Denzin - B Cells

Question 1

Neutralization

Answer 1

Antibody can bind to the microbe and not let it come into the epithelium
Antibody can also bind to the microbe as it is leaving one cell on the way to another cell and not let it infect that other cell.
Antibody can also block binding of toxin to cellular receptor.

Question 2

Opsonization

Answer 2

Antibody molecules bind to microbe. The antibodies with bound microbe on it has it’s constant region bind to the Fc receptors on the phagocyte. Then the Fc receptors signal to the phagocyte to eat the coated microbe.

Question 3

ADCC

Answer 3

If there is a virally infected cell, the antibodies will bind to the surface molecules of the cell. Then a NK cell comes along with its specific type of receptor, FCgRIII that recognizes the antibody bound to the infected cell and kills that cell.

Question 4

Complement

Answer 4

Antibodies will activate the complement pathway via the classical pathway. In doing this there are 3 consequences:

1) Opsonization and phagocytosis - a receptor on the phagocyte will recognize the C3 on the surface of the microbe.
2) stimulation of inflammatory reactions. (C3a and C5a)
3) complement-mediated cytolysis - pokes holes in cell (MAC)

Question 5

Central TOlerance

Answer 5

Getting rid of antibodies that are self reactive

• named as such because it happens in the bone marrow (centrally)
• the way that this works is that in the bone marrow the B cells are introduced to self antigens and if the affinity is too high then the cell is destroyed because of the immense amount of signaling.
• If the affinity is too low it will go into a state of anergy
• there is also receptor editing as part of this (different card)

Question 6

Receptor editing

Answer 6

If there is initially a strong affinity between B cell and self antigen and thus a large signal is given off, then the receptor can be rearranged to give it a second chance. If the affinity is still too high then it will be killed.

Question 7

Peripheral Tolerance

Answer 7

If a B cell with affinity that is too high for self-antigen it is Usualy destroyed in central tolerance but it can get through by accident. Additionally, in the bone marrow the B cell will not be introduced to all types of self antigens because the bone marrow is different than the periphery.

• When they now encounter high affinity antigens in the periphery they will undergo apoptosis or they will be functionally inactivated.
• If they have a low affinity, they will be controlled by inhibitory molecules to minimize its impact.

Question 8

What are the 4 ways that B cells act to fight. Pathogens?

Answer 8

Neutralization
Opsonization
ADCC
Complement

Question 9

How do B cells get activated?

Answer 9

Can be either T cell dependent or T cell independent.

Question 10

Main differences between T cell dependent and independent?

Answer 10

Dependent - only uses proteins. Needs the T cell to be activated.
Independent - does not have to be proteins, can be polysaccharides, and lipids as well. However, these microbes need highly repetitive sequences so that the B cell receptors can cross link.

Question 11

First signal in activating B cell receptors?

Answer 11

There has to be cross-linking

- this induces downstream affects that activate transcription factors of

Question 12

How can complement be used to activate B cells?

Answer 12

Rather than cross linking BCRs, a B cell Receptor can cross link with a receptor called CR-2. This occurs when a complement protein called C3d is attached to the microbe, which is then recognized by CR-2. CR2 and BCR then crosslink and an immune response is triggered.

Question 13

WHat is the second signal for activation for B cells in the T dependent? T independent?

Answer 13

Dependent - A T cell comes along with a protein on its surface called CD40L, which then plugs in to the CD40 receptor on the B cell.

Independent - There needs to be a danger signal sent, usually from a Toll Like Receptor.

Question 14

What are some consequences of activating B cells?

Answer 14

1) increased survival and proliferation
2) Increased B7 production on the surface of the B cell
3) Increased cytokines receptors on the surface
4) Increased migration to the proper place

Question 15

What is the full order of T-dependent B cell activation?

Answer 15

First, the dendritic cell has to phagocytize an antigen and become activated. Then the dendritic cell has to present the antigen on an MHC Class II molecule to the T cell in order to activate the T Helper Cell. Then the T Helper Cell will interact with the B cell and activate it via the CD40/CD40L interaction.

Question 16

WHat. Are the different types of Bcells and what do they do?

Answer 16

B-1 B cells - made in fetal liver and circulate in the blood. Are very cross-reactive.
B-2 B cells - made in the bone marrow. Can be made into a follicular B Cell or Marginal B cell In the spleen.
— follicular B cell - Involved in T-dependent activation. It makes IgG, IgA, and IgE.
— Marginal Zone B Cell - role is unclear. Involved in T-independent activation. Makes IgM.

Question 17

Humoral Immune Responses - what happens after clonal expansion?

Answer 17

1) Antibodies will be secreted from plasma cells
2) isotope switching - the constant region will switch so that you have the proper antibodies to have the proper immune response.
3) affinity maturation - the receptors will mutate so that there is a higher affinity for the antigen.
4) memory B cell

Question 18

When you are introduced to an antigen what B cells will be acting at what times?

Answer 18

B1 B cells will be first, then Marginal Zone B cells, then follicular.

Question 19

Germinal Center response

Answer 19

When a B cell gets activated it makes its way over to the spleen to areas called germinal centers. In the germinal centers, there are germinal center reactions in which affinity maturation and isotype switching takes place. The B cells with the highest antigen affinity will survive and the others will die. The way it is introduced to the antigen is through dendritic cells presenting it over and over again. Remember, the antigen is very limited, so they all fight for its attention.

Question 20

Affinity maturation

Answer 20

When there are mutations induced in the CR regions of the BCRs that cause them to have higher affinity for antibodies.

• this is done by an enzyme called AID (Activation Induced Deaminase).
• The BCR is reintroduced to the antigen via follicular dendritic cells in order to ensure that it can still bind the antigen.
• Because antigen is the limiting reagent, only the highest affinity BCRs interact with the antigen and proliferate.

Question 21

Isotype Switching (Class Switch Recombination)

Answer 21

When the Helper T cell is interacting with the B cell it will excrete cytokines in the direction of the B cell. Depending on what kind of cytokines are used, the antibodies will class switch.

• Normally IgM antibodies are excreted
• If the T cell excretes IFN-gamma then IgG class switch will occur
• If IL-4 is excreted then IgE class switch will occur
• If TGF-beta is excreted then IgA class switch will occur.

Question 22

Where are B cells made and at what point does it enter circulation?

Answer 22

In the bone marrow - it enters circulation as an immature B cell as it goes towards the secondary lymphoid organs.

Question 23

What occurs at the checkpoint?

Answer 23

It checks to make sure that the heavy chain is competent.The heavy chain meets up with a surrogate light chain and the complex is put on the B cell surface. If it is a competent match then it will signal intracellularly and it will live. Otherwise it will die. Then there is a second one of these where there is light chain rearrangement. The heavy chain and this light chain will meet up and go out onto the cell surface. If it is a good match then there will be intracellular signaling. Otherwise it will die. If it is good it will move to the secondary lymphoid organs and mature.

Question 24

What happens if the antigen is not polyvalent and only has one epitope on it?

Answer 24

The BCRs will find a way to cluster the antigen so that it presents like a polyvalent microbe.

Question 25

When the T cell interacts with the B cell, how does the B cell know which antibodies to make?

Answer 25

Usually IgM (and IgD) are the default, but when the two cells are connected, the T cell will spit cytokines at the B cell. Depending on what cytokines are spit at it, the antibodies being released will class switch to something else.

• IFNgamma - IgG
• IL-4 - IgE
• TGFbeta (and others) - IgA

Question 26

AID

Answer 26

Enzyme involved in isotope switching and affinity maturation