• Epstein-Barr virus (EBV) is the cause of infectious mononucleosis, also known as glandular fever, an acute, benign, self-limiting lymphoproliferative illness.
PATHOGENESIS
• Mode of transmission: Saliva is spread through kissing, hence the moniker "kissing disease."
• The incubation period lasts between four and eight weeks.
B lymphocytes and maybe oropharyngeal epithelial cells are infected by EBV. The CD21 (CR2) receptor found on the B cell membrane is bound by an EBV envelope glycoprotein. The complement's C3d component is receptive to CD21. The submucosal lymphoid tissues of the oropharynx and nasopharynx, in particular the tonsils, are where the viral infection first appears. There are two types of B cell infections: latent and productive (lytic).
Effective Infection
This kind of infection affects a very small percentage of B cells. The virions are produced and released by the infected B cells, and these B cells eventually die. Other B cells become infected by the released virions.
Dormant Infection
The majority of EBV infections result in latent viral infection within the B cells. They have not been changed or "immortalized" to allow for endless expansion.
The Biology of B Cell Multiplication
A small number of EBV genes are expressed during latent infection, disrupting regular signaling pathways. Among the EBV gene products are:
The gene product known as Epstein-Barr nuclear antigen 1 (EBNA1) is responsible for attaching the EBV genome to the B cell chromosomes during mitosis.
Latent membrane protein 1 (LMP1): It imitates a constitutively active type of CD40, a B cell surface receptor, to activate and proliferate B-cells. Like active CD40, LMP1 binds to adaptor molecules called TNF receptor-associated factors (TRAFs), which in turn triggers events that activate the JAK/STAT signaling pathway and NF-κB. Moreover, LMP1 inhibits apoptosis by triggering Bcl-2.
B-cell activation and replication are also brought on by EBNA2. Numerous genes in the host cell, including those encoding proteins that control the cell cycle (such cyclin D), are activated in transcription.
IL-10 homologue (vIL-10): EBV is the producer of it. It inhibits antiviral T cell responses and suppresses dendritic cells and macrophages.
EBV Infection-Related Immune Reactions
Both a humoral and a cell-mediated immune response are triggered by EBV.
• Humoral immune response: EBV activates B cells, which proliferate polyclonal B cells and generate a range of antibodies. They're separated into:
- Antibodies specific to the EB virus: The most effective EBV-specific antibodies are directed against: ◆ EBV nuclear antigen (EBNA) ◆ Viral capsid antigens (VCAs)
Antibodies against VCA and EBNA are first of the IgM type, then of the IgG type.
Anthems against heterophile
The Greek terms hetero and phile, which mean "different" and "affinity," respectively, are the origin of these words. Heterophile antibodies are those that are produced in response to an antigen from one species but that also cross-react with antigens on the cells of other species. These are nonspecific and generated against poorly defined antigens.
A small number of patients with infectious mononucleosis may experience transitory immune-mediated thrombocytopenia due to autoantibodies, such as those directed against platelets. This is the cause of the Wassermann reaction that is positive.
• Cell-mediated immune response: Activated B cells also trigger the immune system's cell-mediated reaction, which in turn activates NK cells and CD8+ cytotoxic T cells. The latter two cells, NK cells and CD8+ cytotoxic T cells, are in charge of eliminating the virus-infected B cells and preventing B cells from producing immunoglobulins. Even though EBV can infect B cells, CD8+ cytotoxic T cells and CD16+ NK cells are the primary atypical lymphocytes observed in peripheral blood. Lymphadenopathy and splenomegaly are caused by T cell proliferation in lymphoid tissues.
The fully developed humoral and cellular immune responses to EBV in healthy persons remove B cells expressing the entire complement of EBV latency-associated genes and prevent viral shedding. These patients may either develop self-limited infectious mononucleosis or the infection may continue to be asymptomatic. When reactivation of EBV occurs in persons with acquired weakness in cellular immunity (AIDS, organ donation), B-cell proliferation may result. This proliferation can lead to EBV-associated B-cell lymphomas through a series of steps, and it can also play a role in the development of Burkitt lymphoma.
