Med Micro 6.2 - Specific Defense Part 1B (AB diversity) Flashcards
Why are live attenuated vaccines so wonderful?
They simulate the normal mode of entry etc of a pathogen
The class involved in the immune response depends on the type of foreign antigen, the portal of entry, and the antibody function needed. Why is this important?
Need to know to produce a good vaccine etc.
Antibody structure
Important parts: Fab (antigen binding), hyper variable sites (somatic mutation), Fc (biological activity mediation - has constant region and complement binding region)
Why is complement binding region important?
Needed to initiate the classical pathway of the complement system
Somatic mutations
Mutations that occur during our life time, not inheritable
B cell receptor (BCR)
AB in cytoplasmic membrane; multiple copies of a single type of BCR, all have same specificity determined by AB variable region; Antigen binding site is identical to that of the secreted antibody
How do we know that each different B-cell is unique genetically?
They all recognize a different epitope, so they must be.
Generation of AB diversity
- Multiple genes in the germ line DNA; 2. Variable recombination during the differentiation of germ line cells into B-cells; 3. Any light chain can combine with any heavy chain; 4. Mutation during the differentiation of germ line (naïve) B-cells into activated B-cells leading to increased affinity of antibodies during the immune response
AB diversity 1: Germ line DNA
Heavy Chain: 300 V, 10 D 4 J; Light: 300 V, 4 J; overall = 24 million; any one cell will only recombine in one of these possible ways resulting in 1 AB. (V = variable, D = diversity, J = junction)
RAG
Recombination activating gene. For heavy chain, randomly combines a D and J, then randomly combines a DJ to a V.
AB diversity 2: Variable recombination during differentiation of germ cells
Diversity can result is through a process of variable or “inaccurate” recombination. RAG involved here. Heavy chain: D + J, then DJ + V, then transcription and translation of polypeptide is completed. Light chain: V and J
AB diversity 3: Heavy and light combos
Any light chain can combine with any heavy chain
AB diversity 4: Somatic mutations
B cell clones that bind an antigen divide rapidly and come to dominate the antibody response to the antigen; The dividing B cell clones producing antibodies undergo affinity maturation for particular epitopes due to elevated mutation rates in their hypervariable regions, Those B cells with relatively higher binding affinities are stimulated to divide more rapidly (weak binding ones get apoptosis, not needed)
B cell activation and mutation: what’s the process?
(T helper dependent) T Helper activated by phagocyte, recognizes epitope on B cell and activates it to become plasma cell; Proliferates in follicle of lymph node, somatic hypermutations; B cells that bind to follicular dendritic cells exit, those that don’t apoptosis; AB secreting B cells and Memory B cells produced
How many possible ABs are there?
Result of RAG, deletions and insertions and mutations, 10^23 B cell receptor genes
