genetics discussion 5 (genetics & immunology) Flashcards
Why does a bone marrow transplant
- cure SCID = bubble boy
Severe combined immunodeficiency (SCID)
in patients with an IL2RG mutation?
50% of SCID patients have a
- mutation on the X chromosome
- that leads to a FAULTY (IL-2) RECEPTOR
==> Activation of IL-2 receptor is
==> important for proliferation of lymphocytes and
==> without it
==> there is no 3rd LINE OF DEFENCE(cell med/humoral).
Treatment for SCID includes
- bone marrow transplantation,
==> because this introduces HEMOPOIETIC STEM CELLS ==> which DIFFERENTIATE into T and B cells,
==> tf REPLACING DEFECTING T & B
»_space;> curing SCID.
Why are more males than females born with SCID?
Females won’t get this disease as they
- have two X chromosomes.
- One “bad” X
- one “good” X.
Their good X can make functional B and T cells for them.
However for boys - only have one X chromosomes - so it is 50/50 chance. If it is a “bad” X, NOT able produce functional B and T cells = SCID. = bubble boy
Why isn’t CTLA-4 expressed in naïve T cells?
- CTLA-4 = TURN OFF activated T cells.
*CTLA4 (cytotoxic T-lymphocyte-associated protein 4),
= a protein receptor
- that functions as an immune checkpoint and
- down regulates immune responses.
In order for naive T cells to be activated it requires two mechanisms.
- T cell receptor + bind to MHC2 (on APC)
- and CD28 (on T cell ) + bind to B7 (on APC)
==> naive T cell becomes activated.
==> CD28 is then down reguated and
==> the CTLA-4 is upregulated.
=========
mutation for the CTLA-4 gene,
= protein not present on the activated T cell
==> T cell remains activated.
People with TYPE 1 DIABETES => DO NOT HAVE the CTLA-4 (on naive T cell) => tf have activated T cells => that are not easily deactivated >>> destroy own tissue
Is class I or class II HLA matching more important in transplantation?
Class 1 HLA alleles are expressed on
= surface of ALL NUCLEATED CELLS
polymorphisms associated w
= making transplantation difficult
Having matching HLA 1 alleles are important between
- donor and recipient
- during transpantation
- so that the RECIPIENT DOES NOT REJECT new tissue.
HLA class 2 are expressed on
- surface APCs
polymorphisms are associated more
= with autoimmune disease.
What is different about the peptide binding sites of class I and class II HLAs?
Class 1 binds SMALLER PEPTIDES
Since class 2 for = activation of T-helper cells
makes sense that it
= displays AS MUCH ANTIGEN AS POSSIBLE
Explain why from an evolutionary perspective mates with different HLA alleles are selected
Mates with different HLA alleles are selected bec..
= This IMPROVES the CHANCE OF SURVIVAL
of the OFFSPRING
==> increased variation
==> means the offspring have an increased range of ability to present different antigens
==> INCREASE chance of SURVIVAL
with MORE ACTIVE IMMUNITY (of the 3rd line of defense)
Why is it hypothesised that HLA variation can be determined by smell?
- individuals looking to reproduce are
- more likely to be attracted to people
- who have different HLA alleles to themselves.
- tested by giving women t-shirts with
- differing male HLA to smell.
- women picked the t-shirt with
- different HLA alleles than themselves.
- also be seen in men that are adopted who
- pick partners with different HLA (to foster mothers)
The benefits of reproducing with a partner with different HLA than you is
- offspring gets
- two differing copies
- meaning they are
- more likely to display antigens
»> increasing chance of fighting infection
»> chance of survival
Why are class II HLA alleles more associated with autoimmune diseases?
==> Class II HLA molecules
==> present antigens to CD4 T helper cells.
»> B cell activation
»> leading to antibody production.
- this mechanism goes astray
- in autoimmune disease
»> leading to OVERPRODUCTION SELF REACTING Abs
»>LOSS OF TOLERANCE for our OWN ANTIGENS
If malaria infection rates increase, what would you expect to happen to sickle cell anaemia allele frequencies and why?
