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an agranulocytic leukocyte that normally makes up a quarter of the white blood cell count but increases in the presence of infection (同)lymph cell

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/20 12:22:22」(JST)

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A lymphocyte is any of 3 types of white blood cell in a vertebrate's immune system. All 3 are agranulocytes. They include natural killer cells (NK cells) (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name lymphocyte.

Types

A stained lymphocyte surrounded by red blood cells viewed using a light microscope.

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

T cells and B cells

T cells (thymus cells) and B cells (bursa-derived cells^[1]) 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 to maximally 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 pathogen is detected again. The T Helper Cell is a sub-type of the T cell that is able to activate all these lymphocytes.

Natural killer cells

NK cells are a part of the innate immune system and play a major role in defending the host from both tumors and virally infected cells. NK cells 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.^[2] They were named "natural killer cells" because of the initial notion that they do not require prior activation in order to kill cells which are missing MHC class I.

Development

Development of blood cells

Mammalian stem cells differentiate into several kinds of blood cell within the bone marrow.^[3] 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. B cells mature into B lymphocytes in the bursa equivalent, which in humans is the GALT, which is thought to be located in the Peyer's patches of the intestine, ^[4] while 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 to a whole lifetime, which is very long compared to other leukocytes.^{[citation needed]}

Characteristics

A scanning electron microscope image of normal circulating human blood showing red blood cells, several types of white blood cells including lymphocytes, a monocyte, a neutrophil and many small disc-shaped platelets.

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 micrometres in diameter).^[3] 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.^[3] Normally, flow cytometry testing is used for specific lymphocyte population counts. This can be used to specifically 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.^[2]

**Typical recognition markers for lymphocytes**^[5]
CLASS	FUNCTION	PROPORTION	PHENOTYPIC MARKER(S)
NK cells	Lysis of virally infected cells and tumour cells	7% (2-13%)	CD16 CD56 but not CD3
Helper T 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
γδ T cells	Immunoregulation and cytotoxicity	5% (2%-8%)	TCRγδ and CD3
B cells	Secretion of antibodies	23% (18-47%)	MHC class II, CD19 and CD21

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

Lymphocytes and disease

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 whereas a decrease is lymphocytopenia.

High

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). A high lymphocyte count with a low neutrophil count might be caused by lymphoma.

Low

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

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). 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. 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

In some cancers, e.g., melanoma^[6] and colorectal cancer, lymphocytes can migrate into and attack the tumor. This can sometimes lead to regression of the primary tumor.^[7]

Blood content

Reference ranges for blood tests of white blood cells, comparing lymphocyte amount (shown in light blue) with other cells.

References

^ The process of B-cell maturation was elucidated in birds and the B most likely means "bursa-derived" referring to the bursa of Fabricius. "B Cell". Merriam-Webster Dictionary. Encyclopædia Britannica. Retrieved 28 October 2011. However, in humans (who do not have that organ), the bone marrow makes B cells, and the B can serve as a reminder of bone marrow.
^ ^a ^b Janeway, Charles; Paul Travers, Mark Walport, and Mark Shlomchik (2001). Immunobiology; Fifth Edition. New York and London: Garland Science. ISBN 0-8153-4101-6. Cite uses deprecated parameters (help).
^ ^a ^b ^c Abbas AK and Lichtman AH (2003). Cellular and Molecular Immunology (5th ed.). Saunders, Philadelphia. ISBN 0-7216-0008-5.
^ Kumar, Abbas, Fausto. Pathologic Basis of Disease (7th ed.).
^ Berrington, J. E.; Barge, D; Fenton, AC; Cant, AJ; Spickett, GP (May 2005). "Lymphocyte subsets in term and significantly preterm UK infants in the first year of life analysed by single platform flow cytometry". Clin Exp Immunol 140 (2): 289–292. doi:10.1111/j.1365-2249.2005.02767.x. PMC 1809375. PMID 15807853.
^ http://professional.cancerconsultants.com/ccj.aspx?id=36989 Current Topics in Oncology
^ http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=34439 Protective effect of a brisk tumor infiltrating lymphocyte infiltrate in melanoma: An EORTC melanoma group study. 2007

External links

Wikimedia Commons has media related to Lymphocytes.

