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CMB2004 - Biology of the Immune System > CMB2004/L06 Lymphocyte Activation > Flashcards

CMB2004/L06 Lymphocyte Activation Flashcards

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1
Q

Explain lymphocyte maturation simply. (4)

A

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

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2
Q

Give 3 functions of antibodies.

A

Neutralisation
Opsonisation
Complement activation

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3
Q

Describe B cell activation. (2 signals)

A

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

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4
Q

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

A

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

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5
Q

What is ITAM?

A

Immunoreceptor tyrosine-based activation motif

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6
Q

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

A

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

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7
Q

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

A

CR2 on B cells to give an increased signal 1

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8
Q

By which mechanisms can B cells receive signal 2?

A

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

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9
Q

How do thymus-dependent antigens work? (4)

A

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

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10
Q

How do thymus-independent antigens work? (3)

A

Activate B cells directly without T cell help
B cells recognise antigen through BCR
Activation produces IgM without additional signals by B cells - less sophisticated

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11
Q

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

A

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

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12
Q

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

A

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

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13
Q

Describe how thymus-dependent antibodies work.

A

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

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14
Q

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

A

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

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15
Q

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

A

Antigen-presenting cells

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16
Q

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

A

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

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17
Q

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

A

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

18
Q

Give an example of a conjugate vaccine.

A

Haemophilus influenzae type B
MenC
Pneumococcal conjugate vaccine

19
Q

How are B/T cell conjugates formed?

A

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

20
Q

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

A

Into blood and lymphatics

21
Q

How are CD40 ligands expressed?

A

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

22
Q

What is the role of CD40L?

A

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

23
Q

Where do B cells receive the signals to proliferate?

A

B cell follicles

24
Q

What are germinal centres (GC)?

A

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

25
Q

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

A

Somatic hypermutation of Ig genes
Isotype switching

26
Q

What is a centrocyte?

A

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

27
Q

What is signal 3 delivered by antigen-presenting cells?

A

IL-6 acting on T(FH) cells

28
Q

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

A

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

29
Q

Describe somatic hypermutation.

A

Introduces point mutations into V regions of Ig
Approx. 1 mutation per V region per cell division
Enzymes involved are AID (activation induced deaminase) and DNA repair genes

30
Q

What is the role of follicular dendritic cells?

A

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

31
Q
A
32
Q

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

A

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

32
Q
A
32
Q
A
33
Q
A
33
Q
A
34
Q

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

A

Protects centrocytes from apoptosis
Induces isotype switching

35
Q

Describe the action of activation-induced deaminase (AID).

A

Induces DNA breakage new constant region of antibody joined without affecting existing VDJ region

36
Q

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

A

a) Polysaccharides
b) Proteins

37
Q

Which kind of antibody do antigens at mucosal surface induce?

A

IgA

38
Q

Which antibody is induced by IL-4?

A

IgE

CMB2004 - Biology of the Immune System (12 decks)

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