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Immunology IR #5

Etiology of IM

-Comes from the Epstein Barr Virus (a DNA virus)
-Part of the herpes virus group
-Transmission primarily through saliva
-Disorder is an acute, benign, and self-limiting lymphoproliferative condition

EBV infection complications can involve

cardiac, ocular, respiratory, hematologic, digestive, renal and neurologic systems


Infectious Mononucleosis


Epstein Barr Virus

Epidemiology of IM

-Reactive (atypical, variant) lymphs seen in peripheral blood smear are T lymphs
-Viral genome persists in B lymph and epithelial cells of oropharynx
-Transmitted primarily by contact with oropharyngeal secretions (saliva)
-After primary exposure, a person is considered to be immune

Signs and symptoms of IR

-Seroconvert (making antibodies) without any significant clinical signs and symptoms of disease
-In children under 5, infection is either asymptomatic or frequently characterized by mild, poorly defined signs and symptoms.
-Extreme fatigue, sore throat, malaise, fever, cervical swollen lymphnodes
-spleenomegaly (50% of cases)
-significant number of cases do not manifest classic signs and symptoms

Incubation period of IM

10-15 days

Heterophile antibody

antibody that is stimulated by one antigen and react with an entirely unrelated surface antigen present on cells from different mammalian species

Causes of heterophile antibody


Where are heterophile antibodies present?

in normal individuals with low titer (<56)

3 types of Heterophile Antibodies

1. Forssman antigen
2. Serum sickness
3. IM

Forssman antigen

emulsions of guinea pig organs into rabbits provoked the formation of antibodies that lysed sheep RBCs in the presence of complement

Serum sickness

hypersensitivity reaction following a single, large injection of serum from an animal of another species

IM heterphile

-reacts with horse, ox or sheep RBCs (no agglutination)
-absorbed by beef RBCs (no agglutination)
-NOT absorbed by guinea pig kidney cells (agglutination)
-Does NOT react with EBV specific antigens (agglutination)

Etiologic agent of IM

Epstein Barr virus
DNA virus
complication can involved cardiac, ocular, respiratory, hematologic, digestive, renal and neurologic systems

T Cells in IM

Where reactive (atypical, variant) lymphs seen in peripheral blood smear
Where virus is seen

B Cells in IM

What the IM virus infects

Paul and Bunnel Screening Test

-measures the number of heterophile antibodies
-max titer at 2-3 weeks (lasts 4-8 weeks and is observed within 2-3 weeks)

Titer DOES NOT correlate with

severity of disease

Hemagglutination test used to detect

heterophile antibodies

Dilutions of inactivated patient serum are mixed with

sheep RBCs

Positive agglutination with a titer >56 is considered

Presumptive positive evidence of infection with EBV

Antigens on sheep RBCs can also be agglutinated by

Forssman and serum sickness antibodies

False positives observed with

Hepatitis and Hodgkin's disease

Improperly inactivated serum will produce


Paul and Bunnel test is

simple, inexpensive and lacks sensitivity
only a screening test

Davidsohn Differential Test

-modified Paul-Bunnell test with an absorption step to remove cross-reacting
-Perform when the Paul-Bunnell titer is >56
-Distinguishes between 3 types of heterophile antibodies

Sheep and beef RBCs bear some common antigens that are not present on the

kidney cells of guinea pigs

guinea pig kidney cells are rich in

Forssman antigen

When guinea pug kidney cells are mixed with patient serum

it will absorb out the Forssman heterophile antibodies

When the absorbed serum is added to the sheep RBCs and the sheep RBCs do NOT agglutinate

no IM antibodies are present

If the absorbed serum agglutinates the sheep RBCs, then the heterophile antibodies are

of the IM type

Major EBV antigens that may produce an antibody response in an infected cell

1. Viral capsid antigen
2. Early antigen
3. Nuclear antigen

VCA, EA, and NA all have

antibodies against them

VCA, EA and NA are always available for

IgM and IgG

In diagnostically inconclusive cases of IM, a more definitive assessment of immune status maybe obtained through an

EBV serologic panel

Candidates for EBV serology include those who

1. do not exhibit classic symptoms
2. who are heterophile negative
3. who are immunocompromised

Viral Capsid Antigen

Anti-VCA IgM is usually detectable early in the course of infections
Anti-VCA IgG detectable within 4-7 days after on set of signs and symptoms

Early Antigen

Made of 2 components
1. EA-D
2. EA-R


Early antigen-diffuse.
Found in nucleus and cytoplasm of B cells

Anti-EA-D IgG is highly indicative of

acute infection


Early antigen-restricted
Found in cytoplasm of B cells

Anti-EA-R IgG

is not usually found in young adults during acute phase but it is sometimes demonstrated in the serum of very young children during the acute phase

Nuclear Antigen

Found in nucleus of all EBV infected cells
Does not become available for AB stimulation until after the incubation period of IM

T-lymphs destroy the EBV infected B cells

as a result, antibodies to NA are absent or barely detectable or barely detectable during acute IM infections

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