- In areas with ongoing malaria outbreaks,
- individuals with sickle cell anaemia have an advantage, ==> as the involved RBC’s are
==> more frequently removed by the spleen, this
==> allows for individuals to
==> live longer lives and
==> therefore be able to produce
more children with that trait. - Sickle cell is an AUTOSOMAL RECESSIVE disease that causes ALTERED HEMOGLOBIN CARRIERS, associated with DECREASED SEVERITY of malaria.
- It DOESN’T COMPLETELY PROTECT
a person from infection,
but it MAKES DEATH LESS LIKELY - If MALARIA INFECTION INCREASED
- the prevalence of sickle cell anaemia
CARRIERS COULD INCREASE
= due to NATURAL SELECTION
Why are sickle cell alleles present in Australian population at a much lower frequency than in African American population?
- POLYMORPHISMS are sometimes SELECTED
- in AREAS HIGH DISEASE incidence
- as they impact susceptibility to that disease.
Sickle cell anaemia is one of those as it
- provides some protection against malaria .
- The HIGH FREQUENCY of the sickle cell ALLELE in the AFRICAN AMERICAN POULATION is
- correlated with their GENETIC ORIGIN.
- In countries which have undergone EPIDEMICS IN MALARIA the
- allele for sickle cells would have
- been naturally be selected,
- giving rise to a population with
- higher rates of the sickle cell allele.
Why is HIV selection pressure
not sufficient to explain the
high frequency of CCR5D32 alleles in Europeans?
**CCR5 Δ32 = PROTECTIVE AGAINST HIV INFECTION
*CCR5 Δ32 is a 32-base-pair deletion that introduces a premature stop codon into the CCR5 receptor locus, resulting in a nonfunctional receptor. CCR5 is required for M-tropic HIV-1 virus entry.
= as data suggests that the CCR5 mutation
- has been around since over 700 years ago.
- HIV is suggested to have been around
- approximately 100 years
- thus is not a sufficient enough time to
- explain the high frequency of CCR5-D32 in Europeans.
Describe
immunotherapy and explain how this could be
active or passive
Immunotherapy is a type of CANCER Rx which
= assists your immune system fight cancer.
Active immunotherapy
= STIMULATES THE BODIES OWN immune RESPONSE to cancer cells.
Passive immunotherapy uses
= parts of the immune system CREATED OUTSIDE THE BODY to fight cancer. (antibodies)
Why is Herceptin (monoclonal antibody (mAB) treatment)
for breast cancer
- a form of passive immunity?
Why can’t all breast cancer patients be treated this way?
Herceptin® is a monoclonal antibody that has been used successfully to treat breast cancer in Australia.
passive immunity = created outside the body
and given to the patient as therapy.
it depends if they are
- RECEPTOR POSITIVE or
- negative.
If Positive ==> treated with Herceptin ==> blocks the growth receptors with the Herceptin antibodies ==> which stops the growth of the cancer
Why does a mutation in the IL-2 receptor cause SCID?
==> IL-2 receptor is required for the activation of B & T cells, ==> without IL-2 there would be ==> no lymphocyte activation or ==> NO proliferation and ==> no immune response which would >>> result in SCID.
Why do lymphocytes need to undergo apoptosis?
Why do we need to break down the
- adenosine
produced by these apoptotic cells?
Apoptosis of lymphocytes is necessary as
==> clonal expansion creates
==> an immune system dominated by activated T cells
specific for a particular pathogen.
==> T cells then occupy in lymphoid tissue,
==> secrete cytokines and
==> inhibit the induction of new immune responses.
Adenosine de-aminase is
- found in highest levels in lymphocytes.
- Adenosine deaminase enzyme eliminates
- a molecule called deoxyadenosine (toxic to lymphocytes)
- which is generated when
- DNA is broken down.
Adenosine deaminase
- converts deoxyadenosine (toxic to lymphocytes)
- into de/oxy/ino/sine (not harmful to lymphocytes)
