L5 - Humeral responses Flashcards

1
Q

What triggers the activation and proliferation (clonal expansion) of B cells?

A

Binding of antigen to the B cell surface.

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2
Q

How do B lymphocytes recognise antigen?

A

By expressing B cell receptors (BCRs) on their surface

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3
Q

When antigen binds, crosslinking Ig molecules, what happens?

A

The B cell is activated and secretes soluble Ig in the form of antibodies.

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4
Q

What types of chain make up an antibody?

A

2 identical light chains and 2 identical heavy chains

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5
Q

What do they light and heavy chains have in common?

A

They both have one variable region

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6
Q

Where do B cells arise from?

A

Lymphoid progenitors in the bone marrow

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7
Q

What are the 2 loci which can encode the light chain?

A

Lambda and kappa loci

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8
Q

How many of each region are there in the kappa chain?

A

40V regions and 5J regions

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9
Q

How many of each region are there in the lambda chain

A

29V regions and 7J regions

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10
Q

What is the first step of generating diversity in light chains and how is this controlled?

A

Somatic recombination of gene segments (V + J) controlled by RAG (recombination activating gene products)

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11
Q

Put these processes in the correct order regarding generating diversity in the light chain; Splicing, transcription, somatic recombination, translation.

A

Somatic recombination. transcription, splicing, translation

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12
Q

Which extra region is involved in somatic recombination in heavy chains?

A

Diversity (D). Therefore there are 2 recombination steps during the generation of diversity on heavy chains

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13
Q

Explain ‘combinatorial diversity’.

A

Any light chain can combine with any heavy chain, so in total there are around 4,000,000 different specificities/structures.

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14
Q

Explain ‘junctional diversity’

A

Imprecise joining of the V (D) J segments during somatic recombination due to deletion or addition of nucleotides between the segments.

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15
Q

What does TdT do?

A

Terminal deoxynucleotidyl transferase adds nucleotides at the junctions

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16
Q

Which process of diversity generation does not occur in T cells?

A

Somatic hypermutation

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17
Q

Which process(es) of diversification occur in the bone marrow?

A

Somatic recombination; combinatorial diversity combinatorial association and junctional diversity

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18
Q

Which two processes of diversity generation occur in secondary lymphoid tissues?

A

Somatic hypermutation and affinity maturation

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19
Q

Explain somatic hypermutation

A

Mutations in V region sequences during B cell replication causing slight changes in specificity.

20
Q

Which enzyme induces hypermutation?

A

AID activation-induced cytidine deaminase

21
Q

Explain affinity maturation

A

The higher the affinity of the immunoglobulins for the antigen, the stronger signals the responsible B cells receive and the more they divide. So antibody affinity increases over time.

22
Q

Which 2 signals are required for B cell activation by a thymus dependent antigen?

A

1) Antigen binding to Ig. 2) CD40L on helper T cell binding to CD40 on B cell

23
Q

Which 2 signals are required for B cell activation by a thymus independent antigen? (T cell help not required)

A

1) Antigen binding to Ig. 2a) Antigen binding to TLR eg. LPS, a T-independent antigen type 1 (TI-1). 2b) Extensive crosslinking by polymeric antigen, a T-independent antigen type 2 (TI-2)

24
Q

Although B cells can be activated without the help of T cells, what are the implications of this which limit to effectiveness of the immune response?

A

Little/no isotype switching
No somatic hypermutation
No affinity maturation
No memory B cells

25
Q

Where do follicular helper T cells reside?

A

In germinal centres of secondary lymphoid tissues

26
Q

Which survival and mitogenic signals do they produce?

A

CXCR5 (chemokine receptor - retains T cells in B area of lymphoid tissue)
CD40L
IL-21 (important in affinity maturation)

27
Q

What is BLIMP-1 and what is its function?

A

B lymphocyte induced maturation protein -1 is switched on by T cells and causes B cell proliferation

28
Q

Memory cells produce Ig on surface and CD27. True or false

A

True

29
Q

What are isotypes?

A

Different classes of immunoglobulin (IgG IgA IgM IgE IgD)

30
Q

Which 2 isotypes have their own subclasses and what are there?

A

IgG (IgG1, IgG2, IgG3, IgG4)

IgA (IgA1, IgA2)

31
Q

Following activation, which 2 isotypes are expressed on newly formed B cells?

A

IgD (never secreted) and IgM

32
Q

Where and when does isotype switching occur?

A

In germinal centres of lymph nodes after B cell activation

33
Q

What determines the isotype secreted by the plasma cell?

A

The cytokines secreted by the T cells

34
Q

Which 2 processes does activation-induced cytosine deaminase (AID) induce?

A

Somatic hypermutation and isotype switching.

35
Q

Which isotype is pentameric

A

IgM

36
Q

Which isotype can be secreted as a monomer or a dimer?

A

IgA

37
Q

Where is (dimeric) IgA best at working?

A

secreted across epithelia eg. intestinal mucosa or lung

38
Q

Where is IgG best at working?

A

Secreted across placenta and extravascular sites

39
Q

Which isotypes are found in the circulation?

A

IgG and IgM

40
Q

Neutralisation, the prevention of the binding of viruses, toxins and bacteria is helped by which isotypes?

A

IgG, IgA, IgM bind to pathogen and prevent it binding to cell surface.

41
Q

Which isotypes aer important in opsonisation?

A

IgG1, IgG3, IgG4, IgA

42
Q

Antibody-dependent cellular cytotoxicity (ADCC) uses which isotypes?

A

IgG1, IgG3

43
Q

What triggers the initiation of the complement cascade via the classical pathway?

A

When antibody binds to pathogen (antibody : antigen complex), the conformation changes slightly, exposing the hinge region where C1q, a key component of the complement cascade binds.

44
Q

List 6 antibody functions

A
Neutralisation
Opsonisation
Antibody dependent cellular cytotoxicity
Activation of the complement cascade (classical)
Triggering mast cell activation
Triggering eosinophil activation
45
Q

Which isotype triggers mast cells and eosinophils

A

IgE

46
Q

What is the main role of eosinophils?

A

To destroy multicellular parasites (by releasing Eosinophil Major Basic Protein and Cationic protein)