BIIC Immunology Lecture 5_B Cell and Humoral Immunity Part 1 and 2

Question 1

What are the 5 steps to b cell maturation and what is unique about each step?

Answer 1

1) stem cell
2) Pro B cell - there is no antibody receptor
3) Pre B cell - There is a receptor that will develop into an antibody receptor
4) Immature B cell - expresses membrane bound IgM
5) Mature B cell - double positive for both membrane bound IgM and IgD

Question 2

What is Bruton Agammaglobulinemia?

Answer 2

It is an x linked disease that is characterized by the lack of antibody production. This leads to recurrent and unusual infections in early childhood. It is treated with purified IV antibodies

Question 3

How do antibodies become specific for an antigen?

Answer 3

Recombination activating gene (RAG)

Question 4

What type of chain rearrangment happens at each step of B cell maturation?

Answer 4

Early Pro B - H chain gene rearrangment
Late Pro B - H chain gene rearrangment
Pre B cell - L chain gene rearrangment
Immature B cell - Rearrangment ceases

Question 5

What is Clonal deletion?

Answer 5

It is the negative selection that eliminates B cells with self reactive receptors. B cells that are self reactive will be killed via apoptosis.

Question 6

What is Anergy?

Answer 6

It is when a lymphocyte becomes unresponsive. This is often a mechanisium to protect against self reactive b cells. Anergetic B cells express less IgM than other B cells and they have a partial blocking of the intracellular signaling cascade.

Question 7

What is B cell receptor editing?

Answer 7

B cells that are strongly self reactive can undergo receptor editing where their heavy and light chains rearange again.

Question 8

What is Clonal Ignorance?

Answer 8

Basically a self reactive B cell co exists with an antigne and because of low consentration, is not activated

Question 9

How do b cells finish maturation?

Answer 9

They travel to the periphery and move to the spleen where they start to express IgD, CD19, CD20, and CD21

Question 10

What drives isotype switching of B cells?

Answer 10

This is driven by the expression of local cytokines by T helper cells and macrophages

Question 11

What is Affinity maturation?

Answer 11

With repeated exposure, antigen binding sites undergo small changes that increase their affinty of the target antigen

Question 12

Why is the B cell immune response stronger with t cell help

Answer 12

It leads to isotype switching, induction of memory cells, affinity maturation etc.

Question 13

What induces signal 1 in B cells?

Answer 13

Crosslinked BCRs activate Ig-alpha and Ig-beta (analog to CD3 in t cells which starts the signaling cascade

Question 14

What 5 outcomes result from signal 1

Answer 14

1) Class II MHC expression is increased
2) B7 expression is increased
3) Antibody/antigen complex is phagocytized for processing and presentation
4) Adhesion molecules are expressed
5) Expression of CCR7 which leads the B cells to a lymphnode

Question 15

What is the 2nd signal for B cell activation

Answer 15

both MHC to TCR and CD40 to CD40L together constitute the 2nd signal

Question 16

What is Transient Hypogammaglobulinemia of Infancy

Answer 16

It is a condition where infants, beginning at 6 month (when maternal protection decreases) until about 24 months are very prone to recurrent infections due to a deficiency in immunoglobulins

Question 17

What three things often happen in germinal centers?

Answer 17

1) Rapid b cell proliferation
2) Affinity maturation
3) Isotype switching

Question 18

What cyctokines drive the veriouse isotypes?

Answer 18

IgG: IFN-gamma (TGF-beta, and IL-4 contribute)
IgE: IL-4
IgA: TGF-beta (BAFF)

Question 19

What happens to B cells before they become memory b cells?

Answer 19

affinity maturation

Question 20

What is selective IgA deficiency.

Answer 20

It is the most common immunodeficiency with approx 90% of people being asymptomatic. It can lead to reccurent GI and URI infections as well as adverse reactions during boold transfusion

Question 21

What is X linked hyper IgM syndrome?

Answer 21

It is contition that is characterized by no isotype switching. This leads to reccurent URIs, often Pneumocystis Jirovecii.

Question 22

What is common variable immunodeficiency?

Answer 22

It is a condition of low levels of IgM, IgG, and IgA (not IgE). It is often diagnosed because effected persons are vaccine non-responders

Question 23

How does loss of tolerance to self antigens occur?

Answer 23

1) Failure of central tolerance in primary lymphoid tissues (negative selection or editing fails)
2) Failure of peripheral tolerance in secondary lymphoid tissues (mehcanisiums to rended self reactive cells anergic or cause apoptosis fail)

Question 24

What are the immune privileged areas?

Answer 24

Brain, eye, uterus, testis

Question 25

What is a cross reactive antibody?

Answer 25

antigens express an epitope that is very similar (mimickry) to a self protein. This gives rise to an antibody that will kill the antigen but also the the host cells. The classic example of this is group A strep leading to rheumatic fever (antibody cross reacts with cardiac myosin).