MY TOOTHY by liaoqinmei


									                                In the Name of Allah

                     the Most Gracious , the Most Merciful

lecture was taken on the 17th of July                             lecture # : 31

  Salam Alikum everyone ..,

 Today we are going to discuss one of the most important recent topic
in the medical field , Tumor Immunology , through studying the
following main points :

   1- Pathogenesis of the immune system (when the immune system is
      diseased )
       B cell cancer
       T cell cancer

   2- The respond of the immune system against cancer
      Tumor antigen
       Evasion of the immune system by tumors

       In addition of having several clinical cases for better

      So let us begin :

       Tumor immunology is the since dealing with the relationship
         or interaction between cancer and the immune system .
   This relationship or interaction has to forms :
    1- The pathogenesis of the immune system by cancer
             different types of cancer arising in the immune cells .

    2- The interaction between the immune system and cancer
             immune system against cancer

       this is clarified by what we call Immune Surveillance which
       represents one of the functions of the immune system , and it
       means that the immune system is capable of checking and
       deleting tumor cells .

       so based on immune surveillance ,when there is an immune
       deficiency there is a higher risk of cancer .

now let us go deeply on each point

1 The pathogenesis of the immune system by cancer (diseased
  immune system ) :

     cancer can rise from both the myeloid and lymphoid series

     cancer is called :
       Leukemia            if the malignant cells are within the blood or
                           the bone marrow

      Lymphoma             if the malignant cells are only within lymph

      Myeloma              if the malignant cells are plasma cells
   leukemia is further subdivided into acute and chronic
depending on the level of maturation of the cell that malignant
cells rise from
     Acute            when it is immature (primitive form)
     Chronic          when it is mature
   as a result we have :
    a- Acute myelocytic leukemia (AML)
       that result from an increase in the # of : RBC’s , platelet …
       there are several types of it from AML0          AML7

    b- Chronic myelocytic leukemia (CML)

    c- Acute lymphoblastic leukemia (ALL)
      usually develops in children

    d- Chronic lymphocytic leukemia (CLL)
      usually develops in elderly people (50,60 year old)
      and the patient survive 10 to 20 years so it is not an
      aggressive type of cancer

  however , we are interested here in ALL and CLL since we are
studying malignant cells arising from B,T lymphocyte

        B-cell cancer
          during the development of B-cells from a stem cell to a
         plasma cell , pre- B cell , B cell and plasma cells are able
         to develop cancer
               pre-B cell :
              The earliest to develop cancer
              Definitely it is going to develop the most
                 primitive form of leukemia               ALL
                 since it is an immature cell.
                 The blasts (malignant cells of an immature
                  origin) are present in the blood and the bone

Notice : when the cell of origin is immature malignant cells are
called blasts , and the developed cancer is called All .

               B cell :
                 This cell can develop both : CLL and lymphoma
                  a. CLL: if malignant cells are within blood and
Clinical case : of CLL
                   Looking at a blood sample of a patient we’ll
                      find the most characteristic cells are mature
                      looking lymphocytes.
                   Usually if the total lymphocyte count exceed
                      5000/mm3 then it is CLL
                          Since the abundant cells are maturely
                      looking lymphocytes but they are numerous we
                      use flow cytometry to determine where is the
                            We use CD19 as a marker for B cells
                                    CD5 as a marker for T cells
                            Each area in the diagram of the flow
                           cytometry indicate sth           CD19+,CD5+

                       Usually in normal peripheral blood
                       cytometry we’ll find that :
                           80% are T lymphocytes
                           10% are B lymphocytes
                           10% are NK cells
                       In a normal flow-cytometry we’ll see a
                         huge group of CD5+ , CD19- which
                         represent T lymphocytes and another
                         small group of CD19+ , CD5- are B
                         lymphocytes .

                       In a patient of CLL we’ll find a huge
                         group of CD19+,CD5+ which represent an
                         abnormal B lymphocytes , leading to the
                         diagnoses of CLL .

?   You might ask yourself what about B-1 cells that express CD5
and defiantly CD19 (CD5+,CD19+) and they are normal cells !!!

