PM3PY3 Immune System: The Adaptive Immune System

Themes (主題)

• Key principles of immunology (免疫學的關鍵原則)

• Allergy and hypersensitivity (過敏和超敏反應)

• Autoimmunity (自身免疫)

• Therapeutics that activate the immune system (激活免疫系統的療法)

• Transplantation and immunosuppression (移植和免疫抑制)

• Cancer Immunotherapy (癌症免疫療法)

Overview: Therapeutics & Immunology (治療學與免疫學概述)

Core Concepts (核心概念)

• Innate immunity (先天免疫)

• Adaptive immunity (適應性免疫)

• Antigen Specificity (抗原特異性)

• Lymphocytes (淋巴細胞)

• Effector Mechanisms (效應器機制)

Focus: Interventions (重點：介入)

• Infection (Immune Activation) (感染（免疫激活))

  • Vaccines (疫苗)

  • Immune stimulators (免疫刺激劑)

• Hypersensitivity (過敏)

  • Antihistamines (抗組織胺藥)

  • Glucocorticoids + Symptom management (糖皮質激素+症狀管理)

• Transplantation (移植)

  • Glucocorticoids (糖皮質激素)

  • Antiproliferatives (抗增殖藥)

  • Calcineurin inhibitors (鈣調神經磷酸酶抑製劑)

  • Other immunosuppressants (其他免疫抑製劑)

• Autoimmunity (自身免疫)

  • Analgesics (鎮痛藥)

  • Glucocorticoids (糖皮質激素)

  • Antiproliferatives (抗增殖藥)

  • Calcineurin inhibitors (鈣調神經磷酸酶抑製劑)

  • Other immunosuppressants (其他免疫抑製劑)

  • Symptom management (症狀管理)

• Cancer (癌症)

  • Checkpoint inhibitors (檢查點抑製劑)

  • Cancer vaccines (癌症疫苗)

  • T cell immunotherapy (T細胞免疫療法)

Learning Outcomes: (學習成果：)

• Contrast the features of adaptive immunity and innate immunity (對比適應性免疫和先天免疫的特徵)

• Explain what antigens are and know the main types (解釋什麼是抗原，並了解主要類型)

• Identify the cells (T and B lymphocytes) of the adaptive immune response and explain their relevance, including their development and functions (識別適應性免疫反應的細胞（T和B淋巴細胞），並解釋它們的相關性，包括它們的發展和功能)

• Understand what is meant by immune tolerance (理解免疫耐受的含義)

• Describe the function of antibody and articulate how they can have different effector mechanisms (描述抗體的功能，並闡明它們如何具有不同的效應機制)

• Compare the effector functions of different subsets of T cells (比較T細胞不同亞群的效應功能)

• Understand the basis for immune memory (了解免疫記憶的基礎)

• Have an awareness of interaction between the innate and adaptive immune system (了解先天免疫系統和適應性免疫系統之間的相互作用)

Activation of Innate and Adaptive Immunity (先天免疫和適應性免疫的啟動)

The 2011 Nobel Prize in Physiology or Medicine was awarded to: (2011年諾貝爾生理學或醫學獎授予：)

• Bruce A. Beutler and Jules A. Hoffmann for their discoveries concerning the activation of innate immunity. (Bruce A. Beutler 和 Jules A. Hoffmann 關於先天免疫激活的發現。)

• Ralph M. Steinman for his discovery of the dendritic cell and its role in adaptive immunity. (Ralph M. Steinman 發現樹突狀細胞及其在適應性免疫中的作用。)

Summary (總結)

• The Nobel Laureates revolutionized the understanding of the immune system by discovering key principles for its activation. (諾貝爾獎獲得者通過發現啟動免疫系統的關鍵原理，徹底改變了對免疫系統的理解。)

• Bruce Beutler and Jules Hoffmann discovered receptor proteins that can recognize microorganisms and activate innate immunity. (Bruce Beutler 和 Jules Hoffmann 發現了可以識別微生物並啟動先天免疫的受體蛋白。)

• Ralph Steinman discovered dendritic cells and their unique capacity to activate and regulate adaptive immunity. (Ralph Steinman 發現了樹突狀細胞及其激活和調節適應性免疫的獨特能力。)

