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immunology > Hematopoiesis > Flashcards

Hematopoiesis Flashcards

1
Q

What is Hematopoiesis

Where begins? after that ?

A
  1. Formation and development of red and white blood cells。
  2. During first weeks of development：Begins in embryonic yolk sac(胚胎卵黃囊)
  3. 3rd month of gestation：Hematopoietic stem cells, HSCs（造血幹細胞）遷移到胎兒的fetal liver(肝臟), then to spleen
  4. By birth, HSC最後會遷移到bone marrow（骨髓 ），骨髓成為出生後造血細胞最重要的部分。
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2
Q

What are the two progenitor that hematopoietic stem cell differentiate into?

After that, what cells do theses progenitor cells differentiate into?

A
  1. Myeloid progenitor :Dendritic cell, granulocyte(monocyte, neutrophil), eosinophil, basophil, megakaryocyte (platelet), erythroid progenitor (erythrocyte)
  2. Lymphoid progenitor: NK cell, T-cell, B-cell, Dendritic cell
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3
Q

What are the half life of neutrophils, memory cell, lymphoblast and effector cell?

A

neutrophils: 1~2 week
memory: ~years

Plasma cell: within 2 weeks

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4
Q

Oxygen dependent killing by macrophage

A

Produce NO, which has antimicrobial activity

take place in the presence of NOS (synthase)

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5
Q

oxygen- independent killing by macrophages

A

(1) defensin: 29-35 aa cysteine-rich peptides(以參與先天性免疫為主，病原侵入數

天、數小時就能被活化)

(2) lysozyme/hydrolytic enzyme(切蛋白質、nucleic acid等等)
1. tumor necrosis factor (TNF)(殺腫瘤細胞的細胞因子，有TNF-α和TNF-β)

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6
Q

TNF-α

A

Cytokine released by activated macrophage

inducing hematopoiesis,

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7
Q

IL1 & 6

A

factor secreted by activated macrophage to promote inflammatory resonses, innate immunity and elimination of pathogens

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8
Q

Polymorphonuclear leukocyte

A

Neutrophil

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9
Q

Is basophil phagocytic? what does it mainly tackle with?

A

No, it usually interact with pathogens by secretion of intracellular substance

related to allergy (mast cell too! )

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10
Q

Mast cell got what??

where to find it?

A

cytoplamic granules containing histamine

IgE-primed causes its release, causing allergy

found on skin, respriratory tract and urinary system

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11
Q
  1. Members of xxxx is expressed in high level of dendritic cell
A

co-stimulatory B7 family

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12
Q

Compare the cells and density in Cortex and medulla of Thymus

A

Cortex:

  • immature T-cells (thymocyte), stromal-cell network (cortical epitheial cells, DC, Macrophage) , nurse cell
  • Densely packed

Medulla

  • Mature T-cells, Hassall’s corpuscles, Medulla epithelial cells
  • loosly packed
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13
Q

Nurse cell

A

present in the cortex of Thymus, responsible for training the immautre thymocyte

  • large capacity, can train 50+ thymocyte at the same time by presenting MHC I and II
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14
Q

B cell development site for the following species

Species of animals

Human, rodent

Birds

Ruminants(反芻獸), pigs, dogs

Rabbits

A

Species of animals

Site of B cell develpemnt

Human, rodent

Bone marrow骨髓

Birds

Bursa of Fabricius 華氏囊

Ruminants(反芻獸), pigs, dogs

Peyer’s patches

Rabbits

appendix闌尾

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15
Q

Structure of lymph node, and what cells does it contain respectively

A

Cortex: mainly B cells

  • including follicles and germinal center

Paracortex：Mainly T cell

(1) interdigitating DC: - high MHC II & B7 expression - training T cell

Medulla: plasma cells

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16
Q

Anatomy of spleen

A

Blood system: splenic artery & vein –> antigen from blood first goes to spleen

lymphatic system: not supplied by lymphatic vessels

  1. Red pulb: abnormal/old RBC being removed here
  2. White pulp
  3. Periarteriolar lymphod sheath (PALS): T cell, macrophages
  4. marginal zone: surrounding PALS, contains primary follicle (B cells mostly)
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17
Q

What antibody does MALT produce ?

A

mucosal - associated lymphoid tissue

的另一個特點是能製造大量的antibody-producing plasma cells，進一步產生 IgA在黏膜下中和抗原

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18
Q

What bond connect havey and light chains as well as the two heterodimer?

