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Immunology > B cells > Flashcards

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
Q

What does a B cell need to be activated?

A
  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
Q

What determines the antibody type when BCR is binded to T helper cell?

A 
Cytokines the B cell receives from T helper cell
Cytokines cause class switching of B cell
27
Q

What antibodies does the cytokines IL-4 inhibit?

A

IgM
IgG3
IgG2a

28
Q

What antiboides does cytokines IFN-Gamma inhibit (MEG)

A

IgM
IgE
IgG1

29
Q

What antibodies do IL-4 induce?

A

IgG1

IgE

30
Q

What antibodies does IFN-Gamma induce?

A

IgG3

IgG2a

31
Q

3 main functions of antibody

A
  1. Opsonisation (IgG)
  2. Neutralisation (IgA, IgG)
  3. Complement activation (IgM, IgG)
32
Q

Opsinisation (IgG)

A

Antibodies coat pathogen
Phagocytes come and bind to constant region via Fc receptor
so phagocyte binds to fc region of Ig
Phagocytosis

33
Q

Neutralisation (IgA and IgG)

A

IgA and IgG bind to bacteria toxins and virus particles

Prevent them binding to receptors on cells and causing damage

34
Q

Complement activation (IgM and IgG)

A

IgM and IgG bind to their antigen= activates complement system (C1q)
Membrane attack complex formed

35
Q

What antibody activates mast cells?

A

IgE

Mast cell releases histamine

36
Q

What antibody activates basophils?

A

IgD

Basophil activates antimicrobial and pro- inflammatory mechanisms (histamine/heparin/cytokines)

37
Q

What antibody activates eosinophils?

A 
IgE
Release granules (histamine/heparin)= death of parasite
38
Q

Which antibodies are important components of mucosal immunity?

A

IgA and IgD

39
Q

Production of B cell in bone marrow

A

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
Q

What happens once immature B cell in bone marrow is made?

A

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
Q

Life cycle of B cell

A

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
Q

VDJ recombination(somatic recombination) of Heavy chain of BCR

A 
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
Q

VJ recombination for light chain gene

Remember VDJ recombo of BCR happens in bone marrow

A

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
Q

What can a progenitor lymphoid cell in bone marrow become?

A

Progenitor B cell

Progenitor T cell

45
Q

What happens once immature B cell (IgM) is made in bone marrow when VDJ recombo is complete?

A

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
Q

What are 2 ways in which a mature B cell can become activated?

A
  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
Q

How does antigen bind to antigen binding site of variable region of antibody?

A

Epitope of antigen makes contact with antigen binding site (variable region)

48
Q

How does antibody (IgG) activate NK cells?

A

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
Q

How does antibody activate mast cells?

A

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
Q

How does antibody (IgE) activate eosinophils?

A

Eosinophils recognise igE bound to parasites
Eosinophils release granules of histamine/heparin= killing parasite
In allergic and parasitic infections

51
Q

How does antibody (Ig D) activate basophils?

A

Soluble IgD binds to basophils

Activates antimicrobial and proinflammatory mechanisms- cytokines/histamine

52
Q

What cytokine induces IgA?

A

TGF-Beta/IL-21

53
Q

Which cytokine induces IgG?

A

IFN-gamma

54
Q

Which cytokine induces IgE?

A

IL-4

55
Q

Which cytokine induces IgM?

A

IL-15

56
Q

What happens once VDJ recombination of BCR is done in bone marrow?

A

B cells receive survival signals to leave bone marrow and enter lymph node- primary follicle

Immunology (7 decks)

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