Histology image: 01701ooa - Histology Learning System at Boston University
Cell Centered Database – Cytotoxic T Lymphocyte
"Overcoming the Rejection Factor: MUSC's First Organ Transplant" A Waring Historical Library online exhibit

UpToDate Contents

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1. リンパ球増加症またはリンパ球減少症を有する患者へのアプローチ approach to the patient with lymphocytosis or lymphocytopenia
2. BおよびTリンパ球の正常な発生 normal b and t lymphocyte development
3. 大顆粒T細胞リンパ球性白血病の臨床症状、病理学的特徴、および診断 clinical manifestations pathologic features and diagnosis of t cell large granular lymphocyte leukemia
4. 古典型ホジキンリンパ腫の疫学、病理学的特徴、および診断 epidemiology pathologic features and diagnosis of classical hodgkin lymphoma
5. ナチュラルキラー（NK）細胞大顆粒リンパ球性白血病 natural killer nk cell large granular lymphocyte leukemia

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Tonsillectomy as a treatment for psoriasis: a review.

Wu W1, Debbaneh M, Moslehi H, Koo J, Liao W.
The Journal of dermatological treatment.J Dermatolog Treat.2014 Dec;25(6):482-6. doi: 10.3109/09546634.2013.848258. Epub 2013 Nov 27.
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Passos CP1, Cepeda MR2, Ferreira SS2, Nunes FM3, Evtuguin DV4, Madureira P5, Vilanova M5, Coimbra MA2.
Food chemistry.Food Chem.2014 Oct 15;161:60-6. doi: 10.1016/j.foodchem.2014.03.119. Epub 2014 Apr 2.
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★リンクテーブル★

リンク元	「100Cases 33」
拡張検索	「cytotoxic T lymphocytes」
関連記事	「lymphocyte」

「100Cases 33」

Lymphocyte
	A scanning electron microscope (SEM) image of a single human lymphocyte.
Latin	lymphocytus
Code	TH H2.00.04.1.02002

　　[★]

☆case33　頭痛と混乱

■glossary

accompany

vt.

(人)と同行する、(人)に随行する。(もの)に付随する。～と同時に起こる。～に加える(添える、同封する)(with)

slurred n. 不明瞭

強直間代痙攣 tonic-clonic convulsion

　意識消失とともに全身の随意筋に強直痙攣が生じ(強直痙攣期tonic convulsion)、次いで全身の筋の強直と弛緩とが律動的に繰り返される時期(間代痙攣期clonic convulsion)を経て、発作後もうろう状態を呈する一連の発作。

■症例

28歳、女性　黒人　南アフリカ　手術室看護師　ロンドン住在

主訴：頭痛と混乱

現病歴：過去3週間で頭痛が続いており、ひどくなってきた。現在も頭痛が持続しており、頭全体が痛い。友人曰く「過去六ヶ月で体重が10kg減っていて、最近、混乱してきたようだ」。発話は不明瞭。救急室にいる間に強直間代痙攣を起こした。

・診察 examination

やせている。55kg。38.5℃。口腔カンジダ症(oral candidiasis)。リンパ節腫脹無し。心血管、呼吸器系、消化器系正常。痙攣前における神経検査では時間、場所、人の見当識無し。神経局所症状無し(no focal neurological sign)。眼底両側に乳頭浮腫有り。

・検査 investigation

血算：白血球増多

血液生化学：ナトリウム低下

CT：供覧

■キーワード＆着目するポイント

・口腔カンジダ症(oral candidiasis)

・頭痛、精神症状、強直間代痙攣

・眼底両側に乳頭浮腫

・CT 所見

・低ナトリウム血症は二次的なもの

■アプローチ

・口腔カンジダ症(oral candidiasis)　→　細胞免疫低下状態(DM、免疫抑制、AIDSなど) or 常在細菌叢の攪乱(長期の抗菌薬の使用)

　・The occurrence of thrush in a young, otherwise healthy-appearing person should prompt an investigation for underlying HIV infection.(HIM.1254)

　・More commonly, thrush is seen as a nonspecific manifestation of severe debilitating illness.(HIM.1254)

・精神症状、強直間代痙攣　→　一次的、あるいは二次的な脳の疾患がありそう

・頭痛　→　漠然としていて絞れないが、他の症状からして機能性頭痛ではなく症候性頭痛っぽい。

・眼底両側に乳頭浮腫　→　脳圧亢進の徴候　→　原因は・・・脳腫瘍、ことにテント下腫瘍と側頭葉の腫瘍、クモ膜下出血、脳水腫など、そのほか、眼窩内病変、低眼圧などの局所的要因、悪性高血圧、血液疾患、大量出血、肺気腫などの全身的要因 (vindicate本のp342も参考になる)

　・頭痛と脳圧亢進　→　頭蓋内圧占拠性病変、脳炎(IMD.274)

