor if you experience fatigue (extreme tiredness) or have unexplained swelling that lasts more than a few weeks or interferes with your daily activities.

How will my doctor test my lymphatic system?

To see if your lymphatic system is working as it should, your doctor may use imaging tests such as a CT scan or MRI. These tests allow your doctor to see blockages in your lymphatic system.

Last reviewed by a Cleveland Clinic medical professional on 02/23/2020.

References

  • Merck Manual. Overview of the Lymphatic System. Accessed 2/10/2020.
  • Canadian Cancer Society. The lymphatic system. Accessed 2/10/2020.
  • National Cancer Institute. Lymphedema – Patient Version. Accessed 2/10/2020.
  • Lymphatic Education & Research network. Facts about the Lymphatic System. Accessed 2/10/2020.

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Contents

The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. [2] Lymphocytes can be identified by their large nucleus.

T cells and B cells Edit

T cells (thymus cells) and B cells (bone marrow- or bursa-derived cells [a] ) are the major cellular components of the adaptive immune response. T cells are involved in cell-mediated immunity, whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize specific "non-self" antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored maximally to eliminate specific pathogens or pathogen-infected cells. B cells respond to pathogens by producing large quantities of antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called T helper cells, produce cytokines that direct the immune response, while other T cells, called cytotoxic T cells, produce toxic granules that contain powerful enzymes which induce the death of pathogen-infected cells. Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form of memory cells. Throughout the lifetime of an animal, these memory cells will "remember" each specific pathogen encountered, and are able to mount a strong and rapid response if the same pathogen is detected again this is known as acquired immunity.

Natural killer cells Edit

NK cells are a part of the innate immune system and play a major role in defending the host from tumors and virally infected cells. [2] NK cells modulate the functions of other cells, including macrophages and T cells, [2] and distinguish infected cells and tumors from normal and uninfected cells by recognizing changes of a surface molecule called MHC (major histocompatibility complex) class I. NK cells are activated in response to a family of cytokines called interferons. Activated NK cells release cytotoxic (cell-killing) granules which then destroy the altered cells. [1] They are named "natural killer cells" because they do not require prior activation in order to kill cells which are missing MHC class I.

Dual expresser lymphocyte - X cell Edit

The X lymphocyte is a reported cell type expressing both a B-cell receptor and T-cell receptor and is hypothesized to be implicated in type 1 diabetes. [6] [7] Its existence as a cell type has been challenged by two studies. [8] [9] However, the authors of original article pointed to the fact that the two studies have detected X cells by imaging microscopy and FACS as described. [10] Additional studies are obviously required to determine the nature and properties of X cells (also called dual expressers).

  1. ^ abJaneway C, Travers P, Walport M, Shlomchik M (2001). Immunobiology (5th ed.). New York and London: Garland Science. ISBN0-8153-4101-6 .
  2. ^ abcde
  3. Omman, Reeba A. Kini, Ameet R. (2020). "Leukocyte development, kinetics, and functions". In Keohane, Elaine M. Otto, Catherine N. Walenga, Jeanine N. (eds.). Rodak's Hematology: Clinical Principles and Applications (6th ed.). St. Louis, Missouri: Elsevier. pp. 117–135. ISBN978-0-323-53045-3 .
  4. ^
  5. Cohn, Lauren Hawrylowicz, Catherine Ray, Anuradha (2014). "Biology of Lymphocytes". Middleton's Allergy: Principles and Practice (8th ed.). Philadelphia: Saunders. pp. 203–214. doi:10.1016/B978-0-323-08593-9.00013-9. ISBN9780323085939 . Retrieved 22 July 2020 .
  6. ^
  7. "NCI Dictionary of Cancer Terms". National Cancer Institute . Retrieved 22 July 2020 . A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. A lymphocyte is a type of white blood cell.
  8. ^
  9. "B Cell". Merriam-Webster Dictionary. Encyclopaedia Britannica . Retrieved 28 October 2011 .
  10. ^
  11. Ahmed, Rizwan Omidian, Zahra Giwa, Adebola Cornwell, Benjamin Majety, Neha Bell, David R. Lee, Sangyun Zhang, Hao Michels, Aaron Desiderio, Stephen Sadegh-Nasseri, Scheherazade (30 May 2019). "A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen". Cell. 177 (6): 1583–1599.e16. doi: 10.1016/j.cell.2019.05.007 . ISSN0092-8674. PMC7962621 . PMID31150624.
  12. ^
  13. "Newly Discovered Immune Cell Linked to Type 1 Diabetes". Johns Hopkins Medicine Newsroom. 30 May 2019 . Retrieved 9 August 2020 .
  14. ^
  15. Japp, Alberto (4 February 2021). "TCR+/BCR+ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes". Cell. 184 (3): 827–839. doi: 10.1016/j.cell.2020.11.035 . PMC 8016147. PMID33545036. S2CID231809927 . Retrieved 4 February 2021 .
  16. ^
  17. Burel, Julie (13 May 2020). "The Challenge of Distinguishing Cell–Cell Complexes from Singlet Cells in Non-Imaging Flow Cytometry and Single-Cell Sorting". Cytometry Part A. 97 (11): 1127–1135. doi: 10.1002/cyto.a.24027 . PMC7666012 . PMID32400942.
  18. ^
  19. Ahmed, Rizwan Omidian, Zahra Giwa, Adebola Donner, Thomas Jie, Chunfa Hamad, Abdel Rahim A. (4 February 2021). "A reply to "TCR+/BCR+ dual-expressing cells and their associated public BCR clonotype are not enriched in type 1 diabetes " ". Cell. 184 (3): 840–843. doi:10.1016/j.cell.2020.11.036. ISSN1097-4172. PMC7935028 . PMID33545037.

