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immunology > comparing different immunoglobulin > Flashcards

comparing different immunoglobulin Flashcards

1
Q

Introduce the two polymeric antibody and where they locate and functions

A
  1. IgM: pentamer & 2. IgA: dimer-tetramer

Both are linked by J-chain

Poly-Ig receptor (pIgR)

  • basolateral surface of most mucosal epithelia (e.g. the lining of the digestive, respiratory, and genital tracts) and on glandular epithelia in the mammary, salivary, and lacrimal glands
  • interacts with the J (joining) chain of both polymeric IgA & IgM

Secretory component (SC):

  • masks sites susceptible to protease cleavage in the hinge region of secretory Ig (sIg)
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2
Q

Compare the half-life of the Igs

A

longer: IgG>IgA>IgM>IgD>IGE

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3
Q

Which one is not found in blood, and where it is located?

A

IgD

It is membrane immuoglobin only found on the surface of B-cell

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4
Q

Which one found in blood in highest amount? Does it occur in mucous membrane?

A

IgG

No

It can activate complement活化母體

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5
Q

What is the role of IgE?

A

IgE appears in monomer form, acting on peripheral nervous system, and causing allergy on the pheripheral tissues.

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6
Q

Compare how ruminants, primates, dog/cats and other non-ruminants fetus acquire maternal antibody.

A
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7
Q

How is antibody absorption be enhanced for newborns?

A
  1. Low level of protease activity in digestive tract + reduced by trypsin inhibitors in colostrum
  2. Colostral Igs binds FcRn
  • special FcRs found on the intestinal epithelial cells of newborns
  • distributed across intestinal epithlium à facilitate endocytosis of Ig which is then transported towards the whole body
  • 一般Fc receptor分佈在吞噬細胞上面，嬰兒有此種情況是為了吸收抗體。
  1. 細胞間排列較疏鬆 –> Highest permeability of epithelium à nutrient absortion enhanced
  • FcRn(+ve) intestinal epithelial cells gradually replaced by FcRn(-ve) cells after 6hr
  • Permeability falls as a result –> antibody absorption falls
  • 初乳內的抗體（IgG）可跑到全身提供全身性免疫；而母乳(milk)內的抗體只能跑到腸道提供腸道免疫
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8
Q

What is anaphylaxis?

A

serious allergic reaction happened rapidly and may cause death

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9
Q

What is IgY

A
  1. Evolutionary ancestor of IgG和IgE in mammals
  2. 所以可以發現IgY介於兩者的特性中。
  3. IgE:多了一個domain，且能媒介一些過敏反應
  4. IgG: Complement fixation, carbohydrate content and distribution, major systemic antibody (maternally derived)
  5. 可在鳥類、爬蟲類(reptiles)、兩生類(amphilbia)體內發現（圖十五）
  6. 分子量為180 kD(即在constant region多一個domain，共四個，構型像IgE)
  7. 雞只產生IgY
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10
Q

what is the use of IgY(triangle Fc)

A
  1. Incomplete IgY(120 kD)à truncated protein (lack of Fc)
  2. Able to recognise antigen, without causing immune response / complement activation / 調理作用(opsonization) / anaphylaxis
  3. 可在雁形鳥類aniseriform birds(鴨、鵝)、爬蟲類(特別是烏龜)、肺魚中發現
  4. 在某些雁形鳥類及烏龜身上可同時存在IgY及IgY (△Fc)
  5. 可調控宿主的免疫反應，避免過強的免疫反應傷害宿主，因為免疫力太好，會對我們造成傷害。（少了CH3、CH4）
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11
Q

How are antibodies distributed in eggs?

A

IgY is secreted by epithelial cells of oviducts and stored in yolk –> absorbed by chick into blood stream

IgA stored in albumin ingested by chick –> protects intestines

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12
Q

What is C3b?

A

An opsonin participating in opsonisation

  1. 調理反應(opsonization)：
  2. Opsonin: any molecule that targets an Ag for an immune response and acts as a binding enhancer for the process of phagocytosis
  3. Both Ab and complements can act as opsonin
  • Ag bound by Ab à Ab then binds to FcR pf phagocyte
  • Complement activation: Ag bound by complement, C3b à C3b binds to CR1
  1. Princle: both phagocytes and Ag are -ve chargedàelectrostatic repulsionàhard for phagocyte to get close to Ag ; 當opsonin與抗原結合，會屏蔽其表面負電，幫助吞噬作用的進行
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13
Q

What is C1?

A

Complement.

