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Immunology > L6&7 B Cells & Antibodies > Flashcards

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
Q

Which form of IgM is secreted?

A

Pentameric form

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26
Q

Where is IgM mainly found?

A

In the blood - does not penetrate tissues v well

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27
Q

Is IgM involved in opsonisation or ADCC?

A

No - there are few Fc receptors on leukocytes

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28
Q

What is IgM very efficient at?

A

Complement activation, and neutralisation of bacteria & viruses

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29
Q

What is the most abundant Ab in serum?

A

IgG

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30
Q

How many subtypes of IgG are there, and how do they differ?

A

4 subtypes, differ in size of Hinge region

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31
Q

Which form of IgG does NOT cross the placenta?

32
Q

What are the main roles of IgG?

A
  1. Complement activation
  2. Neutralisation of bacteria & viruses
  3. Promote opsonisation or ADCC
33
Q

What is the most abundant Ab in the body in terms of quantity?

34
Q

What are the 2 IgA subclasses and where are they found?

A

IgA1 (longer Hinge region) - found in serum

IgA2 - mainly found in secretions

35
Q

What does secretory IgA do?

A
  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
Q

What is the only antibody subclass that significantly crosses the placenta?

37
Q

When is IgE usually produced?

A

When controlling worm infections, and greatly increased in Hypersensitivity (e.g. asthma, food allergies, allergic rhinitis)

38
Q

Which Ab subclass is normally present in trace amounts in serum?

39
Q

What do CDRs (complementary determining regions) provide?

A

Huge variation

40
Q

What are the 6 mechanisms for generation of antibody diversity?

A
  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
Q

Are V pseudogenes usually functional or non-functional?

A

Non-functional

42
Q

What does allelic exclusion prevent?

A

Co-expression of both alleles

43
Q

What does allelic exclusion maintain?

A

The Law of Clonal Selection

44
Q

What is VDJ recombination?

A

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
Q

How do membrane-anchored and secreted Abs differ?

A

In their C-terminus

46
Q

What is the direct effector function of antibodies?

A

Neutralisation of bacterial toxins/viruses

47
Q

What is the secondary effector function of antibodies?

A

Opsonisation, which leads to phagocytosis and promotes ADCC

48
Q

What happens in Antibody-Dependent Cellular Cytotoxicity (ADCC)?

A

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
Q

What is the most immature antibody-producing B cell?

A

Plasmablast

50
Q

What do plasmablasts secrete?

A

Low-affinity antibodies

51
Q

Are plasmablasts short or long-lived?

A

Short lived

52
Q

What cells supply the very earliest antibodies to the pathogens?

A

Plasmablasts

53
Q

What would you find in germinal centres?

A

Proliferation of LLPCs and memory B cells

54
Q

Where do long-lived plasma cells mainly relocate?

A

Bone marrow & GALT

55
Q

Features of memory B cells:

A

GC-derived
Class-switched
Hypermutated

56
Q

What markers are T follicular helper cells positive for?

A

CD4+, Bcl-6+, CXCR5+

57
Q

Where do Tfh cells interact with memory B cells?

A

at the B-T cell junction

58
Q

Tfh cells play a role in memory B cell survival by secreting…

A

IL-4, IL-21, IFNγ

59
Q

Re-exposure to antigen leads to a rapid reactivation of memory B cells in…

A

spleen and lymph nodes, to produce Ab-secreting SLPCs

60
Q

What changes in germinal centres are seen in severe cases of COVID-19?

A
  • 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
Q

What is the consequence of loss of germinal centres?

A

Compromises the production of long-lived B cell memory and high affinity antibodies

62
Q

What is the purpose of somatic mutations and where do they take place?

A

Produces antibodies with the highest affinities (increases specificity). It takes place in the GCs in LNs & spleen

63
Q

What brings about affinity maturation of antibody?

A

Somatic point mutations in V gene (H and L chain genes)

64
Q

What is the mechanism of somatic hypermutation?

A

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
Q

What enzyme is only turned on in memory B cells?

A

AID: activation-induced cytidine deaminase

66
Q

What are the different types of immunity?

A
  • 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
Q

What are the two types of first generation vaccines developed?

A
  1. Killed (inactivated)

2. Live, non-virulent (attenuated) e.g. MMR vaccine

68
Q

What are the present day vaccine developments?

A
  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
Q

Examples of subunit vaccines:

A
  • Hepatitis B sAg vaccine (Recombivax HB)
  • HPV subunit to HPV 16 & 18 (Gardasil & Cervarix)
  • COVID-19 Spike protein (Novavax)
70
Q

When producing recombinant subunit vaccines, what is the predominant host used to produce therapeutic proteins?

A

CHO cells (Chinese Hamster Ovary) - about 70% of all recombinant proteins are made in CHO cells

71
Q

Are there any DNA vaccines approved for human use?

72
Q

What virus was used to develop one of the first virus vector vaccines?

A

Vaccinia virus (Smallpox)

73
Q

Are there live components in subunit vaccines?

74
Q

What is the HAMA effect?

A

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
Q

Name a method developed to ‘humanise’ the mAb

A

CDR grafting - replace as much of the mouse gene regions with human gene regions

76
Q

In biological therapies for rheumatoid arthritis, what inflammatory cytokines are the mAbs against?

A

TNFα, IL-6, IL-1

77
Q

What is an ADC? Give an example

A

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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