WordNet

a large phagocyte; some are fixed and other circulate in the blood stream

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/10 21:25:50」(JST)

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For the ecological classification, see Macrophage (ecology).

Macrophages (Greek: big eaters, from makros "large" + phagein "eat"; abbr. MΦ) are cells produced by the differentiation of monocytes in tissues. Macrophages were discovered by Ilya Mechnikov, a Russian bacteriologist, in 1884.^[1] Human macrophages are about 21 micrometres (0.00083 in) in diameter.^[2] Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals. Their role is to phagocytose, or engulf and then digest, cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens. They are specialized phagocytic cells that attack foreign substances, infectious microbes and cancer cells through destruction and ingestion. Macrophages can be identified by specific expression of a number of proteins including CD14, CD40, CD11b, CD64, F4/80 (mice)/EMR1 (human), lysozyme M, MAC-1/MAC-3 and CD68 by flow cytometry or immunohistochemical staining.^[3] They move by action of amoeboid movement.

1 Life cycle
2 Function
- 2.1 Phagocytosis
- 2.2 Role in adaptive immunity
- 2.3 Role in muscle regeneration
3 Tissue macrophages
4 Disease
- 4.1 As a host for intracellular pathogens
  - 4.1.1 Tuberculosis
  - 4.1.2 Leishmaniasis
  - 4.1.3 Chikungunya
- 4.2 Heart disease
- 4.3 HIV infection
- 4.4 Cancer
5 Media
6 References
7 External links

Life cycle

When a monocyte enters damaged tissue through the endothelium of a blood vessel, a process known as the leukocyte extravasation, it undergoes a series of changes to become a macrophage. Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens and cytokines released by macrophages already at the site. At some sites such as the testis, macrophages have been shown to populate the organ through proliferation. Unlike short-lived neutrophils, macrophages survive longer in the body up to a maximum of several months.

Function

Steps of a macrophage ingesting a pathogen:
a. Ingestion through phagocytosis, a phagosome is formed
b. The fusion of lysosomes with the phagosome creates a phagolysosome; the pathogen is broken down by enzymes
c. Waste material is expelled or assimilated (the latter not pictured)
Parts:
1. Pathogens
2. Phagosome
3. Lysosomes
4. Waste material
5. Cytoplasm

6. Cell membrane

Phagocytosis

Main article: Phagocytosis

One important role of the macrophage is the removal of necrotic cellular debris in the lungs. Removing dead cell material is important in chronic inflammation, as the early stages of inflammation are dominated by neutrophil granulocytes, which are ingested by macrophages if they come of age (see CD-31 for a description of this process).

The removal of necrotic tissue is, to a greater extent, handled by fixed macrophages, which will stay at strategic locations such as the lungs, liver, neural tissue, bone, spleen and connective tissue, ingesting foreign materials such as pathogens and recruiting additional macrophages if needed.

When a macrophage ingests a pathogen, the pathogen becomes trapped in a phagosome, which then fuses with a lysosome. Within the phagolysosome, enzymes and toxic peroxides digest the pathogen. However, some bacteria, such as Mycobacterium tuberculosis, have become resistant to these methods of digestion. Macrophages can digest more than 100 bacteria before they finally die due to their own digestive compounds.

Role in adaptive immunity

Macrophages are versatile cells that play many roles. As scavengers, they rid the body of worn-out cells and other debris. Along with dendritic cells, they are foremost among the cells that "present" antigen, a crucial role in initiating an immune response. As secretory cells, monocytes and macrophages are vital to the regulation of immune responses and the development of inflammation; they produce a wide array of powerful chemical substances (monokines) including enzymes, complement proteins, and regulatory factors such as interleukin-1. At the same time, they carry receptors for lymphokines that allow them to be "activated" into single-minded pursuit of microbes and tumour cells.

After digesting a pathogen, a macrophage will present the antigen (a molecule, most often a protein found on the surface of the pathogen, used by the immune system for identification) of the pathogen to the corresponding helper T cell. The presentation is done by integrating it into the cell membrane and displaying it attached to an MHC class II molecule, indicating to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface.

Eventually, the antigen presentation results in the production of antibodies that attach to the antigens of pathogens, making them easier for macrophages to adhere to with their cell membrane and phagocytose. In some cases, pathogens are very resistant to adhesion by the macrophages.

