疑似免疫缺陷immunodeficiency (郭和昌醫師)
DESCRIPTION
An introduction of Immunodeficiency by Ho-Chang Kuo from Taiwan.TRANSCRIPT
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免 疫 缺 陷 疾 病 簡 介
郭和昌 醫師
高雄長庚兒童過敏免疫風濕科July 2008 Waikiki beach, Hawaii
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郭和昌醫師國立陽明大學醫學士長庚大學臨床醫學研究所博士
候選人
高雄長庚醫院 兒童過敏氣喘免疫科主治
醫師 長庚醫院講師級主治醫師
中華民國小兒科專科醫師台灣兒童過敏氣喘暨免疫科專
科醫師中華民國免疫科專科醫師
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免疫系統
• 原始免疫 (innate immunity)
• 適應免疫 (adaptive immunity)
• 吞噬細胞• T 細胞• B 細胞• 補體
Source: National Cancer Institute
Ab
MΦ
complement
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免疫缺陷• 先天性
– CGD, hyper IgE ….• 後天性
– AIDS– KD (IVIG supplement)– Chemotherapy – Steroid
• oral• Inhalation • IV• pulse
– Immunosuppressant agent – Age (6 month)– Severe infection
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Primary vs. secondary exposure
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Question 1
•何時該懷疑免疫缺乏症 ?
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Q. 何時該懷疑免疫缺乏症 ?• 二次或以上的 systemic bacterial infections
(eg: sepsis, osteomyelitis, meningitis)
• 一年內三次或以上的 serious respiratory or documented bacterial soft tissue infection(eg: cellulitis, draining otitis media, lymphadenitis ≦ 1 y/o)
• 不尋常部位的感染(eg: liver or brain abscess)
• 不尋常菌種的感染(eg: Aspergillus, Serratia marcescens, Nocardia, Pseudomonas)
• 尋常菌種的感染卻有不尋常的嚴重表現
Nelson 17th edition: p.681
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北海道 - 小樽運河
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東京 - 皇居二重橋
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明治神宮 , 東京
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北海道 - 小樽
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北海道 - 函館山
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北海道 - 函館山 - 百萬夜景
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Question 2
•如何安排進一步檢查與診斷 ?
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進一步評估分三方面• History taking
• Physical examination
• Routine laboratory examination
• Immunological survey
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家族及個人病史
• History
– Detailed family tree
• Premature death
• Sex of affected individuals
•近親結婚– Medical history
• The age at onset of symptoms
• The nature & etiology of infections, 感染菌種,侵犯的器官,使用的抗生素,治療的反應,長期感染狀況
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免疫系統理學檢查Appearance:
• Failure to thrive, Pale, Wasted, • Hair color ( 白髮 -CHS)
Skin:• Impetigo, Cellulitis, Candidiasis• Rash, Seborrhoic dermatitis
HEENT:• Oral ulcer, oral candidiasis, periodonitis• Chronic sinusitis, otitis media • Lymphoadenopathy, Tonsil hypotrophy or hyper
trophy• Palpable neck LNs
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– Chest:• Lobar pneumonia, bronchiectasis, PCP
– Abdomen:• Splenomegaly, Hepatosplenomegaly• Cholangitis, Liver abscess (CGD), • Chronic diarrhea (B def. ), Crohn’s disease (CGD)• Prolong detachment of cord, Omphalitis (LAD)
– Extremities:• Palpable Inguinal LNs• Arthritis (B def.), Osteomyelitis (CGD)
– Other:• Lymphadenopathy (B def, CGD)
免疫系統理學檢查
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清溪川 = 李明博 總統
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首爾 - 雪景
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首爾 - 民俗村
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為何有兩種蛋糕 ???
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見微知著 !
Laboratory diagnosis:• 一般性檢查:
– CBC /DC• ANC cyclic neutropenia, • RBChemolytic anemia,• platelet Wiskott-Aldrich syndrome (X linked, immun
odeficiency, thrombocytopenia, dermatitis)
– ESR• R/O chronic infection or inflammatory
– Bacterial culture• R/O infection
• 顯示病人可能有特別的免疫學診斷,再使用特殊檢查
免疫細胞的質與量均須考量 !!!
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應該安排哪些免疫進階檢查抽絲撥解
• Phagocyte : chemotaxis, chemileuminence, NBT, CD11b, IL12Rb1, phagocytosis, Actin function
• T cell : DTH, lymphocyte surface marker, lymphocyte proliferation, CD40L
• B cell : IgG, IgM, IgE, IgA, IgD, IgG subclass, CD40
• Complement: C3, C4, CH50
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吞噬細胞缺損篩檢• 症狀
– 反覆皮膚感染、反覆肛門膿瘍、反覆淋巴腺炎、反覆口腔潰瘍、臍帶太晚脫落、傷口不易癒合
• 臨床評估– 淋巴腺大小 ,牙齦肥厚
• 實驗室評估– 吞噬細胞染色劑還原試驗 (NBT):M25-016-Z – 吞噬血球氧化殺菌檢查 (chemiluminescence): M25-017-Z(自費 1100)
– 吞噬血球沾黏分子檢查 (adhesion molecule, CD11b) M32-151(自費 1100)
– 趨化性試驗 (chemotaxis) M32-152
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Phagocyte function
Adhesion
Migration Phagocytosis
chemotaxis
Respiratory burst
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睡著了嗎 ?
