Lecture 9: Antibody Responses and Biology of T Lymphocytes

Question 1

True or False: IgA can be passively acquired via breastmilk

Answer 1

True

Question 2

True or False: At 6 months of age, newborns have compromised humoral immunity

Answer 2

True

Question 3

Compare the maternally derived antibody vs. the infant derived antibodies?

Answer 3

Maternally derived = IgG
Infant derived = IgG, IgA, and IgM

Question 4

If a baby appears sick after and you want to investigate the case, which antibodies should you inquire into?

Answer 4

IgM and IgA

Question 5

In utero synthesis of antibody indicates ___ exposure to infectious agent/antigen

Answer 5

in utero

Question 6

How can T-independent antigens become T-dependent?

Answer 6

If they are conjugated to T-dependent antigen, as in the case of the H. influenzae vaccine

Question 7

True or False: In T-independent antigens, there is affinity maturation and memory response

Answer 7

False - there is neither affinity maturation or memory response in T-independent antigens

Question 8

What is the ONLY class of Ab made in T-independent antigens?

Answer 8

IgM

Question 9

True or False: there are cytokines present in T-independent antigens

Answer 9

False - no T cells means no cytokines

Question 10

How does activation occur in T-independent antigens?

Answer 10

Cross-linking of Ig receptors leads to intracellular signaling and activation (antibody secretion)

Question 11

True or False: Both T-dependent and T-independent antigens require processing

Answer 11

False - only T-dependent antigens require processing (exogenous)

Question 12

True or False: Carbohydrates can be put into HLA II molecules

Answer 12

False - they cannot since they are carbs and not peptides

Question 13

T-dependent antigens are typically ___ while T-independent antigens are typically ___

Answer 13

T-dependent = proteins
T-independent = carbohydrates

Question 14

True or False: As the immune system/response develops, the overall affinity for antibodies found in a person will increase as well

Answer 14

True

Question 15

True or False: At the end of an immune response, antibody molecules will have a lower affinity compared to initial stages

Answer 15

False - at the end of an immune response, antibody molecules will have a HIGHER affinity compared to initial stages

Question 16

As the immune response proceeds and antigen disappears, there is a selection for best binding antibody, which is known as: ____

Answer 16

Affinity maturation (T-dependent only)

Question 17

True or False: Antigen specificity never changes in a mature B cells

Answer 17

True

Question 18

Where does processing of first and second dose of antigen occur?

Answer 18

Secondary lymph organs (spleen and lymph nodes)

Question 19

How long before Ab is detected in response to first dose of Ag in T-dependent interactions? second dose of Ag?

Answer 19

First dose = 7 to 10 days
Second dose = 3 days

Question 20

What is the predominant Ab isotype in secondary response?

Answer 20

IgG

Question 21

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)

Answer 21

IgM

Question 22

True or False: During the second antigen dose, more IgG is made and it “sticks around longer than IgM

Answer 22

True - IgG has longer half life

Question 23

Elevated IgG that you see during end of first antigen dose response is the result of what?

Answer 23

IgG becoming plasma cells

Question 24

True or False: IgG can convert to plasma or memory cells

Answer 24

TRUE

Question 25

What would a clinician see with a second antigen dose? What sort of response is this?

Answer 25

Elevated IgG and total - Memory Response

Question 26

What is the net result of primary antibody response to T-dependent antigen?

Answer 26

Increase number of memory cell clones, which respond more rapidly to second challenge with antigen

Question 27

True or False: During T-dependent antibody responses, Th2 cells promote ____ while Th1 cells promote ___

Answer 27

Th2: IgG, IgA, and IgE Th1: Specific switch to IgG3

Question 28

In T-dependent response, interaction with T cell and its cytokines induces ____

Answer 28

isotype switch

Question 29

True or False: Cells in T-dependent antibody responses will undergo proliferation, expansion, and differentiation (plasma or memory cell)

Answer 29

True

Question 30

True or False: Activate T Helper cells give co-stimulatory signals through both cell:cell interactions and cytokines

Answer 30

True

Question 31

How does the T-dependent response work?

