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Genetics of Immunity (PowerPoint) by dfhdhdhdhjr


									Genetics of Immunity
Sunne Woo and Naoko Charity
                Table of Contents
     •   Pathogens
     •   Genetic Control of Immunity
     •   Blood Groups
     •   The Human Leukocyte Antigens(HLA)
     •   Physical Barriers And The Innate Immune Response
     •   The Adaptive Immune Response
     •   Inherited Immune Deficiencies
     •   Acquired Immune Deficiency Syndrome (HIV)
     •   Autoimmunity
     •   Allergies
     •   Vaccines
     •   Immunotherapy
     •   Transplants
     •   Crowd diseases
     •   Bioweapons
                   The Immune System is more than
                   just cells attacking foreign bodies
                   to prevent getting sick.

  The Immune System is a powerful tool that consists
             of about 2 trillion cells and biochemicals.
Click here   It’s attacking actions are highly coordinated
  And multipronged with both general and specific responses.
  Basic logic of the immune system = Recognize “foreign” or
  “non-self” surfaces.

                  When the Immune system shuts down (death),
                  the body starts decomposition.
     Overview of the Immune System
Immune response and cell
   signaling by amino acid
   sequence (LTL):

1.   Diapedesis occurs.
2.   Cell membrane begins to
     surround its target
3.   Two calcium waves begin to
     circulate around the cell.
4.   When the target is
     completely surrounded, one
     wave splits in two, with the
     second wave encircling the
     phagosome (sac).
5.   This second wave allows the
     digestive enzymes to enter
     the phagosome and destroy
     the target.

      The Importance of Cell Surface

    Bacteria               Virus              Prions

Non-membrane         Single and Double    Infectious
bonded prokaryotic   stranded DNA or      Proteins.
cell treated by      RNA.                 Not recognized
antibiotics          Reproduce by         by the Immune
                     entering and using   System.
                     the host cell.       Not treatable.
                     Can not be treated   (e.g.. Mad cow
                     by antibiotics       disease)
                     Attacked by
                     Immune system.
            Genetic Control of Immunity
Genes oversee immunity by encoding Antibodies, Cytokins, and Antigen.
                          Antibodies (protein) – respond to antigen

                          Antigen (protein or carbohydrates molecule)
                          -mark the cell surface as “self”

                          Cytokines (protein) - released by immune cells
                          to act as intercellular mediators in an immune

                 Mutation of gene = impair immune function
    •Immune deficiencies - Inherited or not inherited. Missing or defective
    Immune System (e.g. Severe Combined Immune Deficiency (boy-in-the-
    bubble disease)).
    •Autoimmune disorders - Attack of own tissue. The genes contribute to
    the susceptibility for developing an autoimmune disease. Maybe triggered
    by outer factor (e.g. Systemic Lupus Erythematosus).
        Inheritance of abnormal genes

X - linked recessive (sex chromosome. No disease are inherited
through Y).
  Female (XX) = carrier or affected.
  Male (XY)    = affected.

Autosomal (non-sex chromosomes).
   Recessive   = abnormal chromosomes from both parents are
                   required to cause disease.
   Dominant    = only one abnormal chromosome is required to
                  cause disease.
   Blood Groups (ABO Group)
I gene alleles encode enzymes to place
antigens A, B, Both or Neither on red blood cells.


                                      RH factor
Blood       A    B      O        AB   (another blood group antigen)
Type                   No A/B
                                      • RH+ produces RH-antibodies
             B    A   A, B            • RH- produces RH+
Antibody                                    antibodies
 against    AB   AB   AB
                                      • ABO group is one of the
             A    B A, B         AB
 OK to                                  major 26 Blood groups
donate to
            AB   AB O, AB
        Human Leukocyte Antigens (HLA)
    Cell surfaces have proteins that are encoded by
    genes that are part of Chromosome 6, called Major
    Histocompatibility Complex (MHC).

               Class I & II genes encode Human Leukocyte
  MHC          Antigens (HLA).
  3 classes
               Class III genes encode proteins in blood plasma.
                   Phagocytosis (eating of an invader) by
                      Macrophage cell (HLA)
               1. The Antigen attaches to MHC.
               2. MHC proteins and Antigens are displayed on
                  the macrophage surface.
               3. Helper T cells recognize both and bind to the
Macrophage        macrophage to initiate the immune events.
          The Human Immune System

   The immune system consists          The adaptive immune
    of 2 defensive barriers that         response has to be
    block pathogens.                     stimulated into action. The
                                         immune response has 3
   They are the innate barrier          characteristics that are:
    which is generally immediate         diverse because it defeats
    to phagocytes, collectins,           many different types of
    and cytokines. Inflammation          pathogens. It is specific
    is part of the innate immune         because it can distinguish
    response. This process               the certain cells and
    engulfs and destroys certain         molecules that are
    pathogens around the injury.         dangerous to cause
    “Inflammaton at the site of an       diseases from the harmless
    injury can prevent infection”        ones. And it remembers so
    (Lewis, 2007).                       it can respond faster than the
                                         first time with a foreign
• The humoral immune response is part of the Adaptive Immune
Response. It is where the B-cells are stimulated and then divided
into plasma and memory cells.

