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IMED2001 > Humoral Immune Responses > Flashcards

Humoral Immune Responses Flashcards

1
Q

What antibody classes do naive B cells express? Are they secreted?

A

IgM and IgD.

No they function as receptors for antigens which when activated trigger secondary messengers.

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2
Q

What happens when B cells are activated?

A

They proliferate (clonal expansion)

They differentiate into plasma cells and memory B cells. Plasma cells actively secrete antibodies and memory cells allow body to have long lived immunity to the antigen.

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3
Q

How many antibodies are produced by a single activated B cell?

A

<4000 plasma cells that produce 10^12 antibody molecules/day

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4
Q

What is the first kind of antibody that is secreted by the humoural immune system?

A

IgM (μ region is closes to the VDJ region during recombination)

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5
Q

What other immunoglobulins are produced by plasma cells?

A

IgG which increase in affinity as a result of affinity maturation.

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6
Q

What is the move from IgM to IgG called?

A

Immunoglobulin class switching.

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7
Q

What is affinity maturation?

A

Antibodies are made and start binding to antigen and B cell receptors become better at binding to the fewer antigens that are present due to increase in specificity and affinity of receptors to the antigen.

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8
Q

What kind of macromolecules are antibodies specific to?

A

They can bind to any type of antigen. They can bind protein, polysaccharides, lipids, and nucleic acids as well as small chemicals.

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9
Q

What are the types of antibody responses?

A

T dependent

T independent

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10
Q

What kind of macromolecules do T dependent antibody responses typically respond to?

A

Protein antigens.

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11
Q

Why is the T helper cell response important for B cell actions?

A

Protein antigens are processed in APCs and recognized by TH cells.

TH cells are important for affinity maturation and class switching.

Without helper T cells there is a weak antibody response (or no response at all)

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12
Q

What kind of response to polysaccharide, lipid of other non-protein antigens elicit?

A

They elicit a T cell independent response which stimulates antibody production without helper T cell involvement.

These responses are simple and don’t show any little heavy-chain isotype switching and affinity maturation.

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13
Q

What do follicular B cells?

A

Majority of B cells which reside in lymphoid organs and make T-dependent, class switched, high-affinity responses to protein.

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14
Q

Where do follicular B cells reside?

A

They reside in the follicles of lymphoid organs (as the name suggests)

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15
Q

What are marginal-zone B cells?

A

Reside in peripheral region of splenic white pulp and respond to blood-borne polysaccharide antigens.

They make lots of IgM and are shorter lived cells.

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16
Q

What are B-1 cells?

A

Respond to non-protein antigens in mucosal tissues and peritoneum.

They respond to lipids and polysaccharide and also make lots of IgM.

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17
Q

Which organ is good for presentation and response to blood-borne antigens?

A

The spleen

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18
Q

How are primary and secondary responses different in B cells?

A

In primary response naive B cells in peripheral lymphoid tissues are activated to proliferate and differentiate into plasma cells and memory cells. Some plasma cells migrate to and survive in bone marrow for long periods of time. (Mostly responded to by IgM)

In secondary response memory cells are already present so they produce a larger amount of antibodies with more heavy chain class switching and affinity maturation. (Protein antigens mostly show this response and the help of CD4 T cells also shows more IgG and IgA or IgE)

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19
Q

How is the peak response different in primary and secondary antibody responses?

A

Smaller in primary larger in secondary.

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20
Q

How long does response take in primary response compared to secondary response?

A

Primary = 5 - 10 days

Secondary = 1 - 5 days

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21
Q

What antibody isotypes dominate in Primary and secondary responses?

A

Primary = IgM and IgG

Secondary = IgG, IgA, IgE

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22
Q

How is affinity of immunoglobulins different between primary response and secondary response?

A

Much higher average affinity in secondary response due to affinity maturation.

23
Q

What is the signalling pathway involved after binding of B cell receptor to antigen?

A

Igalph and Igbeta assemble near the BCR and their ITAM region is phosphorylated by Fyn Lyn and Blk. Syk (The B cell equivalent of Zap70) then activates:

Myc

NFAT

NFkappaB

AP-1

24
Q

What is the role of complement protein in B cell activation?

A

B cells recognize antigen by Ig receptors and C3d is recognized by CR2.

CR2 activation enhances B cell activation.

25
Q

What are the functional consequences of B cell activation?

A

B cell proliferation and IgM secretion.

B cell prepared to activate Th cells and to be activated by Th cells by migrating towards the T cell rich zones of lymphoid organs.

B cell increases expression of cytokine receptors

IgM secretion.

26
Q

How do helper T cells activate B cells?

A

The same protein antigen can activate both B and T cells in different regions of lymphoid organ and they then migrate towards each other.

Effector T cells interact with activated B cells outside follicles.

T cells express CD40L and secrete cytokines which act on B cells to initiate proliferation and differentiation to plasma cells.

Early antibody responses including some isotype switching occurs in extra follicular foci.

