Lecture 9: Antibody Responses and Biology of T Lymphocytes Flashcards
True or False: IgA can be passively acquired via breastmilk
True
True or False: At 6 months of age, newborns have compromised humoral immunity
True
Compare the maternally derived antibody vs. the infant derived antibodies?
Maternally derived = IgG
Infant derived = IgG, IgA, and IgM
If a baby appears sick after and you want to investigate the case, which antibodies should you inquire into?
IgM and IgA
In utero synthesis of antibody indicates ___ exposure to infectious agent/antigen
in utero
How can T-independent antigens become T-dependent?
If they are conjugated to T-dependent antigen, as in the case of the H. influenzae vaccine
True or False: In T-independent antigens, there is affinity maturation and memory response
False - there is neither affinity maturation or memory response in T-independent antigens
What is the ONLY class of Ab made in T-independent antigens?
IgM
True or False: there are cytokines present in T-independent antigens
False - no T cells means no cytokines
How does activation occur in T-independent antigens?
Cross-linking of Ig receptors leads to intracellular signaling and activation (antibody secretion)
True or False: Both T-dependent and T-independent antigens require processing
False - only T-dependent antigens require processing (exogenous)
True or False: Carbohydrates can be put into HLA II molecules
False - they cannot since they are carbs and not peptides
T-dependent antigens are typically ___ while T-independent antigens are typically ___
T-dependent = proteins
T-independent = carbohydrates
True or False: As the immune system/response develops, the overall affinity for antibodies found in a person will increase as well
True
True or False: At the end of an immune response, antibody molecules will have a lower affinity compared to initial stages
False - at the end of an immune response, antibody molecules will have a HIGHER affinity compared to initial stages
As the immune response proceeds and antigen disappears, there is a selection for best binding antibody, which is known as: ____
Affinity maturation (T-dependent only)
True or False: Antigen specificity never changes in a mature B cells
True
Where does processing of first and second dose of antigen occur?
Secondary lymph organs (spleen and lymph nodes)
How long before Ab is detected in response to first dose of Ag in T-dependent interactions? second dose of Ag?
First dose = 7 to 10 days
Second dose = 3 days
What is the predominant Ab isotype in secondary response?
IgG
What is the first isotope produced in response to first dose of Ag? (In other words: during a T-dependent response, what molecule is always secreted first)
IgM
True or False: During the second antigen dose, more IgG is made and it “sticks around longer than IgM
True - IgG has longer half life
Elevated IgG that you see during end of first antigen dose response is the result of what?
IgG becoming plasma cells
True or False: IgG can convert to plasma or memory cells
TRUE
What would a clinician see with a second antigen dose? What sort of response is this?
Elevated IgG and total
- Memory Response
What is the net result of primary antibody response to T-dependent antigen?
Increase number of memory cell clones, which respond more rapidly to second challenge with antigen
True or False: During T-dependent antibody responses, Th2 cells promote ____ while Th1 cells promote ___
Th2: IgG, IgA, and IgE
Th1: Specific switch to IgG3
In T-dependent response, interaction with T cell and its cytokines induces ____
isotype switch
True or False: Cells in T-dependent antibody responses will undergo proliferation, expansion, and differentiation (plasma or memory cell)
True
True or False: Activate T Helper cells give co-stimulatory signals through both cell:cell interactions and cytokines
True
How does the T-dependent response work?
1) APC takes in bacteria (exogenous pathway)
2) Puts peptide in HLA/MHC II context
3) APC activates T Helper Cell
At the same time: there is a B cell with antibody on the surface, specific for SAME antigen
1) B cell binds to antigen and takes it in (exogenous pathway)
2) Same peptide presented HLA/MHC II on B cell
Ultimately, the T helper cell and B cell find each other
True or False: T-dependent antibody antigens are proteins and require processing
True
True or False: Clonal anergy is associated with soluble molecules while clonal deletion is associated with apoptosis
True
If circulating, self-reactive cells come into contact with self antigens WITHOUT co-stimulation, what occurs?
Anergy
- Peripheral B Cell Tolerance
What happens once mature B cell leaves bone marrow? Possible outcomes?
Looks for antigens in circulation
1) Finds Ag = B cell activated
2) Does not find Ag = die (death by neglect)
What are the two major checkpoints during B cell development?
Checkpoint 1: Pre-B Cell (does the heavy chain work)
Checkpoint 2: Immature B cell (is Ig on surface of self reactive)
During immature B cell stage, if cell encounters antigens that it CANNOT interact with ___ occurs.
If cell encounters antigens that it CAN interact with ____ occurs.
CANNOT interact = Clonal anergy
CAN interact = Clonal deletion (apoptosis)
When does antigen specificity occur in B cell development?
- When genes for variable region of molecule are rearranged
True or False: Specificity remains same throughout one’s life
True
Allelic exclusion is associated with which stage of antigen-independent differentiation?
Pre B Cell
What distinguishes Pre-B cell?
1) Cytoplasmic mu
2) Fully re-arranged Ig heavy chain
Net result of primary T-dependent antibody response?
Increase number of clones that will be pre-committed to responding to antigen that induces response
If self-reactive B cell escapes central tolerance, how is it maintained?
Peripheral B Cell Tolerance
Where does Central B Cell Tolerance occur? What stage?
Bone marrow
- Immature B cell stage
What happens as a result of Central B Cell tolerance?
- Multivalent self molecule = clonal deletion (apoptosis)
- Soluble self molecule = clonal anergy (non-responsive)
True or False: Soluble self molecules/anergy is associated with WEAK signals whereas clonal deletion/apoptosis is associated with STRONG signals
True
At what stage of antigen-independent B cell differentiation does selection for self-reactivity occur?
Immature B cell stage
What theory explains how selection occurs? What does the theory state?
Ag Clonal Selection Theory
1) Selection is by the antigen
2) Once B cell is activated, it will undergo proliferation and differentiation (plasma or memory cell)
3) Self reactive B cells must be controlled
Net effect of clonal anergy and clonal deletion?
Get rid of cells prone to responding to self antigens
Where does antigen dependent differentiation occur?
Where does antigen independent differentiation occur?
Antigen dependent = 2 lymphoid tissues (Spleen)
Antigen independent = bone marrow
Where are mature B cells found?
Spleen, Lymph, Peripheral blood
What two molecules are found on surface of mature B cell? Do they have same specificities?
sIgM and sIgD (due to differential splicing of RNA)
- Same specificity, despite different Fc portions
Two possible fates of Immature B cell?
1) Clonal Anergy = B cell becomes tolerant
2) Clonal Deletion = B cell undergoes apoptosis
At what stage do immunoglobulins genes for variable heavy region undergo rearrangement?
Pro B cell stage
What defines a Pre-B cell?
What defines an Immature B cell?
Pre-B cell
- Variable heavy chain is rearranged; mu heavy chains
Immature
- sIgM (u heavy chain + light chain)
At what stage of antigen-independent differentiation of B cells is the rearranged heavy chain tested (checkpoint 1)
Pre B cell stage (if it works: no further rearrangement is needed)
What can one conclude if surrogate light chain and heavy chain get to surface of cells during Pre-B cell stage?
1) Heavy chain is functional
2) Allelic expression can be achieved