• The discoveries revealed how the innate and adaptive phases of the immune response are activated, providing novel insights into disease mechanisms and opening new avenues for prevention and therapy against infections, cancer, and inflammatory diseases. (這些發現揭示了免疫反應的先天性和適應性階段是如何被啟動的，為疾病機制提供了新的見解，併為預防和治療感染、癌症和炎症性疾病開闢了新的途徑。)

The Adaptive Immune System (適應性免疫系統)

• Learned response to ‘antigens’ (對“抗原”的習得反應)

• Memory (記憶)

• Lymphocyte responses (淋巴細胞反應)

• Expansion of specific T and B cells (特異性 T 細胞和 B 細胞的擴增)

• Production of antibodies (抗體生產)

• How can our body ‘remember’ previous infections? (我們的身體如何「記住」以前的感染？)

• What molecular elements can the adaptive immune system respond to? (適應性免疫系統可以對哪些分子元件做出反應？)

Adaptive vs Innate Immunity (適應性免疫與先天免疫)

Adaptive vs Innate Immunity

Antigen Specificity (抗原特異性)

• The adaptive immune system can learn to recognise: (適應性免疫系統可以學習識別：)

  • Structures (Antibody, BCR): (almost) anything… (結構（抗體、BCR）:(幾乎)任何東西……)

  • Peptides ≥8 amino acids (T cell receptor) (肽 ≥8 個氨基酸（T 細胞受體）)

• Structural Antigens: Recognised by Antibody (結構抗原：抗體識別)

  • Variable region binds to antigen via a mixture of hydrophobic/hydrophilic, electrostatic, hydrogen bonding, van-der-waals interactions (可變區通過疏水/親水、靜電、氫鍵、范德華相互作用的混合物與抗原結合)

  • Binding is high-affinity and stable (結合具有高親和力且穩定)

  • Not always specific – some binding sites shared (並不總是特異性 – 一些結合位點共用)

  • Antibodies can be soluble or on B cells (BCR) (抗體可以是可溶性的，也可以是 B 細胞 (BCR))

  • Examples: everything from infectious agents to small organic molecules (示例：從傳染性病原體到小有機分子的所有內容)

• Peptide Antigens: Recognised by T cell Receptor (TCR) (肽抗原：被 T 細胞受體 （TCR） 識別)

  • Proteins made of many overlapping peptides (由許多重疊肽組成的蛋白質)

  • For an 8mer, theoretically 208208 different ones! (對於 8mer 來說，理論上 208208 有不同的!)

  • T Cell recognises MHC:epitope (T 細胞識別 MHC:表位)

  • All cells: MHC class I (endogenous) (所有細胞: MHC class I (內源性))

  • Professional APC: MHC class I & MHC class II (exogenous) (專業 APC: MHC class I & MHC class II (外源性))

  • Epitopes may be inside protein structure (表位可能位於蛋白質結構內部)

  • Proteins are broken down into peptides (蛋白質被分解成肽)

  • Specific epitopes are presented by MHC molecules (特異性表位由 MHC 分子呈現)

  • Antigens ‘presented’ to T cells (抗原 ‘presented’ 給 T 細胞)

    • CD8 T cell (CD8 T 細胞)

    • CD4 T cell (CD4 T 細胞)

• Lymphocytes (淋巴細胞)

  • Lymphocytes enable the adaptive immune system to: (淋巴細胞使適應性免疫系統能夠:)

    • recognise any antigen (識別任何抗原)

    • ‘learn to respond’ and ‘remember’ (‘學會回應’ 和 ‘記住’)

    • kill microbes (殺死微生物)

  • B cells (make antibody – recognise structural antigen) (B 細胞 (產生抗體 – 識別結構抗原))

  • T cells (respond to peptides (antigens) presented) (T 細胞 (對 peptides (antigens) 呈現))

  • Found in blood and lymphatic system (after development) (發現於血液和淋巴系統 (發育後))

  • Both have random, clonal antigen receptors (兩者都有隨機的,克隆抗原受體)

Lymphocyte Recognition of Antigen

• Lifestages of Lymphocytes (淋巴細胞的生命週期)

