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Infection and immunity > 5. Humoral responses > Flashcards

5. Humoral responses Flashcards

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1
Q

what cells are involved in the humoral response

A

B cells and antibodies

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2
Q

where do b cells develop and mature?

A

the bone marrow

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3
Q

what is the b cell receptor?

A

a surface immunoglobulin with a transmembrane region and attached to a signalling domain
the same Ig the b cell will secrete

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4
Q

when b cells first encounter the antigen what is phosphorylated?

A

Src family kinases to activate downstream signallinig pathways

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5
Q

how does a b cells change in morphology once activated?

A

a bigger nucleus for replication
proteins and machinery to make antibodies

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6
Q

general antibody structure

A

2 identical light chains
2 identical heavy chains
linked with a disulphide bond

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7
Q

where does papain cleave antibodies?

A

above the disulphide bond leaving 2 FAB fragments and 1 Fc region

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8
Q

where does pepsin cleave antibodies?

A

below the disulphide bond leaving 1 FAB fragment and 1 Fc fragment

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9
Q

what does each light chain consist of?

A

one variable region
one constant region

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10
Q

What does each heavy chain consist of?

A

one varible region
multiple constant region domains

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11
Q

what is the function of the hinge region ?

A

allows flexibility when binding to multiple antigens

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12
Q

what are the hypervariable regions?

A

exposed loops on the outside of the antibody that bind to antigens
they are hypervariable to bind to a diverse range of antigens

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13
Q

What are the framework regions?

A

a series of B sheets to provide structural integrity to the antibody and keep the variable regions in place

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14
Q

where are the 3 hypervariable regions encoded?

A

on a single v-region exon

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15
Q

how do we generate a diverse range of antibodies?

A

somatic recombination of seperate gene segments

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16
Q

what gene segments do light chains have?

A

variable and joining and a constant region

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17
Q

what gene segments do heavy chains have?

A

variable, diversity and joining and 1 of 5 constant regions

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18
Q

what is the leader peptide?

A

a signal sequence that directs the Ig to secretory pathways

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19
Q

what are the 2 light chain gene loci?

A

lambda and kappa
only 1 is used in each antibody

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20
Q

what heavy chains can light chains combine with?

A

any heavy chain

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21
Q

what flanks each gene segment?

A

Recombination signal sequences (RSS)

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22
Q

why are RSSs highly conserved?

A

they prevent rearrangment with the same cluster
eg a j cant join to a j
v cant join to v

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23
Q

what is the 12/23 rule with signal sequences?

A

a 23 RSS can only bind with a 12 RSS
prevents joining of different segments of the same type and ensures D region is included in heavy chain recombination

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24
Q

what enzymes are in the VDJ recombinase enzyme complex?

A

Lymphocyte specific RAG-1 and RAG-2 endonuclease
Artemis:DNA-PK
DNA ligase 4

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25
what do RAG1 and RAG2 do?
binds to an RSS region and recruit another RSS region to it then cleaves and loops out the DNA between the 2 RSSs
26
Artemis:DNA-PK does what in double-stranded break repair?
opens the hair pin formed during cleavage
27
what does terminal deoxynucleotide transferase do in double-strand break repair?
randomly adds nucleotides to the gap
28
what does DNA ligase do in double-strand break repair?
joins the new DNA backbone together making a continuous piece of DNA
29
how do B cells generate diversity?
combinatorial diversity junctional diversity somatic hypermutation
30
what is combinatorial diversity?
differnet VDJ combinations different heavy chain light chain combination
31
what is junctional diversity?
imprecise addition and removal of nucleotides in recombination
32
what needs to happen for somatic hypermutation?
encountering the antigen CD4 T cells
33
what does somatic hypermutation do?
Increases the mutation rate in the antibodies to make variable regions fit the antigen better
34
what enzyme initiates the hypermutations?
Activation-induced cytidine deaminase (AID)
35
what is affinity maturation ?
selects for the survival of the antibodies that have the highest affinity for the antigen
36
what is a disadvantage of hypermutation?
some mutations can be detrimental and prevent function these b cells are apoptosed
37
how are the affinity matured cells selected?
the b cells with the better antigen presentation as a result of antigen binding receive enhanced survival signals from CD4 T cells
38
what secondary signal is needed for activation in a thymus dependent antigen?
the CD40 receptor and MHC2 on the B cell binding to a CD40L and TCR on a CD4 helper cell (1st signal is BCR binding)
39
what secondary signal is needed for activation in a thymus independent antigen?
binding of a common microbial part to a TLR (1st signal is BCR binding)
40
what determines antibody effector function?
the Fc portion
41
what functions do antibodies have?
neutralisation opsonisation antibody mediated cellular cytotoxicity trigger mast cell activation activation of complement
42
where does class switching occur?
at the genome level
43
where are the Fc genes located?
downstream of the VDJ regions
44
what is IgA functions?
secreted across mucosal membrane
45
IgM
Pentamer early in response no hypermutation so more binding sites
46
As IgM and IgD are derived on the same pre-mRNA transcript what determines which is expressed?
alternative splicing of the mRNA and polyadenylation
47
What does AID do?
cuts out switch regions at the 5' end to loop out other heavy chain genes
48
what process is AID involved in?
Class-switching and Double-strand break repair mechanisms
49
what does an AID deficiency result in?
No ability to class switch or affinity mature Leads to Hyper IgM type 2 immunodeficiency
50
what is the dynamics of the different antibodies in the immune response?
Initially IgM dominates and then as affinity maturation occurs IgG dominates somatic hypermutation means affinity increases
51
what determines which class the antibody switches to?
the cytokines secreted by T helper cells
52
Which antibodies are stimulated by IL-4?
IgE and IgG1
53
Which antibodies are stimulated by IFNy?
IgG3 and IgG2a
54
Which antibodies are stimulated by TGFb?
IgA and IgG2b
55
Which antibodies are stimulated by IL-21?
IgA, IgG3 and IgG1
56
Which antibodies are stimulated by IL-5?
IgA and IgG1
57
where do you find IgG and IgM?
in the circulation
58
where do you find IgA?
in mucosal sites like GI tract and Respiratory tract also breast milk
59
where do you find IgE?
directly under the skin in mouth and nose lining external surfaces
60
what is antibody neutralisation?
bind to viruses, bacteria and toxins to prevent interaction with receptors in the cells
61
what antibodies mainly carry out neutralisation?
IgG and IgA
62
what is antibody opsonisation?
Coating the bacteria with the antibodies and then binding to the pathogen surfaces to trigger phagocytosis by crosslinking Fc receptors
63
what antibodies carry out opsonisation?
IgA, IgG1, IgG3 and IgG4
64
what does IgE opsonisation look like?
binding to parasites and eosinophils Fc receptors crosslinking to trigger degranulation
65
what is Antibody-dependant cellular cytotoxicity?
Recognising Viral proteins on host cells and bind Fc receptors on NK cells crosslinking of NK cell Fc receptors causes degranulation and killing of host cells
66
what antibodies are involved in Antibody-dependant cellular cytotoxicity?
IgG1 and IgG3
67
what is antibody sensitisation of mast cells?
cross-linking of IgE triggers degranulation and inflammatory mediators like histamine allergy response
68
how do antibodies activate the complement cascade?
IgM or IgG binding to the antigen C1q then binds to multiple IgG or 1 IgM which can then produce a C3 convertase

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