The antigen presentation on the surface of infected macrophages (in the context of MHC class II) in a lymph node stimulates TH1 (type 1 helper T cells) to proliferate (mainly due to IL-12 secretion from the macrophage). When a B-cell in the lymph node recognizes the same unprocessed surface antigen on the bacterium with its surface bound antibody, the antigen is endocytosed and processed. The processed antigen is then presented in MHCII on the surface of the B-cell. T cells that express the T cell receptor which recognizes the antigen-MHCII complex (with co-stimulatory factors- CD40 and CD40L) cause the B-cell to produce antibodies that help opsonisation of the antigen so that the bacteria can be better cleared by phagocytes.

Macrophages provide yet another line of defense against tumor cells and somatic cells infected with fungus or parasites. Once a T cell has recognized its particular antigen on the surface of an aberrant cell, the T cell becomes an activated effector cell, producing chemical mediators known as lymphokines that stimulate macrophages into a more aggressive form.

Currently, it is a major opinion that there are several activated forms of macrophages.^[4] In spite of a spectrum of ways to activate macrophages, historically they have been classfied into two main groups designated M1 and M2. M1 macrophages, or classically activated macrophages, are immune effector cells that are aggressive against microbes and can engulf and digest affected cells much more readily, and they also produce many lymphokines.^[5] M1 macrophages are activated by LPS and IFN-gamma, and secrete high levels of IL-12 and low levels of IL-10. As more ways to activate macrophages become apparent, the M2 designation is becoming a catch-all to describe other types, including those that function in wound healing and tissue repair, and those that turn off immune system activation by producing anti-inflammatory cytokines like IL-10. M2, or alternatively activated macrophages, are activated by IL-4 and produce high levels of IL-10 and low levels of IL-12. Tumor-associated macrophages are thought to be M2 macrophages.^[6]

Role in muscle regeneration

The first step to understanding the importance of macrophages in muscle repair, growth, and regeneration is that there are two “waves” of macrophages with the onset of damageable muscle use – subpopulations that do and do not directly have an influence on repairing muscle. The initial wave is a phagocytic population that comes along during periods of increased muscle use that are sufficient to cause muscle membrane lysis and membrane inflammation, which can enter and degrade the contents of injured muscle fibers.^[7]^[8]^[9] These early-invading, phagocytic macrophages reach their highest concentration about 24 hours following the onset of some form of muscle cell injury or reloading.^[10] Their concentration rapidly declines after 48 hours.^[8] The second group is the non-phagocytic types that are distributed near regenerative fibers. These peak between two and four days and remain elevated for several days during the hopeful muscle rebuilding.^[8] The first subpopulation has no direct benefit to repairing muscle, while the second non-phagocytic group does.

It is thought that macrophages release soluble substances that influence the proliferation, differentiation, growth, repair, and regeneration of muscle, but at this time the factor that is produced to mediate these effects is unknown.^[10] It is known that macrophages' involvement in promoting tissue repair is not muscle specific; they accumulate in numerous tissues during the healing process phase following injury.^[11]

A study conducted in 2006 showcased macrophage influences on muscle repair of soleus muscle on mice.^[12]

The first procedural step was to make sure macrophages are present in the muscle after onset of muscle injury, and then decrease their presence to see what effects were had on the muscle. By using anti-F4/80 to bind to macrophages and render them useless, it was seen that when the second wave of macrophages were depleted, there were many more lesions in the muscle cell membrane between the second and fourth day – showing muscle damage when repairing is supposed to occur. After testing for membrane lesions in both the total amount of muscle fibers present, it was noticed that most of the damage occurred in muscle cells that did not have the second subpopulation of macrophages present. Macrophages depletion prevents muscle membrane repair.

When examining muscle regeneration, a significant reduction was found in the amount of myonuclei. Depletion of macrophages was found to cause, between the second and fourth day of repair, much less muscle regeneration compared to muscle with macrophage population.^[12] Macrophages promote muscle regeneration between the second and fourth day.

To determine the influence of macrophages in muscle growth, muscle cross-sectional area in macrophage-depleted muscle area was measured against two muscle sets: muscle that was injured and had macrophage presence and muscle that was not injured and had macrophage presence. The macrophage-depleted muscle showed less growth after four days, and injured muscle with macrophages nearly grew back to the level of uninjured muscle.^[12] Macrophage depletion reduces muscle growth during a growth period.

