Adaptive Immunity

Question 1

Name the mechanisms of antibody diversity

Answer 1

• Somatic (V-(D)-J) recombination I’m immature B lymphocytes
• Somatic hypermutation (SHM)
• Variable Combinations of H and L chains (incl. class switch recombination)

Question 2

What is the chromosomal location of antibodies/BCR

Answer 2

H chains: alpha, delta, epsilon, mu and gamma (Chromosome 14)
L chains
- lambda: chromosome 22
- kappa: chromosome 2

Question 3

What does V-(D)-J stand for

Answer 3

Variable gene segments
Diversity gene segments
Joining gene segments

Question 4

True or false: each light chain can choose multiple variable segments

Answer 4

False, they can only choose one to recombine with

Question 5

How many recombination the L chain need

Answer 5

1, joining V segment and J segment

Question 6

How many recombination does the H chain need

Answer 6

3

• D seg with J seg
• JD seg with V

Question 7

Describe VDJ recombination

Answer 7

Highly specific and tightly controlled process which ensures that only 1V (1D) and 1J are linked together to produce the variable region of the heavy and light chains

Question 8

Describe junctions diversity

Answer 8

Introduction of random mutations and deletions during VDJ recombination which leads to amplification of the antibody diversity

Question 9

True or false: immature B cells don’t express completed VDJ gene segment rearrangements

Answer 9

False, they do

Question 10

What molecules cause the activation of somatic hypermutation

Answer 10

Antigens and Th cells

Question 11

Where do B cells develop

Answer 11

Bone marrow and spleen (white pulp)

Question 12

Describe B cell development on the bone marrow

Answer 12

Production
Partial maturation: expression of IgM BCRs
Clonal deletion (central tolerance): apoptosis or immature B cells that recognise self-molecules with its IgM BCRs

Question 13

Describe B cell development in the Spleen (white pulp)

Answer 13

Complete maturation
Expression of IgM and IgM BCRs
Clonal deletion: apoptosis of immature B cells that recognise self molecules with its IgM BCRs

Question 14

What do nature (naive) B cells do

Answer 14

Released into circulation to survey secondary lymph nodes and tissues for complementary antigens for activation

Question 15

What is the action of activated B cells

Answer 15

Differentiate into effector (plasma) cells
- loss of BCRs and stop dividing
Main function: secretion of antibodies
- most die within 1-2 weeks of activation
- some cells become memory cells and sit in bone marrow and lymph nodes until needed

Question 16

Where are blood borne antigens developed

Answer 16

Spleen

Question 17

Where are antigens from tissues produced

Answer 17

Lymph nodes or lymphoid nodules

Antigens concentrate in peripheral lymphoid organs

Question 18

What happened to naive B cells that recognise free antigens or APCs (or interact with Th CD4 cells) undergo

Answer 18

Somatic hypermutation
Proliferation
Class-switch (start producing IgAny) 
Clonal expansion 
Or death
- B cell goes to lymph nodes, interacts with Th cells, Th then secreted cytokines to tell B cell to proliferate and produce antibodies

Question 19

Characteristics of somatic hypermutation

Answer 19

Occurs only in rapidly proliferating B lymphocytes within w week of exposure to pathogen

• enzyme induced cytosine deaminase (AID)
• immune response starts with lower affinity Immunoglobulins

Question 20

What is enzyme induced cytidine deaminase

Answer 20

When a B cell divides, it introduces mutations into the variable domain of gene responsible for production of antibodies
- High rate ransoms point mutation in VJ and VDJ hyper variable complementary determining regions (CDRs)

Question 21

What is affinity maturation

Answer 21

When higher affinity immunoglobulins are produced later due to somatic mutation

Question 22

True or false: 10 antigen binding sites can activate the classical complement pathway

Answer 22

True

Question 23

True or false: activation of BCRs by antigen leads to class switch recombination

Answer 23

true, Removes original C-mu and C-delta and replaces them with an alternative C-region through DNA recombination

Question 24

True or false: class switch is reversible

Answer 24

False: irreversible as redundant DNA is deleted

Question 25

What are negative consequences that may arise from such antibody diversity

Answer 25

• So diverse that BCRs and antibodies may recognise self as foreign e.g. type 1 diabetes
• Tolerance educates B cells and T cells to distinguish between self and foreign
• Autoimmune diseases are a breakdown of tolerance-

Question 26

What are some positive consequences arising from antibody diversity

Answer 26

• Antibody quality improves over adaptive response
• Immunological memory: faster response next time
• Clonal selection makes B and T cells tolerant to self and responsive to pathogens