The document discusses Epstein-Barr virus (EBV), which can cause infectious mononucleosis and is associated with cancers like Burkitt's lymphoma and nasopharyngeal carcinoma. EBV exists in three phases - latent, early, and late - and is transmitted through saliva. It infects B cells and sometimes escapes immune surveillance, causing proliferation. Diagnosis of EBV infections involves detecting heterophil antibodies through tests like Paul-Bunnell and Davidsohn differential. EBV-specific antibody testing provides further confirmation.

1. EB VIRUSES

2. Epstein-Barr Virus (EBV)
• Spread through oral transmission
(SALIVA)
• Infectious Mononucleosis.
• Other Diseases include:
– African or Burkitt’s lymphoma
– Nasopharyngeal carcinoma
– B cell lymphoma

3. Viral Antigens
• There are three classes :1.Latent phase(EBNAs & LMP)
2.Early phase(proteins)
3.late phase

4. Epstein-Barr virus
• African or Burkitt’s Lymphoma
– malignant B-cell neoplasm
– presents as a rapidly growing tumour of
the jaw, face or eye
– grows very quickly, and without treatment
most children die within a few months
– Epstein-Barr virus (EBV) has been
strongly implicated

5. African or Burkitt’s Lymphoma
• Although BL is a very rapidly growing tumour it
responds well to treatment.
• Three pictures: before treatment, 3 days and 6
days after treatment

6. Nasopharyngeal Carcinoma
• Endemic in South China, Africa, Arctic
Eskimos
• This is a malignant tumour of the squamous
epithelium of the nasopharynx.
• 100% contain EBV DNA
• Rates are less than 1 per 100,000 in most
populations
• Nasopharyngeal carcinomas are found in
association with reactivation of latent
Epstein-Barr Virus.
• The exact mechanisms of association are
unknown

7. B-Cell Lymphoma
• In most individuals infected with EBV, the
virus is present in the B-cells, which are
normally controlled by T-lymphocytes
• When T-cell deficiency exists, one clone of
EBV-infected B-lymphocytes escapes
immune surveillance to become
autonomously proliferating.
• EBV induced B cell lymphomas are most
prevalent in immunocompromised patients.

8. Oral Hairy Cell Leukoplakia
• Viral infection of the oral cavity.
• Indicator of HIV infection as well as of a
person's lessening or weakening immunity

9. Infectious Mononucleosis
•
•
•
•
•
•
4 to 7 week incubation
Acute self-limiting infection of the RE system
Enlarged lymph nodes in the neck.
Sore throat, fever, rash
Malaise, lethargy, extreme tiredness
Liver and spleen involvement and
enlargement
• Hematology: High WBC, over 20% atypical
reactive lymphocytes also known as Downey
cells.

10. Infectious Mononucleosis
• Downey cells may be present

11. Heterophile Antigens/Antibodies
• Heterophile antigens are a group of
similar antigens found in unrelated
animals, IE, man, sheep, horse, dog
cat, mouse.
• Heterophile antibodies produced
against heterophile antigens of one
species will cross react with others.

12. Heterophile Antigens/Antibodies
• Forssman antigen is an example of a
heterophile antigen and is found on the
RBCs of many species (guinea pig,
dog, cat, mouse, sheep, fowl, horse)
• Forssman antibodies formed against
Forssman antigens will agglutinate
sheep RBCs.

13. Paul Bunnell Test
• The original Paul-Bunnell test was a simple titration of sheep
cell agglutinins but this procedure was subsequently modified
in order to distinguish between sheep cell agglutinins formed in
IM and the Forssman-type antibodies found in normal serum,
serum sickness and in certain other conditions.
• Tissues rich in Forssman antigen (guinea pig kidney) absorb
Forssman antibodies but do not affect the heterophil antibodies
in IM.
• Heterophil antibodies are absorbed by beef cells,
• Forssman hapten is a glycolipid usually associated with a
protein, the determinant being largely carbohydrate and
therefore heat stable.

14. Davidsohn Differential
• The principle behind the Paul-Bunnell-Davidsohn test is that
the two types of sheep agglutinins are distinguished by titrating
them before and after absorption with guinea pig kidney and ox
cells.
• Patients serum containing antibodies due to IM is added to
guinea pig kidney cells. These antibodies are not absorbed by
the kidney cells. These antibodies then react with Beef (Ox)
red blood cells which causes agglutination and is a positive test
for IM.
• Patients serum containing Forssman antibodies are added to
guinea pig kidney cells. Antibodies are absorbed by the kidney
cells. These antibodies are then allowed to react with Beef red
blood cells which does not cause agglutination. This is a
positive test for Forssman antigens.

15. Davidsohn Differential
* To be considered absorbed there must be greater than a three tube difference
between the presumptive titer and the differential titer.
Heterophil Antibody
------------------------
Kidney Extract
------------------
Beef Erythrocyte
---------------------
Infectious Mono
Not Absorbed
Absorbed
Forssman
Absorbed
Not Absorbed
Serum Sickness
Absorbed
Absorbed

16. Davidsohn Differential
Advantages
•
When properly performed, this
test is specific for Infectious
Mononucleosis and falsepositive results are rare.
Disadvantages
•
Davidsohn Differential test is
very time consuming and
burdensome.

17. Infectious Mono Slide Tests
• It was discovered that horse RBCs
possess antigens which react with the
antibody associated with IM.
• Patient serum mixed with horse RBCs,
agglutination is positive.
• Latex agglutination
• Not diagnostic, must look at total
clinical picture.

18. EBV Specific Antibodies
• EBV specific antibodies may be measured.
• Pattern of appearance of EBV antigens.
• Most valuable is IgM antibody to viral capsid
antigen (VCA), indicates a current infection
(best marker), lasts about 12 weeks.
• Can also detect anti-early antigen (EA)
(recent infection) and anti EB nuclear antigen
(EBNA) (older infection).
• ELISA and IFA most commonly used