牙周病的发生课件

Immunity and Inflammation: Host Defense Against Microbial Plaque,牙周病科 江正陽,牙周病的發生,寄居在口腔表面或牙周等特殊部位的各種微生物之間，維持著菌群之間的相對平衡，且保有著菌群與宿主之間的動態平衡，這種平衡對口腔健康十分重要的，稱之為口腔正常菌群（oral normal flora）。 當正常菌群間失去相互制約，也就是某一群毒力較大的內生性微生物，因為環境關係適合其生長，使得其比例變成絕對多數時，其毒力侵入牙周組織中的機會便增加，或是牙菌斑量的增加，其產生的總毒性量，宿主無法將其毒性中和，這將使牙周微生物與宿主間的動態失去平衡，而產生病理變化，便容易發生牙周病。 牙周病的成因，細菌的角色是間接的，最主要歸因於宿主免疫反應的結果。,Histopathological fatures of gingival inflammation,Within 24 hrs,One week,Page 和 Schrodeder 1976,根據臨床與組織病理的發現，將牙齦與牙周疾病的病理過程分為四類，前三期為牙齦炎，第四期才是牙周炎。 起始病灶（initial lesion）：在細菌感染後2-4天，血管擴大，組織內主要免疫細胞為多型核嗜中性白血球，血管附近的膠原蛋白被破壞。 早期病灶（early lesion）：在細菌感染後4-7天，血管增生，組織內主要免疫細胞為淋巴球，更多的膠原蛋白被破壞。 建立期病灶（established lesion）：在細菌感染後14-21天，血管增生及血管炎（vasculitis），組織內主要免疫細胞為漿細胞，更多的膠原蛋白被破壞 嚴重期病灶（advanced lesion）：因為組織內的膠原蛋白被嚴重破壞，牙齦溝的上皮往下移動而形成牙周囊袋，隨著牙周囊袋的加深，附著在牙骨質的膠原蛋白也被破壞，使得細菌更易往下侵犯，最後造成牙周韌帶及齒槽骨的破壞。,Clinically healthy gingiva（The initial lesion）,Size (%volume) of various components of normal CT (NCT) and the infiltrated CT (ICT) at various days (4,14, and 28) after onset of plaque formation,The established lesion as defined by Page and Schroeder is one dominated by plasma cells. This conclusion was based mainly on data from animal experiments. Brecx et al. 1988 demonstrated that even following 6 months of oral hygiene neglect, the plasma cell fraction in human biopsies comprised only 10% of the cellular infiltrate and was clearly not the dominant cell type. The human established lesion apparently requires much more time to mature than its animal counterparts.,牙周病屬於感染性疾病 導致宿主產生免疫反應,先天免疫反應以中性白血球為主的急性發炎，後天免疫反應包含體液免疫及細胞免疫。 體液免疫是製造特異性抗體，主要作用形式是以血清中的抗體來對抗外來的微生物抗原，其中以免疫球蛋白為最重要的因子。 而細胞免疫則是由T細胞和巨噬細胞及其分泌胞激素所引起的免疫反應，而非抗體（即體液性免疫）所引發。 宿主產生免疫反應在防禦與破壞之間維持動態的平衡，研究這動態平衡將有助於我們對整個牙周病致病機轉、臨床表徵和症狀的了解，尤其是輔助診斷依據，更可預測疾病的活性和牙周健康與疾病的狀況。,牙菌斑導致牙周病的機轉,牙周病是多重因子疾病。牙菌斑細菌及其產物是引發牙周病必須的起始因子，但單有細菌還不夠，認為細菌需通過激活宿主的炎症反應和免疫機制而形成臨床的牙周病變。 牙周感染，實際上由細菌、宿主、環境三方面條件決定，影響動態平衡的一些局部促進因素，可增強細菌的堆積和侵襲力，一些全身促進因素，如內分泌失調、抽菸、精神壓力、糖尿病、遺傳因素、營養不良等，可降低宿主的防禦力和修復力，或加重牙周組織的炎症反應和破壞作用。,牙周病致病菌之毒性因子,細菌的抗原成分、各種酶、毒素及許多代謝產物，可直接刺激和破壞牙周組織，或引起牙周組織局部的免疫反應，造成組織損傷，歸納起來可以分為以下三大類。 菌體表面物質 相關的致病酶 毒素,1. 菌體表面物質,內毒素(endotoxin)是磷脂-多醣-蛋白質的大分子複合物激活單核球，產生多種胞激素(cytokine)，或激活補體，誘生和釋放調控物質，如介白質-1(interleukin-1，IL-1)、腫瘤壞死因子(tumor necrosis factor-，TNF-)、過敏毒素、前列腺素等。 磷脂壁酸(lipoteichoic acid, LTA)為革蘭氏陽性菌的細胞壁、細胞膜和筴膜上一種含磷酸甘油殘基的聚合物。它可直接刺激噬骨細胞而引起骨吸收，濃度高時可使細胞死亡；也可促使巨噬細胞釋放溶解酶。,1. 菌體表面物質,外膜蛋白(outer membrane proteins, OMP)它是多種蛋白大分子的嵌合體，包括外膜主蛋白和次蛋白，其結構及其分佈傳染，具菌株特異性，各菌株都具有其獨特的傳染生物學特性，如毒力傳遞等。 纖毛蛋白：菌毛或纖毛等為特選配體，與宿主細胞膜上的特選接受器相互作用，為誘發牙周病先決條件。 膜泡：是由細菌外膜向外膨出呈芽狀，並可與細菌外膜游離進入周圍微環境的一種泡狀膜結構。生物學活性主要包括：(1)體積小，容易透過上皮屏障；(2)包含與細菌表面相同的主要抗原和功能成分，可與宿主的抗體及免疫細胞反應，“消耗”掉一部分防禦成分，而削弱了宿主免疫防禦機轉對細菌本體的抑殺作用；(3)可作為細菌毒性產物如內毒素、白血球毒素(leukotoxin)和蛋白質分解酶(proteinase)的載體，導致深部組織的破壞。,2. 相關的致病酶,玻尿酸酶(hyaluronidase)：可分解牙齦溝上皮的細胞間質，和結締組織的間質分解，組織水腫，血管通透性增加，炎症加劇。這些作用與細菌及其產物的穿透和炎症迅速擴散有關。 鏈激酶(streptokinase)：由鏈球菌產生的一種酶，能導致血凝塊破壞，促使細菌在感染部位擴散。 膠原蛋白酶(collagenase)：可使結締組織破壞、附著喪失，使骨膠原蛋白分解，分解的膠原蛋白片段可刺激或吸引噬骨細胞，進一步造成齒槽骨吸收。,2. 