Mammalian stem cells differentiate into several kinds of blood cell within the bone marrow. [1] This process is called haematopoiesis. All lymphocytes originate, during this process, from a common lymphoid progenitor before differentiating into their distinct lymphocyte types. The differentiation of lymphocytes follows various pathways in a hierarchical fashion as well as in a more plastic fashion. The formation of lymphocytes is known as lymphopoiesis. In mammals, B cells mature in the bone marrow, which is at the core of most bones. [2] In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, [2] (B for bursa) and not from bone marrow as commonly believed. T cells migrate to and mature in a distinct organ, called the thymus. Following maturation, the lymphocytes enter the circulation and peripheral lymphoid organs (e.g. the spleen and lymph nodes) where they survey for invading pathogens and/or tumor cells.

The lymphocytes involved in adaptive immunity (i.e. B and T cells) differentiate further after exposure to an antigen they form effector and memory lymphocytes. Effector lymphocytes function to eliminate the antigen, either by releasing antibodies (in the case of B cells), cytotoxic granules (cytotoxic T cells) or by signaling to other cells of the immune system (helper T cells). Memory T cells remain in the peripheral tissues and circulation for an extended time ready to respond to the same antigen upon future exposure they live weeks to several years, which is very long compared to other leukocytes. [ citation needed ]

Microscopically, in a Wright's stained peripheral blood smear, a normal lymphocyte has a large, dark-staining nucleus with little to no eosinophilic cytoplasm. In normal situations, the coarse, dense nucleus of a lymphocyte is approximately the size of a red blood cell (about 7 μm in diameter). [1] Some lymphocytes show a clear perinuclear zone (or halo) around the nucleus or could exhibit a small clear zone to one side of the nucleus. Polyribosomes are a prominent feature in the lymphocytes and can be viewed with an electron microscope. The ribosomes are involved in protein synthesis, allowing the generation of large quantities of cytokines and immunoglobulins by these cells.

It is impossible to distinguish between T cells and B cells in a peripheral blood smear. [1] Normally, flow cytometry testing is used for specific lymphocyte population counts. This can be used to determine the percentage of lymphocytes that contain a particular combination of specific cell surface proteins, such as immunoglobulins or cluster of differentiation (CD) markers or that produce particular proteins (for example, cytokines using intracellular cytokine staining (ICCS)). In order to study the function of a lymphocyte by virtue of the proteins it generates, other scientific techniques like the ELISPOT or secretion assay techniques can be used. [3]

Typical recognition markers for lymphocytes [4]
Class Function Proportion (median, 95% CI) Phenotypic marker(s)
Natural killer cells Lysis of virally infected cells and tumour cells 7% (2–13%) CD16 CD56 but not CD3
T helper cells Release cytokines and growth factors that regulate other immune cells 46% (28–59%) TCRαβ, CD3 and CD4
Cytotoxic T cells Lysis of virally infected cells, tumour cells and allografts 19% (13–32%) TCRαβ, CD3 and CD8
Gamma delta T cells Immunoregulation and cytotoxicity 5% (2–8%) TCRγδ and CD3
B cells Secretion of antibodies 23% (18–47%) MHC class II, CD19 and CD20

In the circulatory system, they move from lymph node to lymph node. [5] [6] This contrasts with macrophages, which are rather stationary in the nodes.

