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L6&7 B Cells & Antibodies Flashcards

1
Q

What are linear epitopes formed by?

A

Several linear/adjacent AA residues

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2
Q

Linear epitopes are only accessible when…

A

they are denatured

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3
Q

Conformational epitopes are formed by…

A

AAs that are spatially juxtaposed

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4
Q

What happens in antibody-class switching?

A

Switch from primary (IgM) to secondary (IgG, IgA or IgE)

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5
Q

What is the first antibody made to a particular infection?

A

IgM

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6
Q

What happens to the Fc region during antibody-class switching?

A

It is exchanged

Fab region stays the same

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7
Q

How does the secondary Ab response differ from the primary Ab response?

A

Secondary Ab response is faster and larger

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8
Q

Where are switch regions found?

A

Upstream of every H chain gene

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9
Q

What is switch recombination?

A

Rearranged VDJ combines with a downstream C gene, with removal (by deletion) of the intervening DNA

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10
Q

IL-4 promotes switch to…

A

IgG4 and IgE

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11
Q

IFNγ promotes switch to…

A

IgG2 (from Tfh lymphocytes)

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12
Q

How long does humoral (Ab) immunity to mumps last?

A

12 years

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13
Q

How long does humoral immunity to measles last?

A

65 years

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14
Q

How long does humoral immunity to polio last?

A

40 years

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15
Q

How long does humoral immunity to Hepatitis A last?

A

25 years

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16
Q

Is memory B cell response to Influenza virus short or long-lived?

A

Very long-lived

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17
Q

What are needed for sterilising immunity?

A

Neutralising antibodies

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18
Q

What is sterilising immunity?

A

Someone who’s vaccinated or naturally infected will neither catch the virus nor transmit it further
(Neutralising Abs block virus entry into cells & prevent replication)

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19
Q

What does the Ab structure relate to?

A

Ag binding

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20
Q

Where does Ag-independent differentiation take place?

A

Bone marrow

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21
Q

Where does Ag-dependent differentiation take place?

A

Peripheral lymphoid tissues

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22
Q

How does the immune system develop specificity?

A

From the clonal selection process

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23
Q

How is IgM held together?

A

J chains

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24
Q

What does IgM exist as?