The study attempted to examine the appearances of Pax7 and MyoD, but data was not consistent with previous findings.

Tissue macrophages

Macrophage

A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of dust is likely to occur. Each type of macrophage, determined by its location, has a specific name:

Name of cell	Location
Dust cells/Alveolar macrophages	pulmonary alveolus of lungs
Histiocytes	connective tissue
Kupffer cells	liver
Microglia	neural tissue
Epithelioid cells	granulomas
Osteoclasts	bone
Hofbauer cell	Placenta
Sinusoidal lining cells	spleen
Giant cells	Connective Tissue
Peritoneal macrophages	Peritoneal cavity

Investigations concerning Kupffer cells are hampered because in humans, Kupffer cells are only accessible for immunohistochemical analysis from biopsies or autopsies. From rats and mice, they are difficult to isolate, and after purification, only approximately 5 million cells can be obtained from one mouse.

Macrophages can express paracrine functions within organs that are specific to the function of that organ. In the testis for example, macrophages have been shown to be able to interact with Leydig cells by secreting 25-hydroxycholesterol, an oxysterol that can be converted to testosterone by neighbouring Leydig cells.^[13] Also, testicular macrophages may participate in creating an immune privileged environment in the testis, and in mediating infertility during inflammation of the testis.

Disease

Due to their role in phagocytosis, macrophages are involved in many diseases of the immune system. For example, they participate in the formation of granulomas, inflammatory lesions that may be caused by a large number of diseases. Some disorders, mostly rare, of ineffective phagocytosis and macrophage function have been described, for example.^{[citation needed]}

As a host for intracellular pathogens

In their role as a phagocytic immune cell macrophages are responsible for engulfing pathogens to destroy them. Some pathogens subvert this process and instead live inside the macrophage. This provides an environment in which the pathogen is hidden from the immune system and allows it to replicate.

Diseases with this type of behaviour include tuberculosis (caused by Mycobacterium tuberculosis) and leishmaniasis (caused by Leishmania species).

Tuberculosis

Once engulfed by a macrophage, the causative agent of tuberculosis, Mycobacterium tuberculosis,^[14] avoids cellular defenses and uses the cell to replicate.

Leishmaniasis

Upon phagocytosis by a macrophage, the Leishmania parasite finds itself in a phagocytic vacuole. Under normal circumstances, this phagocytic vacuole would develop into a lysosome and its contents would be digested. Leishmania alter this process and avoid being destroyed; instead, they make a home inside the vacuole.

Chikungunya

Infection of macrophages in joints is associated with local inflammation during and after the acute phase of Chikungunya (caused by CHIKV or Chikungunya Virus). ^[15]

Heart disease

Macrophages are the predominant cells involved in creating the progressive plaque lesions of atherosclerosis.^[16]

HIV infection

Macrophages also play a role in Human Immunodeficiency Virus (HIV) infection. Like T cells, macrophages can be infected with HIV, and even become a reservoir of ongoing virus replication throughout the body. HIV can enter the macrophage through binding of gp120 to CD4 and second membrane receptor, CCR5 (a chemokine receptor). Both circulating monocytes and macrophages serve as a reservoir for the virus.^[17]

Cancer

Macrophages are believed to help cancer cells proliferate as well. They are attracted to oxygen-starved (hypoxic) tumour cells and promote chronic inflammation. Inflammatory compounds such as Tumor necrosis factor (TNF) released by the macrophage activates the gene switch nuclear factor-kappa B. NF-κB then enters the nucleus of a tumour cell and turns on production of proteins that stop apoptosis and promote cell proliferation and inflammation.^[18]

Macrophages have been shown to infiltrate a number of tumors. Tumor-associated macrophages are thought to acquire an M2 phenotype, contributing to tumor growth and progression.

Media

An active J774 macrophage is seen taking up four
conidia in a cooperative manner. The J774 cells were treated with 5 ng/ml interferon-γ one night before filming with conidia. Observations were made every 30s over a 2.5hr period.
Two highly active alveolar macrophages can be seen ingesting conidia. Time lapse is 30s per frame over 2.5hr.

