B cell immunity I Flashcards
what are antibodies? describe them
soluble polypeptide molecules manufactured and secreted by B cells
they have neutralizing or cytotoxic activities
they have cell or complement-mediated activities
they can recognize any substance
they have enormous medical and commercial importance
explain the enormous medical and commercial importance of antibodies
]4/10 of top 10 best-selling drugs are human antibodies
overall best-selling drug: keytruda
—– anti-PD-1 antibody
—– anticancer antibody!
another of the top 10: anti-TNF-alpha
—– tumor necrosis factor, one of the key cytokines involved in inflammation
—– therefore, reduces inflammation and the included joint swelling and pain
what proteins assist in BCR signalling?
BCR has its own set of proteins IgAlpha and IgBeta that assist in signalling
describe the structure of the BCR
made up of 2 sets of proteins: 2 heavy chains and 2 light chains - covalently linked via disulfide bonds
variable region includes both the heavy and light chain while the constant region is just the heavy chain
—– the variable region is where antigen binding occurs
there are 2 different types of light chains: kappa (κ) and lambda (λ)
there are 5 different types of heavy chains that determine the class/type of antibody
what are the 5 different types of heavy chains / classes of antibodies
there are 5 different types of heavy chains that determine the class/type of antibody:
mu (μ) = IgM
delta (δ) = IgD
gamma (γ) = IgG
—— has 4 different subclasses
epsilon (ε) = IgE
alpha (α) = IgA
—— has 2 different subclasses
what’s FAB and FC in regards to BCR?
FAB = fragment antigen binding (variable region)
—- there’s two of them!
—- made up of both the light and heavy chains
FC = fragment crystallization (constant region)
—- one of them
—- made up of just the heavy chain
describe the variability antibodies of an individual B cell would have
like T cells, individual B cells can only make 1 type of antigen specificity (variable region)
unlike T cells, B cells can make more than 1 class at the same time by swapping out the constant region thru out the immune responses
there are 9 different types of “classes” of antibodies
what’s the order of the antibody genes for B cells?
M, D, G, E, A
describe the antibody IgM and its structure and function
there are 2 binding sites on each individual IgM molecule… IgMs tend to form pentamers with 10 binding sites
the pentamers are held together by a J chain and disulfide bonds
pentameric IgM can bind to different pathogens in a planar (flat) or staple conformation
C1q, a component of complement system and plasma binds to IgM to start classical complement pathways to kill target cells
opsonization, marking cells for better recognition by phagocytic cells – marking them for degradation
what antibody do immature/developing B cells make?
IgM
describe the antibody IgD and its function
it’s right next to IgM’s gene on the genome…. because of this, immature B cells can make/express IgM and IgD at the same time
main function of IgD as an antibody isn’t understood - we don’t know what it does in the immune response
—– but as a BCR and like other BCRs it can bind to antigens…
IgD only makes up 0.2% of the circulating antibodies
— considered irrelevant LOL
describe the antibody IgG and its function
most important antibody type for immune responses
efficient at activation of phagocytosis and complement
—– IgG is said to the be the most efficient in activating complement
long lived
includes 4 different subclasses: IgG1, IgG2, IgG3, IgG4
describe the structure and function of the antibody IgA
mainly present in secretions e.g. saliva, mucus of the gut, tears, and breast milk
although it is the most abundant in serum (blood - clotting factors, so just the plasma), it is found in low levels in circulation
can exist in monomeric form, but is mainly found in it’s dimeric form in secretions
2 molecules of IgA joined together via J chain, and with 4 binding sites
includes 2 different subclasses: IgA1, IgA2
does not mark cells for destruction (opsinization) or activate complement BUT
it neutralizes pathogens and toxins
—– IgA can be actively transported across epithelial cells and other cell layers in the body to reach areas with pathogens/toxins
describe the structure and function of the antibody IgE
mainly known for roles in allergy and asthma and parasitic immune response
made and found in the blood in very small quantities – but with potent effects
activates and primarily interacts with mast cells, basophils, and eosinophils
what are mechanisms of antibodies (6)
1) neutralization of pathogens and toxins
—– inactivates and prevents binding to cells
2) agglutination of particulate antigens
—– antibodies have multiple binding sites, allowing for cross-linking – which allows for efficient phagocytosis and accelerated immune response (bc it’s all clustered up in one spot, easy to eat!)
—– prevents binding to cells and enhances clearance
3) opsonization
—– allows for efficient recognition via FC receptor
4) complement activation
—– when antibody molecule bound to microorganism causing it to lyse (lysis)
5) NK cell-induced apoptosis
—– antibody can be recognized by NK’s FC receptor
—– NK can be activated by multiple methods; one being thru antibodies
6) degranulation
mainly by IgE antibodies recognized by FCR on surface of mast cells, basophils, and eosinophils causing them to degranulate and release toxic substances on the parasite/microorganism
