innate immunity 先天性免疫
DESCRIPTION
Innate Immunity 先天性免疫. Memory ?. The front line of host defense. SP-A & D, defensin (opsonization). colicins of E. coli lactic acid from lactobacilli *antibiotic treatment. Establish an infection. (macrophage). (neutrophil). Macrophages are activated - PowerPoint PPT PresentationTRANSCRIPT
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Innate Immunity 先天性免疫
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Memory ?
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colicins of E. colilactic acid from lactobacilli*antibiotic treatment
SP-A & D, defensin (opsonization)
The front line of host defense
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Establish an infection
(macrophage)
(neutrophil)
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Macrophages are activated
by pathogens and both engulf
them and initiate inflammatory
responses.
co-stimulatory molecules (B7)
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Neutrophil : short-livedMacrophage : long-lived, continued to generate new lysosomes
Genetic deficiency of NADPH oxidase – chronic granulomatous disease
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Mycobacteria
抑制酸化阻止融合
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Macrophages are activated
by pathogens and both engulf
them and initiate inflammatory
responses.
co-stimulatory molecules (B7)
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Pattern-recognition receptors : A. 直接辨識 pathogen ,引發吞噬 (phagocytic receptor)
Mannose-binding lectin (MBL) : free in plasma 與細菌細胞壁的 mannose 結合 細菌表面分子的相對位置很重要 opsonization Macrophage mannose receptor : 與細菌及一些病毒 ( 如 HIV) 上的 mannose 結合 Scavenger receptors ( 與老化 RBC 的清除亦有關 )
B. 傳遞訊號 (signaling receptor)
Toll-like receptor (TLR) : 10 種 gene
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interferon
TNF-α, IFN-β
LTA TNF-α
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adjuvant
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Macrophages are activated
by pathogens and both engulf
them and initiate inflammatory
responses.
co-stimulatory molecules (B7)
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Macrophages release cytokines and chemokines to initiate an inflammatory response
1. 血流量增多但變慢 ( 紅、熱 ) 3. 血管通透性增加 (腫、痛 )
發炎細胞的到達 1.WBC 2.Monocyte 3. Others (eosinophil, lymphpcyte)
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Enzyme cascades : (trigger by tissue damage)
1. Kinin system : 產生影響血管的 peptides ( 如 bradykinin) ,使血管通透性增加, plasma proteins 進入”病灶“,阻止病原擴散。 造成疼痛2. Coagulation system : 形成 fibrin clot ,阻止病原進入血流。
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The complement system :
由不同分子誘發,但產生相同的作用分子
3. pore2. phagocytosis1. chemoattractants
4. 清除有問題的細胞
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Triggered-enzyme cascade
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Classical pathway : initiation by activation of C1 complex
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MB-lectin pathway
MASP-2: cleavage C4 and C2MASP-1: uncertain
缺乏 MBL 者,幼年期易受感染,此時 adaptive immunity 尚未成熟,移行抗體已下降。
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*C3 的活化作用只發生在病原體表面,不會發生於 宿主細胞上。
因 C4b 會與病原表面的蛋白或醣類結合, 若無儘快結合,則 C4b 會發生水解,變成不可逆且不具活性,無法形成 C3 convertase 。 C3b 也需儘速結合於病原表面。
C2 只在與 C4b 結合時,才可被 C1s 切割。
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Hydrolysis of C3 causes
initiation of the alternative
pathway
Fluid-phase C3 convertase
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Amplification loop
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Positive regulatory factor : 缺乏者易感染 Neisseria
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Ingestion of complement-tagged pathogens by
phagocytes is mediated by receptors (CR) for bound
complement proteins.
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6 types of complement receptors
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Anaphylactic shock(anaphylatoxin)
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The terminal complement proteins polymerize to
form pores in membranes that can kill the pathogens
membrane-attack complex
C8 = C8 (bind)
+C8- (insert)
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Neisseria
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Complement control proteins regulate all three pathways
and protect the host from its destructive effects
(serpin)
Hereditary angioneurotic edema excess cleaved C4 and C2 fragmentsC2b C2 kinin
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Induced innate responses to infection local and distant effects
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cysteine
CXCR1-6
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CCR1-9
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Chemokines 的功能及特性1. 一種 chemokine 可與一種以上的 receptor 結合,即可被 多種 receptor 辨識。2. 一種 chemokine 可由多種不同細胞產生且可影響多種細胞3. 引起趨化反應,藉由濃度梯度引導 effector cells 聚集於 感染部位。4. 有些種類與淋巴球的發育、移行及血管生成有關。
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Adhesion molecules : 3 family
subunitTNF-
C5aTNF-LPS
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Neutrophils leave the blood and migrate to sites of infection in a multistep process mediated through adhesive interactions.
fast
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extravasation
往濃度高處移動
(peaks within first 6 hrs)
slow
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TNF-α is an important cytokine that triggers local containment of
infection but induces shock when released systemically.
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Blood pressure↓
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clot
Septic shock
mice with mutant TNF-α receptor ?
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endogenous pyrogens
leukocytosis
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bind C1q
Acute-phase response
Pneumoncystis carinii
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Intracellular pathogen
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NK : release cytotoxic granules onto the target cell, the effector proteins penetrate the membrane and induce apoptosis.
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