Humoral Immunity

Question 1

How are complementary determining regions of antibodies coded?

Answer 1

By VDJ regions in heavy chains and DJ regions in light chains.

Question 2

IgA

Answer 2

Dimer, functions in mucosal immunity.

Question 3

IgD

Answer 3

Naive B cell antigen receptor, never secreted

Question 4

IgE

Answer 4

Functions in allergic reactions (mast cells) and helmith defense.

Question 5

IgG

Answer 5

Work horse antibody, functions in complement, opsonization, cell-mediated cytotoxicity. Can pass placenta.

Question 6

IgM

Answer 6

Secreted as a pentamer, functions in complement activation. Also present on naive B cells.

Question 7

T Cell Dependent Antibody Response

Answer 7

Naive B Cell encounters a microbe, is activated by helper T cells. Clonal expansion occurs (IL-2), and differentiation occurs. IgM antibodies are secreted, isotype switching and affinity maturation occur, and memory cells are created.

Question 8

Affinity Maturation

Answer 8

Each exposure to an antigen causes stronger antibody binding.

Question 9

What happens when a naive B cell encounters a microbe and T cells aren’t present?

Answer 9

Only IgM secretion occurs.

Question 10

Follicular B Cells

Answer 10

Exist in spleen and other lymphoid organs. Express IgD and IgM. When they encounter protein antigens and helper T cells, they can isotype switch, and create high affinity antibodies and long lived plasma cells.

Question 11

Marginal Zone B Cells

Answer 11

Exist in spleen and other lymphoid organs. Only express IgM and react to lipids/polysaccharides. Secrete mainly IgM and short lived plasma cells.

Question 12

B-1 Cells

Answer 12

Exist in mucosal tissues. Express IgM and CD5, react to lipids/polysaccharides. Produce mainly IgM and short lived plasma cells.

Question 13

Primary antibody response

Answer 13

Naive B cells exposed to antigen and activated. From day 5 to 10, IgM and some IgG are created. Some plasma cells created.

Question 14

Secondary antibody response

Answer 14

After repeat infection, memory B cells activate and proliferate, create plasma cells that secrete large amounts of high affinity IgG. Plasma cells and memory B cells persist in higher quantities.

Question 15

B Cell signal transduction after microbe binds to receptor

Answer 15

Microbe binds, Igalpha and Igbeta have ITAMs that start cascade to increase TFs that activate B cells.

Question 16

How is complement recognized by B cells?

Answer 16

C3 on a microbe will bind to both the B cell receptor and CR2. CR2 will enhance B cell activation. This occurs in the follicle of lymph node before T cells arrive.

Question 17

CR2

Answer 17

A complement receptor on B cells that quickly induces B cell activation.

Question 18

What happens when follicular B cells encounter a pathogen?

Answer 18

They are quickly driven into cell cycle to induce clonal expansion. They upregulate cytokine receptors, then leave lymphoid follicles to interact with T cells, and secrete some IgM.

Question 19

What happens when B cells move out of the lymphoid follicle?

Answer 19

Active B cell will digest microbe and present it on MHC class II. Simultaneously, helper T cells are being activated to effectors by interacting with other pAPCs. The active B and T cells will interact and cross stimulate. This occurs when CD4+ TCR interacts with B cell MHC, CD40 (on B) and CD40L (on T) bind, and T cell releases cytokines. Extrafollicular B cells will proliferate, and will move back into follicle to set up the germinal center reaction.

Question 20

Germinal Center Reaction

Answer 20

Stimulated in follicles by extrafollicular B cells that have moved back in after interacting with effector T cells in the peripheral lymphoid space. Selects for memory B cells that have high affinity.

Question 21

Besides the Germinal Center Reaction, what happens when B cells interact with helper T cells?

Answer 21

IgM secreted and isotype switching occurs. IFN gamma induces IgG, IL-4 induces IgE, mucosal specific cytokines induce IgA. Once switching has occurred, B cell stays that way.

Question 22

Mechanism of B Cell Class Switching

Answer 22

Dependent on interaction with T cells. VDJ does not change, but the switch recombination site does. Meaning chromosome will rearrange thanks to AID (activation induced deaminase) and will bring C gamma, C epsilon, etc genes next to VDJ site.

Question 23

AID

Answer 23

Activation induced deaminase, a mediator of class switching.

Question 24

How does affinity maturation occur?

Answer 24

Through somatic hypermutation in the germinal center. Mutations accrue in CDR regions in both heavy and light chains. Many mutations will decrease affinity, but the ones that increase it will bind strongly to follicular dendritic cells/helper T cells and will then be multiplied.

Question 25

How does antibody feedback work?

Answer 25

When sufficient antibodies have been made, many microbes are bound. These antibody bound microbes will eventually find B cells and will bind to B cell receptors and ITIM.

Question 26

ITIM

Answer 26

Antibody receptor that causes inhibition of antibody generation. A major player in antibody feedback.

Question 27

Where do antibodies work?

Answer 27

Away from their point of release (not near bone marrow or lymph nodes).

Question 28

How do antibodies work?

Answer 28

They can neutralize a microbe/toxin, induce opsonization by phagocytes (both independently and dependently of complement), can bring microbe to NK cells and kill cells directly. Through complement, can induce inflammation, lysis, or inflammation.

Question 29

How do antibodies neutralize microbes/toxins?

Answer 29

Prevent their attachment to cell receptors.

Question 30

How do antibodies induce opsonization independent of complement?

Answer 30

IgG main antibody in this process. Fc region will be bound by phagocyte receptor. Causes endocytosis and destruction of microbe.

Question 31

Antibody Dependent Cellular Toxicity

Answer 31

IgG: Binds to microbe, brings it to NK cell, granule release and killing. IgE, binds to helminth, brings it to eosinophil, granule release and killing.

Question 32

Which antibodies activate the classical pathway?

Answer 32

IgG and IgM

Question 33

IgA structure

Answer 33

Wrapped in secretory piece that is picked up when it passes from lamina propria, through mucosal epithelium, to the lumen. This protects the antibody against digestive enzymes and acids.