References

^ Semyon Zalkind (2001). Ilya Mechnikov: His Life and Work. Honolulu, Hawaii: University Press of the Pacific. pp. 78, 210. ISBN 0-89875-622-7.
^ Krombach, F., Münzing, S., Allmeling, A. M., Gerlach, J. T., Behr, J., Dörger, M. (1 September 1997). "Cell size of alveolar macrophages: an interspecies comparison". Environ. Health Perspect. 105 Suppl 5 (Suppl 5): 1261–3. doi:10.2307/3433544. JSTOR 3433544. PMC 1470168. PMID 9400735. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1470168/.
^ Khazen, W., M'bika, J. P., Tomkiewicz, C., et al. (October 2005). "Expression of macrophage-selective markers in human and rodent adipocytes". FEBS Lett. 579 (25): 5631–4. doi:10.1016/j.febslet.2005.09.032. PMID 16213494.
^ David M. Mosser and Justin P. Edwards (December 2008). "Exploring the full spectrum of macrophage activation". Nature Reviews Immunology 8 (12): 958–969. doi:10.1038/nri2448. PMC 2724991. PMID 19029990. http://www.nature.com/nri/journal/v8/n12/full/nri2448.html.
^ "The human immune system: The lymphocyte story". New Scientist (1605): 1. March 1988. http://www.newscientist.com/channel/health/hiv/mg11716050.100. Retrieved 2007-09-13.
^ Galdiero (2012). "Tumor associated macrophages and neutrophils in tumor progression". J Cell Phys. PMID 23065796.
^ Krippendorf, BB; Riley, DA (January 1993). "Distinguishing unloading-versus reloading-induced changes in rat soleus muscle". Muscle Nerve 16 (1): 99–108. doi:10.1002/mus.880160116. PMID 8423838.
^ ^a ^b ^c St Pierre BA, JG Tidball (1994). "Differential response of macrophage subpopulations to soleus muscle reloading following rat hindlimb suspension". Journal of Applied Physiology 77 (1): 290–297. PMID 7961247.
^ Tidball JG, Berchenko E, Frenette J (1999). "Macrophage invasion does not contribute to muscle membrane injury during inflammation". Journal of Leukocyte Biology 65 (4): 492–498. PMID 10204578.
^ ^a ^b Schiaffino S, Partridge T (2008)). Skeletal Muscle Repair and Regeneration. Advances in Muscle Research. 3. pp. 380.
^ Brechot et al.; Gomez, Elisa; Bignon, Marine; Khallou-Laschet, Jamila; Dussiot, Michael; Cazes, Aurélie; Alanio-Bréchot, Cécile; Durand, Mélanie et al. (2008). Cao, Yihai. ed. "Modulation of Macrophage Activation State Protects Tissue from Necrosis during Critical Limb Ischemia in Thrombospondin-1-Deficient Mice". PLoS ONE 3 (12): e3950. doi:10.1371/journal.pone.0003950. PMC 2597179. PMID 19079608. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2597179/.
^ ^a ^b ^c Tidball JG, Wehling-Henricks M (2007). "Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo". The Journal of Physiology 578 (Pt 1): 327–336. doi:10.1113/jphysiol.2006.118265. PMC 2075127. PMID 17038433. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2075127/.
^ http://www.andrologyjournal.org/cgi/reprint/19/4/394
^ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9.
^ "Chikungunya Disease: Infection-Associated Markers from the Acute to the Chronic Phase of Arbovirus-Induced Arthralgia". http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0001446#. Retrieved 2012-06-14.
^ Lucas AD, Greaves DR (November 2001). "Atherosclerosis: role of chemokines and macrophages". Expert Rev Mol Med 3 (25): 1–18. doi:10.1017/S1462399401003696. PMID 14585150.
^ Sebastiaan Bol, Viviana Cobos-Jiménez, Neeltje Kootstra and Angélique van ’t Wout, Future Virology, February 2011,Dr.Andy Pozo Vol. 6, No. 2, Pages 187–208. http://www.futuremedicine.com/toc/fvl/6/2
^ Gary Stix (July 2007). "A Malignant Flame". Scientific American: 46–9. http://www.sciam.com/article.cfm?id=a-malignant-flame.