相關的致病酶,硫酸軟骨素酶(chondrosulfatase)：可由口腔中的類白喉桿菌及齒垢密螺旋體所產生，它能水解牙骨質、骨組織及牙周結締組織間質中的一種硫酸軟骨素，參與牙周囊袋形成及齒槽骨吸收等牙周組織的破壞過程。 神經氨酸苷酶(neuraminidase)：即唾液酸苷酶(sialidase)，由許多口腔鏈球菌、類白喉桿菌產生，能水解黏多醣，使結締組織的另一主要成分神經氨酸破壞。同時能使唾液中的唾液酸喪失，造成黏多醣蛋白沉澱，促進牙菌斑的形成和成熟。 細菌還可產生蛋白質分解酶、去氧核糖核酸酶、核糖核酸酶及溶血素等，能分解牙周組織細胞的蛋白質、核酸等，都能對牙周組織造成破壞。,3. 毒素,白血球毒素(LT)：是放射桿菌產生的外毒素 LT只對人的多形核白血球和單核球有毒性，白血球受LT作用後1小時內即可死亡Kato S, 1995。LT具有強烈的抗原性，能刺激宿主產生相對應的IgG型抗體Engstrom PE,1999 。可損傷牙齦溝或牙周囊袋中多形核白血球和單核球的細胞膜，導致細胞死亡，釋放溶解體，還可誘導白血球介素(leukotriene)、腫瘤壞死因子和干擾素等胞激素的產生，進而造成牙周組織破壞Claesson R, 2002; Loesche WJ 1993。,抗嗜中性白血球因子(anti-neutrophil factor)：能使嗜中性白血球的形態及其趨化性發生缺陷。 白血球趨化抑制因子(leukocytic chemotaxis inhibitor)，是二氧化碳噬纖維菌和放射桿菌產生的一種能抑制人類多形核白血球趨化功能的物質，能阻礙白血球向炎症中心部位集中，目前有人提出這種物質是致病微生物的第IV型毒性因子； 膜動抑制因子(membrane mobility inhibitor)，最近發現二氧化碳噬纖維菌產生一種可透析的因子，主要抑制多形核白血球的運動性，如能抑制白血球膜包繞吞噬細菌的偽足運動，降低多形核白血球的吞噬功能。,細菌侵入及破壞 牙周組織的可能機轉,細菌侵入組織 :細菌利用各種因子侵入牙周組織，同時躲避宿主的免疫反應後，可以促進牙周組織的破壞。可以釋放溶解酶來破壞抗體和免疫細胞，或抑制胞激素的分泌造成免疫功能的失調。功能發揮不完全的宿主免疫，也就讓細菌能有侵入和破壞宿主組織及細胞的機會。 細菌破壞牙周組織的可能機轉:目前有兩條可能路徑是比較多學者研究與討論的。一是細菌釋放酶直接造成宿主細胞的分解（degradation）；另一則是細菌誘導宿主細胞分泌調控物質造成組織的破壞。,Microbiology and immunology in periodontal disease,Gingivitis Chronic periodontitis Aggressive periodontitis Necrotizing periodontal disease Periodontal abscesses,Plaque-induced gingivitis,Histopathologic changes are the vascular inflammation and infiltration of PMNs and then lymphocytes in the early stages. Early lymphocytic infiltrate is dominated by T-cells, but eventually B-cells become dominant. Established lesion is characterized by a predominance of B-cells that have transformed into plasma cells in the CT tissue.,Chronic periodontitis,Chronic periodontitis is characterized primarily as involving alternative pathway activation of complement, with C3 and B cleavage in gingival fluids observed. Activation of the classical complement pathway by processes involving Ab-Ag binding does not predominate. Bacteria enzyme cleave complement in GCF: P. gingivalis can cleave C5 to C5a,Chronic periodontitis,Collagenase activity is elevated by T. denticola , such as, MMP-8, whereas the levels of TIMP are not. Most of the collagenase activity associated with CP is due to the neutrophil MMP-8. The phagocytosis of F. nucleatum and T. denticola are associated with the release of high levels of elastase and MMP-8 from PMN.,Aggressive periodontitis,About 75% of LAP have dysfunctional neutrophils. The defect is a decrease in chemotactic response to C5a, N-FMLP, and leukotriene B4. In LAP the predominant collagenase found in tissue and GCF is MMP-1(altered neutrophil functions), and elevated levels of TIMP-1 are present. Elevated Ab to A.a. as well as complement is essential for opsonization and efficient phagocytosis.,Localized aggressive periodontitis,The dominant serum Ab isotype IgG2 is specific for surface Ag of A.a., including LPS and at least one major outer membrane protein. A.a. is capable of tissue destruction and inhibition of host defenses through the production of a leukotoxin and an immunosuppressive factor.,Necrotizing periodontal disease,HIV