・CT 所見　→　ringformの病変、脳浮腫、脳圧亢進

・低ナトリウム血症　→　脳ヘルニアに続発して起こることがあるらしい。実際には下垂体にトキソプラズマによる病変が形成されることにより起こりうる。

・そのほか出身地、体重減少もHIVを疑わせる点

パターン認識でHIV + 精神症状 + てんかん発作(強直間代痙攣) + 脳圧亢進 + CT 所見 = 一番ありそうなのはToxoplasma gondiiによるトキソプラズマ脳症 cerebral toxoplasosis (トキソプラズマ脳炎 toxoplasmic encephalitis)

■Toxoplasma gondii

　原虫　胞子原虫類

(感染予防学 080521のプリント、CASES p,92、HIM p.1305-)

・疫学：西洋では30-80%の成人がトキソプラズマの感染の既往がある・・・うぇ(CASES)。日本では10%前後(Wikipedia)。

・生活環

　・終宿主：ネコ：ネコの小腸上皮細胞で有性・無性生殖　糞便にオーシストの排泄

　・中間宿主：ヒト.ブタを含むほ乳類と鳥類：無性生殖で増殖、シストの形成

　　　急性期の増殖盛んな急増虫体 tachyzoiteとシスト内の緩増虫体 bradyzoite

・病原、病因 phathogenesis

　・緩増虫体(bradyzoite)、接合子嚢(oocyst)

・感染経路

　1. オーシストの経口摂取

　2. 中間宿主の生肉中のシストの経口摂取

　3. 初感染妊婦からの経胎盤感染。既感染なら胎盤感染しないらしい(HIM.1306)

　(4)移植臓器、輸血。確率は低い(at low rate)(HIM.1306)

・病態

　1. 先天性トキソプラズマ症　congenital toxoplasmosis

　　　①網脈絡膜炎、 ②水頭症、 ③脳内石灰化、 ④精神・運動障害

　2. 後天性トキソプラズマ症　acquired toxoplasmosis

　　(1) 健常者

　　　・多くは不顕性感染。発熱、リンパ節腫脹、皮疹(rash)

　　　・(少数例)筋肉痛、暈疼痛、腹痛、斑状丘疹状皮疹(maculopapular rash)、脳脊髄炎、混乱(HIM.1308)

　　　・(まれ)肺炎、心筋炎、脳症、心膜炎、多発筋炎

　　　・網膜、脈絡叢に瘢痕や、脳に小さい炎症性の病変を残すことあり(CASES)。

　　　・急性感染の症状は数週間で消失　筋肉や中枢神経系に緩増虫体が残存

　　(2)HIV 感染者、臓器移植例、がん化学療法例

　　　シスト内緩増虫体→急増虫体→播種性の多臓器感染

　　　AIDSでは、トキソプラズマ性脳炎が指標疾患 AIDS-defineing illness(CASES)

・治療

　(日本)アセチルスピラマイシン、ファンシダール(感染予防学 080521)

■トキソプラズマ脳炎 toxoplasmic encephalitis、トキソプラズマ脳症 cerebral toxoplasosis

・症状

　発熱、頭痛、混乱ｍ、痙攣、認知の障害、局所神経徴候(不全片麻痺、歯垢、脳神経損傷、視野欠損、感覚喪失)(CASES)

・画像検査

　(CT,MRI)多発性、両側性、ring-enhancing lesion、特に灰白質-白質境界、大脳基底核、脳幹、小脳が冒されやすい(CASES)

・鑑別診断(臨床症状・画像診断の所見で)

　リンパ腫、結核、転移性脳腫瘍(CASES)

・病歴と画像所見からの鑑別診断

　リンパ腫、結核、転移性腫瘍

？

このCTがcerebral toxoplasmosisに特徴的かは不明

□最後に残る疑問

　AIDSでWBC(leukocyte)の数はどうなるんだろう？？？AIDSの初診患者ではWBCが低い人が多いらしいし()、HIVはCD4+ T cellとmacrophageに感染して殺すから、これによってB cellは減るだろうし、CD8+ T cellも若干減少するだろうからWBCは減るんじゃないか？！好中球はAIDSとは関係ない？好中球は他の感染症に反応性に増加している？ちなみに、好酸球は寄生虫(原虫)の感染のために増える傾向にあるらしい(HIMのどこか)。

葉酸拮抗剤である。

サルファ剤と併用され、抗トキソプラズマ薬、抗ニューモシチス・カリニ薬として相乗的に働く。

ST 合剤

SMX-TMP

スルファメトキサゾール・トリメトプリム合剤 sulfamethoxazole and trimethoprim mixture

□AIDSの定義(http://en.wikipedia.org/wiki/CDC_Classification_System_for_HIV_Infection_in_Adults_and_Adolescents)