  • Generation, selection (生成、選擇)

  • Priming, replication, clonal expansion (引發、複製、克隆擴增)

  • Effector function (執行器功能)

  • Learning what to respond to - and remembering (學習回應什麼 - 並記住)

  • Enabling the body to recognise anything (使身體能夠識別任何東西)

  • Recognising and killing microbes (識別和殺死微生物)

• Lymphatic System (淋巴系統)

  • Lymph nodes, spleen, mucosa-associated lymphoid tissue (MALT), tonsils (淋巴結、脾臟、粘膜相關淋巴組織 （MALT）、扁桃體)

  • T cells – Thymus (from BM) (T 細胞 – 胸腺（來自 BM）)

  • B cells – Bone marrow (B 細胞 – 骨髓)

  • Required site in the body (正文中所需的網站)

• Generation of Lymphocytes (淋巴細胞的產生)

  • Lymphocytes, like other blood cells, are derived from bone marrow cells (HSC) but are unique: (與其他血細胞一樣，淋巴細胞來源於骨髓細胞 （HSC），但是獨一無二的：)

    • Their genome is randomly rearranged to give each cell a single antigen receptor (它們的基因組被隨機重排，為每個細胞提供單個抗原受體)

    • After rearranging, lymphocytes are selected for safe and effective function – “tolerance” (重新排列後，選擇淋巴細胞以實現安全有效的功能——“耐受性”)

  • 100 美元 100 萬美元 different antigen receptors (不同的抗原受體)

• Tolerance (寬容)

  • Tolerance = the mechanism by which our immune system removes those antigen receptors that recognise ‘self antigen’ (耐受性 = 我們的免疫系統去除識別“自身抗原”的抗原受體的機制)

  • By definition, any immune response to own antigens is ‘failure of tolerance’ (根據定義，任何對自身抗原的免疫反應都是“耐受失敗”)

  • Many examples of autoimmune adaptive immune responses with no clinical pathology (許多無臨床病理的自身免疫性適應性免疫反應的例子)

  • Some rare extreme conditions where the immune system is destructively activated at birth, e.g., APS-1 (mutation in AIRE gene) or IPEX syndrome (mutation in FOXP3) – lead to loss of tolerance… (一些罕見的極端情況，免疫系統在出生時被破壞性啟動，例如 APS-1（AIRE 基因突變）或 IPEX 綜合征（FOXP3 突變）——導致耐受性喪失……)

• Central Tolerance (中心公差)

  • Occurs in thymus (T cells) and bone marrow (B cells) (發生在胸腺（T 細胞）和骨髓（B 細胞）中)

  • Want functional, non-self-reactive lymphocytes (想要功能性、非自身反應性的淋巴細胞)

  • Those that have no binding (majority) – eliminated (那些沒有約束力的 （大多數） – 被淘汰)

  • Of those that bind, remove highly autoreactive lymphocytes before they mature (AIRE gene), but need to engage with MHC (MHC restricted) (在那些結合的淋巴細胞中，在成熟之前去除高度自身反應性的淋巴細胞（AIRE 基因），但需要與 MHC 結合（MHC 受限）)

  • Other cells become naïve T cells (CD4 or CD8+), some become Treg cells (-ve effects) (其他細胞變成幼稚 T 細胞（CD4 或 CD8+），一些變成 Treg 細胞（-ve 效應）)

  • Mainly during development / early life (主要在發育/早期)

• Peripheral Tolerance (週邊容差)

  • Occurs in the periphery (tissues and lymph nodes) to regulate self-reactive T cells that ‘escape’ the thymus [escape is important to allow variation…] (發生在外周（組織和淋巴結）以調節“逃逸”胸腺的自身反應性 T 細胞 [逃逸對於允許變化很重要…])

  • Self-reactive cells can undergo apoptosis or anergy (自身反應性細胞可發生細胞凋亡或無反應)

  • Peripheral Treg lymphocytes can also be generated (也可產生外周 Treg 淋巴細胞)

  • Mainly in adult life (主要發生在成年生活中)

  • As no innate ‘alert’ e.g., if checkpoint inhibition (PD1, CTLA4) (由於沒有先天性的「警報」，例如，如果檢查點抑制（PD1、CTLA4）)

