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CSIM 1: Immunology Strand > CSIM 1.18 Humoral Immunity > Flashcards

CSIM 1.18 Humoral Immunity Flashcards

1
Q

What is the ‘unit’ of humoral immunity?

What is humoral immunity?

A

Antibodies produced by B cells

The molecular aspect of the adaptive immune response

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2
Q

What are the markers for B cells?

A

Proteins: CD19 and CD20

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3
Q

What is a terminally differentiated B cell called?

A

A plasma cell

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4
Q

What are B cell receptors?

A

B cell receptors are actually just antibodies

recall CGP book

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5
Q

Describe the structure of antibodies

A
  • 2 heavy chains
    • 2 light chains
    • Hinge regions
    • Constant region at C terminus
    • Variable region at N terminus
    • Disulphide links

IMG 45

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6
Q

What is the role of the constant region and the variable region? How many different forms does each have?

A

Constant region: (5 forms)
• Effector region that has a function depending on the antibody

Variable region: (10^18)
• Binds to pathogen

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7
Q

What are the 5 classes/isotypes of antibodies? What do these depend on?

A 
The identity of the heavy chain of the constant region
  •  IgG (γ-chain)
  •  IgM (μ-chain)
  •  IgD (δ-chain)
  •  IgA1 (α-chain)
  •  IgE (ε-chain)
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8
Q

What is the first antibody class produced?

What happens after this?

How can this be used clinically?

A

IgM

After antigen stimulation, some antibodies undergo isotype class switching, and substitute the μ heavy chain for α, ε or γ (NOT δ)

If the identity of the most prevalent antibody for a particular infection (e.g. measles) is IgM, the infection was recent, whereas if it is mostly IgG the infection is less recent

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9
Q

What are the types of heavy and light chain in the constant region?

A

Heavy:
• α, μ, δ, ε, γ
• All can be transmembrane OR secretory

Light:
• κ, λ (no real functional difference)

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10
Q

Describe how antibodies undergo isotype class switching

A

By ‘looping out’ heavy chain genes between ‘switch regions’ until the variable region is spliced next to the desired heavy chain gene
(example of alternative DNA splicing)
IMG 46

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11
Q

Which antibody isotype has the correct chain to be:

1) transferred through the placenta?
2) Classical pathway of complement activation?
3) Binding to mast cells
4) Secreted in the breast milk

A

1) IgG ONLY
2) IgG and IgM
3) IgE
4) IgA ONLY

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12
Q

Which antibody is found in gut, lung and eye secretions? Why this antibody?

A

IgA, because it’s constant region is designed for the transport across epithelia

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13
Q

Why are specific antibodies not coded for by genes?

What process is used instead to make a functional gene for all different antibody variable regions?

A

Because there are 10^18 variable region combinations and only 30,000 genes. B cells for ANY pathogen must be available at all times (just not activated yet).

V(D)J somatic recombination

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14
Q

Describe V(D)J somatic recombination

A

Instead of having separate genes for all possible variations of antibodies, the genetic information for ALL is stored in one super gene

There are three genes coding for variable region segments:
  •  Variable (all possible versions)
  •  Diversity (all possible versions)
  •  Joining (all possible versions)
One version for each variable region segment is randomly picked every time a progenitor differentiates into a B cell, e.g:
  •  V1D1J1
  •  V1D2J1
  •  V5D4J4

Heavy chains need one V, one D and one J. Light chains need only one V and one J

Junctional diversity is then added, to give an overall vast number of possible variable regions

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15
Q

Which VDJ gene segments are found in the heavy chain portion of the variable region, and the light chain portion of the variable region?

A

Heavy chain portion of variable region has:
• One Variable
• One Diversity
• One Joining

Light chain portion of variable region has:
• One Variable
• One Joining

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16
Q

Describe what is meant by junctional diversity

A

When joining the V, D and J segments, the joining is done imprecisely, so that there are minor differences in position of V-D and D-J join

Furthermore N regions are added at random (nucleotides at V-D and D-J junction)

17
Q

Which enzyme adds N regions during junctional diversification?

A

Terminal transferase

18
Q

How are V, D and J versions selected at random?

