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B cells Flashcards

1
Q

Structure of an antibody

A

2 heavy chains
2 light chains
Heavy and light chains are identical= 2 identical antigen binding sites

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2
Q

What links 2 heavy chains together?

A

Disulfide bonds

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3
Q

What links a heavy chain to a light chain?

A

Disufide bond

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4
Q

What does it mean for the antibody if it has 2 identical antigen binding sites?

A

Can bind simultaneously to 2 identical antigens
Increases total strength of interaction (avidity)
Antibody can cross-link 2 antigens and bind to antigen much more stably
Single antigen binding site and antigen have high affinity

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5
Q

What is the name of membrane bound immunoglobulins?

A

BCRs

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6
Q

variable region of antibody

A

Antigen-binding region

Varies in different antibodies= bind to a different specific antigen

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7
Q

constant region of antibody

A

Bottom part of antibody
Does not vary
C region remains inserted into membrane of B cell

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8
Q

Function of BCR?

A

Recognise and bind to a specific antigen via V regions
Transmits a signal to activate B cell
B cell presents antigens= B APC MHC II
Becomes activated by T helper cell
Leads to clonal expansion and antibody production (by plasma cells)

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9
Q

What is a major histocompatibility complex?

A

Large cluster of genes that codes for MHC molecules

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10
Q

What are MHC molecules?

A

Transmembrane glycoproteins

Encoded by MHC

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11
Q

What does it mean that MHC molecules are highly polymorphic?

A

each type of MHC molecule occurs in different versions within population
Increases range of antigens that can be bound to MHC molecule

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12
Q

What are the 5 different classes(isotypes) of antibody?

A

IgM, IgD, Ig,G, IgA, IgE

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13
Q

Most abundant antibody?

A

IgG

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14
Q

Hinge region

A

At centre of Y shaped antibody

gives flexibility to allow antibody to bind to 2 antigens

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15
Q

What does the variable region determine?

A

The antigen binding site

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16
Q

What does the constant region determine?

A

Isotype

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17
Q

What part of BCR allows it to anchor itself into b B cell membrane?

A

Hydrophobic amino acid sequence of carboxy terminus

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18
Q

name of process that allows different Ig’s to be made

A

Class switching of B cell

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19
Q

Y shape of antibody

A 
Fc region (constant region)
2 fab regions= variable region
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20
Q

IgG

A

High affinity and tightly binds to antigen
Crosses placenta to baby
Enhances phagocytosis of bacteria and viruses (opsonisation)

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21
Q

IgM

A

First antibody to be made by cells in an immune response
Pentameric- 5 antigen binding sites connected to 1 constant region
Pick up trace amounts of infection to mark for recognition by phagocytes
Activates complement system
First to be made in an immune response
Most commonly produced but in blood plasma IgG>IgM

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22
Q

IgA

A

Dimeric- joining chain and secretory protein
Secreted at mucosal sites
Inhibiting bacterial and viral adhesion to epithelial cells Neutralisation of bacterial toxins and virus
Main Ig found in breast milk

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23
Q

IgD

A

B cell receptor
Enhances mucosal homeostasis
Activates B cells

24
Q

IgE

A

Parasites and allergies
Induces activation of mast cells and basophils
Found on mast cells- bind to antigen= histamine released