MEDICAL ASPECTS
• Age: Young adults from higher socioeconomic groups in industrialized countries and youngsters from lower socioeconomic classes are typically affected.
• Symptoms and indicators: Typically, nonspecific precursor symptoms precede the traditional trio of fever, pharyngitis, and lymphadenopathy in cases of infectious mononucleosis.
- Pharyngitis: The majority of individuals experience sore throats.
- Lymphadenopathy: The cervical, axillary, and inguinal lymph nodes are frequently swollen.
About 50% of patients have mild-to-moderate splenomegaly.
LABORATORY RESULT
IM can be diagnosed using the following information:
Side Smear
Serological testing can confirm the diagnosis, which is supported by the smear findings, which offer crucial hints.
• RBCs: Display a normochromic, normocytic image.
• WBCs: Absolute lymphocytosis, which accounts for more than 60% of the leukocytes, causes an increase in the overall leukocyte count, which is typically between 12,000 and 25,000 cells/cu mm.
The presence of altered lymphocytes in the smear is a distinctive finding. The illness is referred to as infectious mononucleosis because of these cells, which are also referred to as virocytes or atypical (activated) lymphocytes (mononuclear cells). These abnormal lymphocytes, which make up between 5% and 80% of lymphocytes, are also seen in other viral fevers and are not pathognomonic (highly imply the diagnosis).
The following atypical characteristics aid in distinguishing atypical cells from normal lymphocytes: - Size and form: large in diameter (12–16 µm) and irregular in shape.
The cytoplasm
Rich in azurophilic granules that are dispersed and abundant. Enhanced cytoplasmic basophilia that is more pronounced at the margins.
◆ At places of contact, the cytoplasm and cytoplasmic vacuoles exhibit scalloped edges.
◆ Round, recessed, or coiled nucleus
◆ Three to five times the size of typical lymphocytes
◆ Nucleoli are prominent and the chromatin pattern is diffuse.
Atypical lymphocyte types: They mostly fall into three morphological categories: blastoid, both plasmacytoid and monocytoid. These were previously known as Downey types 1, 2, and 3.
- Blastoid (Downey type 1): These cells should be distinguished from blast cells due to their thin cytoplasmic border and open reticular nuclear chromatin.
- Monocytoid (Downey type 2): The cells have a kidney-shaped or lobulated nucleus with cytoplasm that is vacuolated and chromatin that is generally open.
- Plasmacytoid cells (type 3; Downey): The cells have chromatin condensation (cartwheel pattern), a perinuclear hof, and basophilic cytoplasm. They resemble plasma cells.
• Platelets: Mildly reduced or normal.
Serological Examinations
• Heterophile antibody demonstration: The assays listed below help demonstrate heterophile antibodies: The Paul-Bunnell test has a typical positive result. A sensitive slide test is a monospot test.
• ELISA is used to show that certain antibodies are present against EBV antigens. The antibodies specific to EBV are:
Antibodies directed against viral capsid antigens, also known as anti-VCA, are first of IgM type and then, after a lifetime, of IgG type.
- Epstein-Barr nuclear antigen (EBNA) antibodies: Polymerase chain reaction (PCR) can be used to show this. nodes of lymph
They are noticeable and swollen all over the body. In terms of microscopy, the paracortical areas get larger as a result of activated T-cell proliferation.
Difficulties
Infectious mononucleosis typically goes away in four to six weeks.
• B cell neoplasms, including African Burkitt lymphoma and B cell lymphoma in immunocompromised individuals; • Infectious mononucleosis
• Hodgkin lymphoma: 90% of cases have lymphocyte depletion, 70% have mixed cellularity, and 40% have lymphocyte enrichment.
• Lymphoma NK/T cell extranodal
• Thymic carcinoma, stomach carcinoma in certain situations, and nasopharyngeal carcinoma.
