B & I - Cell Mediated Immunity and MHC Flashcards
where do immature lymphocytes from bone marrow travel to to mature
thymus
what surface antigens are expressed in this immature stage
CD4 and CD8
they encounter MHC ______ __ and _____ __ molecules expressed on thymic epithelium and respond accordingly or die by neglect
class I and class II
If they respond to MHC class II they become?
CD4 helper T cells
If they respond to MHC class I they become?
CD8 cytotoxic T cells (CTL) and their fate is sealed in the thymus before they exit into the blood stream
what do the CD4 helper cells do
respond by secreting cytokines
what do the CD8 cytotoxic cells do
kill other infected cells
what are the 4 subsets of CD4 helper
treg
Th1
Th2
Th17
what does treg do
suppresses the immune response
what does Th1 do
promotes cell-mediated immunity
what does Th2 do
promotes antibody mediated immunity
what does Th17 do
promotes inflammation
what type of organ is the thymus and when is it the largest
it is a primary lymphoid organ that is largest at birth and shrinks with age
where is the thymus located
sits at the top of the pericardium above the heart
haemopoietic lymphoid precursors migrate from the bone marrow to the thymus where they mature into ?
T lymphocytes
only a small percentage of T cells survive the thymus as mature T cells, most die from
neglect
T cell that survive the thymus have been educated to do what
educated to recognise self MHC molecules expressed in thymic tissue
viruses replicate ____ cells
inside
immune system is regulated by a set of?
what do these genes make up
highly polymorphic genes that were first identified as controlling tissue transplantation - these genes make up the MHC (Major Histocompability Complex)
what do these genes code for
human leukocyte antigens (HLA ) on the cell surface
unlike antibodies, the TcR recognises only ___ antigen
one
what antigen does the TcR recognise and why
the proteins of the MHC because the T cells were selected during thymic development for their ability to respond to self MHC molecules
unlike Ig, the TcR (does/does not?) under go affinity maturation
does not
why does TcR not undergo affinity maturation
because you don’t want the affinity of TcR to increase to a self antigen
When do cytotoxic T cells (CTL) react to your own cells
when there is a change in MHC class I molecules - i.e. when the express a “neo-antigen” picked up from inside the cell
the “neo-antigen” can be a ____ or _____ ___ antigen
viral
altered self
what do histocompatibility genes control
viral immunity
what are the two antigens viral immunity requires
self and non-self
what are self antigens
antigens encoded by MHC
what are non-self antigens
antigens encoded by the virus
what do T cells detect
small fragments of virus picked up inside the cell and expressed in the binding groove of MHC molecules on the cell surface
viral immunity depends on ____ to present antigens
MHC
what is the T cell receptor
a membrane bound Ig-like molecule on T lymphocytes
HLA molecules are expressed on most cells and present what to T cells?
peptide antigens
Are HLA molecules polymorphic
yes they are highly polymorphic
what does the antigen binding surface of the TcR bind to
the top of MHC which represent the “peptide groove”
what does the peptide groove contain
the foreign peptide antigen
the TcR has affinity towards ?
the combination of MHC
MHC refers to ?
the genetic locus that regulates histocompatibility
HLA refers to ?
the 6 different molecules expressed on human cells
H2 refers to ?
the antigens on mouse cells
What are the three human Class I molecules
A B C
what are the three human class II molecules
DR, DP, DQ
what are CD4 and CD8
accessory molecules that physically associate with the TcR
what do CD4 helper T cells do in this context
recognise antigens in MHC class II
what do CD8 cytotoxic T cells
recognise antigens in MHC class I
what component of CD4 and CD8 initiates T cell signalling
CD4 and CD8 have intracellular tyrosine kinases associated with their cytoplasmic tails that initiate T cell signalling through phosphorylation.
what are CD4 and CD8 crucial for
immune activation
CD4 and CD8 are ___________ that define two ______ _______ __ _ __________
co-receptors
important subsets of T lymphocytes
peptide source of MHC class I
intracellular
pathogen in MHC class I
viruses
responding T cells in MHC class I
CD8
effector function of MHC class I
cytotoxic
Peptide source of MHC class II
extracellular
pathogen of peptide source MHC class II
bacteria
responding T cells of MHC class II
CD4
effector function of MHC class II
help
T cells ______ and produce _______ that ____ other cells
proliferate
produce
help
what does CTL produce that punches holes and destroys cell viability (and what does it punch holes in)
CTL produces granzyme and perforins that punch holes in the target cell membrane and destroy
cell viability
there are hundreds of different amino acid variations at each ____ _______
MHC locus
polymorphism is restricted to
the protein domains that form the peptide groove
what genes and molecules does an individual express
both maternal and paternal genes 2 x 3 MHC class I A B C and 2 x 3 MHC class II DR DP DQ molecules
how are the genes and molecules in an individual expressed
with co-dominance
how many polymorphic molecules are expressed on cells
12
can two people have the same MHC profile
no everyone is completely different (identical twins excluded)
why can’t tissue be transplanted from one person to another
because of MHC polymorphism - T cells from the recipient recognise the donor MHC antigens as foreign
what must people who get transplants do
take an immunosuppressive drug for the rest of their lives to suppress the T cell response
what are the two major consequences of MHC polymorphism
1) tissue transplantation is difficult except for identical twins. this requires careful matching and immunosuppressive drugs.
2) MHC polymorphism are strongly linked to many autoimmune diseases.
why is MHC so strongly associated with many autoimmune diseases
because the MHC locus is the only polymorphic part of your entire genome
in autoimmune disease, what are your T cells doing?
reacting to self-antigens that are best presented by these MHC molecules
MAIN POINT: what is MHC
a set of highly polymorphic genes coding for a group of membrane molecules called HLA in humans
MAIN POINT: the TcR is an Ig like membrane molecule with a gene locus that is
segmented and undergoes rearrangement
MAIN POINT: Graft rejection was used to create? what did this show?
congenic strains of mice that were then used in a famous experiment showing that viral immunity requires both self MHC and foreign antigen
MAIN POINT: MHC molecules come in which two types and what do both have
class I and class II
both have a peptide binding groove that holds a foreign peptide
MAIN POINT: T cells are divided into two functionally different populations marked by the?
CD4 and CD8 antigens
MAIN POINT: CD4 and CD8 are accessory molecules associated with the T cell receptor responsible for
intracellular signalling through associated tyrosine kinases
MAIN POINT: CD8+ T cells are _____ and recognise _____ antigens presented by MHC class _
cytotoxic
viral antigens
MHC class I
MAIN POINT: CD4+ T cells are _____ ___ ___ and recognise _____ antigens presented by MHC class _
helper T cells
bacterial antigens
MHC class II
MAIN POINT: why is tissue transplantation so difficult
MHC polymorphism
MAIN POINT: Why are MHC polymorphisms so strongly linked to many disease susceptibilities
because it is the only part of your genome that is so polymorphic
