The host immune response involves cytotoxic (CD8-positive) T cells against infected B lymphocytes, resulting in enlarged, atypical lymphocytes (Downey cells).When the infection is acute (recent onset, instead of chronic), heterophile antibodies are produced.Cytomegalovirus, adenovirus and Toxoplasma gondii (toxoplasmosis) infections can cause symptoms similar to infectious mononucleosis, but a heterophile antibody test will test negative and differentiate those infections from infectious mononucleosis.Mononucleosis is sometimes accompanied by secondary cold agglutinin disease, an autoimmune disease in which abnormal circulating antibodies directed against red blood cells can lead to a form of autoimmune hemolytic anemia. The cold agglutinin detected is of anti-i specificity. Diagnosis
Diagnostic modalities for infectious mononucleosis include:

Persons age, with highest risk at 10 to 30 years. Medical history, such as close contact with other people with infectious mononucleosis, and the presence and time of onset of "mononucleosis-like symptoms" such as fever and sore throat. Physical examination, including palpation of any enlarged lymph nodes in the neck, or enlarged spleen. The heterophile antibody test is a screening test that gives results within a day, but has significantly less than full sensitivity (70–92%) in the first two weeks after clinical symptoms begin. Serological tests take longer time than the heterophile antibody test, but are more accurate. Physical examination
The presence of an enlarged spleen, and swollen posterior cervical, axillary, and inguinal lymph nodes are the most useful to suspect a diagnosis of infectious mononucleosis.
Symptoms may be reduced by drinking enough fluids, getting sufficient rest, and taking pain medications such as paracetamol (acetaminophen) and ibuprofen.Mononucleosis most commonly affects those between the ages of 15 to 24 years in the developed world. In the developing world, people are more often infected in early childhood when there are fewer symptoms. In those between 16 and 20 it is the cause of about 8% of sore throats. About 45 out of 100,000 people develop infectious mono each year in the United States. Nearly 95% of people have had an EBV infection by the time they are adults. The disease occurs equally at all times of the year. Mononucleosis was first described in the 1920s and is colloquially known as "the kissing disease". Signs and symptoms
The signs and symptoms of infectious mononucleosis vary with age. Children
Before puberty, the disease typically only produces flu-like symptoms, if any at all. When found, symptoms tend to be similar to those of common throat infections (mild pharyngitis, with or without tonsillitis). Adolescents and young adults
In adolescence and young adulthood, the disease presents with a characteristic triad:
Fever – usually lasting 14 days; often mild
Sore throat – usually severe for 3–5 days, before resolving in the next 7–10 days. Swollen glands –  mobile; usually located around the back of the neck (posterior cervical lymph nodes) and sometimes throughout the body.Another major symptom is feeling tired. Headaches are common, and abdominal pains with nausea or vomiting sometimes also occur. Symptoms most often disappear after about 2–4 weeks.