properties of EDTA and citrated plasma. what can be collected? - Answer -no clot
-no complement activity (no calcium and magnesium ions)
-can count cells, cells for DNA and fluid for analysis of complement proteins
how many proteins are involved in the complement system? - Answer 70
how to collect complement - Answer through the blood
what ions are important in the lectin pathway and classical pathway and what for? -
Answer calcium
-for MASP-2 and C1q structure and function
magnesium
-alternative pathway
why take serum from the blood - Answer the blood will clot so it with trigger the
coagulation pathways to get active complement
what is a good marker of complement activation? - Answer c3a (its highly sensitive to
how it is sorted)
what do you have to be careful of when using serum as your measure of the
biomarker/function of the drug - Answer higher baseline activity (as activating the
coagulation pathway as well)
what do most doctors look at when looking for disease? - Answer C3 and C4 level
(decrease)
what is the C1-INH?
what is its role in hereditary angioedema? - Answer C1 inhibitor
involved in the contact, complement system
-control of the clotting system
what is C3b function ? - Answer covalently attached to the cell surface so can
opsonising bacteria, cell, immunglobulin
,how can you monitor complement? - Answer look at the level of receptors that interact
with the C3b, iC3b, C3c, C3d or the level of the molecule itself
what is CR1? - Answer very large protein expressed on our white blood cells
-lots of polymorphisms from different ethnic populations
-receptor that lots of pathogens use
-can be used as a biomarker as you can measure the expression on blood cells
what is SLE (systemic lupus erythematosus) - Answer a chronic inflammatory systemic
autoimmune disease of unknown etiology characterized by polyclonal B-cell activation
and abnormal autoantibodies
what are the several complement deficiencies associated with SLE? - Answer C1q, C1r,
C1s, C4, C2, C1 inhibitor deficiency, CR1 receptor deficiency
SLE patients have low levels of... - Answer CR1
-due to the turn over of complement or the low levels of CR1 driving the disease
SLE in animal models - Answer MRL/Mp-Fas mutation leads to lack of apoptosis so you
get necrotic cell death and autoimmune disease
level of CR1/CR2 decreased prior to disease development
MRI as a marker - Answer attach an ion to the marker (CR2) and use MRI to see the
progression of the disease
however ion molecules can trigger the alternative pathway
C4d - Answer -no biological function but be a marker for whether the classical or lectin
pathway has been active
-used in transplant biology if they have more C4 they could be at a higher risk (more
complement fire power)
-multiple copies of C4 in your genome has a major impact on C4 concentration
what are the 2 categories of acute rejection? - Answer -acute cellular rejection (ACR)
-antibody mediated rejection (AMR)
What is paroxysmal nocturnal haemoglobinuria? (PNH) - Answer rare, acquired, life
threatening disease of the blood
due to having missing complement regulators on the RBCs and WBCs
-lose the CD59 and CD55 (GPI anchor) off the cell surface so haemolysis is ready as cant
block MAC attack and get thrombosis
,-eculizumab (anti-C5b) used for treatment but once opsonized by C3 it will become prey
to phagocytes
the link between C3 loading and CR1 expression - Answer more C3 loading onto the cell
surface with low CR1 expression
what is vaccination? - Answer deliberate induction of an adaptive immune response by
injecting a vaccine (a dead, attenuated or non pathogenic) form of pathogen
what is passive immunity? - Answer -protection by transfer of specific, high titre,
antibody from an immune donor to a non-immune recipient (passive transfer)
-alternatively immune cells from an immunized individual may be used to transfer
immunity (adoptive transfer)
what does passive immunity give? - Answer immediate protection
what is naturally acquired immunity? - Answer -required from neonatal protection
-IgG is transferred from mother to foetus (through placenta)
-maternal IgA is transferred through digestive tract (early milk)
why is there an IgG trough in neonates between 3-6 months - Answer due to a decline in
maternal igG
what is artificial passive immunity - Answer pooled specific immunoglobulin
eg animal sera (anti-toxins, anti-venom)
-isolated from immunized large animals
-works very quickly
How does ebola virus effect the body? - Answer infects endothelial cells, mononuclear
phagocytes and hepatocytes (via C-type lectins, integrins)
EBOV encoded glycoprotein (GP) and its secreted from (sGP) play an essential role in
pathogenesis
what is the name of a recombinant antibody to the EBOV GP protein? - Answer Zmapp (3
humanized mAbs produced in tobacco
what is immunological memory? - Answer ability of the immune system to generate rapid
and effective responses to antigen that had previously been encountered
-can measure it with B cell response (antibodies)
the 1st phase of the immune response - Answer establishment of infection (lag phase)
a secondary response reflects a smaller or larger frequency of antigen (Ag) - Answer
, larger
how do memory B cells form? - Answer during initial expansion of Ag specific B cell
clones dont develop into plasma cells instead they revert to small lymphocytes that
maintain the same Ag specific BCR on their surface
what do memory B cells aid? - Answer a quicker and more effective response
what is a naive B cell - Answer a Ag specific B cell that has yet to interact with the same
Ag
what causes clonal expansion? - Answer a very small number of B cells specific to the
antigen
what type of immunoglobulin are memory cells? - Answer IgG or IgA
a mutation in CDR(complementarity-determining regions) of a B cell causes what? -
Answer potentially higher affinity so survival
what is the primary response? - Answer B cell has to bind its antigen to get a signal for it
to survive
the B cell has to compete with other B cells which are binding the same antigen but have
different somatic hypermutations
what is a secondary/tertiary response? - Answer the B cells are still attaching to the
antigens but in the presence of antibodies that have already been secreted against that
antigen from previous B cells
what do naive T cells express - Answer tyrosine phosphatase CD45RA which does not
associate with the TCR
what do memory T cells express - Answer CD45RO which associates with both the TCR
and co-receptor (CD4)
-this signals more effectively than the receptor on the naive T cell
what molecule adds phoshates - Answer kinases
what are the 2 types of memory T cells - Answer -effector
-central
what do effector memory T cells do? - Answer upon Ag re-stimulation, they rapidly
mature into effector cells and then move into tissues (lose CCR7 expression)
release lots of effector associated cytokines eg IFN-gamma and IL-4
what do central memory T cells do? - Answer mature into effector cells slower and stays
in lymph node for longer due to maintenance of CCR7 so take longer to secrete effector
associated cytokines
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