• Learned Response (學習的回應)

  • Innate signals activate ‘dendritic cells’ which present [viral] peptide on MHC (先天信號啟動“樹突狀細胞”，在 MHC 上呈遞 [病毒] 肽)

  • Only 1 個 recognises a particular peptide in the new [virus] (只有 1 個識別出新 [病毒] 中的特定肽)

  • Single cell replicates 20 or more rounds over 2-3 weeks (單細胞在 2-3 週內重複 20 輪或更多輪次)

  • Peak時血液中高達 1% 的 T 細胞 (Up to 1% of T cells in blood at peak)

  • XX millions of identical T cells (XX 數百萬個相同的 T 細胞)

  • Innate signals control adaptive responses (先天信號控制適應性反應)

• Naïve T-cell Priming (初始 T 細胞啟動)

  • Priming by (mainly) dendritic cell APC: MHC-II for CD4, MHC-I for CD8 (由（主要）樹突狀細胞 APC 引發：CD4 的 MHC-II，CD8 的 MHC-I)

  • Occurs in lymphoid tissues (e.g., lymph nodes) (發生在淋巴組織（例如淋巴結）)

  • Interface innate & adaptive responses (DC and T cells: DC to local lymphoid tissue) (介面先天性和適應性反應（DC和T細胞：DC到局部淋巴組織）)

  • 啟動 requires 兩個 signals: (Priming requires TWO signals:)

    • Interactive TCR and MHC:antigen and CD4/8 receptor (相互作用 TCR 和 MHC：抗原和 CD4/8 受體)

    • Interaction co-stimulating molecules (e.g., CD80/86 (B7) APC, CD28 T cell) (相互作用共刺激分子（例如，CD80/86 （B7） APC、CD28 T 細胞）)

  • due to IL-2/IL-2R, the induced (activated) T cells proliferate (a large number of clonally identical cells appear in a few days) - being regulated by signals above (然後，由於 IL-2/IL-2R 的作用，引發（活化的）T 細胞增殖（幾天內出現大量克隆相同的細胞）——被上述信號上調)

  • For CD4 Th cells, during this time decide what type of Th cell (see below) (對於CD4 Th細胞，在此期間決定Th細胞的類型（見下文）) -CD8 usually needs additional stimulation (“help”) from CD4 cellsnote: (CD8 細胞通常需要 CD4 細胞的額外刺激（“説明”）注意：)

  • Cross-Priming refers to DC presenting the acquired antigen from outside cell to CD8 T cells (MHC-I, the common endogenous antigens) (交叉引發是指 DC 將從細胞外獲得的抗原呈遞給 CD8 T 細胞（MHC-I，通常是內源性抗原）)

  • cross-Priming is important for inspecting tumor and DC cells under Virus Infection (交叉引發對於檢測腫瘤和病毒感染的DC細胞很重要)

• Lymphocytes Initiation (淋巴細胞的啟動)

  • Occurs in lymphatic tissues e.g. (發生在淋巴組織中，例如)

    • Peyer 斑塊 (Peyer’s patches (GI))

    • 扁桃體 (Tonsils (NALT))

    • 脾臟（如果來自血液）(Spleen (if from blood))

    • 淋巴結 (Lymph nodes)

  • -(Once initiation), CD4 T cells will up-regulate CD40L – binding CD40 which is on APC-aiding clonal expansion ( once initiated, CD4 T cells up-regulate CD40L – 在APC上結合CD40 – 有助於克隆擴擴)

  • Co-stimulate deficiency will lead to unresponsiveness (tolerance) (缺乏共刺激導致無反應（耐受性）)

• T Cell Activation/Tolerance (T 細胞活化/耐受)

  • Negative feedback: (負面反饋：)

    • T cells needs signals to be activating (*induced) (T 細胞需要 2 個信號才能被啟動（引發）)

    • Co-stimulating deficiency (CD80/86:CD28; the unguided IL-2) - to prevent activation (缺乏共刺激（CD80/86：CD28;無誘導 IL-2）- 阻止啟動)

    • non-responsiveness can result the suppression check point namely CTLA-4, PD-1 (無反應可導致抑制性檢查點（例如 CTLA-4、PD-1）)

