lecture 2 immunology (week 1) Flashcards
what are the characteristics of antibodies
glycoprotein molecules
antibodies can only attach to their specific antigen
produced by B lymphocytes
recognises proteins, carbohydrates, nucleic acids, glycolipids and small inorganic molecules
can mediate a number of responses:
interact with complement – cell lysis/attach innate cell
interact with phagocytic cells (via Fc portion of antibody)
can have neutralising effect – e.g., block viral entry into cell
how were antibodies discovered?
Late 19th century (emil von behring and shibasaburo kitasato): serum from animals immunised against diphtheria or tetanus toxins could transfer immunity to other animals
early 20th century: demonstration that something in immune serum could neutralise toxins, precipitate toxins, lyse bacteria and agglutinate bacteria
1930s: realisation that all activities are due to one molecule - called “antibody” (or “immunoglobulin”)
1950s: antibody structure elucidated by rodney porter and gerald edelman
what are the 5 classes of antibodies
IgA, IgD, IgE, IgG, IgM
describe the antibody structure
two identical light chains
two identical heavy chains - isotope class
antigen binding region made up of both chain types
2 binding sites per antibody
fc portion (heavy chain constant regions) bind to a cell surface receptor
describe antibody flexibility
the flexibility of the IgG molecule is crucial for the function of binding simultaneously to pathogens and receptors of the immune system
angle between arms moves between 60 degrees and 90 degrees
hinge region between fc and fab portions in IgG allow for some independent movement between the two fab arms
what is the hypervariable region?
complementarity determining regions (cdrs)
regions between cdrs are called framwork regions (fr)
cdrs that make up the antibody combining site constitute the paratope
paratope is complimentary to the antigen binding site; the epitope
describe the antigen binding site structure
the V regions of any given antibody molecule are specific - e.g. IgA and IgG are not the same
sequence variability is not equally distributed through the V region
hv1, hv2, and hv3 are the most variable segments (in the vh and vl domains)
most variable is hv3
regiosn between comprise the rest of the v domain - less variable - framework regions
what are the framework regions responsible for?
the framework regions form the beta sheets that provide the structural framework of the Ig domain
describe the structure of how the antibdoy is folded
in the folded structure of the light chain v domain, hv loops are brought together to form antigen binding regions
when the vh and vl Ig domains are paired in the antibody molecule, the three hv loops from each domain are brought together, creatin a single hv site at the tip of each arm of the molecule - antigen binding site
six hv loops are the cdrs
what forces hold together the antigen - antibody complex
non covalent forces - the contribution depends on the overall interaction of the antigen and antibody
hydrophobic and van der waals forces operate over very short ranges and serve to pull together two surfaces that are complimentary in shape
electrostatic interactions between charged side chains and h bonds bridging oxygen and/or nitrogen atoms, accommodate more specific chemical interactions, while strengthening the interaction overall
covalent bonds never occur between antigens and naturally produced antibodies
describe germline organisation of gene segments
gene segments that encode these chains are organized into three clusters or genetic loci—the κ, λ, and heavy-chain loci—each of which can assemble a complete v-region sequence
each locus is on a different chromosome and is organised slightly differently
the heavy-chain locus differs in one important way: instead of a single c region, it contains a series of c regions one after the other, each of which corresponds to a different immunoglobulin isotype
what are the two theories that were proposed to explain antibody diversity? and what was found when they were studied?
germline theories and somatic variation theories
cloning of antibody genes indicated both theories were correct
the DNA sequence encoding each variable region is generated by rearrangements of a relatively small group of inherited gene segments
diversity is further enhanced by the process of somatic hypermutation in mature activated B lymphocytes
describe vdj recombination
v,d, and j gene segments recombine in a process unique to developing b cells
heavy chains undergo recombination of v, d , and j segments
light chains only recombine v and j segments
process shuffles the segments –> different combinations –> wide variety of antibodies
mediated by rag1/rag2 enzymes, which cut out and join different gene segments
describe junctional diversity
during recombination, the rag enzymes and tdt add or remove nucleotides at the junctions between v,d, and j segments
creates additional variability by altering the sequence at the recombination sites –> unique amino acid sequences in the antigen binding regions
describe somatic hypermutation
b cell encounters antigen –> somatic hypermutation at variable regions
point mutations increased, particularly in the cdrs of the antibody
b cells producing antibodies with higher affinity for the antigen are selected for –> higher specificity and diversity
