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Immunology > Antigen receptor on lymphocytes > Flashcards

Antigen receptor on lymphocytes Flashcards

1
Q

What is the composition of the BCR?

A

our polypeptides, two identical light chains and 2 identical heavy chains, connected by disulphide bonds

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2
Q

What are the two types of light chains?

A

Lambda and Kappa

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3
Q

What is the valency of the BCR?

A

2

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4
Q

What is the composition of the TCR?

A

two polypeptides, also disulphide linked and spanning the membrane.

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5
Q

What is the valency of the TCR?

A

1

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6
Q

What are the two types of TCR?

A

alpha/beta or gamma/delta heterodimers

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7
Q

What are the 2 fundamental differences between the TCR and the BCR?

A
  1. T cells do not secrete TCR while B cells secrete immunoglobulin molecules by deleting the
    transmembrane-spanning exon during alternative splicing of the primary RNA transcript
  2. The BCR is specific for native or intact antigen, but the TCR is not. Instead, antigen must be presented by self MHC molecules to the TCR
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8
Q

What are 2 other differences between the BCR and the TCR

A
  1. The BCR variable region undergoes hypermutation during affinity maturation while the TCR variable regions do not hypermutate
  2. The constant regions of the BCR heavy chain can be replaced during class switching while the equivalent does not occur with the TCR
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9
Q

What is a similarity between the TCR and the BCR

A

both receptors associate with additional polypeptides that don’t bind antigen but transmit a signal

  • Ig alpha and beta for the BCR
  • CD3 for the TCR
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10
Q

What are the 2 theories explaining the variable amino terminus on the light chain but the constant carboxy terminus

A
  1. Germ line theory

2. Somatic variation theory

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11
Q

What does germ line theory propose?

A

Different genes for each immunoglobulin

-this would take up a huge portion (15%) of our genome

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12
Q

What does somatic variation theory propose?

A

The genome contains a relatively small number of Ig genes from which a larger repertoire arises by recombination or mutation events

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13
Q

What did Dreyer and Bennet propose in 1965?

A

wo genes encode a single immunoglobulin light or heavy chain, and that a recombination event explained their contributing to a single polypeptide

Also that there were a larger number of variable genes than constant region genes

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14
Q

What did Tonegawa and Hozumi prove in 1976

A

Showed direct evidence that seperate genes encode the V and C regions of immunoglobulins

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15
Q

What are the 3 types of gene segment regions?

A

(V)ariable, (D)iversity, (J)oining

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16
Q

Where is the D region present?

A

Only in the heavy chain DNA and only in one of the heavy chains

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17
Q

What is the order of recombination events?

A

D to J rearrangement followed by a V to D rearrangement

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18
Q

What is the splice site it in each segment called?

A

The coding joint

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19
Q

What is the RSS

A

recombination specific sequence

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20
Q

What are the two forms of RSS and what is the general composition?

A

The two forms are based on the size of the variable spacer
-one is 12 bp the other is 23 bp

both forms contain conserved PALINDROMIC heptamer and nonamer sequences separated
by variable sequences

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21
Q

What is the relevance of the variable spacer lengths?

A

may related to the number of bases in a turn of supercoiled DNA, where 12 bp is a single turn while 23 bases encompass two turns

22
Q

What multiprotein complex is responsible for recombinations?

A

the V(D)J recombinase

23
Q

What are the two lymphoid cell specific molecules in the V(D)J recombinase?

A

RAG1 and RAG2

24
Q

how do the RSS elements impact the order and process of recombination?

A

A 12 bp RSS matches with a 23 bp RSS to identify a site suitable for recombination

25
Q

What are the 5 steps of Variable region recombination?

A
  1. RAGs bind to the RSS and catalyze synapse formation - forms a hairpin coding end and blunt signal end
  2. Opening of hairpin loop by Artemis yields 3 possible options
    - P nucleotide additions results in a short palindrome
  3. ** in heavy chain VD and DJ joint only there is exonuclease trimming at either side of the joint
  4. N nucleotide additions by terminal deoxynucleotide transferase (TdT)
  5. Ligation of free ends to seal coding joint by DNA ligase IV and NHEJ proteins
26
Q

What are 5 mechanisms that contribute to antibody diversity?