    • CTLA-4 （on T cells) bounded with CD80/86 however to prevent from activation (CTLA-4 （在 T 細胞上） 結合 CD80/86 但阻止啟動)

      • -CTLA-4 will up-regulate during T cells activation and it acts as the -ve feedback (CTLA-4 在 T 細胞活化時上調 – 充當 –ve 反饋)

    • -PD-1 (on T cells) combined to PD-L1 which is on target cells-suppressing from activating (PD-1（在 T 細胞上）與靶細胞上的 PD-L1 結合 – 抑制活化)

      • -relevant to the Cancer Immunotherapies (與以後的癌症免疫治療非常相關……)

• Naïve B cell activation (初始 B 細胞活化)

  • In lymph nodes (secondary lymphatic tissues), BCR will recognise towards antigen (在淋巴結（次級淋巴組織）中，BCR識別抗原)

  • BCR: antigen is internalised and peptide antigen presents on MHC surface (BCR：抗原內化，肽抗原呈遞在 MHC 表面)

  • this B cells is under priming (這個 B 細胞被啟動) Can the be activate and is interacting with CD4T helper cells especialliy for Tfh,leading to proliferation and class switching and differentiation for (CD40L Th:CD40 B cell) (然後可以被啟動（與 CD4 輔助性 T 細胞相互作用，尤其是 Tfh），導致增殖、類別轉換和分化（CD40L Th：CD40 B 細胞）)

  • depends on T helper cells stimulation and the Cytokines Signal transductions (類別轉換和分化取決於 T 輔助細胞的共刺激和細胞因數信號傳導（IgG 亞型 （IL-4/5/6/13， IFNg）， IgA （IL-5， TGFb）， IgE （IL-4/13）， IgM （IL-4/5） 成熟）;從 IgM 開始)

  • Short-lived plasma B cells makes large amount of the antibodies against antigens (短壽命血漿 B 細胞 – 產生大量抗原抗體)

  • Memory B cells- is capable to react rapid encounter the same antigens and long-lived (記憶 B 細胞 – 能夠在將來遇到相同抗原時快速反應 [數量更少，壽命更長])

  • -Long-live plasma B cells maintain in BM for Years or lifetime (長壽命血漿 B 細胞（留在 BM 中，存在數年或終生）)

  • Note, can also gain T cells independent activation for B cells with forming memory B cells (注意：還可以獲得 T 細胞非依賴性啟動 B 細胞和記憶 B 細胞形成（例如，一些外來多糖、非 mCpG - 參見後面的疫苗……)

• Normal Immune Response: Virus infection (正常免疫反應：病毒感染)

  • Stimulate (刺激：)

    • -Innate Immune System: through PAMP ( within hours infection) (先天免疫系統：通過PAMP（感染后數小時內）)

    • -Adaptive Immune responses are induced by the Priming and are cellular with humoral for days later (先天成分引發后的適應性免疫反應（幾天后細胞和體液反應）)

• Effector Functions (執行器函數)

  • -A great mount of T cells effectors-CD4+ T helper cells or CD8+ cytotoxic T cells CTL (大量效應 T 細胞-CD4+ 輔助性 T 細胞、CD8+ 細胞毒性 T 細胞 （CTL）)

  • -B cells clonal cell get chosen with large expansion (B 細胞克隆也被選擇並進行大規模擴增)

  • -large amount of B cells effectors generates secretion antibodies (大量效應 B 細胞產生分泌抗體)

• Effector Mechanisms(效應器機制)

  • Antibodies Subtypes (抗體類型：)

    • -Bonding and shielding for neutralization (結合和封閉（中和）)

    • -Histamine (組胺)

    • -Opsonization is and starting complements by with phagocytosis (調理作用、補體啟動和吞噬作用)

  • T lymphocytes types(T 淋巴細胞的類型：)

    • -killers: directly killing the virus infected cells (殺手：直接殺死病毒感染的細胞)

    • -Helpers: the release cytokines with inflammations (*cells are mediators) (輔助方法：細胞因數釋放和炎症（細胞介導）)

    • -Helper: control what responses from B cells antibodies (輔助方法：對照 B 細胞抗體反應)

Types of Antibody

Antibody Effector Mechanisms 1

• Binding and blocking (結合和封閉)

  • Toxins can be bound and inactivated by IgG and IgA (毒素可被IgG和IgA結合和滅活)

  • IgG and IgA antibodies can directly block viral infection (IgG 和 IgA 抗體可以直接阻斷病毒感染)

Antibody Effector Mechanisms 2

• Antigen bound by IgG and IgM activates ‘complement’ which can punch holes in cell walls (與 IgG 和 IgM 結合的抗原會啟動「補體」，從而在細胞壁上打孔).