Some activated B cells migrate back into follicle accompanied by Th cells which are further activated by B cells to produce follicular helper T cells.

In response to follicular Th cells B cells proliferate and form organised structure of a germinal center and then B cells undergo mutations of antibody V regions as well as isotype switching. High affinty B cells are selected for resulting in high-affinity antibodies.

Result is long-lived plasma cells and memory B cells.

27
Q

How does affinity maturation take place?

A

In response to follicular Th cells B cells proliferate and form organised structure of a germinal center and then B cells undergo mutations of antibody V regions as well as isotype switching. High affinty B cells are selected for resulting in high-affinity antibodies. Result is long-lived plasma cells and memory B cells.

28
Q

How do Th cells and B cells migrate towards each other?

A

T cells reduce CCR7 and increase CXCR5. This promotes T cells leaving the T cell zones (CCR7 takes them there) and going towards the B cell follicles which is an action promoted by CXCR5.

B cells increase CCR7 and decrease CXCR5. So opposite effect takes place.

The result of this is that antigen-activated B and T cells migrate towards each other and meet at edges of lymphoid follicles or in inter-follicular areas.

29
Q

True or False?

B cells can present antigens on MHCII

A

True

30
Q

True or False?

B cells are capable of activating response in naive T cells.

A

False, B cells are capable of activating previously differentiated effector T cells but are inefficient at initiating responses in naive T cells.

31
Q

What co-stimulation molecules are present between B cells and T cells?

A

B cells are acting as APCs in this instance so they express CD40 which binds to CD40L on Th cell receptor surface.

32
Q

What happens when Th cell binds to B cell MHCII and the co-receptor?

A

T cell releases cytokines that activate antigen specific B cells.

33
Q

What influences the generation and function of follicular helper T cells?

A

Co-stimulator of CD28 family (ICOS or inducible co-stimulator)

34
Q

What CD4+ T cells develop into follicular Th cells?

A

From committed or uncommitted T cells including Th1, 2, and 17. (the characteristic cytokines of the subsets may also continue to be produced)

35
Q

What cytokines do Follicular T cells often produce?

A

Most Tfh cells secrete the characteristic cytokines of their subset (based on pathogen being responded to) and most produce IL-21 (most important cytokine)

36
Q

What is the main function of IgM?

A

Complement activation

37
Q

What is the function of IgG subclasses of antibodies?

A

Fc receptor mediated phagocytosis.

Complement activation

Neonatal immunity

38
Q

What is the function of IgE?

A

It triggers mast cell degranulation which is effective against helminths but causes hypersensitivity in people who aren’t.

39
Q

What is the function of IgA?

A

Mucosal immunity (Transport of IgA through epithelia)

40
Q

What Ig do naive B cells express?

A

IgM and IgD

41
Q

What do secreted IgM look like?

A

Star shaped pentamer of antibodies

42
Q

What signals trigger production of IgG antibodies?

A

IFN-γ (important for phagocytic responses)

43
Q

What signals trigger IgE production?

A

IL-4

44
Q

What signals trigger IgA?

A

Cytokines produced in mucosal tissues (TGF-β, BAFF and others)

45
Q

Rule to follow with B cell and Th1, 2, and 17 response:

A

The cytokines produced by the Th subtype guides which antibodies are going to be produced as a result.

46
Q

How does secreted IgA look?

A

It is a dimer

47
Q

How do IgG promote phgagocytosis?

A

IgG1 and IgG3 can bind to Fc receptor on phagocytes to trigger receptor mediated endocytosis.

48
Q

How does heavy-chain of immunoglobin get selected?

A

In an IgM secreting cell that hasn’t received any cytokines the μ mRNA is expressed and everything else is cleaved off because μ is closest to the rearranged VDJ region.

When Th cells provide signals this results in signalling cascade which results in production of an enzyme called AID (Activation-induced deaminase) which alters nucleotides to switch regions so that they can be cleaved by other enzymes.

49
Q

What does the switch region do?

A

It gets cleaved off and brings the constant regions closer to each other.

50
Q

How is affinity maturation conducted?

A

Some B cells activated by antigens with help from T cells migrate into follicles to form germinal centers. (Rapid proliferation takes place and V genes accumulate mutations)

Mutations generate some B cells with greater affinitry and some with lower affinity.

Greater affinity B cells are selected for if they can successfully bind antigens and receive T cell help and the rest of the B cells undergo apoptosis.

Antigens that are used for testing are presented by follicular DCs

51
Q

What kind of mutations are undergone by the V region in B cells?

A

Somatic hyper-mutations (Point mutations) particularly in antigen-binding hypervariable regions in dividing B cells.

52
Q

Why is affinity maturation necessary?

A

B cells that have strongest and highest affinities can recognize antigens with lowest concentrations more easily and can eliminate pathogens more easily.

53
Q

What are plasmablasts?

A

Antibody-secreting cells produced in germinal centers that have not fully differentiated.

Plasmablasts can enter circulation and migrate to bone marrow where they can mature into complete plasma cells.

IMED2001 (44 decks)

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