A

S-S bond

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19
Q

RSS

A

Recombination signal sequence

During variable-region DNA rearragement: one turn RSS must be matched with two turn RSS

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20
Q

N-addition vs P-addition

A

Takes place before mRNA is transcripted finally

P-addition

  1. Cleavage of Hairpin (produced by RAG-1 and RAG-2)
  2. Random site of cleavage
  3. Complementary nucleotides added
  4. By Repair enzymes

N-addition

  1. New nucleotides added in addition to P-addition
  2. up to 15 nucleotides
  3. N-addition只在heavy chain發生
  4. TdT enzymes are essential。
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21
Q
A
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22
Q

RAG-1, RAG-2

A

Enzymes involved in VDJ rearragment and recombination

RAG1, RAG2在序列中找到欲刪除範圍兩端的recombination signal sequences (RSS)，分別黏上並將DNA彎起、互相靠近。夠近時切開兩端，並將被刪除的序列黏成一個環

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23
Q

TdT

A

Enzymes essential for N-addition

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24
Q

Repair enzymes

A

enzymes involved in P-addion or N-additon, help adding complementary nucleotides to the nucleotides newly added

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25
Q

Junctional flexibility

A

(1)Vk和Jk之間可以擷取各自片段的序列進行重組(也就是丟棄掉一部分的序列後接在一起)，使密碼子順序改變，創造出新的antibody

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26
Q

non-productive rearragement

A

the resultant VJ/VDJ unit contains stop codons

hence, interrupt translation

Examples: TAG, TAA, TGA

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27
Q

Somatic hypermutation

A

(1) 原本已經重排重組好，但突然發生突變Mutation的現象
(2) presence of antigen increases the mutataion chance
(3) 可以說是B cell最後增加多樣性的機會。
(3) Mutation rate突變率: 10-3/bp/division per every2 cell divisionà at least one
(4) To enhance the affinity towards antigen
(5) Occurs in Germinal center, where plasma cells are produced

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28
Q

VLA-4

A
  • Adhesion molecule found on pro-B cell, interact with VCAM-1 on the stromal cell of bone marrow
  • 此交互作用促使 Pro-B cell 上的 c-Kit 結合到 Stromal cell 上的幹細胞因子 (SCF)，並活化啟動 訊號，刺激 Pro-B cell 表現 IL-7 receptor
  • binding of IL-7 released by stromal cells on the IL-7 receptors of pro-B cells causes
  1. pro-B cells –> pre B cells (maturation)
  2. downregulates adhesion molecules –> reduce interaction with stromal cell –> B cell can therefore leave the stromal cell and continue its maturation
29
Q

VCAM-1

A

Adhesion molecule found on stromal cell of bone marrow, interact with VLA-4 on the pro-B cells

此交互作用促使 Pro-B cell 上的 c-Kit 結合到 Stromal cell 上的幹細胞因子 (SCF)，並活化啟動 訊號，刺激 Pro-B cell 表現 IL-7 receptor

binding of IL-7 released by stromal cells on the IL-7 receptors of pro-B cells causes

pro-B cells –> pre B cells (maturation)

downregulates adhesion molecules –> reduce interaction with stromal cell –> B cell can therefore leave the stromal cell and continue its maturation

30
Q

IL-7

A

a molecule released by the stromal cell of bone marrow, binding to IL-7 receptor found on the pro-B cell (after a series of activation), causing

  1. pro-B cells –> pre B cells (maturation)
  2. downregulates adhesion molecules –> reduce interaction with stromal cell –> B cell can therefore leave the stromal cell and continue its maturation
31
Q

B7

A

membrane protein found on activated APC (eg B-cells after Ig-Ag complex formed)

  • once expressed, it binds to CD28 of Th cell, as co-stimulation to the Th cell
  • on the contrary, binding of B7 to CTLA-4 produce inhibitory effect on the Th cell(act as balance–> prevent over stimulation)
  • on dendritic cell, 平常就有很多b7 on its surface​, front-liner of innate response
32
Q

CD28

A

membrane protein expressed on T cells that provide co-stimulatory signals required for T cell activation and survival.

When B7 is expressed on an APC once antigen is bound to the surface receptor it, it binds to CD28, so as to provide co-stimulatory signal to the Th cell for activation.

33
Q

CD40

A

membrane protein found on B cell suface, binds to CD40R

CD40R is expressed on Th cell when it is activated by detecting antigen on the MHC of APC.

The binding of CD40 to CD40 R is essential for the Th cell to release various cytokines(IL-2,4,5) which promote B cells proliferation.