• Opsonisation/complement link to phagocytosis (Opsonisation/complement 與吞噬作用有關)

• Phagocytes (e.g., macrophages) are coated with receptors for IgG and rapidly phagocytose antibody bound to antigen (吞噬細胞（例如巨噬細胞）包被有IgG受體，並迅速吞噬與抗原結合的抗體)

Antibody Effector Mechanisms 3

• Mast cells are ‘sentinels’ (肥大細胞是「哨兵)

• Can be coated with IgE following immune activation (bind IgG via FceRs) (免疫啟動后可塗覆 IgE（通過 FceRs 結合 IgG）)

• Antigen recognition triggers histamine and other mediator release (抗原識別觸發組胺和其他介質的釋放)

• Useful for extracellular pathogens (e.g., helminths) (對細胞外病原體（例如蠕蟲）有用)

Types of T cells and Function (T 細胞的類型和功能)

• CD8 CTL: Cytotoxic - direct killing of virally infected cells or those infected with some other types of intracellular pathogens or tumour cells (granzymes, perforin – trigger apoptosis, IFNg) (CD8 CTL：細胞毒性 - 直接殺死病毒感染的細胞或感染某些其他類型的細胞內病原體或腫瘤細胞（顆粒酶、穿孔素 - 觸發細胞凋亡、IFNg）的細胞)

• Often requires help of CD4 ‘Helper’ (Th) Cells for full activation (通常需要CD4“輔助”（Th） 細胞的説明才能完全啟動)

CD4 T cell Effector Function (CD4 T 細胞效應器功能)

• Primed CD4+ T cells can then differentiate into effectors – these no longer require co-stimulation to deploy effector functions (然後，引發的CD4+ T細胞可以分化為效應器——這些細胞不再需要共刺激來部署效應器功能)

• Other changes help to target them to sites needed (其他更改有助於將他們定位到所需的網站)

• Primed CD4 T cells can become different types of effector cells: Th1, Th2, Th17 (引發的CD4 T細胞可以變成不同類型的效應細胞：Th1、Th2、Th17)

• Type of CD4 effector cell depends on the pathogen and cytokine signalling (CD4 效應細胞的類型取決於病原體和細胞因數信號傳導)

• Why different effector functions?: (為什麼效應器功能不同？:)

  • Th1 – cell-mediated immunity; required for intracellular pathogens (since antibodies cannot ‘see’ them); activate macrophages (IFNg and CD40L) and expand CD8+ CTL (IL-2) (Th1 – 細胞介導的免疫;細胞內病原體需要（因為抗體無法“看到”它們）;啟動巨噬細胞（IFNg 和 CD40L）並擴增 CD8+ CTL （IL-2）)

  • Th2 – humoral immunity; required for extracellular pathogens – depends more on actions of antibody; Th2 cells are effective at stimulating proliferation, class switching and differentiation of B-cells (IL-4/5/13 - IgE) and induction of eosinophils (IL-5) and proliferation of mast cells (IL-3/4) (Th2 – 體液免疫;細胞外病原體需要 – 更多地取決於抗體的作用;Th2 細胞可有效刺激 B 細胞的增殖、類別轉換和分化 （IL-4/5/13 - IgE） 以及誘導嗜酸性粒細胞 （IL-5） 和肥大細胞增殖 （IL-3/4）)

  • Th17 – skin/mucosal immunity; required for extracellular bacterial and fungal infections. Trigger inflammatory response from non-immune cells (e.g., endothelial) and recruit neutrophils (IL-17/22) (Th17 – 皮膚/粘膜免疫;細胞外細菌和真菌感染需要。觸發非免疫細胞（例如內皮細胞）的炎症反應並募集中性粒細胞 （IL-17/22）)

