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Infection and Immunity > Introduction to antibodies and B lymphocytes > Flashcards

Introduction to antibodies and B lymphocytes Flashcards

1
Q

What are antibodies produced by?

A

B lymphocytes

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2
Q

What is a surface bound antibody called?

A

B cell receptor

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3
Q

Describe the structure of an antibody

A

4 polypeptide chains
- 2 identical heavy chains
- 2 identical light chains
Held together by S-S bonds
Glycosylated

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4
Q

What do the heavy and light chains consist of?

A

V and C domains

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5
Q

What does each V and C domain do?

A

Folds into a characteristic 3 dimensional shape = immunoglobulin (Ig) domain

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6
Q

What does an Ig domain consist of?

A

2 layers of a beta pleated sheet held together by disulfide bridge

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7
Q

What is the F(ab’)2 region?

A

Constitutes the 2 antigen binding regions

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8
Q

What is the antigen recognition site composed of?

A

variable region of both heavy and light chain

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9
Q

what does the antigen recognition site determine?

A

specificity, affinity and avidity of interaction with the antigen

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10
Q

What is the Fc region?

A

The tail region (the part of the antibody that is not the Fab regions)

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11
Q

Why is the Fc region crystallisable?

A

It is identical in all antibody molecules of a particular type so crystallises in solution

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12
Q

What does the Fc region confirm?

A

Functional properties of antibody

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13
Q

What is the Fc region recognised by?

A

FcR

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14
Q

What does the Fc region bind?

A

Complement

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15
Q

What are the 4 functions of antibodies?

A

Complement
Opsonisation/phagocytosis
recognition killing
sensitisation/cell activation

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16
Q

How many classes of antibodies are there?

A

5 classes and 9 subclasses in humans

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17
Q

What are antibody classes defined by?

A

heavy chain constant region

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18
Q

Describe the structure of IgM

A

Pentameric stabilised by J chain
4 constant regions on heavy chain
Heavy chain encoded by mu gene

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19
Q

What does the monomer of IgM do?

A

forms BCR on most B cells in association with Ig-alpha and Ig-beta chains (acts as membrane bound receptor)

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20
Q

What are the properties of IgM?

A

Low affinity
High avidity
Activates complement (classical)
Major antibody in primary response

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21
Q

Describe the structure of IgG

A

Monomeric
3 constant regions on heavy chain
heavy chain gamma gene

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22
Q

What are the properties of IgG?

A

major antibody in secondary response
can cross placenta and protect foetus
activates complement classical and opsonin (FcR)

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23
Q

What are the 4 sub-classes of IgG?

A

G1, G2, G3, G4

24
Q

Describe the structure of IgA

A

Heavy chain encoded by alpha gene
3 constant regions on heavy chain

25
Q

What are the subclasses of IgA?

A

IgA1 and IgA2

26
Q

Where is IgA found?

A

In tears, milk, saliva, sweat etc.

27
Q

What are properties of IgA?

A

Can get localised mucosal response, different to systemic response
Protects external surfaces (mucosal immunity)
does not activate complement by classical pathway

28
Q

How is IgA secreted?

A

IgA is produced by plasma cells in dimeric form in the lamina propria
IgA dimers bind Poly-Ig receptors on basolateral surface of epithelial cells
Complex is endocytosed
Vesicles fuse with the luminal surface and receptor is cleaved by a protease
Dimer is released into the lumen with part of the receptor bound to it (secretory component)

29
Q

Why does IgA need to be transported to the lumen?

A

To neutralise microbial pathogens in the lumen before they invade

30
Q

Describe the structure of IgD

A

Heavy chain encoded by delta gene
Monomeric
3 constant regions on heavy chain

31
Q

Where is IgD expressed?

A

On the surface of B cells with monomeric IgM

32
Q

What are properties of IgD?

A

Has specific antigen binding activity but NO effector functions
Sensitive to proteolytic degradation and heat
Involved in antigen triggered B-cell differentiation

33
Q

Describe the structure of IgE

A

Heavy chain encoded by epsilon gene
4 constant regions on heavy chain (looks like monomer IgM)

34
Q

Where is IgE found?

A

Majority bound to mast cells and basophils through high affinity Fc-epsilon-R1

35
Q

What are properties of IgE?

A

Key in allergic response
Important role in parasitic infections as mast cells are very effective at killing multicellular organisms

36
Q

What do most B cells express?

A

monomeric IgM and IgD

37
Q

What do both IgM and IgD have on B cells?

A

Same specificity on each individual cell

38
Q

What do surface bound Ig have?

A

Short intracytoplasmic tail and is associated with accessory molecules to form the BCR

39
Q

What are ITAMs?

A

Stands for immunoreceptor tyrosine-based activation motifs
They are amino acid motifs found in the cytoplasmic tails
Essential for signalling

40
Q

What does ligation of the BCR lead to?

A

Phosphorylation of ITAM molecules

41
Q

What does phosphorylation of ITAM lead to?

A

Downstream cascade of events resulting in differentiation into plasma cell and antibody production

42
Q

What is the outcome of BCR ligation?

A

Clonal expansion

43
Q

What is clonal expansion?

A

When 1 B cell is activated and becomes a clone of cells, each with the same BCR specificity

44
Q

What do the majority of B cells become?

A

Plasma cells

45
Q

Describe plasma cells

A

Limited life-span
Apoptose after few days

46
Q

What do a small proportion of the B cells remain as?

A

Memory cells

47
Q

What is the first Ab response?

A

IgM

48
Q

What happens in the secondary response?

A

Class switching to other classes of Ab, especially IgG

49
Q

How does class switching occur?

A

Mutation of variable region sequences - somatic hypermutation

50
Q

What happens after class switching?

A

Affinity maturation (requires T cell help)

51
Q

How are monoconal antibodies produced?

A

Inject a mouse with antigen
Extract the B cells from the mouse
Fusion of these B cells with myeloma cells
Results in hybridoma cells
Isolate antibody from these cells = monoclonal antibodies

52
Q

What are the problems with monoclonal antibodies?

A

Most early McAb were murine - humans will recognise mouse Ab as foreign
Constant region heterogeneity (not the same in mice and humans)
Can produce anti-antibodies
Inflammation can occur

53
Q

What were the solutions to the problems with monoclonal Ab?

A

Chimeric antibodies - retain the antigen-binding V region of murine Ab and replace the rest with human Ab
Humanised antibodies - murine hypervariable regions grafted to human antibodies
Fully humanised antibodies - replace Ig genes of mice with human Ab genes and immunise the mice with antigen to produce human mAbs

54
Q

What is Ipilimumab?

A

Anti-CTLA-4 (CTLA-4 turns off T cells)

55
Q

What is Nivolumab?

A

Anti-PD1 (PD1 kills T cells)

56
Q

Why are molecules like CTLA-4 and PD1 needed?

A

To prevent autoimmune responses/diseases

Infection and Immunity (33 decks)

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