The                     • Plasma cells secrete a bunch of antibodies
Humoral                 of a single type.
                        • Antibodies are of Y-shaped polypeptides,
Immune                  that consist of 2 heavy chains and 2 light
Response–               chains. “Each of these chains consists of a
                        constant and a variable region, and the tips
                        of the Y form and antigen binding site with a
B-cells &               specific idiotype” (Lewis, 2007).
The T-cells give cellular immune response        In the picture below, it shows a
because the cells travel to where they need to   death of a cancer cell… the
act. T-cells are unlike B-cells because they     cytotoxic T-cells binds to the cancer
don’t secrete antibodies in the blood stream.    to inject perforin.* The cell then
The bone marrow lets the T-cells descend from    dies and leaves debris that
each stem cell to travel to the thymus gland.    microphages come to clear away.

        “T” in T-
        cells refer
        to the
*Perforin is a protein
that punctures the
cancer cell’s plasma
        Altering Immune Functions
 This sections contains different areas of possible
  cures to bacteria and viruses. They are vaccines,
  immunotherapy, and transplants.
 Vaccines are drugs that “trick the immune system
  into acting early” (Lewis, 2007).
 Immunotherapy increases and redirects the immune
  response. This is done by monoclonal antibody
  technology (MAb), and cytokines that boost cellular
 Transplants are done after suppressing the immune
  system in order to accept the organs from another
  person, self, or animal.
            The Abnormal Immunity

There are more than 20 types of inherited immune

Possible causes

• Abnormal Phagocyte cells
                                              Thymus gland
• No thymus or natural killer cells

• Deficiencies of T cells, B cells, and Neutrophils

                Acquired Immune Deficiency

                    Aids Virus                      Immune cells being attacked by HIV virus
HIV enters Macrophages
                                 Encountering HIV virus
HIV sticks to the primary receptor
                                                          The lack of CCR5
HIV sticks to a second receptor
”CCR5”                                                    receptor
                                                          by gene defect prevents
CCR5 ensures HIV to dock at a                 CD4
helper T cell for infection to         CCR5
                                                          HIV infection.

         Quick replication + Fast mutation + Able to hide = No Cure
            Human Immunodeficiency Virus
                               From RNA to DNA
                             (Reverse transcriptase)
                                             Transcription of the viral DNA begins with
                                             the activation of lymphocyte, resulting in the
Enzyme"integrase"                            multiple copies of viral RNA(codes) to
incorporates the viral DNA                   produce new proteins and to be packaged
into the host cells DNA.                     later as new viruses.
The integrated DNA is
called a provirus.

                                Viral RNA is translated into     Finally, viral RNA and
                                chain of proteins with           proteins are packaged and
                                polypeptide sequence             released from the
                                (reverse transcriptase,          lymphocyte surface with a
HIV enzyme "reverse
                                protease, integrase). Later,     membrane containing viral
                                Viral protease cuts the          surface proteins. These
transcribes the sequence
                                chain into its individual        proteins will bind to the
into a complementary
                                enzyme components to             receptors on other immune
DNA sequence.
                                facilitate the production of     cells and infect other cells.
                                new viruses.
Is there a cure for
                    But, You can slow the disease by
AIDS?               combining drugs with different actions,
                                       such as inhibiting reverse transcritase,
             “ NO ”                    stopping the cutting action of viral
                                       proteins that assemble to make new
                                       viral particles, and blocking the virus’s
                                       ability to bind and fuse with the plasma

                     1. Inhibiting reverse transcritase   2. Stopping the cutting action
  HIV + since 1991
                       (Recoding of RNA to DNA).             Of Protease.

     I am on HAART or Highly Active
       Anti-Retroviral Therapy that                          3. Blocking the entry.
     targets multiple HIV life cycles.

                          New Therapy for the future:
Structured treatment interruption (STI) = the practice of alternating time spent on
                 antiretroviral drugs with time spent off drugs.

•   Vaccines technology was first started in China back in the 11th
•   Vaccines are a pathogen that stimulate the B-cells in the
    immune system to produce antibodies against the disease.
•   Vaccines against several different illnesses can be combined
    into only one injection– so you don’t need more than one shot
    per vaccine!!
•   A popular vaccine was made for the smallpox disease. When
    people in China observed the recovery of smallpox, and that
    the person never had it again… people started crushing scabs
    into a powder to inhale or rub onto the blistered skin.
•   Vaccines are still dispensed through injections, but with new
    technology, patients can use nasal sprays and eat genetically
    modified fruits and vegetables.
                                          •To the left, a collection of
                                          pictures of smallpox. The
                                          black & white picture shows
                                          Edward Jenner, the creator
                                          of the smallpox vaccine.
                                          This boy was the last known
                                          victim of smallpox. The
                                          bottom-left pictures shows
                                          the vaccine in 1798.