  1. Activation of complement 補體的活化 (打洞器!)
    (1) 當immune complex (IgG或IgM binding tp Ag) binds to C1 (complement) àC1 complex à Trigger the classical pathway
    (2) 因IgM為pentamer，一個即可活化補體；而IgG為monomer，故須多個才可活化補體。
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14
Q

Which Igs can cause complement activation?

A
  1. Activation of complement 補體的活化 (打洞器!)
    (1) 當immune complex (IgG或IgM binding to Ag) binds to C1 (complement) àC1 complex à Trigger the classical pathway
    (2) 因IgM為pentamer，一個即可活化補體；而IgG為monomer，故須多個才可活化補體。
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15
Q

What is ADCC

A

Immune complex所引發的細胞毒殺作用(Ab-dependent cell-mediated cytotoxicity or Ab- dependent cellular cytotoxicity ＝ADCC)

(1) Immune complex binds via FcR on immune effector cell吞噬細胞(macrophages, neutrophils, eosinophils或natural killer cells)

–> triggers release of lethal cellular products from the bound immune effector cells(細胞致死物)，或是打洞使之滲透壓內外失衡。

Examples：lytic enzymes, perforins（打洞的）, granzymes（進入細胞內導致凋亡，與前者合作）, tumor necrosis factor（接在細胞膜上面，不用進入細胞內讓細胞凋亡）, oxidants, etc)

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16
Q

Isotypic determinants

A
  1. 抗體在不同物種間，會有不同的heavy-chain class and subclass, and light-chain type and subtype，如：鳥類有IgY，人類沒有
    * Determined by C regions
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17
Q

Allotypic determinants

A

抗體在同種不同individuals之間，constant region的genetic sequence不相同(除非是雙胞胎) –> subtle amino acid differences

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18
Q

idiotypic determinants

A
  1. 在同一個體內，不同抗體間variable region的序列不相同。
    * Antigenic determinants of the V region
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19
Q

how’s signal 2 produced?

A
  1. T-cell’s CD40L (CD154)與B cell’s CD40 binding
  2. T cell’s CD28與B cell’s CD86 binding
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20
Q

Clonal selection theory

A

The Ag-mediated activation and proliferation of members of a clone of B cells that have receptors for the Ag (or for complexes of MHC and peptides derived from the Ag, in the case of T cells)

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21
Q

What is IL-4?

A

Interleukin-4 (cytokines secreted by T cells)

  1. stimulating T-cell proliferation
  2. a key regulator in humoral and adaptive immunity. IL-4 induces B-cell class switching to IgE (and IgG1, IgA),
  3. Up-regulates MHC class II production.
  4. IL-4 binds to IL-4R on the suface of B-cells, producing signal 3 --> proliferation and differentiation into plasma cell and production antibody are all activated.
  • Also stimulating class swithcing IgG1, IgE, IgA
22
Q

What are involved in signal 2? (B-cell activation and proliferation)

A

After Ag-Ab complex formed,

1. T-cell’s CD40L (CD154) binds B cell’s CD40

2. T cell’s CD28 binds B cell’s CD86

23
Q

Anergy of B cells

A

Unable of B cell to produce antibody

  1. When more than 5% of mIgM molecules are occupied by monomeric soluble因為B cell認為有可能是自自身的抗原，故抑制免疫反應，推測是抗原的量太多，會被視為自己的antigen。
  2. Absence of T-cell help à lack of signal 2，稱為免疫耐受性(immune tolerance)
  3. Unresponsiveness to antigenic stimulation (即便有T細胞的幫忙也不會製造抗體)
24
Q

What is CD154?

A

=CD40L, receptor found on the suface of Th cells, responsible for binding to CD40 ligand present in APC (B-cell, dendritic cell, macrophages)

Their corresponding activations are as follows

25
Q

Which antibody rises greatly in second exposure to the same Ag?

A

IgG

Showing that IgG should be the real protector of the adaptive immune system. In reality, if high level of IgM is detected–> chronic infection

If high level of IgG is detected, indicating previous experience of infection

26
Q

What class of mIg present on the surface of naive B-cells? What is the sequence of class switching?

How does class switching change affinity and specificity?

A

In naive B-cells, only mIgD and mIgM are present.

