introduction to adaptive immunity Flashcards
describe the history of adaptive immunity / vaccination (china, edward jenner, louis pasteur)
15th century, in China, they took a bit of pustule from a small pox infested person and innoculated it into a healthy person
—— the healthy person would then develop a mild case and would later be protected for life
later, Edward Jenner discovered that innoculating patients with cow pox protected them from small pox for life
later, Louis Pasteur discovered if you cultured dangerous organisms, they’d lose some of their ability to cause disease and would cause mild symptoms but also still protect the patient from subsequent infections
—— patient had rabies and was innoculated with cultured rabies and survived
what did the sidechain theory propose? what was it correct and incorrect about?
highly-specific “side-chains”, little soluble molecules made by every cell in the body and in response to infection, cells could ramp up production of the side-chains that’d fight off infection
he was correct about the small, soluble, highly-specific molecule part
he was incorrect about:
——- how every cell can produce these – only specialized cells can
——- also cells can’t be instructed to make these – they are instead secreted
how were T cells discovered?
Jacques Miller, working in England discovered that surgical removal of the thymus of the thymus from newborn mice eliminated adaptive immunity
mice could no longer make antibodies in response to immunization
mice could no longer immunologically reject a skin graft
how were B cells discovered?
the surgical removal of Bursa (mammals do not have this, it’s only found in birds) eliminated antibody production – but the chickens could still reject skin grafts – this meant there are more than just T cells in adaptive immunity
first piece of evidence that there are multiple cells in adaptive immunity (2 distinct cell types)
where is hematopoiesis (blood cell formation) active in?
active in the bone marrow of long bones
specifically the sternum, humerus, ilium, and femur
what is the key difference between B and T cells?
the key difference between these lymphocytes are their receptors
remember, lymphocytes generally resemble one another
differentiate between the composition of the T and B cell receptors
the T cell receptor is made up of 2 proteins, an alpha chain and a beta chain
the B cell receptor is made up of 4 proteins, 2 heavy chains and light chains
each B and T cell has a different amino sequences in the variable region
—— but sequences are the same respectively for the constant region
note: BCR has two binding sites, TCR only has one binding site
what part of the receptor is involved in transmitting their signal?
their cytoplasmic tails are involved in transmitting signals from receptors with signal transduction pathways
why is the variable region, variable?
different due to alternative RNA splicing
differentiate between the membrane bound receptor and antibody of B cells, physically
when membrane bound, it has a hydrophobic cytoplasmic tail that allows it to be tethered to the membrane
when secreted, it does not have a tail and instead ends at with a hydrophilic segment that prevents it from being tethered and allows it to be soluble
what is an antigen?
a molecule that is recognized by a B cell or T cell receptor
it stimulates B cells to produce antibodies
differentiate between antigens and epitopes? describe the importance of epitopes
the antigen is the whole molecule
the epitope is the molecular surface of the antigen that interacts directly (very intimately) but non-covalently with the B cell or T cell receptor
each individual cell makes BCRs/TCRs/antibodies of one single specificity - one single epitope
—— the unique epitope is important for preventing diseases – allows them to target a wide variety of pathogens, each of which may have distinct molecular structures
how is BCR/antibody recognition of antigens different from TCRs?
unlike T cell receptors, B cell receptors and their antibodies can be generated to recognize ANY type of antigen in any 3-dimensional conformation
BCRs/antibodies can adapt any conformation to facilitate molecular interaction
describe how BCRs can be crosslinked by large antigens
BCR’s have 2 binding sites
individual receptors bind a multivalent ligand and nucleate receptor cluster formation
multivalent ligand (multivalent antigen) mediates cluster formation
—- strengthens the transmitted signal
if antigen has multiple epitopes it would be capable of crosslinking antibodies to one another
because BCRs can recognize any type of antigen, 1 antigen can be recognized by multiple BCRs, allowing BCRs to be clustered together
what are the associated molecules of BCRs?
IgAlpha and IgBeta
— also important for signalling
which are then attached with Syk and P proteins via B-cell linker (BLNK) protein – they help transmit the signal from BCR
