B Cell Block Flashcards

1
Q

What are antibodies?

A

Glycoproteins that specifically bind target antigens, present in body fluids and external secretions but can also be found on specialised cells (e.g. IgE bound to mast cells)

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2
Q

What is an antigen?

A

Molecules that induce an immune response through the activation of antigen specific B lymphocytes and/or T lymphocytes

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3
Q

What is an epitope (antigenic determinant)?

A

The molecular structure recognised by the binding site of an antibody molecule or a T cell receptor

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4
Q

How many classes of human immunoglobulin are there?

A

5

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5
Q

What are the 5 classes of human immunoglobulin?

A

IgM, IgMG, IgA, IgD, IgE

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6
Q

What are the different classes of Ig defined by?

A

structure of the constant region of their heavy chains, which in turn determines function

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7
Q

How many subclasses of IgG are there?

A

4 - IgG1, IgG2, IgG3, IgG4

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8
Q

How many subclasses of IgA are there?

A

2 - IgA1, IgA2

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9
Q

On which chromosome are the genes encoding for the heavy chains of Ig located?

A

Chromosome 14

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10
Q

Structure of IgM

A

Heavy chain comprised of 4 constant domains
Expressed as a monomeric transmembrane molecule on B cells
Secreted by plasma cells as a pentamer (polymerisation facilitated by inclusion of J chain, a polypeptide produced within the plasma cell)

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11
Q

Structure of IgA

A

Heavy chains comprised of 3 constant domains
IgA1 has an extended, highly glycosylated hinge region
IgA present in plasma results from production in bone marrow, monomeric
IgA present in external secretions a product of the local immune system and is produced by plasma cells a dimer (includes a J chain)

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12
Q

How is secretory IgA formed? What is the process called?

A
  1. Dimeric IgA binds to poly-Ig receptor on the basal surface of epithelial cells
  2. Complex is transported to the apical surface where the receptor is cleaved to release the IgA dimer attached to a portion of a receptor (“secretory piece”)

Process called ‘transcytosis’

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13
Q

Structure of IgE

A

Heavy chain comprised of 4 constant domains

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14
Q

Structure of IgD

A

Heavy chain comprised of 3 constant domains and an extended, glycosylated hinge region
Expressed as a transmembrane receptor molecule on the surface of mature B cells

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15
Q

What does the Fc region do?

A

Mediate the effector functions of antibody - acts as a target for Fc receptor of phagocytes

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16
Q

What are the 6 functions of antibodies?

A
  1. Opsonisation
  2. Neutralisation
  3. Precipitation (immune complex formation)
  4. Complement activation
  5. Direct cell activation by Fc receptors - phagocytes, mast cells
  6. Antibody dependent cell mediated cytotoxicity (NK cell activation)
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17
Q

What is opsonisation?

A

Process by which a pathogen is marked or highlighted for ingestion and removal by a phagocyte

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18
Q

What does opsonisation involve?

A

Binding of an opsonin (eg antibody) to an antigen or pathogen which then attracts phagocytes

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19
Q

What does antibody/Fc receptor binding on phagocytes result in?

A

Facilitates phagocytosis

Activates important components of the complement system such as C3b and C4b (more opsonisation)

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20
Q

What is the name of the process where antibody can block internalisation of toxins/virus by blocking binding to virus receptor?

A

Neutralisation

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21
Q

What is the other way of neutralising viruses?

A

Antibodies can bind to the viral envelope proteins that allow docking and entry into their host cell

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22
Q

What is the name of the complex lattice work o antigen & immunoglobulin?

A

Immune complex

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23
Q

What do immune complexes do to provide protection?

A

Limit diffusion of the antigen molecules

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24
Q

What is precipitation of protein/antibodies?