A lymphocyte count is usually part of a peripheral complete blood cell count and is expressed as the percentage of lymphocytes to the total number of white blood cells counted.

A general increase in the number of lymphocytes is known as lymphocytosis, [7] whereas a decrease is known as lymphocytopenia.

High Edit

An increase in lymphocyte concentration is usually a sign of a viral infection (in some rare case, leukemias are found through an abnormally raised lymphocyte count in an otherwise normal person). [7] [8] A high lymphocyte count with a low neutrophil count might be caused by lymphoma. Pertussis toxin (PTx) of Bordetella pertussis, formerly known as lymphocytosis-promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes, which can lead to a condition known as lymphocytosis, with a complete lymphocyte count of over 4000 per μl in adults or over 8000 per μl in children. This is unique in that many bacterial infections illustrate neutrophil-predominance instead.

Low Edit

A low normal to low absolute lymphocyte concentration is associated with increased rates of infection after surgery or trauma. [9]

One basis for low T cell lymphocytes occurs when the human immunodeficiency virus (HIV) infects and destroys T cells (specifically, the CD4 + subgroup of T lymphocytes, which become helper T cells). [10] Without the key defense that these T cells provide, the body becomes susceptible to opportunistic infections that otherwise would not affect healthy people. The extent of HIV progression is typically determined by measuring the percentage of CD4 + T cells in the patient's blood – HIV ultimately progresses to acquired immune deficiency syndrome (AIDS). The effects of other viruses or lymphocyte disorders can also often be estimated by counting the numbers of lymphocytes present in the blood.

Tumor-infiltrating lymphocytes Edit

In some cancers, such as melanoma and colorectal cancer, lymphocytes can migrate into and attack the tumor. This can sometimes lead to regression of the primary tumor.


PRODUCTION OF SHEEP ERYTHROCYTE ROSETTE FORMING CELLS BY LYMPHOCYTES CULTURED WITH LEUCOCYTE DIALYSATES

Robert S. Holzman , . H.S. Lawrence , in Transfer Factor , 1976

METHODS

Human peripheral blood was obtained by venipuncture and diluted 1:10 with a solution of preservative free heparin (2 mg/ml, Schwartz-Mann). Mononuclear cells were purified from the buffycoat by Ficoll-Hypaque centrifugation. They were washed and resuspended to a concentration of 4 × 10 6 lymphocytes/ml in MEMS supplemented with 50% autologous plasma, penicillin, streptomycin and glutamine. One-half ml aliquots of this cell suspension were dispensed to culture tubes and varying amounts, usually 1.0 ml, of leucocyte dialysate were added. The dialysate was prepared by the method described by Ascher et al. ( 7 ). The total culture volume was made up to 1.5 ml with additional MEMS. Each tube, therefore, initially contained 2 × 10 6 lymphocytes and dialysate obtained from 6 × 10 6 donor lymphocytes. Control cultures contained no dialysate. After a variable period of cell culture, aliquots were taken for duplicate determination of total cells present, percent cells viable by Trypan Blue testing and percent sheep erythrocyte rosette forming cells (ERFC). In some cases cells were incubated with trypsin 0.125 mg% prior to culture.

Percent ERFC were measured by washing the lymphocytes free of autologous plasma and resuspending them to 4 × 10 6 /ml in MEMS. An equal volume of 0.5% washed sheep erythrocytes was added and the mixture incubated for 7 minutes at 37°C. The cells were centrifuged at 150g for 5 minutes at room temperature and incubated overnight at 4°C. They were gently resuspended and examined by phase contrast microscopy. Two hundred lymphocytes were counted and all lymphocytes binding 3 or more erythrocytes were considered to be rosettes ( 8 ). Results were expressed both as percent rosette forming cells and as the total number of rosette forming cells present in each tube after varying periods. All experiments were done in duplicate or triplicate and replicated at least three times.