Adaptive Immunity Flashcards
Name the mechanisms of antibody diversity
- Somatic (V-(D)-J) recombination I’m immature B lymphocytes
- Somatic hypermutation (SHM)
- Variable Combinations of H and L chains (incl. class switch recombination)
What is the chromosomal location of antibodies/BCR
H chains: alpha, delta, epsilon, mu and gamma (Chromosome 14)
L chains
- lambda: chromosome 22
- kappa: chromosome 2
What does V-(D)-J stand for
Variable gene segments
Diversity gene segments
Joining gene segments
True or false: each light chain can choose multiple variable segments
False, they can only choose one to recombine with
How many recombination the L chain need
1, joining V segment and J segment
How many recombination does the H chain need
3
- D seg with J seg
- JD seg with V
Describe VDJ recombination
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
Describe junctions diversity
Introduction of random mutations and deletions during VDJ recombination which leads to amplification of the antibody diversity
True or false: immature B cells don’t express completed VDJ gene segment rearrangements
False, they do
What molecules cause the activation of somatic hypermutation
Antigens and Th cells
Where do B cells develop
Bone marrow and spleen (white pulp)
Describe B cell development on the bone marrow
Production
Partial maturation: expression of IgM BCRs
Clonal deletion (central tolerance): apoptosis or immature B cells that recognise self-molecules with its IgM BCRs
Describe B cell development in the Spleen (white pulp)
Complete maturation
Expression of IgM and IgM BCRs
Clonal deletion: apoptosis of immature B cells that recognise self molecules with its IgM BCRs
What do nature (naive) B cells do
Released into circulation to survey secondary lymph nodes and tissues for complementary antigens for activation
What is the action of activated B cells
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
Where are blood borne antigens developed
Spleen
Where are antigens from tissues produced
Lymph nodes or lymphoid nodules
Antigens concentrate in peripheral lymphoid organs
What happened to naive B cells that recognise free antigens or APCs (or interact with Th CD4 cells) undergo
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
Characteristics of somatic hypermutation
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
What is enzyme induced cytidine deaminase
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)
What is affinity maturation
When higher affinity immunoglobulins are produced later due to somatic mutation
True or false: 10 antigen binding sites can activate the classical complement pathway
True
True or false: activation of BCRs by antigen leads to class switch recombination
true, Removes original C-mu and C-delta and replaces them with an alternative C-region through DNA recombination
True or false: class switch is reversible
False: irreversible as redundant DNA is deleted
