MIMM 465 Lecture Notes - Lecture 5: Immunoglobulin G, Relative Risk, Cirrhosis

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Published on 16 Apr 2013
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MIMM 466 Lecture 5
Viruses and hematology: A quest for a cause-effect relationship
Host and milieu
The following are some viruses that have been linked to blood diseases
EBV and epidemiologic studies
HTLV-1
Human T-lymphotropic virus 1 linked to some leukemia
HTLV-3 alias HIV
Immunosuppression and cancer:
- Generally linked with chronic viral infection
- Host, immune control and virus
New strategy for patient management
Historical perspective
1909: Ellerman and Bang in Copenhagen transmitted leukemia in chicken through cell free, filtered
extract suggested infectious etiology
They take liquids from the tumor of a chicken. They were able to induce tumors into other
chickens by giving them this liquid even though it was filtered and the liquid itself did not contain
any tumor cells
1911: Rous USA transmission of chicken sarcoma by use of filtrates
1973: Diamandopoulos simian virus (SV40) can induce leukemia in certain experimental conditions
Oncogenic virus can promote malignancies in several animals
Can induce cell growth by anti-apoptosis, BCL2
EBV and lymphoma
1952: Denis Burkitt described specific childhood lymphoma in Uganda, closely related to malaria
Rare tumor in the lymph node by the jaw. Only in the wet parts of Africa, where there are lakes and
ponds for mosquitoes to grow. They found that the people that were taking preventive measures
against mosquitoes, they didn’t have this tumor. The link with malaria was really strong that initially
they thought that the tumor was a manifestation of malaria. But in reality, it is not due to malaria
1965: Epstein and Barr through EM discovered herpes virus particles in Burkitt lymphoma: EBV or HHV-4
EBV associated with nasopharingal carcinoma, gastric carcinoma, HL, B cell lymphoma in
immunosuppressed patients
However: 90% of adults worldwide are seropositive for EBV: genetic or environment factor
Almost all of has have been infected with that virus, but we did not get a tumor. So there must be
another factor, like genetics or the environment, in the development of the tumor
The virus is a necessity to get the tumor, but it is not sufficient. The cause and effect chain is more
complex.
Parvovirus B19 and malignancies
1975 Cossart, in Australia, discovered the virus in well B19 of a large series of microplates- Hence,
parvovirus B19
Parvoviruses, genus erythrovirus
Childhood rash called fifth disease or erythema infectiosum
Pure red cell aplasia or pancytopenia
In some cases with people that have blood disease, there can be total aplasia where the formation
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of WBC and platelets are blocked. This is easily reversible by treatment with Ig, IgG.
Symptomatic in person with impaired hematopoiesis
In healthy individuals, you might get a little sick but that is all. Those that have a sickle cell, blood
disease which is chronic anemia, if you get the virus you may get aplastic anemia for a few months.
If you are not treated, you can die from lack of RBCs.
If you already have a blood disease, it is likely that you will develop a more sever type of anemia
2001: Persistent B19 infection and ALL??
Mucosa-associated lymphoid tissue NHL (MALT) bacteria not virus
Arise from a prolonged lymphoid proliferation in the mucosa
Occur in people with chronic inflammation. This causes persistent immune activation, causing
abnormalities
Chronic gastritis,
Helicobacter pillory-
a famous cause
Remission of local small gastric lymphoma with antibiotic
2005:
Campilobacter jejuni
and small bowel MALT- can cause lymphoma in association. It is not a direct
cause
2004:
Chlamydia psittaci
ocular adnexa NHL- rare case of lymphoma of the eyes, in the glands that
waters your eyes
2010:
Borrelia burgdorferi
and cutaneous NHL
***NHL= Non- Hodgkins lymphoma
Viruses are not the only causes of lymphomas.
HCV
Cirrhosis and hepatoma in non-A non-B hepatitis
Originally had no name. It was called non-A non-B hepatitis
1996: B cell lymphoma and HCV in Italy. (There are lots of IV drug users. So it has one of the highest
rates of HepC in Europe)
Cryoglobulimemia and B cell clone: 1-3%
Cryoglobulins are protein that coagulates when it is cold
This is an abnormal protein (single or mixed immunoglobulins) that is in reaction with Hep. C. It is
monoclonal. It is not a cancerous clone but a persistent clone which can lead to lymphoma.
2002: Hemine et al, Marginal-zone lymphoma: remission during INF and ribavirine therapy
They found people with a rare case of lymphoma in the spleen. When they treated the patients
HepC, in a few patients the lymphoma also disappeared.
- 2013: HepC may help understand the link between lymphoma of cancer because it induces immune
activation mainly in the liver but also in the blood. There are new discoveries that it induces insulin
resistance and cholesterol metabolism. Neuro-cognition and effective curative treatment
Three weeks ago, there was a study introducing a new drug that does not require injection. And all 20
subjects were cured of Hep. C
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HTLV-1 (Human T-lymphotropic virus-1)
Some people have T cell Lymphoma or leukemia.
Leukemia when it circulates in the blood and lymphoma
when it stays in the tissues or nodes.
HTLV-1 and Adult T-cell leukemia-lymphoma (ATLL)
1976: Takatsuki described a distinct entity with
unique geographic distribution and clinical and pathological
features: leukemia, lymphoma, myelopathy
Distribution: Japan (highest incidence), Carribbean,
Western Africa, South America and Central Asia
Same virus in different host may give different disease
1980: Poesz, first retrovirus to cause human disease via Tax protein 1995, Franchini
1986: Transmitted like HIV
2003: Viral proliferation and immune control
2012: We can now measure your viral load. More virus, the more likely you will develop
leukemia/lymphoma. There is a link between having the virus, lack of immune control and the chance of
the survival of the B-cell, and it becoming immortal B-cell lymphoma.
8-9% of our genome is integrated retro virus :D
HTLV-1 virus replication cycle
SKIPPED THE SLIDE
Immunosuppressed patients
HIV epidemic: 1981-1983 HIV
Most of our knowledge about immunosuppression and viral lymphoma came from AIDS epidemic
1981: first case
1983- discover of the virus
Recipients of organ transplants also develop lymphoma
Hard to pin point if the lymphoma is virally caused because there are many causes:
- Immunodeficiency
- Presence of chronic viral infections
- Immunosuppressive drugs
HIV infection and the risk of cancer
We have a virus. Now the question is did HIV lead to cancer or lymphoma? Answer is No. It is not an
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Document Summary

Viruses and hematology: a quest for a cause-effect relationship. The following are some viruses that have been linked to blood diseases. Human t-lymphotropic virus 1 linked to some leukemia: htlv-3 alias hiv. Host, immune control and virus: new strategy for patient management. 1909: ellerman and bang in copenhagen transmitted leukemia in chicken through cell free, filtered extract suggested infectious etiology. They take liquids from the tumor of a chicken. They were able to induce tumors into other chickens by giving them this liquid even though it was filtered and the liquid itself did not contain any tumor cells. 1911: rous usa transmission of chicken sarcoma by use of filtrates. 1973: diamandopoulos simian virus (sv40) can induce leukemia in certain experimental conditions: oncogenic virus can promote malignancies in several animals. Can induce cell growth by anti-apoptosis, bcl2 . 1952: denis burkitt described specific childhood lymphoma in uganda, closely related to malaria. Rare tumor in the lymph node by the jaw.

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