infection is associated with alterations in CD4+ T-cells and monocytes/macrophages. HIV patients may exhibit ANUP, particularly when CD4+ T-Cell levels are very low. Stress is associated with NUG and an increased prevalence of periodontitis.,Periodontal abscesses,Histologic studies indicate the presence of neutrophils and macrophages surrounding and internal region of dead leukocytes and tissue debris.,免疫反應調控失常導致牙周病的機轉:分成二條主要系統,一為骨髓系統可產生吞噬細胞，包括單核球及多形核顆粒球（polymorphonuclear granulocytes）兩種基本型態。後者常稱為多形核球（polymorph），依其顆粒染色程度的不同，又可分為嗜中性白血球、嗜鹼性球（basophil）或嗜酸性球（eosinophil）。其中嗜中性白血球在先天性免疫反應中佔有重要的角色。此外，還有大量的輔助細胞，包括：抗原呈現細胞（APCs），此細胞有非常多種，能夠具專一性地將抗原呈現給T淋巴細胞和B淋巴細胞。,免疫反應調控失常導致牙周病的機轉:分成二條主要系統,二為產生淋巴細胞：人體內的免疫系統包含體液免疫及細胞免疫兩大部份。體液免疫是指由B淋巴細胞製造特異性抗體，來對抗入侵體內之物質。而細胞免疫則是由T淋巴細胞和巨噬細胞及其分泌胞激素所媒介的免疫反應，而非抗體（即體液性免疫）所引發。此兩種淋巴細胞在表面都具有抗原接受器Roitt IM 1994。,先天性免疫反應與牙周病的關係,嗜中性白血球可依外來刺激之不同，進而執行複雜程度不一的反應，例如黏著、趨化作用、細胞吞噬、胞外微生物毒殺反應以及胞內微生物毒殺反應等Hart TC, 1994 。 牙周組織中直接面對微生物入侵衝擊的便是接合上皮(junctional epithelium)。IL-8訊息RNA可在牙齦組織被發現，並且多半侷限於接合上皮內，這也使得IL-8在嗜中性白血球向牙齦溝移動的過程中，扮演重要地位之原因；,急性發炎期:接合上皮內之構造因應微生物之入侵，便會展開一連串之轉變。由微生物產生之脂多醣與刺激一些胞激素分泌；如IL-1、TNF-等，會造成血管內皮細胞的啟始反應Bevilacqua MP, 1985，包括血管擴張、血流速趨緩、血液滯流、管壁通透性增加、白血球黏附分子出現。嗜中性白血球會在C5a、IL-8、白血球介素、及微生物抗原之促進下，先後經歷隨機接觸、滾動、黏附、外滲之過程，使嗜中性白血球能於血液中移動到受侵襲之部位McEver RP,1992，Adams DH, 1994。,Events associated with acute inflammation,Vascular changes Fluid exudate Cellular exudate Cell migration Phagocytosis Chemical mediators of inflammation,Vascular changes,It may last from minutes to days. Redness, heat, swelling, and pain It becomes apparent within 15 to 30 minsutes after injury. First minutes: vasoconstriction The follows the vasodilation of arterioles, and immediately afterward, vasodilation of venules and capillaries. Blood flow increases: redness and heat Intravasular hydrostatic pressure increases: fluid leakage.,Fluid exudate,Chemical mediators cause contraction of endothelial cells and generate gaps; this results in increased vascular permeability. Rich in proteins such as fibrinogen and immunoglobulins. Accumulation of both the cellular and fluid exudates causes swelling( edema). Chemical mediators released during these reactions produce pain.,Cellular exudate：白血球於血液中移動,多形核嗜中性白血球受到selectins之調控不僅可沿著血管內皮滾動甚至可與內皮細胞接合，selectins在嗜中性白血球與其他白血球表面為 L-selectin，內皮細胞則為E-selectin。 經由selectins間的交互作用，不僅可以在管壁內滾動，甚至白血球被作用啟始後，藉由beta-2 integrin與血管內皮細胞(intercellular adhesion molecule 1，ICAM-1)相結合，因此便可貼附於管壁。,當白血球移動穿透血管壁後，便可能浸潤於血管周邊結締組織或者是逐漸的通過接合上皮向微生物侵襲區域移動。其不僅會選擇性的向微生物侵襲區域移動，並且多半朝接合上皮冠部方向移動，目前認為有兩種可能的調控機轉： 其一為受上皮細胞的ICAM-1 調控 另一則為受一些趨化激素或如IL-8等胞激素等調控，研究指出IL-8對於嗜中性白血球之效應是與IL-8濃度相關的(dose-dependent)，低濃度的IL-8可以促進細胞移動，而高濃度IL-8則可啟動嗜中性白血球對抗微生物之機轉。