Answer 31

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

Question 32

True or False: T-dependent antibody antigens are proteins and require processing

Answer 32

True

Question 33

True or False: Clonal anergy is associated with soluble molecules while clonal deletion is associated with apoptosis

Answer 33

True

Question 34

If circulating, self-reactive cells come into contact with self antigens WITHOUT co-stimulation, what occurs?

Answer 34

Anergy - Peripheral B Cell Tolerance

Question 35

What happens once mature B cell leaves bone marrow? Possible outcomes?

Answer 35

Looks for antigens in circulation 1) Finds Ag = B cell activated 2) Does not find Ag = die (death by neglect)

Question 36

What are the two major checkpoints during B cell development?

Answer 36

Checkpoint 1: Pre-B Cell (does the heavy chain work) Checkpoint 2: Immature B cell (is Ig on surface of self reactive)

Question 37

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.

Answer 37

CANNOT interact = Clonal anergy CAN interact = Clonal deletion (apoptosis)

Question 38

When does antigen specificity occur in B cell development?

Answer 38

- When genes for variable region of molecule are rearranged

Question 39

True or False: Specificity remains same throughout one's life

Answer 39

True

Question 40

Allelic exclusion is associated with which stage of antigen-independent differentiation?

Answer 40

Pre B Cell

Question 41

What distinguishes Pre-B cell?

Answer 41

1) Cytoplasmic mu 2) Fully re-arranged Ig heavy chain

Question 42

Net result of primary T-dependent antibody response?

Answer 42

Increase number of clones that will be pre-committed to responding to antigen that induces response

Question 43

If self-reactive B cell escapes central tolerance, how is it maintained?

Answer 43

Peripheral B Cell Tolerance

Question 44

Where does Central B Cell Tolerance occur? What stage?

Answer 44

Bone marrow - Immature B cell stage

Question 45

What happens as a result of Central B Cell tolerance?

Answer 45

- Multivalent self molecule = clonal deletion (apoptosis) - Soluble self molecule = clonal anergy (non-responsive)

Question 46

True or False: Soluble self molecules/anergy is associated with WEAK signals whereas clonal deletion/apoptosis is associated with STRONG signals

Answer 46

True

Question 47

At what stage of antigen-independent B cell differentiation does selection for self-reactivity occur?

Answer 47

Immature B cell stage

Question 48

What theory explains how selection occurs? What does the theory state?

Answer 48

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

Question 49

Net effect of clonal anergy and clonal deletion?

Answer 49

Get rid of cells prone to responding to self antigens

Question 50

Where does antigen dependent differentiation occur? Where does antigen independent differentiation occur?

Answer 50

Antigen dependent = 2 lymphoid tissues (Spleen) Antigen independent = bone marrow

Question 51

Where are mature B cells found?

Answer 51

Spleen, Lymph, Peripheral blood

Question 52

What two molecules are found on surface of mature B cell? Do they have same specificities?

Answer 52

sIgM and sIgD (due to differential splicing of RNA) - Same specificity, despite different Fc portions

Question 53

Two possible fates of Immature B cell?

Answer 53

1) Clonal Anergy = B cell becomes tolerant 2) Clonal Deletion = B cell undergoes apoptosis

Question 54

At what stage do immunoglobulins genes for variable heavy region undergo rearrangement?

Answer 54

Pro B cell stage

Question 55

What defines a Pre-B cell? What defines an Immature B cell?

Answer 55

Pre-B cell - Variable heavy chain is rearranged; mu heavy chains Immature - sIgM (u heavy chain + light chain)

Question 56

At what stage of antigen-independent differentiation of B cells is the rearranged heavy chain tested (checkpoint 1)

Answer 56

Pre B cell stage (if it works: no further rearrangement is needed)

Question 57

What can one conclude if surrogate light chain and heavy chain get to surface of cells during Pre-B cell stage?

Answer 57

1) Heavy chain is functional 2) Allelic expression can be achieved