Well the answer is as simple as that those cells have a very little
amount in the peripheral blood participating in natural
immunity so they won’t show that enormous cluster in flow
cytometry diagram , further more if you look carefully at the
diagram of the normal blood you’ll find few dots in the area of
CD5+,CD19+ represent them .
                  b. Lymphoma :if malignant cells are only in the
                    lymph node
Clinical case :
                   A lot of lymphoma cases result from an
                    infection by Epstein-Barr Virus (EBV)
                   Remember : EBV uses CD21 -which is a
                    complement receptor 2 (CR2) - on a B
                    lymphocyte to enter it .

                   In this case we have a woman that has been
                    infected by EBV , as usual the infection was
                    controlled by T cells without showing any
                       Looking at her lymphocytes we’ll find some
                        infected B cells but the others aren’t
                        because the infection was controlled .

                   After that for one reason or another she
                    needed renal transplantation .
                       Accordingly she was supplied with
                        immune suppression drugs (such as
                        cyclosporine ) and other medical mediators
                        following the transplant
                       As a result T cells can’t control any more ,
                        which lead to a polyclonal growth and an
                        increased number of infected B cells .
                Due to giving here immune suppression drugs
                 then there is less immune surveillance
                 And the chance of having genetic changes
                 with the increased polyclonal growth is higher
                     Leading to an enormous growth of one
                      clone which is malignant
                     The monoclonal growth (of the malignant
                      clone) will continue even if cyclosporine

           Plasma cell :
Clinical case : Myeloma

                Multiple myeloma is a disease affects elderly ,
                 where the bone marrow expands and poses
                 several resorptive lytic lesions
            Looking at the figure we’ll see the histologic
              appearance of the plasma cells in the bone
              marrow which should be in normal situations
              less than 5%

            Plasma cells produce immunoglobulin in the
              extensive, very big Golgi Apparatus that
              pushes the nucleus to the periphery of the cell
              making it excentric .
            All of these plasma cells produce an enormous
              dysfunctional unneeded immunoglobulin
            We get use of the increased immunoglobulin in
              the diagnosis using electrophoresis
                      Where we’ll find an abnormal spike in
                       the gamma wave indicating an
                       abnormal monoclonal growth .
                      We’ll find also slight decrease in the

  95% of acute and chronic leukemia of a lymphoid type
are of a B cell origin

   T cell cancer:

     it is very rare to have T-cell leukemia/lymphoma

     one classical example is :

    Adult T-cell leukemia/lymphoma (ATLL) It develops as
a result of an infection of a retrovirus called : Human T
lymphocyte virus type 1 (HTLV1)
      In general the pathogenesis of cancer is multifactorial ; more
        than one etiology leading to cancer such as :

       1- Genetic factors
       2- Infection
       3- Chemicals
       4- Radiation   :   such as what happened in Hiroshima in
         Japan and Chernobyl in Russia where people were
         exposed to radiation giving them a risk factor for
         developing cancer .

2 The action of the immune system against cancer :

   Tumor antigens :

    Malignant cells express tumor antigens that can be potentially
  recognized by the immune system or used as markers for certain
  types of cancer , and they are several types :
  1- Developmental proteins :
        During fetal period , we don’t have albumin in our blood
         instead we have a protein which is called alpha
         fetoprotein , normally this protein disappears and
         albumin appears .
        However in hepatocellular carcinoma there is recurrence
         of this protein in the blood .
        So we could use this developmental protein (alpha
         fetoprotein ) as a marker for liver cancer .
  2- Lineage –specific protein :
        Certain proteins are specifically produced from a certain
          type of tissues at a certain level
      If the level increased this indicate an abnormality
      For example :
        Prostate produces prostate specific antigen (PSA) if its
        level is abnormal this indicate a cancer
        So we use PSA as a test for prostate cancer
3- Viral proteins:
      Papilloma virus was recently documented as a very
       important etiologic factor for cervical cancer in females
      In purpose of reducing the risk of getting infected with
       such a virus authorities have stated to vaccinate against
       it .
      So it was found that certain viral proteins are markers
       for certain cancers
      Likewise EBV is a marker for B lymphocyte
4- Specific translocation protein
      Certain translocation events leads to the development of
       certain cancers as well as expressing certain antigens ,
       like what happen in case of philadelphia chromosome .
      These antigens are sometimes used to diagnose the type of
       cancer produced by that process

