disease of immunity Flashcards
C3a, C4a, C5a
complements segments that are responsible for increasing vascular permeability
chemokines –> attract neutrophils
Arachidonic Acid
Newly synthesized mediator in type I sensitivity
例如: prostaglandin、leukotriene造成血管通透性增加、平滑肌收縮
PAF (platelet-activating factor)
Type I hypersensitivity
Newly synthesized Mediator (secondary) :受到活化才會開始表現，要經過代謝、合成
活化血小板、平滑肌收縮、血管通透性增加
c-kit
tyrosine kinase receptor on the mast cell; ligand is SCF (stem cell factor)
promoting mast cell development and function
Asphyxiation
- Asphyxiation(窒息): 上呼道水腫、循環障礙、血中含氧量不足造成
pruritus
搔癢
- Anaphylactoid reaction
- 定義: 不需要透過IgE就能引發type1 hypersensitivity reaction，可以直接活化mast cell、basophil，導致他們釋放granule。
- 刺激、調控因子
- Cytokine (IL-8)
- complement products (anaphylatoxins C3a and C5a)
- drugs (nonsteroidal antiinflammatory drugs, codeine, and morphine)
- physical stimuli (冷、熱、創傷)
*其中最重要的為C3a和C5a，會不斷地出現在過敏反應中，像是一個快捷鍵，一出現就會產生免疫反應。
type II hypersensitivity causes what?
- decrease in cells. causing anemia, agranulocytosis, thrombocytopenia
- altering cell or tissue function followed by inflammation
Myasthenia gravis
重症肌無力: 來自Ach receptor受到攻擊，肌肉無法作用，造成肌肉無力、甚至出現麻痺。
- 抗體作為antagonist，抗體接上Ach receptor，阻擋住Ach結合到receptor，因此後續動作無法進行，肌肉的作用會被抑制，重肌無力症就是這個原因造成的。
Autoantigen
An autoantigen is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease.
CTL4
inhibitory receptor in T cells for binding to B7 on APC
causing anergy of lymphocytes
AIRE
thymic expression of self antigen
Fas
expressed on lymphocyte
FasL: ligand on it expressed primarily on activated T lymphocyte
the two binding results in apoptosis of activated T lymphocyte or B lymphocyte
how genetic defect leads to autoimmune disease?
- defect of Fas/FasL –> disruption of activation induced cell death signal in lymphocyte
- lacking transcription factor AIRE whcih is responsible for thymic expression of self antigen
- defective in the expression of CTLA-, the inhibitory receptor involved in T-lymphocyte anergy
how infection of virus or bacteria results in autoimmune disease?
- 有些可辨識自身抗原的B and T lymphocytes在分化過程中沒有被清除掉，而之後又被活化
- peripheral tolerance中anergy效果不好時
- Induction of co-stimulators on APCs：非特定抗原，組織受傷時self-antigen被呈現給self-reactive T cell，而他沒有被成功anergy反而是接收到APC的costimulators。
- molecular mimicry：特定外來抗原長的很像自己身體裡面的抗原，被self-reactive T cell辨認。
Systemic Lupus Erythematosus (SLE)
- 產生對抗細胞核的抗體antinuclear antibody (ANA)：人是針對DNA，動物則是以histones或nonhistone proteins(黏在RNA上)當作抗原。
- 也會針對紅血球、血小板、淋巴球產生autoantibodies
- 動物公母沒有明顯差異，人類女性較容易發生(coz targeting estrogen)。
- 狗通常在五歲發病，貓在這種疾病表現不明顯。
- 產生Immune complexes存在於 glomeruli, blood vessels, skin and joints
- 因為Immune complexes堆積會造成炎症反應，造成腎臟炎、皮膚炎、關節炎(臨床上會看到動物跛行、不願行走)
- SLE in Dogs
- 公狗多於母狗
- 診斷：透過偵測ANA, Coombs test, rheumatoid factor(anti IgG antibody), immune complexes(出現在皮膚、血液中)
- 可以活化both humoral and cellular immunity
- Humoral immunity：透過活化self-reactive B lymphocytes產生autoantibodies。
- Cellular immunity：造成淋巴球減少(lymphopenia)，導致high CD4+ /CD8+ ratio，也就是說CD4+比CD8+多，但其實兩者數量都下降。
- 診斷疾病：透過criteria來評估，看看符合幾項
- 狗：4/11以上就絕對符合，3種或是多發性關節炎並且測到ANA就代表可能是。
- 人：透過判斷關節、血清裡蛋白
- 臨床症狀：
- Non-erosive polyarthritis：immune complex堆積造成，會出現在關節、手腕、腳掌、temporomandibular joints(顳骨與下顎關節)，而下顎這裡出現炎症反應時，會抗拒進食。
- 臉部、耳朵、四肢末端出現紅腫、潰瘍、脫皮性皮膚炎(UV照射有關)
- Epidermis的basal cell 出現vacuolation(空胞化)、壞死
- Dermis跟Epidermis交界處有mononuclear inflammatory cells浸潤，甚至出現脂肪炎、血管炎。