A

-

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25
What is agglutination?
-
26
Which pathway of complement system is activated by antibodies?
Classical pathway
27
What are the two immunoglobulins that cause complement activation on binding to microbial surfaces?
IgM (pentamer) | >2 IgG molecules
28
How do antibodies cause direct cellular activation?
Fc receptors on cells can trigger specific functions | e.g. IgE triggers mast cell activation through the high affinity Fc epsilon receptor 1 (FceR1) in allergic reactions
29
What does ADCC stand for?
Antibody Dependent Cell-mediated Cytotoxicity
30
Which cells re involved in ADCC?
Effector cells of the innate immune system - NK cells, monocytes, macrophages, eosinophils
31
What is the consequence of ADCC?
Lysis of the cell being opsonised by specific antibodies
32
Which portion of the antibody is recognised by what receptor on the effector cell?
Fc portion of the antibody recognised by Fc receptor of an effector cell
33
What do NK cells release on binding to antibody?
Cytokines such as interferon (IFN)
34
How do cytokines help in the immune response?
They attract and activate phagocytes, and cytotoxic granules containing perforin and granzymes
35
What is anti-helminth immunity an example of?
ADCC
36
Which type of antibody recognises the antigens on the parasites (helminth)?
IgE
37
What receptor of an eosinophil binds the IgE in anti-helminth immunity?
Fc receptor (FceR1)
38
What do polyclonal antibodies recognise?
Multiple epitopes on one antigen - inexpensive, low tech
39
What do monoclonal antibodies recognise?
Only one epitope on antigen - high tech, expensive
40
What type of antibody does immunoglobulin replacement therapy involve?
Polyclonal IgG
41
What is an example of monoclonal antibodies?
anti TNFa therapy in rheumatoid arthritis
42
Where are the secondary lymphoid tissues found?
Lymph nodes, spleen, lining of the internal body surfaces (gastrointestinal, respiratory & urogenital)
43
What does the spleen filter?
Blood - for pathogens
44
What do the lymph nodes filter?
the lymphatics that drain peripheral tissues
45
What are the lymphoid tissues in the gut called?
Peyer's patches
46
Where do Peyer's patches drain from?
They drain antigen directly from the gut where most of our pathogens that we face are located into mesenteric lymph nodes
47
Why do lymphocytes recirculate between secondary lymphoid tissue?
In order to maximise opportunity to encounter and therefore respond to antigen
48
What percentage of lymphocytes are in the blood, spleen and other secondary lymphoid tissues?
5% in blood 20% in spleen 75% in other secondary lymphoid tissues
49
How do lymphocytes enter the spleen? (specialised vessels)
Through the walls of the marginal zone blood sinusoids
50
How do lymphocytes enter all other secondary lymphoid tissues?
Through high endothelial venules (afferent lymphatics)
51
What molecule co-ordinates the migration of lymphocytes towards secondary lymphoid tissues?
Selectins
52
How do lymphocytes leave the spleen?
Through the red-pulp blood sinuses
53
How do lymphocytes leave other secondary lymphoid tissues?
Via the efferent lymphatics which ultimately drain via the main lymph vessels into the venous system
54
What do T zones do?
Provide the microenvironment where T and B cells are recruited into antibody responses
55
What happens to T cells once in the secondary lymphoid tissue?
Once through the wall of the high endothelial venule, recirculating T cells are attracted by chemokines produced by dendritic cells to move over their surface. A peptide expressed by MHC on the cell surface of a DC has the best chance of being quickly recognised by a recirculating T cells and activated
56
What happens to B cells once in the secondary lymphoid tissue?
Recirculating B cells migrate from the high endothelial venules, along the walls of the intra-nodal lymphatics into the follicles In the walls of the lymphatics they have the opportunity of encountering antigen in the lymph. The antigen may be free in the lymph or carried by cells that transport intact antigen.
57
What is T cell priming?
Antigen-specific activation of naive recirculating helper T cells at the surface of a DC
58
What does priming require?
Encounter with appropriate costimulatory molecules on the surface of DC as well as the interaction of the T cell receptor with an MHC class II/peptide complex it recognises
59