34
Q

IL-2, 4,5

A

Cytokines released by activated Th cells

Effect: causing B cell proliferation

Cause: Ig-Ag complex formed –> signaling –> at last CD40 binds to CD40R on Th cell

35
Q

B cell activation： describe the sequence involved

A

(1) Antigen binds to BCR of B cell → signal 1

Ag-mIg: induce B cell to express of MHC-II & (co-stimulatory) B7

→ interact with TH cell

(2) Activation of TH cell by binding of TCR to MHC

TH cell begins to express CD40L → binds to CD 40 of mIg (B7-CD28interactions provide co-stimulation to the TH cell)

→TH cell releases cytokines(例如:IL-2,4,5)傳遞出支持 B 細胞進行 DNA 合成及分化的訊號

→ stimulates B cell activation

3. Proliferation of B cells Starts

  1. cytokines for proliferation and class switching during the differentiation of B cells into plasma cells
  2. 分化成Plasma cell(漿細胞)時，會因為 TH1, TH2 刺激不同，而產生不同 Ig
37
Q

haplotype

A

each set of alleles (specific gene inherited from one parent)

38
Q

β2-microglobulin

A

a component on the MHCI, encoded by non-MHC gene

若缺少，MHC I就無法作用，推測是作為支撐功能

39
Q

What are the components of MHC I and MHC II ? are they polymorphic?

A

MHC I: monomer plus a microglobulin

  1. α1 & α2: polymorphic
  2. α3 & β2-microglobulin: non-polymorphic

MHC II： heterodimer (α chain + β chain)

  1. α1, β1: polymorphic
  2. α2, β2: non-polymorphic
40
Q

Ab-mediated effector function

A
  1. opsonisation: IgG for helping phagocytosis
  2. Neutrolisation: binding to Ag
  3. Complement activation: IgM/IgG
  4. ADCC: binding to FcR –> killing
41
Q

Antigen - MHC binding

A

MHC1： form anchor residue （not all MHC is in contact with the antigen, only anchor residues can do this), relatively more compacted bond

MHC II:

  1. no anchor residues: hydrogen bonds between the backbone of the peptide and the class II molecule are distributed throughout the binding site
  2. more loose binding compared to MHC I
  3. require longer peptide (13-18aa)
42
Q

What is T-cell made up of? any different classes?

A

Heterodimer: variable region, constant region, transmembrane region, cytoplamic tail, hinge region (S-S bond connecting C regions)

Classes: αβ T cell和γδ T cell\

43
Q

Difference between αβ T cell 和 γδ T cell

A

αβ T cell:

  • consists of majority of T-cell, very diverse
  • CD4, CD8 phenotype exists
  • recognize peptide presented by MHC I, II

γδ T cell:

  • not diverse
  • majority： CD4, CD8 negative
  • recognize microbial phospholipids presented by CD1 family
  • Regulatory: 可以secret各式各樣的cytokinesà recruiting αβ T cells to invasion site of pathogens
  • mainly Arm of the innate immune response: allowing rapid reactivity without need for a processing
  • 在新生家畜(豬&反芻獸)較多（~66%）
45
Q

VDJ rearragement for the chain in TCR

A

α-chain, y-chain: VJ rearrangement

β-chain, d-chain : VDJ rearrangement

46
Q

Alternative joining of D gene segments

A
  1. 發生在β or δ chain
  2. 由於D segments本身有兩種RSS（one-turn & two-turn RSS），可以把許多個D segments放進來，自行先joining，再去和V、J segments組合
  3. B-cell receptor（BCR）不會發生
47
Q

Somatic mutation for T-cell

A

Somatic mutationBCRgerminal centermutationself-reactive

-No somatic mutation ensures that T-cell specificity does not change after thymic selection and therefore reduces the possibility that random mutation might generate a self-reactive T cell. T cellmutationTCR,

48
Q

CD3

A
  1. accessory molecule: for transduction of signal
  2. ITAM located at the cytoplasmic tail: for signal transduction through interaction with protein tyrosin kinase （the more copies the chain got, the stronger the signal is transducted)
  3. 3 dimers composed by 5 invariant chains：

γε heterodimer,

εδ heterodimer,

ζζ homodimer（90%）or ζη heterodimer（10%）

49
Q

ITAM

A

ITAM（Immunoreceptor Tyrosine-based Activation Motif）：

  1. Located at cytoplasmic tail of CD3
  2. Found on the motif of a number of receptors (B-cell receptor complex / IgE/IgG Fc receptors)
  3. Interact with protein tyrosine kinasesà以傳遞activating signal to cell
  4. γ，δ，ε chains → single copy，每條cytoplasmic tail含單一ITAM
    *
50
Q

