CMB2004/L06 Lymphocyte Activation

Question 1

Explain lymphocyte maturation simply. (4)

Answer 1

Progenitor cell gives rise to many LYMPHOCYTES with DIFFERENT specificity
REMOVAL of potentially self-reactive immature LYMPHOCYTES
Pool of mature NAIVE lymphocytes
PROLIFERATION and DIFFERENTIATION of activated SPECIFIC lymphocytes to form a clone of effector cells

Question 2

Give 3 functions of antibodies.

Answer 2

Neutralisation
Opsonisation
Complement activation

Question 3

Describe B cell activation. (2 signals)

Answer 3

Binding of Ag to BCR provides signal 1
Signal 2 provided by antigen or extensive cross-linking of BCR

Question 4

Describe the molecular basis of Ag/BCR signal 1. (2)

Answer 4

BCR-associated polypeptides involved in signalling
Crosslinking BCR activates intracellular kinases

Question 5

How can signal to B cells be increased/enhanced? (2)

Answer 5

If antigen has activated complement cascade
Lots of C3b
Complement receptor 2 (CR2) on B cell surface (CD21)
CR2/CD19/CD81 form the BCR co-receptor complex

Question 6

If an Ag that binds BCR is coated with C, then it can bind what?

Answer 6

CR2 on B cells to give an increased signal 1

Question 7

By which mechanisms can B cells receive signal 2?

Answer 7

Dependent on type of Ag they bind
From Ag itself OR
Extensive cross-linking of BCR

Question 8

How do thymus-dependent antigens work? (4)

Answer 8

Require T cell help for B cell activation and antibody production
B cells recognise antigen through BCR
Once activated, B cells present processed antigen to helper T cells (CD4+)
Helper T cells provide signals for B cell proliferation and differentiation into plasma cells

Question 9

What is the difference between TI-1 Ag and TI-2 Ag?

Answer 9

TI-1 Ag
Bind to other receptors on B cells providing signal 2
Act as polyclonal activators in high concentrations
TI-2 Ag
Cross-link many BCR molecules on B cell surface
Take longer to induce B cell activation
Don’t develop response until >5 years

Question 10

Describe the effect that TI-2 antigens elicit on dendritic cells.

Answer 10

TI-2 antigens signal B cells to produce IgM
Activated dendritic cells release cytokine, BAFF, that augments production of antibody against TI-2 antigens and induces class switching

Question 11

Describe how thymus-dependent antibodies work.

Answer 11

T cells activated by MHC/peptide on APC
BCR binds antigen - signal 1
B cell internalises Ag, processes and presents Ag to CD4+ T cells - signal 2
Cytokines secreted by T cell (class switching)
All classes of antibodies can be produced to TD Ag

Question 12

Describe how binding of a viral epitope leads to antibody production. (4)

Answer 12

B cell binds virus through viral coat protein
Virus particle internalised and degraded
Peptides from internal proteins of virus presented to T cell, activating B cell
Activated B cell produces antibody against viral coat protein

Question 13

How would B cells be described in terms of their relationship to TD Ag?

Answer 13

Antigen-presenting cells

Question 14

How must epitopes recognised by the antibody and T cell be physically linked? (2)

Answer 14

Either from different parts of the same molecule
Or from different molecules of complex (e.g., viral proteins)

Question 15

How do B cells convert TI Ag to TD Ag to improve efficiency of a vaccine against pathogens that have T1 antigens? (4)

Answer 15

B cell binds bacterial polysaccharide epitope linked to tetanus toxoid protein
Antigen internalised and processed
Peptides from protein component presented to T cell
Activated B cell produces antibody against polysaccharide antigen on surface of bacterium

Question 16

Give an example of a conjugate vaccine.

Answer 16

Haemophilus influenzae type B
MenC
Pneumococcal conjugate vaccine

Question 17

How are B/T cell conjugates formed?

Answer 17

If Ag is TD, B cell presents peptide from Ag to CD4+ T(H) cells at boundary of T/B areas wihtin lymph node

Question 18

Where to B cells migrate after surviving the bone marrow selection process?

Answer 18

Into blood and lymphatics

Question 19

How are CD40 ligands expressed?

Answer 19

B cell binds BCR and presents peptide (on MHC class II) from Ag to activated T(H) cell
T cell expresses CD40L

Question 20

What is the role of CD40L?

Answer 20

Ligand provides signal 2 to B cells
Signal also induces activation induced deaminase (AID) for class-switching and somatic hypermutation

Question 21

Where do B cells receive the signals to proliferate?

Answer 21

B cell follicles

Question 22

What are germinal centres (GC)?

Answer 22

Conjugates of B lymphoblasts and T cells moved to primary follicles (B cell areas)
Within a B cell follicle in secondary lymphoid tissues

Question 23

Once B cells divide rapidly and form centroblasts, what else can occur? (2)

Answer 23

Somatic hypermutation of Ig genes
Isotype switching

Question 24

What is a centrocyte?

Answer 24

B cell with a cleaved nucleus
Non-dividing cell formed after activation with TD Ag

Question 25

What is signal 3 delivered by antigen-presenting cells?

Answer 25

IL-6 acting on T(FH) cells

Question 26

What can occur with B ells once they are in a germinal centre (GC)? (3)

Answer 26

Differentiate into plasma cells
Form long-lived memory cells
Die within lymphoid tissue

Question 27

What is the role of follicular dendritic cells?

Answer 27

Cells in primary follicle that capture intact Ag for centrocytes to bind via BCR
Present antigen for B cells

Question 28

What is the role of CD40 expressed by B cells? (2)

Answer 28

Protects centrocytes from apoptosis
Induces isotype switching

Question 29

Which types of Ag induce:
a) IgM
b) IgG1, IgG3 or IgG4?

Answer 29

a) Polysaccharides
b) Proteins

Question 30

Which kind of antibody do antigens at mucosal surface induce?

Answer 30

IgA

Question 31

Which antibody is induced by IL-4?

Answer 31

IgE

Question 32

What happens to an activated B cell with mutated BCR with lower affinity for Ag?

Answer 32

BCR not cross-linked
Cannot present antigen to cell
Death by apoptosis