Will the T cell be primed if it encounters an MHC II/peptide complex it recognises, but appropriate co-stimulation is not available?
No - the T cell may be induced to kill itself by apoptosis
60
What do regulatory CD4 T cells do?
Prevent self-reactive T cells that escape negative selection in the thymus causing autoimmunity
61
How do regulatory CD4 T cells work?
Act by intefering with the priming of naive T cells
62
What happens when there are no Treg influences?
the process of T cell priming alters the behaviour of helper T cells
63
What are the two physical parts of the spleen?
``` Lymphocyte rich white pulp area (with T zones + follicles + a capillary blood supply) Red pulp (consists of blood sinusoids perfusing a macrophage bed) ```
64
What is the function of the red pulp?
Remove debris and pathogens from the blood
65
What is the function of the white pulp?
Mount immune responses
66
Where is the primary interface between pathogens and the adaptive immune system in the spleen?
Marginal sinus
67
How do lymphocytes enter white pulp areas?
Through fenestrated epithelium
68
What is another name for red pulp sinusoids?
Cords of Billroth
69
Where does the blood go after passing the cords of Billroth?
Drains into venous sinusoids, which in turn drain into the splenic vein
70
How do recirculating T & B cells and newly-produced virgin B cells enter the T zones of the white pulp?
By crossing from the marginal zone blood sinusoids
71
What are patients at risk from following splenectomy?
System infection from encapsulated bacteria, especially pneumococcus
72
What is hyposplenism?
A poorly functioning but not an absent spleen
73
What are some causes of hyposplenism?
Coeliac disease, sickle cell anaemia
74
What types of immunoglobulin are natural antibodies?
IgM and IgA
75
Do natural antibodies need antigen for production?
No
76
What are natural antibodies important in?
In providing resistance to common pathogens in the first 48hrs of infection as they are sticky and bind to many different bacteria
77
What are B cells that produce natural antibodies called?
B1 cells
78
Where are B1 cells found?
In the peritoneal and pleural cavities - do not require secondary lymphoid organs for their maintenance
79
Where are B1 cells produced?
In the foetal liver and early in life in the bone marrow. (Ceases after infancy)
80
Why is the repertoire of antigen receptors on B1 cells more restricted than that on recirculating B cells?
Because only a proportion of the V segments in immunoglobulin V region genes is used and junctional diversity between D and J segments and V and DJ is not increased by the action of Tdt during heavy chain variable gene rearrangement
81
What is Lipid A? In what type of TI antibody response is it used?
The lipid component of the lipopolysaccharide | Type 1 TI antibody response
82
In what type of bacteria is lipid A found?
Gram (-)
83
Why is Lipid A an obvious target for the immune system to recognise bacteria?
Lipid A is not produced by mammals
84
What are the bacterial cell wall components and the LPs directly recognised by?
Pattern recognition family of Toll receptors
85
What type of antibdy is the Type 1 TI antibody response associated with?
Mainly IgM but also some IgG
86
Why can't Type 2 TI antibody responses be evoked in the first 5 years of life?
Some bacteria have a thick polysaccharide capsule that hide components of the cell wall that stimulate Toll receptors
87
What type of bacteria cannot be recognised by Toll receptors?
Polysaccharide encapsulated bacteria - Streptococcus pneumoniae, Haemophilus influenzae, Neisseria menigitidis
88
What sort of B cells are involved in the Type 2 TI antibody responses?
Non-recirculating, pre-activated B cells in the splenic marginal zone
89
What can marginal zone B cells originate from?
B1 cells or recirculating B cells
90
What are the properties of marginal zone B cells?
They are rapidly recruited into immune responses after re-exposure to the antigen that evoked them
91
What are the two components to T cell dependent responses?
1. Rapid extrafollicular (not dependent on B follicles) antibody responses 2. Germinal centre dependent B follicular responses
92
What type of antibody are produced by rapid extrafollicular antibody responses?
Mainly IgM but some IgG
93
Are the antibodies produced extrafollicularly of high affinity of low affinity?
Not particularly high affinity
94
What type of antibody are produced by germinal centre dependent B follicular responses?
IgG high affinity antibodies