A

A monomer on the surface of B cells

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25
Which form of IgM is secreted?
Pentameric form
26
Where is IgM mainly found?
In the blood - does not penetrate tissues v well
27
Is IgM involved in opsonisation or ADCC?
No - there are few Fc receptors on leukocytes
28
What is IgM very efficient at?
Complement activation, and neutralisation of bacteria & viruses
29
What is the most abundant Ab in serum?
IgG
30
How many subtypes of IgG are there, and how do they differ?
4 subtypes, differ in size of Hinge region
31
Which form of IgG does NOT cross the placenta?
IgG2
32
What are the main roles of IgG?
1. Complement activation 2. Neutralisation of bacteria & viruses 3. Promote opsonisation or ADCC
33
What is the most abundant Ab in the body in terms of quantity?
IgA (70%)
34
What are the 2 IgA subclasses and where are they found?
IgA1 (longer Hinge region) - found in serum | IgA2 - mainly found in secretions
35
What does secretory IgA do?
1. Prevents pathogen adherence to mucosal surfaces (neutralisation) 2. Promotes ADCC by interacting with Fc receptors of NK cells 3. Poor at complement fixation and opsonisation
36
What is the only antibody subclass that significantly crosses the placenta?
IgG
37
When is IgE usually produced?
When controlling worm infections, and greatly increased in Hypersensitivity (e.g. asthma, food allergies, allergic rhinitis)
38
Which Ab subclass is normally present in trace amounts in serum?
IgE
39
What do CDRs (complementary determining regions) provide?
Huge variation
40
What are the 6 mechanisms for generation of antibody diversity?
1. Multiple germ line V genes 2. V-J and V-D-J recombinations 3. N-nucleotide addition 4. Recombinational inaccuracies 5. Somatic hypermutation (SHM) 6. Assorted H and L chains
41
Are V pseudogenes usually functional or non-functional?
Non-functional
42
What does allelic exclusion prevent?
Co-expression of both alleles
43
What does allelic exclusion maintain?
The Law of Clonal Selection
44
What is VDJ recombination?
The process by which T & B cells randomly assemble different gene segments - known as variable (V), diversity (D) & joining (J) genes - in order to generate antigen receptors.
45
How do membrane-anchored and secreted Abs differ?
In their C-terminus
46
What is the direct effector function of antibodies?
Neutralisation of bacterial toxins/viruses
47
What is the secondary effector function of antibodies?
Opsonisation, which leads to phagocytosis and promotes ADCC
48
What happens in Antibody-Dependent Cellular Cytotoxicity (ADCC)?
The Ab is opsonised Virus-infected cells & cancer cells are killed by CTLs & NK cells They release cytotoxins into the target cell, triggering its death by apoptosis
49
What is the most immature antibody-producing B cell?
Plasmablast
50
What do plasmablasts secrete?
Low-affinity antibodies
51
Are plasmablasts short or long-lived?
Short lived
52
What cells supply the very earliest antibodies to the pathogens?
Plasmablasts
53
What would you find in germinal centres?
Proliferation of LLPCs and memory B cells
54
Where do long-lived plasma cells mainly relocate?
Bone marrow & GALT
55
Features of memory B cells:
GC-derived Class-switched Hypermutated
56
What markers are T follicular helper cells positive for?
CD4+, Bcl-6+, CXCR5+
57
Where do Tfh cells interact with memory B cells?
at the B-T cell junction
58
Tfh cells play a role in memory B cell survival by secreting...
IL-4, IL-21, IFNγ
59
Re-exposure to antigen leads to a rapid reactivation of memory B cells in...
spleen and lymph nodes, to produce Ab-secreting SLPCs
60
What changes in germinal centres are seen in severe cases of COVID-19?
- GCs appear to be damaged/lost in LNs & spleen - Bcl-6+ GC B cells & Bcl-6+ Tfh cells markedly diminished - Low levels of somatic hypermutation in GC B cells
61
What is the consequence of loss of germinal centres?
Compromises the production of long-lived B cell memory and high affinity antibodies
62
What is the purpose of somatic mutations and where do they take place?
Produces antibodies with the highest affinities (increases specificity). It takes place in the GCs in LNs & spleen
63
What brings about affinity maturation of antibody?
Somatic point mutations in V gene (H and L chain genes)
64
What is the mechanism of somatic hypermutation?
Deamination of cytosine to uracil in DNA by the enzyme activation-induced cytidine deaminase (AID). The C:G bp is now a mutated U:G bp mismatch. The U base(s) are removed by a repair enzyme, uracil-DNA glycosylase
65
What enzyme is only turned on in memory B cells?
AID: activation-induced cytidine deaminase
66
What are the different types of immunity?
- Natural: active immunity - get disease, immune response (Abs & T cells), develop lifelong or partial immunity - Natural: passive - Abs from mother cross placenta to foetus - Artificial: vaccination - Artificial: passive - direct injection of mAbs, short-lived
67
What are the two types of first generation vaccines developed?
1. Killed (inactivated) | 2. Live, non-virulent (attenuated) e.g. MMR vaccine
68
What are the present day vaccine developments?
1. Live attenuated (recombinant) vaccines - deletion of virulence gene(s) 2. Subunit vaccines - a single protein from the pathogen 3. Virus vector vaccines - live non-pathogenic carrier 4. RNA vaccines - pathogen gene(s) as an mRNA (also DNA) 5. Plant-derived vaccines
69
Examples of subunit vaccines:
- Hepatitis B sAg vaccine (Recombivax HB) - HPV subunit to HPV 16 & 18 (Gardasil & Cervarix) - COVID-19 Spike protein (Novavax)
70
When producing recombinant subunit vaccines, what is the predominant host used to produce therapeutic proteins?
CHO cells (Chinese Hamster Ovary) - about 70% of all recombinant proteins are made in CHO cells
71
Are there any DNA vaccines approved for human use?
No
72
What virus was used to develop one of the first virus vector vaccines?
Vaccinia virus (Smallpox)
73
Are there live components in subunit vaccines?
No
74
What is the HAMA effect?
HAMA = human anti-mouse antibodies | A person's immune system 'sees' the murine mAb as a non-self protein and develops its own antibodies against the mAb
75
Name a method developed to 'humanise' the mAb
CDR grafting - replace as much of the mouse gene regions with human gene regions
76
In biological therapies for rheumatoid arthritis, what inflammatory cytokines are the mAbs against?
TNFα, IL-6, IL-1
77
What is an ADC? Give an example
ADC = antibody-drug conjugate e.g. Kadcyla - ADC consisting of the mAb Trastuzumab (Herceptin) linked to the cytotoxic agent mertansine (DM1), a Tubulin inhibitor

Immunology (10 decks)

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