 Evasion mechanisms of the immune system by tumors :
 1- Expressing self antigens :
       Tumor cells develops from normal cells that have self
       Because of the protective mechanisms the immune
        system undergoes by eliminating the cells that recognize
        self antigens , immune system become unable to
        recognize and kill those malignant cells .
 2- Lowering the level of costimulatory molecules and danger
   signals expression :
       Even with the presence of certain cells (such as T cells)
        that are able to recognize abnormal antigens on the
        surface of malignant cells , the reduction in the
        production of these molecules won’t be able to activate
        those cells ( T cells and innate immunity )
 3- Reducing the expression of MHC molecules :
       This is in comparison to normal cells
       This will empire CTL but it might facilitate NK cells to
        take part as normal immune response
 4- Reducing antigen expression through MHC molecules :
      This is done by certain viruses which inhibit proteosome
        processing of antigens

  In general , the more evasion mechanisms the cancer have the
        harder to fight it

 Immunotherapy :
    As we’ve said earlier regarding immune surveillance that
     an immune deficiency or immune suppression will lead to
     cancer development .

    Using chemo or radio therapy has many side effects of
     killing normal cells in addition to the abnormal . especially
     killing normal bone marrow, GI mucosal and hair cells .

     This is due to the reality that a drug is a drug , it can’t
     differentiate between normal and abnormal cells!
 Accordingly some thought has developed about using
  immunotherapy .

 In general , to treat cancer we need :

   1- To improve the immune system
   2- To treat immune deficiency if present
     So that if we improve the immune system we might
     treat cancer.

 There are 2 general kinds of immunotherapy to improve
     the immune system performance :
  1- General :
     by controlling infections
         good nutrition
         and so on

  2- Specific :
     which is used against certain specific cancers and it
     could be performed in 2 ways :
      a- Passive way : preparing the immune response
        outside the body
      b- Active way : the improved immune response
        develops inside the body .

      a- The Passive way :
            This is when we know a certain marker for a
              certain cancer , so that we don’t have to kill all
              the cells by generalized therapy , instead we
              direct a monoclonal antibody to that cell
              depending on that marker
     An example is CD20 in B cell
       leukemia/lymphoma , so we give the patient
       anti CD20 killing B cells without the need to kill
       T lymphocyte as well .

   So in general it depends on preparing monoclonal
     antibodies depending on the markers of that

b- The Active way :
  Actually we have two simple examples :
  1- In case of bladder cancer :
        We can look inside the bladder using
          cystoccopy to see the malignant areas or
          whatever else
        It was found that if we inject the bladder
          with BCG vaccine it will mount cell
          mediated immunity against that cancer ,
          being an improvement as well as curing to
          the translational cell bladder cancer
        BCG vaccine is a TB vaccine which uses alive
          mycobacterium (bovis).

  2- In case of hypernephroma :
    In this case we treat the patient by :
        Taking his blood outside him

           Isolating lymphocyte

  Activating them using IL-2 and cytokines
              Then we send the patient blood back to him

                The activated cells are named as :
                 Lymphokine activated killer cells
                The process of activating lymphocytes occur in
                It gives excellent results

           In general , these are the best 2 results of active immune
           therapy at least the cells of the body are doing sth !

Abu Huraira related that the prophet (PBUH) said :
Whoever fasts during Ramadan with faith and seeking reward from Allah
Will have his past sins forgiven. Whoever prays during the nights in
Ramadan with faith and seeking his reward from Allah will have his past sin
forgiven . and he who passes Lailat al-Qadr in prayer with faith and
seeking his reward from Allah will have his past sins forgiven. (Bukhari,

So you still have a great chance don’t ruin it ! and how knows if we are
          going to be alive next year to have such a chance !!

                                                          Nour Audi

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