B cells and antibodies Flashcards

1
Q

What are immunoglobulins and why are they important? (2)

A

Mediate humoral immunity by binding to antigens. These may either be ‘free’ antigens such as bacterial toxins or antigens exposed on the surface of pathogens

Important element of the adaptive immune response to pathogens in particular in combating bacteria, extracellular phases of viruses and parasites and toxins

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2
Q

Where are immunoglobulins present? (2)

A

Present in extracellular fluids including the blood, tissue fluids and mucous secretions

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3
Q

What is X-linked agammaglobulinemia (XLA)? (2)

A

Rare immunodeficiency in which patients are deficient in B-lymphocytes and immunoglobulin production
Subjects with XLA have an increased susceptibility to infection

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4
Q

Function of immunoglobulins (3)

A

Bind antigens and these can be proteins, peptides, nucleic acids, lipids, oligosaccharides and polysaccharides

Immunoglobulins do not directly kill microbes or catabolise antigens

Immunoglobulins bind antigens, but in doing so they can combat pathogens or pathogen associated molecules

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5
Q

What are the three different ways in which immunoglobulins combat pathogens or pathogen associated molecules (3)

A

Neutralisation
Opsinisation
Complement activation

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6
Q

What is immunoglobulin neutralisation of antigens? (3)

A

Block interaction with their targets
Immunoglobulins binding bacterial toxins to prevent interacting with their targets

Immunoglobulins can prevent viruses and bacteria attaching to the surface of host cells

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7
Q

How do immunoglobulins opsinise antigens for uptake by phagocytes (2)

A

Fc receptors bind to Fc region of immunoglobulins

Phagocytosis of immunoglobulin-antigen complexes via Fc receptors leads to the degradation of the antigen

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8
Q

Which classical complement pathway do immunoglobulins activate (3)

A

Complement mediated
neutralisation

Complement
mediated lysis

Phagocytosis via complement receptors

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9
Q

Describe Immunoglobulin structure I (3)

A

2 heavy chains and 2 light chains (kappa or lambda) that are linked together by disulfide bonds
There are two identical antigen binding sites
The Fc region is bound by Fc receptors expressed by phagocytes and other immune cells

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10
Q

Describe Immunoglobulin structure II (5)

A

Heavy and light chains are made up of immunoglobulin domains:
- The light chains have 2 immunoglobulin domains. - One is a variable domain (VL) and one a constant domain (VC)
- The heavy chains have at least 4 immunoglobulin domains
- One is the variable domain (VH) and the others are constant domains (CH1, CH2 and CH3)

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11
Q

Variable domain of the immunoglobulin structure II (2)

A

Variable domain of the light chain (VL) and the variable domain of the heavy chain (VH) combine to form the antigen binding site

The variable domains vary in sequence between different immunoglobulin clones and their sequence defines the antigen specificity of an immunoglobulin molecule

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12
Q

Constant domains of the immunoglobulin structure II (1)

A

The constant domains do not differ between different immunoglobulins of the same class

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13
Q

What forces bind epitopes to immunoglobulins (4)

A

Non-covalent bonds:
Electrostatic interactions - attraction between oppositely charged ionic groups
Hydrogen–bonds
Hydrophobic ‘interactions’: clustering of water-hating groups
Van-der Waals forces - attraction between oscillating dipoles in two electron clouds

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14
Q

How to maximises the non-covalent interactions with the epitope and antibody (2)

A

A complementary binding surface on an antibody maximises the non-covalent interactions with the epitope

Maximises number of weak bonds

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15
Q

What are epitopes? (1)

A

An epitope is the part of the antigen recognised/bound by an antigen receptor

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16
Q

Where is an epitope found? (1)

A

Epitopes are exposed on the surface of the antigen molecule

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17
Q

What are epitopes in proteins? (3)

A

Epitopes in proteins may be continuous (ie residues that make up the epitope are all directly linked)

Epitopes in proteins may be discontinuous (ie formed by the apposition of distant residues as a result of molecular folding).

Discontinuous epitopes in proteins are typically lost by unfolding or denaturing protein antigens

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18
Q

What are the 5 different immunoglobulin classes? (5)

A

IgM
IgG
IgA
IgE
IgD

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19
Q

How to distinguish immunoglobulin classes? (1)

A

Distinguished from each other by their heavy chains

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20
Q

What chain does IgM have? (1)

A

mu heavy chain

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21
Q

What chain does IgG have? (1)

A

Gamma heavy chain

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22
Q

What chain does IgA have? (1)

A

alpha heavy chain

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23
Q

What chain does IgE have? (1)

A

IgE has an epsilon heavy chain

24
Q

What chain does IgD have? (1)

