Humoral immunity block 2

Question 1

Humoral immunity involves :

Answer 1

B cells

Mediated by Ab
Neutralization and elimination of extracellular microbes and microbial toxins
Principle defense mechanism against microbes with capsules rich in polysaccharides and lipids

Question 2

Thymus dependent response of B cells respond to what type of antigens ?

Answer 2

Peptides

Question 3

T independent response of B cells respond to what antigens ?

Answer 3

Polysaccharides

Question 4

Production of good Ab by B cells takes about how many days ?

Answer 4

10-14 days

Question 5

B cells that are located in the peripheral region of the splenic white pulp ?

Answer 5

Marginal B cells

They respond to blood born polysaccharides and lipid antigens.
They are involved in T-INDEPENDENT RESPONSE.

Marginal zone (MZ) B cells are strategically located at the interface between the circulation and the white pulp of the spleen, where they provide a first line of defence by rapidly producing IgM and class-switched IgG antibodies in response to infections by blood-borne viruses and encapsulated bacteria.

Question 6

B cells that prefer to hang out in cortex of lymph nodes ? (majority of B cells)

Answer 6

Follicular B cells

These follicular B cells make the bulk of T-DEPENDENT, classed switched, and high affinity Ab response to protein An and give rise to long lived plasma cells (memory).

Question 7

B1 cells respond to nonprotein antigens in the mucosal tissues and peritoneum. They make what kind of response ?

They act like marginal B cells.

Answer 7

T-independent IgM response

IgM antibodies may be produced spontaneously by B-1 cells, without overt immunization i.e. they make ‘‘natural antibodies’’.

Question 8

True or false.
All B cells require activation via their BCR ?

Answer 8

TRUE

Both T dependent and T independent responses start with activation.

Question 9

Ways to activate BCR with T dependent & T-independent antigens ?

Answer 9

CR2 (CD21) binding to C3d (T-dep) and TLR binding to PAMP (T-ind)

At least 2 BCRs need to bind the An and cross-link in order to be activated in T-dep.

Question 10

How does the T-dependent response work ?

Answer 10

A multistep interaction that requires, in orderly fashion:
Activation of T cell
Activation of B cell
Interaction between B & T cells that share ‘‘antigen interest’’ outside the follicle.

B & T cells must physically contact with each other.

1st interaction : T helper cell in paracortex instruct B cell to proliferate and increase binding affinity via somatic hypermutation.
2nd interaction : TfH cell instruct B cell to switch class of Ig.

Question 11

When physical contact is made between the B cell and the T cell, forming an immune synapse, what cytokine is released by the T cell ?

Answer 11

IL-4

T cell expresses CD40L, B cell CD40 (signal 2)
IL-4 is secreted by T cell (signal 3)

Question 12

Some B cells decide to become Ab secreting cells immediately following the first B cell T cell interaction. This is called ?

Answer 12

Extrafollicular response

These cells can rapidly make Ab which can be class-switched, but they don’t live for very long.

Question 13

TfH cells require what interaction to initiate differentiation and subsequent migration to the germinal center ?

Answer 13

ICOS-ICOSL

ICOS (TfH cell)
ICOSL (B cell)

When TfH cell enter the germinal center, they can make CD40-CD40L interaction with B cell and induce class-switch in high affinity B cells.

Question 14

Grab and display antigens to B cells in the follicle. They are not considered APCs however, as they do not express antigen on MHC :

Answer 14

Follicular dendritic cells

Instead, they have CR1, CR2, CR3 and Fc receptors.

Question 15

Where do you get somatic hypermutation in the germinal center

Answer 15

In the dark zone

Question 16

Where do you get class switch in the germinal center ?

Answer 16

Light zone

Question 17

Low affinity Ab —> High affinity Ab is the result of somatic hypermutation. What enzyme is required for that process to occur ?

Answer 17

AID

Activation induced deaminase

B cells only express this enzyme when they are activated and proliferating.

Question 17

Low affinity Ab —> High affinity Ab is the result of somatic hypermutation. What enzyme is required for that process to occur ?

Answer 17

AID

Activation induced deaminase

B cells only express this enzyme when they are activated and proliferating.

