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Tuberculosis (Primary (Granulomatous 為了有效清除細菌,防止擴散 # (!!granuloma (Ghon…

- - - - Th 1
        IL12促進
        
        細胞調節性免疫
        
        活化內皮細胞：急性發炎
        
        T cell數目增加：強化發炎
        
        藉由IFN gamma and CD40活化巨噬細胞
        1.加強免疫
        2.消滅不掉細菌：肉芽腫
        
        Th 1大量複製增生
      - Th 2
        
        體液性免疫：這次不討論
        
        IL4 activate B cell
      - 如何活化
        
        Initial
        TCR(Th cell)--MHC2(APC)
        
        Costimulation增加Th cell產生IL2 receptor，促進其增生，增加免疫
        CD28(Th cell)--B7(APC)
  - - - critical mediator that enables macrophages to contain the M. tuberculosis infection
      - stimulates maturation of the phagolysosome in infected macrophages,
        exposing the bacteria to a lethal acidic, oxidizing environment.
      - stimulates expression of inducible nitric oxide synthase, which produces nitric oxide
        NO combines with other oxidants to create reactive nitrogen intermediates,particularly important for killing
      - mobilizes antimicrobial peptides (defensins) against the bacteria
      - stimulates autophagy, a process that sequesters and then destroys damaged organelles and intracellular bacteria
    - - Th 1分泌細胞激素
        1.IFN gamma：胞吞能力增加
        2.TNF alpha：活化內皮,adhesin，促巨噬細胞由血管中擠向組織, epitheloid cell
        3.IL2：T cell proliferation
        4.IL3,GM CSF：促巨噬細胞在骨髓中分化
        5.CXCL2：趨化作用，利用濃度梯度引導促巨噬細胞聚集
      - 召集活化非轉一發炎細胞
      - 24小時後才發炎反應
        延遲過敏
        
        主要是巨噬細胞
        1.吞噬作用
        2.氧自由基
        3.一氧化氮
        4.利用非專一性的組織破壞來消滅抗原
        5.MHC 2數量增加，抗原呈現能力增加：正回饋
        
        如果無法消滅，就是肉芽腫
  - - - 四周：Alveolar macrophages+ epithelioid cells+ Langhans giant cells (fused epithelioid cells)
        （巨噬細胞因為IFN-γ or THF 而誘發轉變成epithelioid histiocytes：aggregate to form granulomas
        （some epithelioid cells may fuse to form giant cells.
      - 最外圍：dense wall of macrophages and CD4, CD8, and NK T cells
        （enclosed within a fibroblastic rim punctuated by lymphocytes
      - 中央：intracellular mycobacteria form the central core of a necrotic mass
  - - - if many bacteria are present,
        the large necrotic or caseous granulomas become encapsulated with fibrin that effectively pro-tects the bacteria from macrophage killing
      - 1.潛伏：The bacteria can remain dormant in this stage
      - 2.progressive TB：免疫很差的人會症狀一開始就很嚴重
        （acute bacterial pneumonia with consolidation of the lobe, hilar adenopathy, and pleural effusion
        （apical lesion expands into adjacent lung and eventually erodes into bronchi and vessels
        （creating a ragged, irregular cavity that is poorly walled off by fibrous tissue：細菌可以跑到其他淋巴,血管,呼吸道
        （Erosion of blood vessels results in hemoptysis
        （附加的胸腔症狀：serous pleural effusions, tuberculous empyema, or obliterative fibrous pleuritis
      - 3.二度感染：reactivated years later when the patient’s immunologic responsive-ness wanes as the result of old age or immunosuppressive disease or therapy
        （乾酪壞死）
    - - If a small antigenic burden is present at the time the macrophages are stimulated,
        the granuloma is small and the bacteria are destroyed with minimal tissue damage
- - - - bronchopneumonia
        （蔓延到下肺：一整個肺都是結核，發炎
    - - Miliary pulmonary disease
        （organisms draining through lymphatics enter the venous blood and circulate back to the lung
        （small,visible(2-mm)foci of yellow-white con-solidation scattered through the lung parenchyma
        （expand and coalesce, resulting in consolidation：大面積甚至整個肺
        （附加的胸腔症狀：serous pleural effusions, tuberculous empyema, or obliterative fibrous pleuritis
      - Extrapulmonary
        