•The picture on the right show the
difference between smallpox and
chickenpox. When someone has
smallpox, the blisters are more on the
extremities– the feet, hands, and face.
Chickenpox is prominent on the
abdomen with a few blisters on the
arms and legs.
It is important for the vaccinations to be dispensed within the
whole population because of “herd immunity.” This is where
the unvaccinated population is rare, and that the pathogens
may resurface; when it does, the disease won’t spread
because the people will have been exposed to it and be
protected. But, when there are pockets of people that haven’t
been vaccinated, and the diseases resurfaces… the pathogen
will have its way and be spread throughout.

   The process was mentioned on the previous page.

   Today MAbs are used in research, veterinary health and human
    health care. It can also be used in agriculture, forestry, and the
    forensics fields. It can be used to diagnose everything spanning
    from strep throat to turf grass disease.

   MAbs can actually be used in home pregnancy tests also! It
    binds with the pregnancy hormone hCG on the paper strip of the
    home pregnancy applicator. You will know you are pregnant
    when the color changes from the MAb hits the target.
    Cytokines Boost Cellular Immunity

   Cytokines can be used to treat different conditions.

   These cells have short periods of activity. If they don’t go to
    where they are needed right away, then overdose or side effects
    can happen.

   They can kill cancer cells!
            Timeline of Transplantation
1899- the 1st allograft transplant, a kidney from dog to dog
1905- the 1st corneal allograft transplant, an eye from a boy to man
1906- the 1st kidney transplant in a human body fails
1954- success of the 1st isograft transplant… kidney from a
   monozygotic twin
1967- the 1st heart transplant leaves patient living for an extra 14 days
1984- a xenograft heart transplant from a baboon was transferred into
   “Baby Fae” whom was born with ½ a heart. She lived for 20 days
   before her body rejected the xenograft.
1998- scientists start transplanting hands and forearms
2003- DNA gene expression microarrays are likely to tell doctors which
   patients will have rejection toward kidney transplants
Future- using stem cells from patients, embryos, or animals may
   replace transplantation
  Baboons and Pigs can transplant
different organs into the human body
4 Different types
 of transplants
These are the different
parts of the body that can
have transplants done.
Some of the most well
known parts of the body
that can be transplanted are
the heart, cornea of the eye,
kidney, liver, blood, bone
marrow, and skin.
Rejection Reactions– Or
   In allograft transplants, the tissue in the recipients body can
    reject the newly transplanted part of the body. Xenograft
    transplants can cause hyperacute rejection. In hyperacute
    rejection, the blood vessels blacken and cut off the blood supply
    within minutes of the transplantation.

   In bone marrow transplants, the recipient can reject to the new
    bone marrow tissue. This can be deadly. According to Lewis,
    “Graft versus Host Disease develops sometimes when bone
    marrow transplants are used to correct certain blood
    deficienceies and cancers” (2007).

   According to Merriam-Webster dictionary, “the bodily condition
    results when cells from a tissue or organ transplant mount an
    immunological attack against the cells or tissues of the host .”
Rejection Reactions – Or
Acceptance cont.
   When the recipient is in need of a transplant, the doctors need
    to match the HLA as closely as they can. If this doesn’t happen,
    then the recipient will reject the donor’s tissue. But, if the HLA is
    matched too closely, there could be a chance that the disease
    will come back again because the same cell surfaces that it had
    earlier will be equally unable to fight the cancer. “The donor
    bone marrow should be different enough to control the cancer,
    but no so different that rejection occors” (Lewis, 2007).
Side effects of GVHD
      Bone Marrow
Bone marrow transplants are for patients that have a deficiency of blood
because the bone marrow doesn’t produces enough blood cells. These
cells are the red and white blood cells, and platelets. Some examples of
the diseases affected by the lack of the bone marrow working are:
Leukemia, Anemia (along with some forms of anemia, for example–
Aplastic Anemia), Hemophilia, etc.
Allogenic transplants are only available to a minority of patients because
70% lack a suitablity of a sibling donor.
Survival rates for transplantation is as high as 90% from a single
experienced institution performing the procedure.
For people who are not candidates, immunosuppression drugs are used.
One of the most common immunosuppression drug is ATG (antithymocyte
globulin), which consists of horse protein. But this can have toxic effects,
this could lead to serum sickness after 11 days after treatment.
Biopsy specimen of bone marrow. Magnetic resonance imaging
scan of the spine shows uniform replacement of bone marrow
with fat. Long-term bone marrow culture-initiating cell number as
a surrogate of stem cell number. Horizontal bars indicate mean
  Bone Marrow
Transplants cont.
The Genomic View of
Immunity– The
Pathogen’s PersPective
   There are 2 subdivisions of this particular subject…

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