Question 18

Only B cells with high affinity antigen receptors recognize antigen on follicular dendritic cells and present it to :

Answer 18

TfH cells.

TfH cells can now interact with high affinity cells and induce class switch.
Note that class-switch is irriversible.

Question 19

Isotype switch depends on what cytokines are present in the environment. The presence of IL-4 would induce class switch to IgE. The presence of BAFF and TGF-b however would induce a class-switch to ?

Answer 19

IgA

Associated with mucosal immunity

Note that TGF-b is also involved in Treg and M2 activation.

Question 20

AID enzyme recognzes CG motifs and is necessary for the process of somatic hypermutation and in turn, class switch. What other interaction is essential for class-switch to occur ?

Answer 20

CD40/CD40L

Question 21

Activated B cells that are unable to class switch result in what condition?

Answer 21

Hyper IgM syndromes

X linked
defect in CD40L signaling or AID enzyme
repeated bacterial infections
You only see IgM in the blood.

Question 22

Negative CD20 cells that leave the lymph nodes and eventually migrate to the bone marrow.

Answer 22

Long lived Plasma cells

Plasma cells are Ab producing machines (rich in rER)

Do not express BCR

Some migrate to the bone marrow where they produce long lived plasma cells where they can secrete Ab for months, years or even a life-time.

Question 23

A lot of Ab being secreted by plasma cells triggers their apoptosis and conversion to memory b cell production. How does this work ?

Answer 23

The Ab-antigen complex binds to B cell Ig and Fc receptors causing termination of B cell activation (blockage in B cell receptor signaling).

A small population of plasma cells remain in the lymph node are converted to memory b cells and upon secondary antigenic stimulation, they respond immediatly, without having to undergo hypermutation. You get immediate formation of a germinal center.

Question 24

Can one antigen-specific T cell initiate activation of multiple B cells with different Ab specificities ?

Answer 24

Yes.
You only need some kind of similar interest.

For instance if a T cell responds to a specific part of an antigen, such as part of a bigger complex, and the B cell would answer to different part of that complex.

Question 25

As plasma cell differentiation is antigen-dependent, the primary response is short lived or lasts ?

Answer 25

Short lived (2 weeks)

Question 26

How do you know the B cell is a memory B cell (i.e. resting cell stage) ?

Answer 26

It is expresing IgG, IgA or IgE

Question 27

Express high levels of adhesion molecules for recirculation and homing ?

Answer 27

Both memory B & T cells

Question 28

Can naive T cells become immediate memory T cells after being presented with the antigen by dendritic cells ?

Answer 28

Yes.

Question 29

After antigen challenge, the Ab response demonstrates 4 phases :

Answer 29

1. Lag phase
2. Log phase
3. Plateau
4. Decline phase

Question 30

Presence of IgM in the serum would indicate ?

Answer 30

Acute infection

Question 31

Presence of IgG in the blood would indicate ?

Answer 31

Pt has recently had an infection or encountered the thing that stimulated the immune response, such as a vaccine.

Question 32

fetus starts making IgM antibodies at what point ?

Answer 32

3 months before delivery

Between 3-9 months of life, congenital immunodeficiency would show up, because mom’s passive immunity has worn off.

Question 33

Responds to peptides antigen
Isotype switching occurs
Affinity maturation occurs
Memory B cells are made

T dependent or independent ?

Answer 33

T-dependent response

Question 34

Responds to polysaccharides
Only IgM are made (no class-switch)
No affinity maturation
No memory b cells

T dependent or independent ?

Answer 34

T-independent response

Mostly B cells of the marginal zone or B1 cells.

Question 35

What are the 2 ways T-independent response can override the need for T cell interactions for B cell proliferation and differentiation?

Answer 35

1. bind BCR along with TLR stimulation (e.g. LPS)
2. bind a tone of BCR at once (extensive cross-linking of BCRs and co-receptors such as bacterial capsular polysaccharides that have highly repetitive structures)

Question 36

Since T-independent responses do not produce good memory, we sometimes use a carrier protein in combination of the polyssacharide - thus you get T dependent response at the same time. This is the principle used for :

Answer 36

Vaccines against encapsulated bacteria