        Endobronchial, endotracheal,laryngeal tuberculosis
        （spread through lymphatic channels or from expectorated infectious material.
        （The mucosal lining may be studded with minute granulomatous lesions：apparent microscopically
        
        Lymphadenitis：scrofula，頸部最常見
        （HIV-positive people, on the other hand, almost always have multifocal disease, systemic symp-toms藉由active tuberculosis？
        
        intestinal tuberculosis
        （未消毒：con-tracted by the drinking of contaminated milk
        （有消毒：swallowing of coughed-up infective material in patients with advanced pulmo-nary disease.
        （mucosal lymphoid aggregates of the small and large bowel, which then undergo granulomatous inflammation
        （overlying mucosa, particularly in the 迴腸：潰爛，然後被束縛
        
        肋膜，骨骼，泌尿生殖器等
      - Systemic miliary tuberculosis
        （bacteria disseminate through the systemic arterial system
        （prominent in the liver, bone marrow, spleen, adrenals, meninges, kidneys, 輸卵管, and epi-didymis #
      - Isolated tuberculosis：hematogenously organ
        1.meninges (tuberculous meningitis)
        2.kidneys (renal tuberculosis)：WBC in urine，膿尿
        3.adrenals (formerly an important cause of Addison disease)
        4.bones (osteomyelitis)
        （vertebrae：Pott disease，腰椎常見
        （寒性膿腫：abscesses in these patients may track along tissue planes and present as an abdominal or pelvic mass，周遭軟組織,韌帶
        （骨質破壞及壞死，有幹酪樣改變和膿腫形成，椎體因病變和承重而發生塌陷，使脊柱形成彎度，棘突隆起，背部有駝峰畸形
        5.fallopian tubes (salpingitis)
        6.liver：肝炎
- - - - 免疫力不佳的人：老人，糖尿病，免疫治療患者，白血病，腎衰竭，近期感染者
      - 嚴重導致死亡
      - apical lesion expands into adjacent lung and eventually erodes into bronchi and vessels
        creating a ragged, irregular cavity that is poorly walled off by fibrous tissue
        Erosion of blood vessels results in hemoptysis
    - - 當免疫力低下時，結核菌會再度活化：次發性
      - 臨床症狀
        1.通常無症狀
        2.x ray出現肉芽腫鈣化和纖維化
        3.PPD陽性
        4.無傳染性
    - - distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe
        usually close to the pleura
      - 1- to 1.5-cm area of gray-white inflammation with consolidation emerges, known as the Ghon focus
      - 中央壞死，細菌可以跑出來或是被困在巨噬細胞裡面，然後跑到鄰近地區
        導致細胞免疫反應，接著纖維化及鈣化
  - - - 在頂小葉，因為那裡氧氣濃度最高
      - 症狀：咳嗽，咳血，發燒，體重減輕，厭食，盜汗
      - 徵候：gohn complex，耐酸性染色陽性，痰液培養有細菌
    - - Endobronchial, endotracheal,laryngeal tuberculosis
        spread through lymphatic channels or from expectorated infectious material.
        The mucosal lining may be studded with minute granulomatous lesions（ apparent microscopically
      - Lymphadenitis：scrofula
        頸部最常見
        HIV-positive people, on the other hand, almost always have multifocal disease, systemic symp-toms,
      - intestinal tuberculosis
        con-tracted by the drinking of contaminated milk
        swallowing of coughed-up infective material in patients with advanced pulmo-nary disease.
        mucosal lymphoid aggregates of the small and large bowel, which then undergo granulomatous inflammation
        overlying mucosa, particularly in the ileum
      - 肋膜，骨骼，泌尿生殖器等
    - - pulmonary disease
        
        Individual lesions are either microscopic or small, visible(2-mm) foci of yellow-white con-solidation scattered through the lung parenchyma
        
        Miliary lesions may expand and coalesce,
        resulting in consolidation of large regions or even whole lobes of the lung
        
        serous pleural effusions, tuberculous empyema, or obliterative fibrous pleuritis may develop
        
        organisms draining through lymphatics enter the venous blood and circulate back to the lung
      - Systemic miliary
        
        bacteria disseminate through the systemic arterial system
        
        most prominent in the liver, bone marrow, spleen,adrenals, meninges,kidneys, fallopian tubes, and epi-didymis