45 terms

Infectious Mononucleosis

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