,Cell migration,This step follows margination and pavementing. This process appears to be confined to the venules. In the first 6- 24 hours of acute inflammation reaction the migrating cells are predominantly PMNs. Later, monocytes, but in some hypersensitivity reactions, eosioophils are the main type of migrating cells. Chemotaxis involved interactions between cell surface receptors and the chemotactic agent. Chemotactic agents (chemokines) are secreted by monocytes and other cells: recruitment of leukocytes and MCP-1,2,3, IL-8, and RANTES products. Some chmokines are highly selective: eotaxin for eosinophils and IL-8 for PMNs.,Phagocytosis,Recognition and attachment: facilitated by opsonins Engulfment: resulting phagosomes fuse with cytoplasmic lysosomal. Killing and degradation: oxygen-dependent mechanism: oxygen-derived metabolites and radicals oxygen-independent mechanism: acidic pH, lysosomal enzymes, and complement, enhanced the bactericidal activity by cationic proteins and lactoferrin. After killing organisms, PMNs are killed by their own enzymes but monocytes/macrophages not killed and continue to produce inflammatory mediators.,Chemical mediators of inflammation,Vasoactive amines and peptides Plasma proteases Arachidonic acid metabolites Platelet activating factor Cytokines, chemokines, and growth factors,Vasoactive amines and peptides,Increasing vascular permeability Histamine and serotonin They are stored in the granules of mast cells, basophils and platelets. Other mediators are derived from the plasma: bradykinin, lysyl bradykinin, and peptides derived from fibrin degradation are also vasoactive.,Plasma proteases (Fig 3-3),Complement cascade kallikrein-kinin system Fibrinolytic clotting system,Complement,Classic pathway:initiated primarily by antigen-antibody complexes, bacterial products, and viruses. These substances bind to the C1q subunit of C1, which self-activates and then trigger the cascade of porteinases in the order C4, 2, 3, 5, 6, 7, 8, and 9. Alternative pathway: is a relatively slower process, and is activated by nonimmune stimuli such as foreign bodies and aggregated immunoglobulins. This pathway utilizes 2 plasma proteins (B and D) instead of C1,2, and 4, other reactions are the same as the classic pathway. The formation of both pathways is a membrane attach complex: C5b-6-7-8-9, which causes cell lysis.,Complement pathway,The central component of complement is C3 The central goal of the complement system is the formation of C3 convertase enzymes (C3bBb, C4bC2b) and the generation of C3b The biologic consequences of C3b formation depend on the presence or absence or regulators. No regulators, the cleavage of C5 products 2 fragements, C5a and C5b C5a is chemoattractant, and C5b associates with C6,7,8,9 to form a membrane attack complex.,Regulators of complement activation,Factors H and C4BP are serum cofactors that are most important in the inactivation of C3b and C4b, respectively. Factor H enables factor I inactivate C3b to form iC3b MCP and DAF are widely distributed on host cells and protect the host cell against C3b and C3 convertase, respectively. CR1 (expressed on phagocytes, B-cells, and red blood cells) binds C3b, which attracts factor I, leading to the inactivation of amplification by formation of iC3b. Phagocytes possess receptors for