immunogenetics Flashcards
what does the disufide bond connect on an antibody
2 heavy chains
what part of the antibody activates complement and phagocytes
constant region
what part of the antibody binds to antigen
variable region
MCH is essential for…
antigen presentation to T cells
self MHC + foreign antigen=
T cell response
self MHC + self antigen=
no T cell response
no MCH + foreign antigen=
no t cell response
where is mhc located
every nucleated cell in the body
MHC 1 alters what
CD 8 + T cells because viruses infect these
____ is a key factor for determining tissue matching for transplant donors and recipients
MHC
MHC molecules have a broad specificity for peptides meaning….
many diff peptides can bind in the MHC binding cleft
true or false: peptides associated with mhc have a slow on and off rate
true
mhc haplotype of a person determines what
which peptides bind and how peptides bind
mhc genes are highly what
polymorphic
how many mhc alleles are in humans? how many recombinations?
hundreds of alleles with 10^13 recombinations
why is it hard to find transplant donors
mhc genes are highly polymorphic
how are mhc genes expressed?
condominantly meaning that all alleles are expressed at equal frequency
mhc haplotype?
set of mhc alleles on an individual chromosome
mhc haplotype can influence…
how an individual responds to certain pathogens
susceptibility to certain diseases
transplant success
first primary immunodeficiency disease to be descibed?
Bruton agammaglobulinemia
when are primary/congenital immunodeficiencies frequently manifested?
infancy and childhood
what are secondary/acquired immunodeficiencies a consequence of?
malnutrition, disseminated cancer, immunosuppressive drugs, infection of cells of the immune system
what is conserved across widely diverse species
TLR
what do primary immunodeficiency disorders affect
B cells, T cells, NK cells, phagocytic cells, and complement proteins
what may immunodeficiencies result from
defects in leukocyte maturation/activation or defects in effector mechanisms of innate and adaptive immunity
principle consequence of immunodeficiency?
inc susceptibility to infection
nature of infection in a pt depends on what
component of the immune system thats defective
deficient humoral immunity results in inc susceptibility to fight infection by what
pyogenic bacteria
what antibody isotopes are low in XLA/brutons agammaglobulinemia
ALL
are circulating B cells present in XLA/brutons agammaglobulinemia
no
are pre B cells present in XLA/brutons agammaglobulinemia
yes but they are reduced in number in the bone marrow
tell me about the tonsil and lymph nodes in XLA/brutons agammaglobulinemia
tonsils are very small and lymph nodes are not palpable
why are tonsils are very small and lymph nodes are not palpable in XLA/brutons agammaglobulinemia
absence of germinal centers
tell me about the thymus in XLA/brutons agammaglobulinemia
theyre normal
who is mainly affected with XLA/brutons agammaglobulinemia
boys
why do boys not usually show symptoms of XLA/brutons agammaglobulinemia during the first 6-9 months of life
they still have the maternally transmitted IgG antibodies
what happens after the maternal IgG antibodies wear off in XLA/brutons agammaglobulinemia
boys repeatedly get infections with extracellular pyogenic organisms such as pneumococci, streptococci, and haemophilus
what type of defect is in XLA/brutons agammaglobulinemia
maturation of B cells
in XLA/brutons agammaglobulinemia,
circulation B cells are____
pre B cells are_____
circulation B cells are absent
pre B cells are reduced
what disease is associated with a loss of function of bruton tyrosine kinase
XLA/brutons agammaglobulinemia
what is X linked immunodeficiency with hyper IgM characterized by
low serum IgG, IgA, IgE and increased IgM
when do ppl with X linked immunodeficiency with hyper IgM usually become symptomatic
1st or 2nd year of life
what types of infections do ppl with X linked immunodeficiency with hyper IgM or XLA have
pyogenic infections such as otitis media, sinusitis, pneumonia, tonsillitis
what do pt with X linked immunodeficiency with hyper IgM that pt with XLA not have
hymphoid hyperplasia
what is the defect in in X linked immunodeficiency with hyper IgM
loss of function of CD40 AKA CD154 ligand that’s expressed on helper T cells
loss of CD40 or CD 154 prevents what
T cell from co-stimulating antigen specific B cells
in this disease, B cells are not signaled by T cells to go through isotope switching and only make IgM
X linked immunodeficiency with hyper IgM
trmt for humoral immunity deficiency
prophylactic antibiotics and/or gamma-globulin therapy
2 diseases of humoral immunity?
X linked immunodeficiency with hyper IgM and XLA/brutons
deficient cell mediated immunity results in inc susceptibility to fight infection by what
viruses and other intracellular pathogens
trmt for deficient T cell responses?
there arent really any (BMT and gene therapy for now); pts usually only live til infancy or childhood
what does not develop in DiGeorge syndrome
thymus and therefore T cells
what causes thymic hypoplasia in DiGeorge synd
defects in morphogenesis in 3rd and 4th pharyngeal pouches during early embryogenesis
what happens with B and T cells in DiGeorge synd
T cells decreased and B cells increased
how do most infants with DiGeorge synd die in first few months/years of life
infections, CV defects, seizures
where are clinical similarities btwn DiGeorge synd and what other synd
fetal alcohol
what is there a deficiency in in XLR SCID?
T and B cell function; they have few or no T cells and NK cells, but increased B cells
mc form of SCID
X liked SCID/XSCID
what do infants with XSCID present with in 1st few months of life
diarrhea, pneumonia, otitis, sepsis, cutaneous infections
candida albicans, pneumocystis carinii, varicella, measles, parainfluenzae, cytomegalovirus, and EBV are in what disease
XLR SCID
what do pts with XLR SCID lack
ability to reject foreign tissue so theyre at greater risk for GVHD
what can GVHD result from
maternal T cells that cross into the fetal circulation while the SCID infant is in utero
what is wrong with B cells in XLR SCID
they dont produce Ig normally
what are the 2 aims of current trmts of immunodeficienceis
minimize and control infection and replace defective/absent components
trmt of choice for immunodeficiencies rn?
BMT
