BIIC Immunology Lecture 5_B Cell and Humoral Immunity Part 1 and 2 Flashcards
What are the 5 steps to b cell maturation and what is unique about each step?
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
What is Bruton Agammaglobulinemia?
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
How do antibodies become specific for an antigen?
Recombination activating gene (RAG)
What type of chain rearrangment happens at each step of B cell maturation?
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
What is Clonal deletion?
It is the negative selection that eliminates B cells with self reactive receptors. B cells that are self reactive will be killed via apoptosis.
What is Anergy?
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.
What is B cell receptor editing?
B cells that are strongly self reactive can undergo receptor editing where their heavy and light chains rearange again.
What is Clonal Ignorance?
Basically a self reactive B cell co exists with an antigne and because of low consentration, is not activated
How do b cells finish maturation?
They travel to the periphery and move to the spleen where they start to express IgD, CD19, CD20, and CD21
What drives isotype switching of B cells?
This is driven by the expression of local cytokines by T helper cells and macrophages
What is Affinity maturation?
With repeated exposure, antigen binding sites undergo small changes that increase their affinty of the target antigen
Why is the B cell immune response stronger with t cell help
It leads to isotype switching, induction of memory cells, affinity maturation etc.
What induces signal 1 in B cells?
Crosslinked BCRs activate Ig-alpha and Ig-beta (analog to CD3 in t cells which starts the signaling cascade
What 5 outcomes result from signal 1
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
What is the 2nd signal for B cell activation
both MHC to TCR and CD40 to CD40L together constitute the 2nd signal
What is Transient Hypogammaglobulinemia of Infancy
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
What three things often happen in germinal centers?
1) Rapid b cell proliferation
2) Affinity maturation
3) Isotype switching
What cyctokines drive the veriouse isotypes?
IgG: IFN-gamma (TGF-beta, and IL-4 contribute)
IgE: IL-4
IgA: TGF-beta (BAFF)
What happens to B cells before they become memory b cells?
affinity maturation
What is selective IgA deficiency.
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
What is X linked hyper IgM syndrome?
It is contition that is characterized by no isotype switching. This leads to reccurent URIs, often Pneumocystis Jirovecii.
What is common variable immunodeficiency?
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
How does loss of tolerance to self antigens occur?
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)
What are the immune privileged areas?
Brain, eye, uterus, testis
What is a cross reactive antibody?
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).