iC3b and will efficiently ingest the iC3b-bound cell or particle (opsonic phagocytosis) MCP protects host cells, and CR1 targets foreign or altered cells for destruction.,kallikrein-kinin system,Active kallikrein cleaves high molecules weight kininogen to bradykinin and lysyl bradykinin. Bradykinin increases vascular permeability, contracts smooth muscle, and produced pain. Kallikrein is chemotactic to, and promotes, aggregation of PMNs.,Fibrinolytic clotting system,The fibrin is degraded by plasmin. Peptides formed from fibrin induce vascular permeability and are chemotactic for leukocytes. The plasmin also catalyzes the conversion of factor XII to XIIA, and activates C3 triggering the complement cascade.,Arachidonic acid metabolites (fig 3-4),Prostanoid pathway- mediated by cyclooxygenase: the prostaglandins induce pain and fever. Thromboxane causes vaso- and bronchoconstriction and also enhances inflammatory cell function. Eicosanoid pathway- metabolized by lipooxygenase: the leukotrienes stimulate smooth muscle contraction and increase microvasucular permeability.LTB4 is a chemotactic agent. Corticosteroid inhibit phospholipase A2. NSAID inhibit the cyclooxygenase.,Platelet activating factor,PAF is highly potent at promoting platelet aggregation and degranulation, and leukocyte adhesion to endothelium. PAF causes vasodilatation and increased permeability in the microvasculature.,Cytokines, chemokines, and growth factors,Cytokines: are pyrogens, and stimulate the release of PGE2, PAF, and corticosteroid into circulation. affect the synthesis activities and adhesion properties of monocytes, lymphocytes. PMNs and fibroblast. Chemokines: leukocyte recruitment. Growth factors: regulate cell proliferation and matrix synthesis during wound healing. The above substances can be potentially harmful to the host if their activities are not carefully controlled.,In summary of PMNs in periodontal disease,They play a primary role in inflammatory process. They may stop the disease process and prevent the consequent antigenic challenge and the more destructive immune processes. Tissue damage from PMNs may be superficial to the underlying attachment apparatus and may be preferable to the stimulation of the immune system that could cause deeper and more long-term destruction.,慢性發炎期 :當微生物對組織的破壞逐漸增加，嗜中性白血球除了扮演第一道防線對抗微生物外，宿主局部與系統性的抗體免疫反應便隨之被啟動，產生抗體對抗微生物，局部抗體免疫反應主要是受組織內胞激素及抗原呈現細胞所影響，因此當經歷急性發炎期後，組織中的淋巴球、漿細胞、巨噬細胞等會逐漸的增加，另外由血液而來的特定抗體佔有牙齦溝中大部分的抗體Kinane D, 1993，系統性抗體免疫反應所扮演的角色會逐漸加重，甚至超過局部免疫的效應。,後天性免疫反應與牙周病的關係,宿主的後天性免疫反應包括體液免疫反應和細胞免疫反應兩大部份。 體液免疫是指由B淋巴細胞製造特異性抗體，來對抗入侵體內之物質，其中以免疫球蛋白為最重要的因子。 而細胞免疫則是由T淋巴細胞和巨噬細胞及其分泌胞激素所媒介的免疫反應為主,牙周組織中免疫球蛋白,在體液免疫反應中，主要作用形式是以血清中的抗體來對抗外來的微生物抗原，其中以免疫球蛋白為最重要的因子。而牙周組織中最主要的免疫球蛋白為G型免疫球蛋白(IgG)和A型免疫球蛋白(IgA) 。 其中又分為幾種亞型，G1亞型免疫球蛋白(IgG1)為牙周疾病中最為顯著的免疫球蛋白，包括在早發性牙周病、慢性成人型牙周病、及牙齦炎中都可以見到，約佔所有IgG的63 %，G2亞型免疫球蛋白(IgG2)約佔23 %，其餘G3、G4亞型只佔一小部分。