A

Each version lies adjacent to recombination signal sequences, which are randomly sought out by complimentary Rag-1 and Rag-2 proteins, which ‘bring together’ whichever versions of each gene they happen to bind adjacent to

This ‘loops out’ the DNA in the middle, forming what is called a signal joint (a ring of useless DNA with no function) which floats away

The loose ends are then joined together, closing the DNA and placing the desired versions together

19
Q

What is the name of an antigen that a B cell is specific for?

What is the name of a B cell which has not encountered this antigen yet?

What is the name of a B cell which has encountered this antigen?

A

Cognate antigen

Naive B cells

Experienced activated B cells

20
Q

What are the two types of B cell activation?

A

Thymus dependent

Thymus independent

21
Q

What are the Igα and Igβ proteins?

A

Transmembrane proteins found next to B cell receptors (transmembrane antibodies) which are closely associated with the heavy chain of the antibody and assist in signalling

NB: has no role in specificity

IMG 47

22
Q

Describe the process of thymus dependent B cell activation

A
  • Naive B cell receptor (BCR) finds complimentary antigen
    • Multiple B cell receptors bind to the same antigen
    • This causes clustering of BCRs, and thus clustering of their associated Igα and Igβ proteins
    • These Igα and Igβ proteins can then dimerise, triggering intracellular signalling
23
Q

What is the difference between a primary and secondary follicle in a lymph node?

A

Secondary follicles have an active germinal centre inside

IMG 48

24
Q

Once B cells are activated by their complimentary antigen-specific T cell counterparts, what are the possible fates for this cell?

A
  • Some become plasma cells and secrete immunoglobulin (IgM)
    • Some become memory B cells
    • Some proliferate in ‘clonal expansion’ with antigen-specific T cells to form a germinal centre (IgG, IgA, IgE)
25
Q

By which process does affinity maturation occur in germinal centres?

What does this result in?

A

Somatic hypermutation
• As the B cells proliferate, single amino acids in the V region mutate (with enzyme help)

The change may or may not make a change (due to codon degeneracy) through synonymous change. Alternatively there may be a change in shape of the variable region, and thus a change in affinity for the antigen

26
Q

During clonal expansion, If somatic hypermutation generates an antibody with a higher affinity for the antigen than the original antibody, what occurs?

What is this process called?

A

The new B cell binds to a complimentary T cell, which sends the B cell a survival signal, causing it to proliferate aggressively. The B cell then undergoes more somatic hypermutation to try and find an even higher affinity antibody

Affinity maturation

27
Q

In which sections of the V region are most affinity maturation changes found and why?

A
  • CDR1 (complimentary determining region)
    • CDR2
    • CDR3

These are the areas of the variable region that typically bind to the antigen

28
Q

If a somatic hypermutation change leads to an antibody with lower affinity for the antigen, what happens?

A

The new BCR cannot bind to the T cell, and thus cannot receive its survival signal, and so undergoes apoptosis.

29
Q

What do memory B cells allow?

A

Secondary humoral immune response:
• The process of presentation, T cell presentation, B cell activation, clonal expansion, somatic hypermutation and affinity maturation can be bypassed as they have already been performed
• Instead the memory cell simply becomes activated and proliferates, neutralising the microbe before symptoms can arise

30
Q

What are the actions of antibodies on pathogens?

A

Neutralisation
• Binds to bacterial toxins

Opsonisation
• Covers pathogen, leaving the constant region exposed as a receptor target for macrophage ingestion

Complement activation
• The antibody activates complement which helps by coating the pathogen by complement opsonisation

31
Q

Name the 3 ways antibodies vary

A

Isotypic differences
• Different isotypes (differing heavy chain)

Allotypic differences
• Slight changes due to genes (e.g. one amino acid difference from person to person)
• No functional difference

Idiotypic differences
• Different specificities (even if on same isotype)

IMG 49

32
Q

What are the names given to the portion of an antigen recognised by a given antibody or antigen receptor?

A

Antigenic determinant or epitope

33
Q

What does the heave chain switched to in isotype class switching depend on?

A

SPECIFIC CYTOKINES BEING EXPRESSED IN THE B CELL ENVIRONMENT

CSIM 1: Immunology Strand (17 decks)

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