External links

Wikimedia Commons has media related to: Macrophages

HIV and the Macrophage A book on the role of macrophages in AIDS pathogenesis
The role of macrophages in HIV pathogenesis
Macrophages News Macrophages News provided by insciences organisation
www.macrophages.com The Macrophage Community Website

UpToDate Contents

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1. 自然免疫系の概要 an overview of the innate immune system
2. 血球貪食性リンパ組織球症（HLH） hemophagocytic lymphohistiocytosis
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5. 免疫系に対するステロイドの影響 glucocorticoid effects on the immune system

English Journal

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Belluzo MS1, Medina LF2, Cortizo AM3, Cortizo MS1.
Ultrasonics sonochemistry.Ultrason Sonochem.2016 May;30:1-8. doi: 10.1016/j.ultsonch.2015.11.022. Epub 2015 Nov 23.
In recent years, there has been an increasing interest in the design of biomaterials for cartilage tissue engineering. This type of materials must meet several requirements. In this study, we apply ultrasound to prepare a compatibilized blend of polyelectrolyte complexes (PEC) based on carboxymethyl
PMID 26703196

Fermentation and dry fractionation increase bioactivity of cloudberry (Rubus chamaemorus).

Puupponen-Pimiä R1, Nohynek L2, Juvonen R2, Kössö T2, Truchado P2, Westerlund-Wikström B3, Leppänen T4, Moilanen E4, Oksman-Caldentey KM2.
Food chemistry.Food Chem.2016 Apr 15;197(Pt A):950-8. doi: 10.1016/j.foodchem.2015.11.061. Epub 2015 Nov 14.
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PMID 26617039

Electrochemical acetylcholinesterase biosensor based on ZnO nanocuboids modified platinum electrode for the detection of carbosulfan in rice.

Nesakumar N1, Sethuraman S2, Krishnan UM2, Rayappan JB3.
Biosensors & bioelectronics.Biosens Bioelectron.2016 Mar 15;77:1070-7. doi: 10.1016/j.bios.2015.11.010. Epub 2015 Nov 9.
The consumption of carbosulfan-contaminated rice affects the immune and lymphocyte response, germinal centers in the spleen, plasma cells in popliteal lymphoid nodes, bone marrow cells and granulocyte-macrophage progenitor cells. Towards this, a highly sensitive acetylcholinesterase (AChE) cyclic vo
PMID 26562329

Japanese Journal

Expression of Fgf23 in Activated Dendritic Cells and Macrophages in Response to Immunological Stimuli in Mice

Masuda Yuki,Ohta Hiroya,Morita Yumiko [他]
Biological & pharmaceutical bulletin 38(5), 687-693, 2015-05
NAID 40020440698

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鎌田耕輔
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Amyloid β oligomers induce interleukin-1β production in primary microglia in a cathepsin B- and reactive oxygen species-dependent manner.

Taneo Jun,Adachi Takumi,Yoshida Aiko,Takayasu Kunio,Takahara Kazuhiko,Inaba Kayo
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… These aggregates induce inflammatory responses, such as interleukin-1β (IL-1β) production by microglia, which are macrophage-like cells located in the brain. …
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Related Pictures

★リンクテーブル★

リンク元	「100Cases 33」「造血幹細胞」「マクロファージ」「貪食細胞」「monocyte-derived macrophage」
拡張検索	「bone marrow-derived macrophage」「macrophage chemotactic factor」「activated macrophage」「fetal macrophage」

「100Cases 33」

Macrophage
	A macrophage of a mouse stretching its "arms" (pseudopodia) to engulf two particles, possibly pathogens. Trypan Blue Exclusion.
Latin	macrophagocytus
Code	TH H2.00.03.0.01007

　　[★]

☆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)

According to the US CDC definition, one has AIDS if he/she is infected with HIV and present with one of the following:

A CD4+ T-cell count below 200 cells/μl (or a CD4+ T-cell percentage of total lymphocytes of less than 14%).

or he/she has one of the following defining illnesses:

01. Candidiasis of bronchi, trachea, or lungs
02. Candidiasis esophageal
03. Cervical cancer (invasive)
04. Coccidioidomycosis, disseminated or extrapulmonary
05. Cryptococcosis, extrapulmonary
06. Cryptosporidiosis, chronic intestinal for longer than 1 month
07. Cytomegalovirus disease (other than liver, spleen or lymph nodes)
08. Encephalopathy (HIV-related)
09. Herpes simplex: chronic ulcer(s) (for more than 1 month); or bronchitis, pneumonitis, or esophagitis
10. Histoplasmosis, disseminated or extrapulmonary
11. Isosporiasis, chronic intestinal (for more than 1 month)
12. Kaposi's sarcoma
13. Lymphoma Burkitt's, immunoblastic or primary brain
14. Mycobacterium avium complex
15. Mycobacterium, other species, disseminated or extrapulmonary
16. Pneumocystis carinii pneumonia
17. Pneumonia (recurrent)
18. Progressive multifocal leukoencephalopathy
19. Salmonella septicemia (recurrent)
20. Toxoplasmosis of the brain
21. Tuberculosis
22. Wasting syndrome due to HIV