,In summary of antibiotics in periodontal disease,Aggregating or clumping microorganisms. Preventing bacteria from adhering to the epithelium. Working with complement to lyse the microbes. In conjunction with PMNs, permit efficient phagocytosis,In summary of antibiotics in periodontal disease,Measurement of specific microbial antibiotics in longitudinal studies may provide information on relationship between antibiotic titer and avidity at both subject and site levels and prognosis. The humoral immune response, especially IgG and IgA, is considered to have a protective role in the pathogenesis of periodontal disease but the precise mechanism are still unknown.,Antibodies of different subclasses have different properties. Thus, IgG2 antibodies are effective against carbohydrate antigens (LPS) whereas the other subclasses are mainly directed against proteins. The proportions of plasma cells producing IgG and IgA subclasses were similar to the proportions of these immunoglobulin subclasses in serum. IgG1-producing plasma cells were predominant (mean 63%) in the gingival lesions; 23% of all IgG-producing plasma cells produced IgG2 antibodies, while IgG3- and IgG4-producing cells were present in much smaller numbers (3% and 10% respectively). Kinane et al. (1997),B cell regulation processes,By the process of binding to antigen the antibody activates different effector systems, e.g. complement The activation of the complement system in turn mediates PMN and macrophage migration and phagocytosis. The process in which the antibody contributes to the elimination of antigen by enhancing phagocytosis is termed opsonization.,Complement,The complement system is a central component of inflammation that enables endothelium and leukocytes to recognize and bind foreign substances.,Complement promotes inflammation by generating the following,A vasoactive substance, termed kinin-like, C2a, which induced pain and increases vascular permeability and dilation. Molecules, termed anaphylatoxins, C3a and C5a, which produce anaphylaxis by inducing mast cell secretion. A chemotaxin, C5a, which attracts leukocytes and stimulates phagocyte secretion. An opsonin, iC3b, covalently bound to molecular aggregates, particles, or cells, which enables phagocytes to ingest them.,Systemic humoral immune response,Homing recruitment of specific inflammatory and immune cells to the periodontium,Leukocytes recruitment Cytokine-induced expression of adhesion molecules Langerhans cells/other antigen presenting cells set up humoral immune response within peripheral lymph nodes,Homing of cells,Involvement of both humoral and cellular immune responses Local proliferation of leukocytes plays a minor role Large number of T cells and B cells in the periodontitis are attracted to the diseased site through selective homing and are not the result of local T and B cell proliferation,細胞免疫中淋巴球與牙周病關係,T淋巴球是細胞免疫中關鍵部分 CD4輔助性T淋巴球在細胞免疫中，扮演許多中心要角：一般相信未曾被刺激過的處女T細胞，（輔助T細胞的前驅，ThP）只釋放IL-2。短時間的刺激將使之發展成為ThO細胞，他可以分泌相當大範圍的各種胞激素。在經過慢性的刺激後，ThO會繼續分化成特化的Th1及Th2。 有些胞激素是Th1及Th2都可產生的（IL-3、GM-CSF及TNF-），但其他的則否。Th1細胞釋放IL-2及IFN-，而Th2細胞釋放I