25
What does a B cell need to be activated?
1. Antigen binding to BCR= MHC II APC 2. Costimulation (e.g CD40) from a T helper cell 3. Cytokines from T helper cell-stimulate class switching of antibodies e.g IL-4,IL-5,IL-13
26
What determines the antibody type when BCR is binded to T helper cell?
``` Cytokines the B cell receives from T helper cell Cytokines cause class switching of B cell ```
27
What antibodies does the cytokines IL-4 inhibit?
IgM IgG3 IgG2a
28
What antiboides does cytokines IFN-Gamma inhibit (MEG)
IgM IgE IgG1
29
What antibodies do IL-4 induce?
IgG1 | IgE
30
What antibodies does IFN-Gamma induce?
IgG3 | IgG2a
31
3 main functions of antibody
1. Opsonisation (IgG) 2. Neutralisation (IgA, IgG) 3. Complement activation (IgM, IgG)
32
Opsinisation (IgG)
Antibodies coat pathogen Phagocytes come and bind to constant region via Fc receptor so phagocyte binds to fc region of Ig Phagocytosis
33
Neutralisation (IgA and IgG)
IgA and IgG bind to bacteria toxins and virus particles | Prevent them binding to receptors on cells and causing damage
34
Complement activation (IgM and IgG)
IgM and IgG bind to their antigen= activates complement system (C1q) Membrane attack complex formed
35
What antibody activates mast cells?
IgE | Mast cell releases histamine
36
What antibody activates basophils?
IgD | Basophil activates antimicrobial and pro- inflammatory mechanisms (histamine/heparin/cytokines)
37
What antibody activates eosinophils?
``` IgE Release granules (histamine/heparin)= death of parasite ```
38
Which antibodies are important components of mucosal immunity?
IgA and IgD
39
Production of B cell in bone marrow
Progenitor B cell converted to Pre B cell ( by somatic recombination (VDJ recombo) of heavy chain) Creates a functional heavy chain in large pre B cell Heavy chain associates with light chain and Somatic recombination of Ig alpha-beta dimer= forms pre BCR (large pre B cell) Small pre B cell= VJ rearrangement of Ig light chain= functional BCR and expressed igM on its surface Immature B cell formed (express IgM on surface)
40
What happens once immature B cell in bone marrow is made?
Enters lymph node/spleen In lymph node: Enters cortex (many b cells there) Mature B cell enters paracortex Activated by T-helper cell or antigen on pathogen Travels to germinal centre Enter dark zone of GC first Dark zone= mature B cells proliferate+ clonal expansion, somatic hypermutation of BCRs(increase specificity and affinity) B cells (centroblasts) enter light zone Light zone= B cell with disadvantaged mutation (bad BCR) are removed (by apoptosis) B cells= differentiate- memory/plasma cells B cells with good BCR mutation= CLASS SWITCHING Class switching- can convert IgM to IgA/G/E
41
Life cycle of B cell
Progenitor lymphoid cell (made from stem cell in bone marrow) Progenitor B cell (Heavy chain arrangement by somatic recombo-VDJ recombo) Precursor B cell (Light chain rearrangement by somatic recombo-VJ recombo) Immature B cell (normally has IgM)
42
VDJ recombination(somatic recombination) of Heavy chain of BCR
``` BCR gene has= Variable region, Diversity region, joining region and constant region DJ recombination- J binds to D= brings C closer VDJ recombo Binds VDJ together Splicing- removes introns mRNA makes protein= HEAVY CHAIN Precursor B cell made THIS HAPPENS IN BONE MARROW ```
43
VJ recombination for light chain gene | Remember VDJ recombo of BCR happens in bone marrow
light chain gene= does NOT contain D segment Light chain gene= V,J,C regions in DNA VJ recombo- V and J bind to bring C c;loser Splicing- introns removed mRNA uses gene VJC to make light chain Immature B cell made THIS HAPPENS IN BONE MARROW
44
What can a progenitor lymphoid cell in bone marrow become?
Progenitor B cell | Progenitor T cell
45
What happens once immature B cell (IgM) is made in bone marrow when VDJ recombo is complete?
Immature B cell migrates to lymph node becomes a mature B cell Mature B cell enters dark zone of germinal centre in LN In dark zone= somatic hypermutation of BCR gene(point mutation)= further increase specificity and affinity of antibody Moves to light zone= class switching, B cell differentiates into memory/plasma cells
46
What are 2 ways in which a mature B cell can become activated?
1. BCR binds to antigen on pathogen 2. T helper cell activates B cell by T hElper cell binding to B cell APC (costimulation via CD40 and cytokines released by T helper= class switching of BCR)
47
How does antigen bind to antigen binding site of variable region of antibody?
Epitope of antigen makes contact with antigen binding site (variable region)
48
How does antibody (IgG) activate NK cells?
Antibodies (BCR) bind to epitope of antigen on surface of target cell Fc receptors on NK cells recognise Fc region of antibody bound to antigen Cross linking of Fc receptors on NK cells signals the NK cell to kill target cell Activated NK cell kills target cell by apoptosis
49
How does antibody activate mast cells?
Plasma B cells secrete IgE Fc receptors on mast cell binds to IgE Mast cell coated with IgE Antigen binding to igE cross links the antibody Mast cells degranulate= release histamine Inflammation
50
How does antibody (IgE) activate eosinophils?
Eosinophils recognise igE bound to parasites Eosinophils release granules of histamine/heparin= killing parasite In allergic and parasitic infections
51
How does antibody (Ig D) activate basophils?
Soluble IgD binds to basophils | Activates antimicrobial and proinflammatory mechanisms- cytokines/histamine
52
What cytokine induces IgA?
TGF-Beta/IL-21
53
Which cytokine induces IgG?
IFN-gamma
54
Which cytokine induces IgE?
IL-4
55
Which cytokine induces IgM?
IL-15
56
What happens once VDJ recombination of BCR is done in bone marrow?
B cells receive survival signals to leave bone marrow and enter lymph node- primary follicle

Immunology (7 decks)

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