Sequence:

mIgD/mIgM –> IgG –> mIgE –> mIgA

Thats why IgE causing allergy only happens after second time of exposure to the allergin

Affinity is improved, specificity is unchanged

27
Q

mIg present on suface of memory cell

A

mIgG, mIgE and mIgA

28
Q

IFN-g

A

cytokine signal produced by T cell acting on B cell for class swithcing

–>IgG3, IgG2a

29
Q

IL-5, transforming growth factor B

A
  1. IgG2b, IgA(黏膜上皮細胞主要cytokine為TGF-β，故較多IgA分布於黏膜)～（cytokine的幫忙，可超車，直接從IgM變成IgA）
30
Q

Bcl-2

A

Anti-apoptotic proteins expressed on B cells.

When continued stimulating signals (cytokines/Th cell/Ag) is stopped, expression of Bcl-2 falls, leading to apoptosis of B cells.

bax oppose bcl-2, promoting apoptosis

31
Q

Idiotypic regulation

A

There is idiotype-specific Ab present: can recognize the Ag-sepcific lymphocytes –> anti-idiotypic response

  • Anti-idiotypic T cells: can also recognize idiotypic determinants of the mIg on B cells MHCII
  • A steady state in the immune system is maintained by the network of reciprocal idiotypes and anti-idiotypes.
  • The introduction of Ag perturbs that balance and leads to detectable immune responses
32
Q

CD22

A

Inhibitory B-cell coreceptor

  1. CD22上的免疫受器immoreceptor tyrosine phosphate inhibitory motif (ITIM)與SHP-1(tyrosine phosphate磷酸水解酶)結合
    • dephosphorylating tyrosines of BCR
    • B cell的signal I被抑制
  2. Igα/Igβ上有免疫受器tyrosine-based activation motifs (ITAM)
33
Q

CD19

A

負責傳遞訊息，attracting kinase –> phosphorylation –>活化B 細胞製造抗體

34
Q

Phagocytosis

Complement activation

A

Phagocytosis: IgG only (IgM unknown)

CA : both IgG and Ig M can do

35
Q

SHP-1

A

Recruited by CD22 on B cells, so as to remove phosphates on Iga/Igb of the CD79 (accessory molecules for BCR)

--> inhibitory

36
Q

Antibody that B cells must contain on its surface

A

mIgM, mIgD

37
Q
A
38
Q

What are the two classes of globulin

A

Ƴ globulin

Most antibodies except IgM

beta globulin: IgM :

39
Q

What determines the class of the Ig?

A

sequence of constant region on the heavy chain

note: light chain sequence is irrelavent

40
Q

Hinge on the antibody

A
  1. 一段胺基酸序列 (amino acid sequence)
  2. 2 heterodimers are connected by disulphide bond
  3. 有proline, 使抗體具有靈活度，可轉動、開張與抗原結合，不同抗體種類間hinge不同，彈性(flexibility)也不同
  4. IgE、IgM沒有hinge的構造
41
Q

Which Ig has subclasses

A
  1. IgG: 4 subclasses in humans, and 2 in canine
  2. IgA: 2 subclasses
42
Q

compare the three types of digestion

  1. pepsin digestion
  2. papin digestion

3.

Mercaptoethanol reduction

A

1. pepsin

  • cleavage under hinge, just separating the Fab and Fc regions

no breakage of disulphide bind，辨識能力較papain digestion處理後的強

    1. papain digestion*
  • cleavage at the hinge: turning Fc separates from Fab, Fabs also separates into two heterodimers. No breaking between heavy chain and light chain, so still remains antigen recognition function

3.mercatoethanol

  • breaking all disulphide bond –> the Ig is cleaved into 4 units
43
Q

CD79

A
  • accessory membrane protein of the BCR, help signal transdcution (tell b cells to produce Ig)
  • 2 groups of CD79 are available next to BCR, and each contains a α and β group

for Igα/Igβ

  • α較深，β較淺，均是往下傳遞訊息的東西
  • b cell上重要的marker，例如要判別是T cell還是B cell來源的腫瘤，可以從CD79有無來判斷
44
Q

Which antibodies got one more constant domain?

A

IgM and IgE: got CH1, CH2, CH3 and CH4(多出來的）

hinge of these two are absent, connected by only one S-S bond

45
Q
A
46
Q

binding forces of Ag-Ig

A

Ionic, hydrophobic, VDW

BUT NO COVALENT BINDING

47
Q

CD21

A

Complement receptor for C3d

  • expressed strongly on mature B-cell
  • complement activation
  • enhance the ability of B-cell for antigen as it interact with CD19 (co-receptor)
48
Q

CD81

A
  • present on both B-cell and T-cell
  • co-stimulatory molecules of their activation
49
Q
A
50
Q
A

immunology (6 decks)

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