CD4 / CD8

A
  1. 為 co-receptors，會辨識並接上peptide-MHC complex，負責細胞訊息傳遞，不具有多樣性
  2. both are expressed on immature T-cells
  3. CD4：
  4. 單鏈（monomer），約55kDa的glycoprotein
  5. 4 extracellular immoglobulin-like domains：D1 ~ D4 + hydrophobic transmembrane region
  6. cytoplasmic tail contains 3 serine residues that can be phosphorylated
  7. 接上MHC-II的α2，β2
  8. MHC-II呈現的抗原較長、結合位置較平坦
      1. CD8：
  9. Dimer（αα homodimer or αβ heterodimer），約30-38kDa，disulphide-linked，其cytoplasmic tails可以被磷酸化
  10. 接上MHC-I的α2，α3
51
Q

CD1 to 4

A

CD1: expressed on the APC, mainly present microbial phospholipids, recognized by yd heterodimer of T cell

CD2: adhesion molecule expressed by T cell to strengthen the bond between it and APC/target cell –> binding LFA-3

CD3: 3 heterodimers of 5 invariant chains expressed on T cell, as accessory molecules for TCR, essential

CD4: co-factor, binding to MHC-peptide comples, 負責細胞訊息傳遞，不具有多樣性

53
Q

CTLA-4

A

membrane protein found on Th cell

binds with B7 of APC, then inhibiting Th cell (maintian balance)

which contradicts to CD28

may be found on tumor, so as to inhibit immune regulation towards the tumor cells by Tcells

54
Q

What are the two classes of globulin

55
Q

CDR

A

Complementarity-determining region

part of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively, where these molecules bind to their specific antige

For TCR: CDR3(on d segment)>CDR2> CDR1

56
Q

kappa, lambda and heavy chain locating on the same chromosomes?

A

all different chromosomes!!!

57
Q

interferon gamma

A

Potent activator for macrophage: (type II) interferon gamma（IFN-γ，促發炎）secreted by activated Th1cell

a. 具更強的Phagocytic activity(吞噬活性)
b. 提升killing ingested microbes(微生物)的能力
c. 增加inflammatory mediators(發炎介質)的secretion
d. 增加activate T cell的ability（T cell活化巨噬細胞後，巨噬細胞扮演APC，可反過來活化 T 細胞）
e. 能分泌各種cytotoxic proteins à eliminate a broad range of pathogens(病原體)
f. 可express更多的 MHC II分子（成為更好的APC）
* MHC II 只表現在 APC 上；MHC I 則是在所有有核細胞上都可以表現

58
Q

Primary and secondary organ

A

Primary organs: Thymus & bone marrow

像是在家庭裡，教育、選擇，且成熟 –> naaive mature B cell and T cell

  1. Secondary organs: Lymphatic tissues and spleen

全身的淋巴結、淋巴管，出社會（進入淋

巴系統），歷經外來抗原的刺激進行受訓

59
Q

Where to synthesis complement

name of its receptor

A

Liver

complement receptor: CR1=C3b

60
Q

function of MHCIII

A
  • Encode secreted proteins (用來產生與發炎反應相關的物質)，如：TNF、complement(補體蛋白)、heat-shock protein
  • binding to xx byCD1
61
Q

halplotype

A

: each set of alleles (specific gene inherited from one parent)

62
Q

co-dominant expression

A

MHC是co-dominant expression。沒有隱性顯性之分，全部都會顯示出來

63
Q

IL-12

A
  • stimulating differentiation of naive T cells into Th1 cells.
  • enhace the ability of NK cells
  • stimulate interferon gamma production (for macrophage activation)
64
Q

CMI

A

cell-mediated immunity

= CTL (Tc cell)

65
Q

Cytokine: autocrine? paracrine? endocrine? exocrine?

cytokine: high MW? high Q? long t1/2? cascade induction?

Cytokine receptor” any specificity?

A

Autocrine paracrine

cascade induction

no specificity

66
Q

Examples inhiniting Th2-cell proliferation

A
  • IL-4: can both binds to Ab or toxin conjugated to it
  • IFN-gamma (which is for macrophage activation)
67
Q

TCR

BCR

A

TCR = bing protein

BCR= mIg+CD79

68
Q

When B-cell activated, it starts to undergo apoptosis.

What is the possible mechanisms?

A
  1. Bcl-2/Bcl-Xl decreased expression ( anti-apoptosis)
  2. Fas protein increased expression (for apoptosis, related to TNF)
  3. SHP-1 activation (inhibitory signal by de-phosphorylation(

immunology (6 decks)

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