People who are not infected with HIV may also develop these conditions; this does not mean they have AIDS. However, when an individual presents laboratory evidence against HIV infection, a diagnosis of AIDS is ruled out unless the patient has not:

undergone high-dose corticoid therapy or other immunosuppressive/cytotoxic therapy in the three months before the onset of the indicator disease
OR been diagnosed with Hodgkin's disease, non-Hodgkin's lymphoma, lymphocytic leukemia, multiple myeloma, or any cancer of lymphoreticular or histiocytic tissue, or angioimmunoblastic lymphoadenopathy
OR a genetic immunodeficiency syndrome atypical of HIV infection, such as one involving hypogamma globulinemia

AND

the individual has had Pneumocystis carinii pneumonia
OR one of the above defining illnesses AND a CD4+ T-cell count below 200 cells/μl (or a CD4+ T-cell percentage of total lymphocytes of less than 14%).

□AIDSのステージング

Revised World Health Organization (WHO) Clinical Staging of HIV/AIDS For Adults and Adolescents (2005)

http://en.wikipedia.org/wiki/WHO_Disease_Staging_System_for_HIV_Infection_and_Disease_in_Adults_and_Adolescents

■参考文献

HIM = Harrison's Principles of Internal Medicine 17th Edition

CASES = 100 Cases in Clinical Medicine Second edition

IMD = 内科診断学第2版

「造血幹細胞」

　　[★]

英: hematopoietic stem cell, HSC
関: 幹細胞

細胞表面マーカー

CD34
c-kit

分化

			血液中	組織
造血幹細胞 hematopoietic stem cell	リンパ球幹細胞 lymphoid stem cell	T細胞 T cell
		B細胞 B cell
		NK細胞 natuarl killer cell
	骨髄球幹細胞 myeloid stem cell	granulocyte/macrophage progenitor	好中球 neutrophil
			好酸球 eosinophil
			好塩基球 basophil
			unknown precursor of mast cell	肥満細胞 mast cell
			単球	マクロファージ macrophage
		赤芽球 erythroblast	赤血球 erythrocyte
		巨核球 megakaryocyte	血小板 platelet

「マクロファージ」

　　[★]

英: macrophage、Mφ
同: 大食細胞、大食球、貪食球
関: 塵埃細胞、組織球; Mononu clear phagocytes

活性化するためのサイトカイン

T細胞由来のIFN-γにより活性化される (PT.248)
IL-1, TNF, GM-CSF, INF-γなど。特にTh1細胞由来のINF-γが重要 (SMC.47)
サイトカインにより活性化され活性化マクロファージとなると、これまで殺せなかった細胞内寄生体の殺菌が可能となる

機能 (PT.248)

抗原提示機能 (抗原提示細胞)
抗菌機能
腫瘍細胞障害活性
IL-1,IL-6,IL-10,IL-12,IFN-α,TGF-β,TNFα,GM-CSFの放出

産生するサイトカイン (SMB.44)

NK細胞や樹状細胞にインターフェロンγを産生させるサイトカインを分泌

IL-12
IL-18
IL-23

「貪食細胞」

　　[★]

英: phagocyte、macrophage
関: 食細胞、大食細胞、マクロファージ

「monocyte-derived macrophage」

　　[★]

単球由来マクロファージ

関: bone marrow-derived macrophage、macrophage

「bone marrow-derived macrophage」

　　[★]

骨髄由来マクロファージ

関: macrophage、monocyte-derived macrophage

「macrophage chemotactic factor」

　　[★] マクロファージ遊走因子

「activated macrophage」

　　[★] 活性化マクロファージ

「fetal macrophage」

　　[★] 胎生マクロファージ

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Macrophage

A macrophage of a mouse stretching its "arms" (pseudopodia) to engulf two particles, possibly pathogens. Trypan Blue Exclusion.
Latin	macrophagocytus
Code	TH H2.00.03.0.01007

匿名

検索

案内

macrophage