A
  1. Multiple gene segments
    - permutations of V to D to J
  2. P nucleotide addition
  3. Exonuclease trimming (at 3’ end)
  4. Non templated N nucleotide additions
  5. Combinatorial diversity
    - 2 chains combining into one antigen binding site
27
Q

How does polyadenylation allow for simultaneous expression of IgM and IgD?

A

polyadenylation signals flag splicing points in the mRNA product of the mu and delta heavy chains

28
Q

What is somatic hypermutation? when does it occur? Where does it occur?

A

Somatic hypermutation occurs in the complementarity determining regions (CDR) of the variable region DNA.

After the BCRs bind antigen, slight alterations are made in the V region to improve affinity of the immunoglobulin for the antigen

29
Q

What is affinity maturation?

A

the net increase in Ig affinity within a B cell population

30
Q

What enzyme is responsible for somatic hypermutation?

A

AID (activation induced cytosine deaminase)

31
Q

Class switch recombination is also known as?

A

Isotype class switching

32
Q

What are switch regions?

A

Highly repetitive DNA stretches

33
Q

What enzyme is used for class switch recombination?

A

AID (activation induced cytosine deaminase)

34
Q

Describe the process of class switch recombination

A
  1. AID makes double stranded break in S regions upstream and downstream of segment to be removed
  2. Switch regions are joined and intervening DNA removed
35
Q

Where is there NOT a switch region present?

A

between the mu and delta regions

36
Q

What class switch does IL-4 induce?

A

to IgG1 and IgE

-has to go through IgG1 to get to IgE

37
Q

What class switch does IL-5 induce?

A

to IgA

38
Q

What class switch does TGFß induce?

A

to IgA and IgG2

39
Q

What class switch does INF gamma induce?

A

to IgG3 and IgG2a

40
Q

What are 6 similarities between TCR and BCR gene rearrangement

A
  1. Multiple gene segments for each of V, (D), and J
  2. ß and ∂ have D regions like the heavy chains of BCR
  3. Like IgH, ß and ∂ chains pair with chains without D regions (alpha and gamma)
  4. Order of recombination is D to J and then V to D
  5. N and P nucleotide additions occur in the coding joint
  6. 2 polypeptides combine their V regions to form the antigen binding site
41
Q

What is a fundamental difference between TCR and BCR gene rearrangement

A

TCR gene segments have RSSs but alternate arrangement of the 12 bp and 23 bp variable sequences allows for recombination between D regions

42
Q

How does alternate joining of D region segments affect the coding joint of delta chains?

A

Allows multiple D regions to be included in the coding joint

43
Q

Do TCR segments undergo somatic hypermutation?

A

nope

44
Q

Name the 5 somatic immunoglobulin deficiencies

A
  1. X-linked agammaglobunlinemia
    (Bruton’s hypogammaglobulinemia)
  2. Hyper IgM syndrome
  3. Common variable immunodeficiency (CVIDs)
  4. Hyper IgE
  5. Selective IgA deficiency
45
Q

X-linked agammaglobunlinemia

(Bruton’s hypogammaglobulinemia) causes:

A

No peripheral B cells
- B cells arrested at pro-B stage

Extremely low IgG

No other classes of Ig

46
Q

Hyper IgM syndrome causes:

A

Deficiency in IgG, IgA, and IgE

Increased IgM

47
Q

What is hyper IgM caused by?

A

T cell defect which prevents B cells from receiving a class switch signal

48
Q

What causes X-linked agammaglobunlinemia

Bruton’s hypogammaglobulinemia

A

Defect in Bruton’s TK = B cells arrested at pro-B stage

49
Q

Common variable immunodeficiency (CVIDs) cause:

A

low # of antibody producing cells and antibody

B cells fail to mature into plasma cells

50
Q

What causes hyper IgE and what is the result?

A

Multisystem disorder with high IgE due to mutates STAT3 resulting from abnormal Th activity

51
Q

What is selective IgA deficiency ?

A

IgA+ cells cannot differentiate into plasma cells

Immunology (19 decks)

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