A

IgD has a delta heavy chain

25
Describe the structure of IgM (3)
The IgM mu heavy chain has 4 CH domains IgM is pentameric: 10 antigen binding sites The J chain promotes IgM polymerisation
26
What are the functions of IgM? (4)
Neutralises antigens Agglutinates (clumps) microbes Activates classical complement pathway IgM is effective in limiting the spread of microorganisms via the bloodstream
27
Properties of IgM (3)
First antibody secreted in response to a foreign antigen: primary response Due to its size IgM is mainly confined to vascular system Often has low affinity (binds weakly) for an antigen, although has 10 antigen binding sites enable it to bind to polyvalent antigens such as bacterial surfaces
28
Describe the structure of IgG (3)
4 distinct isotypes: IgG1, IgG2, IgG3 and IgG4 Monomeric Each gamma-heavy chain has 3 CH domains
29
Functions of IgG (4)
Neutralises antigens Opsinises antigens for uptake by by Fc receptors on phagocytes e.g. antibodies bound to bacteria Activates the classical complement pathway During pregnancy it is actively transported across placenta into the foetus to protect newborn babies for the first 3-6 months
30
Properties of IgG (3)
Produced in secondary response to antigen by B-cells in the lymph nodes and spleen (systemic antibody) Major antibody in normal human blood, IgG1 being the most abundant isotype in the blood Small size enables it to diffuse from the bloodstream into extra-vascular sites (40% extravascular) ie the tissues of the body
31
Describe the structure of IgA (2)
alpha-heavy chain has 3 CH domains Exists as both a monomer and a dimer, with J-chain required to link two monomers together
32
Functions of IgA (3)
The principal function of IgA is to neutralise antigens: - IgA prevents bacterial toxins binding their cellular targets - IgA inhibits microbial adhesion to epithelia - IgA inhibits viral infectivity
33
Why is IgA poor at opsonisation and complement activation? (2)
As mainly found in the mucous secretions where phagocytes and complement are absent, but by neutralising antigens it prevents infection in the first place
34
Where is IgA produced and secreted? (2)
IgA is produced by B-cells in the mucosal associated lymphoid tissues during secondary immune response Majority is secreted onto mucosal epithelial surfaces
35
Describe the structure of IgE (1)
Monomeric and the epsilon heavy chain has 4CH domains
36
Functions of IgE (5)
Produced in response to some antigens, usually by B-cells in the mucosal associated lymphoid tissues Important for immune responses against helminths (worms) and other parasites Also involved in type I hypersensitivity responses (allergic reactions) Low concentration in the blood, vast majority of IgE is bound to Fc receptors on mast cells, basophils and eosinophils Binding of IgE molecules to polyvalent antigens cross-links Fc receptors and triggers release of inflammatory mediators
37
Describe the structure of IgD (1)
Monomer, 3CH domains
38
Function of IgD (2)
Acts as antigen receptor on immature B-cells and is present in the blood at very low concentrations No other biological function has yet been described
39
What are B-lymphocytes (3)
B-lymphocytes are concerned with the production of immunoglobulins B-lymphocytes express on their cell surface a membrane bound immunoglobulin: the B-cell receptor (BCR) for antigen Each B-lymphocyte expresses an immunoglobulin that is specific for one antigenic epitope
40
What does recognition and capture of antigen by the BCR do? (3)
Drives the proliferation of that B-lymphocyte and the generation of: - long lived memory cells - short-lived immunoglobulin secreting plasma cells that secrete large quantities of immunoglobulin specific for the antigen
41
Where are plasma cells found? (1)
Found in secondary lymphoid tissues and also migrate back to the bone marrow
42
What are plasma cells? (1)
Short lived terminally differentiated B-cells. Live only 24-48 hours
43
Function of plasma cells (1)
Secrete large amounts of immunoglobulins and are responsible for the majority of immunoglobulins made in response to an antigen
44
How do immunoglobulins circulate (2)
Immunoglobulins enter the blood within the lymphoid tissue and are able to circulate throughout the vascular system
45
What are memory B-lymphocytes (4)
Long-lived cells They express membrane immunoglobulin, but do not secrete significant quantities of immunoglobulins If antigen is encountered again, memory cells are stimulated to divide generating additional memory cells and plasma cells On subsequent exposure to the same antigen memory cells enable a response that is more rapid and greater in amplitude than the initial response to antigen
46
Loops that project from the VL and VH domains forming the antigen binding site are called what? (2)
Complementary determining region Hypervariable loops
47
What kind of interaction occurs between immunoglobulin binding to antigenic epitopes ? (1)
Reversible
48
What is molecular complementation? (1)
A complementary binding surface on an antibody maximises the non-covalent interactions with the epitope
49
Size of epitopes (2)
~12-16 amino acids or ~5-6 sugar residues
50
What do heavy chains determine in immunoglobulins? (1)
The functional specialisation of immunoglobulins
51
What happens in the absence of an antigen? (1)
B-lymphocytes will not proliferate and therefore immunoglobulins are only made that recognise antigens that the host is exposed to
52
How do Antigen specific T-lymphocytes regulate the B-lymphocyte response to antigen? (5)
Signals from T-lymphocytes promote the proliferation and differentiation of B-lymphocytes into memory cells and plasma cells The B-lymphocyte must capture and present the antigen to a T-lymphocyte that is specific for the same antigen. NB they do not have to recognise the same epitope. Antigen is endocytosed, processed into peptides and these peptides are presented by MHC class II molecules to CD4+ T-lymphocytes The T-lymphocyte will give help (signals) to the B- lymphocyte that will activate the proliferation and Antigen specific T-lymphocytes regulate the B-lymphocyte response to antigen
53
When are B-lymphocytes generated? (1)
Continually generated in the bone marrow and these cells then migrate the secondary lymphoid tissues: spleen, MALT and the lymph nodes
54
How are antigens delivered to the lymph nodes? (1)
Via the lymphatic vessels that drain fluid from the tissues, whereas the antigens are delivered to the spleen by the bloodstream
55
What happens when a B-lymphocyte captures an antigen and receives help from a T-lymphocyte specific for the same antigen? (1)
This drives the proliferation of the B-lymphocyte in the secondary lymphoid tissue
56
What are germinal centres? (3)
The sites where B-lymphocytes proliferate are germinal centres. Plasma cells are generated and move to the medullary cords or to the bone marrow. Once the antigen is cleared the germinal centres shrink