Cross-repress each other (交叉壓制彼此)

Sub-types of CD4 Helpers (CD4 輔助細胞的亞型)

• Tfh is important for B cell activation for Th1/2/17 (IgG/IgE/IgA) (Tfh 對 Th1/2/17 （IgG/IgE/IgA） 的 B 細胞活化很重要)

• Treg is important for regulating other T cells (Treg 對調節其他 T 細胞很重要)

  • Th1: Cellular immunity (intracellular) (Th1：細胞免疫（細胞內）)

  • Th2: Humoral immunity (extracellular parasites) (Th2：體液免疫（細胞外寄生蟲）)

  • Th17: Mucosal/skin immunity (extracell. bacteria and fungi) (Th17：粘膜/皮膚免疫（細胞外細菌和真菌）)

CD4 Th1 Effector Functions (CD4 Th1 效應器功能)

1. Activate macrophage killing of microbes at the site of infection (激活巨噬細胞對感染部位微生物的殺傷)

2. Increase activation and proliferation of CD8 CTL at the site of infection (增加感染部位CD8 CTL的活化和增殖)

Key Roles CD4 Th2 Cells (CD4 Th2細胞的關鍵作用)

1. Activate B-cell – generate pathogen-specific antibody (啟動 B 細胞 – 生成病原體特異性抗體)

2. High levels of antibody against the same antigen that peptide was derived from (針對肽來源的相同抗原的高水準抗體)

• HIV infects and leads to the death of CD4 cells and MP Hence loss adaptive immunity (HIV 感染並導致CD4細胞和MP死亡，因此喪失適應性免疫)

Adaptive Immunity: Memory (適應性免疫：記憶)

• After resolution of infection, large numbers of activated lymphocytes reduce (undergo apoptosis) (感染消退後，大量活化的淋巴細胞減少（發生細胞凋亡）)

• Retain smaller numbers of ‘memory’ cells (保留較少數量的 「memory」 儲存格:)

  • Long-lived plasma B cells and memory B cells (長壽命血漿 B 細胞和記憶 B 細胞)

  • Memory B cells: located in lymphoid tissues and circulation; long-lived plasma B cells in bone marrow (記憶 B 細胞：位於淋巴組織和迴圈中;骨髓中長壽命的血漿 B 細胞)

  • CD4+ and CD8+ memory T cells (CD4+ 和 CD8+ 記憶 T 細胞)

  • Memory T-cells: Some persist in secondary lymphoid tissues, some in lymph nodes, and others in tissues or circulation (記憶 T 細胞：一些存在於次級淋巴組織中，一些存在於淋巴結中，另一些存在於組織或迴圈中)

• Allow a faster, more specific, and targeted response on re-exposure (允許在再次曝光時做出更快、更具體和更有針對性的回應)

Adaptive Immunity Summary (適應性免疫總結)

• Can respond to any antigen (可對任何抗原有反應)

• Only after priming (僅在灌注後)

• Body retains long-lived memory of encounter (身體保留了對相遇的長壽記憶)

• Developed during the lifetime of the individual (在個人的一生中發展)

• Antigen comes in two forms and is recognised by two types of lymphocyte (抗原有兩種形式，可被兩種類型的淋巴細胞識別):

  • Structural antigens: B cells make antibody (結構抗原：B 細胞產生抗體)

  • Short peptide antigens: T cells have T cell receptors (短肽抗原：T 細胞具有 T 細胞受體)

Adaptive Immunity Effector Mechanisms

Learning Outcomes: Recap

After this lecture and further reading, students should be able to:

• Contrast the features of adaptive immunity and innate immunity

• Explain what antigens are and know the main types

• Identify the cells (T and B lymphocytes) of the adaptive immune response and explain their relevance, including their development and functions

• Understand what is meant by immune tolerance

• Describe the function of antibody and articulate how they can have different effector mechanisms

• Compare the effector functions of different subsets of T cells

• Understand the basis for immune memory

• Have an awareness of interaction between innate and adaptive immune system

適應性免疫效應器機制