13 - B Cell Effector Functions

Question 1

Humoral immune response

Answer 1

Mediated by antibodies secreted by plasma cells

Question 2

Signals that induce B cells to proliferate and differentiate into plasma cells

Answer 2

Signals from the bound antigen and from helper T cell in the form of CD40L and cytokines

Question 3

Three main ways antibodies protect the host from infection

Answer 3

• Neutralisation
• Opsonisation
• COmplement activation

Question 4

Signals required for B cell activation

Answer 4

• First signal is delivered through the B cell antigen receptor
• Second signal is either thymus dependent (TD) or thymus independent (TI)

Question 5

Thymus dependent antigen second signal

Answer 5

Delivered by helper T cells that recognise antigen bound to MHC-2 molecules. (CD40, CD40L is essential part of second signal)

Question 6

Thymus independent antigen second signal

Answer 6

Delivered with antigen, through TLR that recognise antigen associated TLR ligands (e.g. bacterial LPS)

Question 7

Helper T cells

Answer 7

Stimulate proliferation and then differentiation of antigen binding B cells in lymph nodes

Question 8

Cytokines secreted by T cells in B cell activation

Answer 8

• IL-4, 5 and 6
• Drive proliferation and differentiation of B cell into antibody secreting plasma cells

Question 9

Linked recognition

Answer 9

B cells and helper T cells must recognised epitopes of the same molecular complex in order to interact

Question 10

Process of linked recognition

Answer 10

• B cell binds virus through viral coat protein
• Virus particle is internalised and degraded
• Peptides from internal proteins of the virus are presented to the T cell, which activated the B cell
• Activated B cell produces antibody against viral coat protein

Question 11

Structure of a germinal centre

Answer 11

• A specialised microenvironment in which B cell proliferation and somatic hypermutation occur
• Composed mainly of proliferating B cells
• Antigen specific T cells make up ~10% of germinal center lymphocytes
• Grows in size as immune response proceeds

Question 12

Germinal center after clearance of infection

Answer 12

• Shrinks and disappears
• Present for about 3-4 weeks after intial antigen exposure

Question 13

Centroblasts

Answer 13

Rapidly proliferating B cells in dark zone

Question 14

Centrocytes

Answer 14

B cells dividing less frequently in light zone

Question 15

IL-4

Answer 15

• Produced by CD4+ helper T cells and upregulate CD40L (on T cells)
• Confined to space between B and T cell after secretion

Question 16

Helper T cell cytoskeleton and secondary apparatus during B cell activation

Answer 16

Reoriented towards the B cells

Question 17

T cell and B cell migration to border between T cell area and B cell follicle in lymphoid tissue

Answer 17

Naive CCR7+ T cells and CXCR5+ B cells home to distinct regions where the chemokines CCL21 and CXCR13, respectively,
are produced

Question 18

Subcapsular macrophages

Answer 18

The low endocytic and degradative activity of subcapsular macrophages preserves the antigens trapped on their surface, allowing B cells to encounter them

Question 19

Iccosomes

Answer 19

immune complexes bound to FDCs form iccosomes which are released and taken up by B cells in germinal centres

Question 20

Activated B cells form germinal centres in lymphoid tissues

Answer 20

• Naive B cells enter the lymph node via HEV and leave via efferent lymphatics
• B cells that encounter antigen in the follicle form a primary focus, some form a germinal center
• Plasma cells migrate to the medullary cords or leave via efferent lymphatics
• Plasma cells migrate to bone marrow

Question 21

Rounds of mutation and selection of activated B cells

Answer 21

Mutation and selection for higher affinity mutants in the germinal centre, resulting in high affinity antibody secreting plasma cells and high affinity memory B cells

Question 22

Somatic hypermutation and affinity maturation

Answer 22

• In the germinal centres of a lymph node, the variable regions of BCRs are constantly acquiring mutations
• Mutations that negatively affect the BCR’s affinity for its antigen will be selected against, while mutations in that positively affect affinity will cause proliferation

Question 23

Processes that germinal center B cells undergo

Answer 23

• Somatic hypermutation
• Affinity maturation
• Class switching

Question 24

What antibody isotype do all naive B cells initially express

Answer 24

IgM and IgD

Question 25

Which part of antibody is specific for antigen

Answer 25

Variable region (must be maintained during recombination events in isotype switching)

Question 26

Recombination events in isotype switching

Answer 26

• Genes encoding the constant region corresponding to each isotype are arranged in a linear fashion
• During isotype switching, a portion of the DNA is looped out as switch regions recombine
• After recombination, the constant region directly downstream of the VDJ region will encode the isotype produced on the surface of the B cell and secreted

Question 27

What is class switching controlled by

Answer 27

Cytokines

Question 28

Polyclonal activation

Answer 28

• At high concentration, the signal delivered by the TI-1 antigen is sufficient to induce proliferation and antibody secretion by B cells in the absence of specific antigen binding to the surface Ig.
• Therefore all B cells respond.

Question 29

Another name for TI-1 antigens

Answer 29

Mitogens (substance that induces cells to undergo mitosis)

Question 30

Disadvantages of polyclonal antibody responses

Answer 30

Pathogens have evolved to induce polyclonal antibody responses so that specific antibody is diluted

Question 31

Multiple cross linking of BCR by TI-2 antigens

Answer 31

• Can lead to IgM production
• Cytokines (e.g. BAFF secreted by DCs) increase these responses and lead to class switching

Question 32

Infant immunity

Answer 32

Capable of mounting adaptive immune responses, but their ability to develop long lasting immunity is limited

Question 33

Hib vaccine

Answer 33

• Against Haemophilus influenzae type b
• Conjugate of bacterial polysaccharide and the tetanus toxoid protein

Question 34

How does Hib vaccine work

Answer 34

• The B cell recognises and binds the polysaccharide, internalises and degrades the whole conjugate and then displays toxoid-derived peptides on surface MHC Class II molecules
• Helper T cells generated in response to earlier vaccination against tetanus toxoid recognize the complex on the B cell surface and activate the B cell to produce anti polysaccharide antibody

Question 35

The immune system antibodies against blood types

Answer 35

Forms antibodies against whichever ABO blood group antigens are not found on the individual’s RBC’s (e.g. Blood group A have antibodies againts blood group B)