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Phagocyte evaluation
• Adhesion:– Flow cytometry to measure CD11b/18,
L-selectin
• Migration:– Chemotaxis assays
• Phagocytosis: E.coli
• Respiratory burst:– Nitroblue tetrazolium (NBT) test– Superoxide O2 assay (chemiluminescence)
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NBT slide test
• Control– NBT dye is reduced to forma
zan, deep blue-black color
CGD patientUnable to reduce NBT
and no deep blue color
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非洲皇冠鶴
Hyatt Regency and resort Maui, Hawaii
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自在
Hyatt Regency and resort Maui, Hawaii
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Swam Court, Hyatt Regency and Resort Maui, Hawaii
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Swam Court, Hyatt Regency and Resort Maui, Hawaii
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吞噬細胞缺陷
Delayed detach of umbilical cord >1 m
Perianal abscess formation Granulation tissue (CGD)
反覆口腔潰瘍 ,牙齦肥厚
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Pictures of CGD
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Pictures of Hyper-IgE syndrome (Job syndrome)
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抗體缺損篩檢 :
• 症狀 – 反覆呼吸道 (鼻竇肺炎 )、腸胃道感染、慢性腸病毒腦膜炎、關節炎、無法解釋的支氣管擴張
• 臨床評估– 淋巴腺及扁桃腺大小
• 實驗室評估– IgG L72-205– IgA L72-207– IgM L72-209– IgG subclass (IgG1-G4) M32-330 (暫定自費 1800)
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抗體缺乏
1. 出生 6個月以後發生
2. 反覆呼吸道腸胃道感染
關節炎
Recurrent sinusitis
Pseudomonas infection Ecthyma gangrenosum
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T 細胞免疫缺損篩檢症狀卡介苗感染、反覆鵝口瘡、 PCP、反覆 CMV 等感染 .
臨床評估胸腺及下巴大小
實驗室評估遲發性過敏反應 (DTH) M32-318淋巴球分群 M32-328淋巴球變形反應 -分裂原刺激 M25-015-Z淋巴球變形反應 -抗原刺激 M32-808淋巴球活化標記 (CD40L) M32-155(自費 1100)接受器缺乏檢查 (IL-12Rb1,IFNR1,IFNrR2…) (自費 1100)
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• T cell quantification ( 數量 )– Absolute lymphocyte count
• T cell function ( 功能 )
– Delayed type hypersensitivity (DTH)
• Candida, PPD (5-10 IU), mumps, tetanus, control – Candida albicans intradermal skin test
0.1 ml of a 1:20 dilution > 6y/o
0.1 ml of a 1:10 dilution < 6y/o
check erythema and induration at 48, 72 hr
> 5 mm: positive
If positive, 可初步排除嚴重的 primary T-cell defects
T cell 功能
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Laboratory diagnosis:• T cell deficiency (other…)
– T cell surface markers• CD3,CD4,CD8,CD19,CD25,CD56 by FACS flow cytometry• CD40L (hyper-IgM)
– Chromosome analysis• 22q11 R/O DiGeorge syndrome
– Production of cytokines by activated lymphocytes• Th1/Th2/Treg cytokines
T cell 功能
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細胞免疫缺乏
Invisible thymus Oral thrush
BCG infection Disseminated varicella infection
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Delay type hypersensitivity
CandidaPPDToxoidMumps
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Waikiki beach, Hawaii
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Waikiki beach, Hawaii
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Westin Resort, Hawaii
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Kalakawa Ave. Hawaii
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Hilo Hatis, Hawaii
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補體免疫缺損篩檢•症狀
–皮疹、關節炎、敗血症、血管水腫、自體免疫疾病症狀
•臨床評估–血管水腫 ,關節腫脹
•實驗室評估– C3, C4, C6, C7, C8, CH50, AH50–補體 C1q esterase inhibitor
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補體功能
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補體缺乏
淋病性敗血症,
多發關節炎
C2, C4 rashes
C3 敗血症
C6, 7, 8, 9 淋病關節炎
關節炎 Skin rash
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個案討論• 十歲男童• 診斷 : CGD
• 住院該住何種病房 ?
• 護理人員須注意事項• 干擾素施打注意事項 , 劑量換算
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歷屆考題牛刀小試• 下列有關免疫系統之敘述,何者正確? (A)IgA及 IgM 隨年齡增加而減少 (B)體液性免疫由T細胞負責 (C) 抑制性 T細胞會溶解感染的細胞 (D). IgG 可通過胎盤,含量也最多
• 下列免疫球蛋白中,和第一型過敏有密切關係者為: (A) IgA (B) IgD (C). IgE (D) IgG 。 (‘ 96專高)
• 下列何者不會導致免疫功能降低而產生伺機感染? (A) 白血病 (B). 心臟病 (C) 腎臟病引起尿毒症 (D) 惡性腫瘤。 (‘ 96專高 )
• IgE抗體與下列哪一類過敏反應有密切關係? (A). 第一類,異位性 (B) 第二類,細胞毒性 (C) 第三類,免疫複合體性 (D) 第四類,延遲性。 (‘99高考)
• 結核菌素試驗( tuberculin test)之皮膚變化是屬於哪一型之過敏反應? (A) 第一型 (B) 第二型 (C) 第三型 (D). 笫四型。 (‘ 02 專高)
• 經由細胞毒殺性抗體( cytotoxic antibody)媒介引起之過敏屬哪一型過敏反應? (A) 一 (B). 二 (C) 三 (D) 四。 (‘ 04專高)
• DiGeorge syndrome 缺乏何種細胞? (A) B細胞 (B) 自然殺手細胞 (C). T細胞 (D) 組織球。 ( '04專高 )
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Thanks for your attention and comment !!!