Hepatitis A virus.
- Hepatitis A (HAV) is a self-limited hepatitis caused by an RNA virus 

- Symptoms last 2 to 4 weeks.
- There is no risk of developing chronic hepatitis in the future.
- Incubation period is short, lasting 2 to 6 weeks.
- Infection is identified by HAV-specific antibodies (IgM if acute, IgG if past disease).
- The usual route of infection is fecal-oral transmission by contaminated food. There is no carrier state and no chronic disease
- Laboratory diagnosis: ELISA test for IgM antibody.
- Vaccine: killed virus.
- Prevention: serum immunoglobulins are available.

Eosinophilia:
Causes

-Allergic disorders.
-Parasitic infection.
-Skin diseases.
-Pulmonary eosinophilia.
-Myeloproliferative lesions and Hodgkin's disease.

HERPES SIMPLEX

An infection with herpes simplex virus characterized by one or many clusters of small vesicles filled with clear fluid on slightly raised inflammatory bases.

The two types of herpes simplex virus (HSV) are HSV-1 and HSV-2. HSV-1 commonly causes herpes labialis, herpetic stomatitis, and keratitis; HSV-2 usually causes genital herpes, is transmitted primarily by direct (usually sexual) contact with lesions, and results in skin lesions

Primary infection of HSV-1 typically causes a gingivostomatitis, which is most common in infants and young children. Symptoms include irritability, anorexia, fever, gingival inflammation, and painful ulcers of the mouth.

Primary infection of HSV-2 typically occurs on the vulva and vagina or penis in young adults

Herpetic whitlow, a swollen, painful, and erythematous lesion of the distal phalanx, results from inoculation of HSV through a cutaneous break or abrasion and is most common in health care workers.

Neuroblastoma and Related Neoplasms
Neuroblastoma is the second most common solid malignancy of childhood after brain tumors, accounting for up to10% of all pediatric neoplasms. They are most common during the first 5 years of life. Neuroblastomas may occur anywhere along the sympathetic nervous system and occasionally within the brain. Most neuroblastomas are sporadic. Spontaneous regression and spontaneous- or therapy-induced maturation are their unique features.  

Gross features
- The adrenal medulla is the commonest site of neuroblastomas. The remainder occur along the sympathetic chain, mostly in the paravertebral region of the abdomen and posterior mediastinum. 
- They range in size from minute nodules to large masses weighing more than 1 kg. 
- Some tumors are delineated by a fibrous pseudo-capsule, but others invade surrounding structures, including the kidneys, renal vein, vena cava, and the aorta. 
- Sectioning shows soft, gray-tan, brain-like tissue. Areas of necrosis, cystic softening, and hemorrhage may be present in large tumors. 

Microscopic features
- Neuroblastomas are composed of small, primitive-appearing neuroblasts with dark nuclei & scant cytoplasm, g rowing in solid sheets.  
- The background consists of light pinkish fibrillary material corresponding to neuritic processes of the primitive cells. 
- Typically, rosettes can be found in which the tumor cells are concentrically arranged about a central space filled with the fibrillary neurites.
- Supporting features include include immunochemical detection of neuron-specific enolase and ultrastructural demonstration of small, membrane-bound, cytoplasmic catecholamine-containing secretory granules.
- Some neoplasms show signs of maturation, either spontaneous or therapy-induced. Larger ganglion-like cells having more abundant cytoplasm with large vesicular nuclei and prominent nucleoli may be found in tumors admixed with primitive neuroblasts (ganglioneuroblastoma). Further maturation leads to tumors containing many mature ganglion-like cells in the absence of residual neuroblasts (ganglioneuroma). 

Many factors influence prognosis, but the most important are the stage of the tumor and the age of the patient. Children below 1 year of age have a much more favorable outlook than do older children at a comparable stage of disease. 

Miscroscopic features are also an independent prognostic factor; evidence of gangliocytic differentiation is indicative of a "favorable" histology. Amplification of the MYCN oncogene in neuroblastomas is a molecular event that has profound impact on prognosis. The greater the number of copies, the worse is the prognosis. MYCN amplification is currently the most important genetic abnormality used in risk stratification of neuroblastic tumors. 

About 90% of neuroblastomas produce catecholamines (as pheochromocytomas), which are an important diagnostic feature (i.e., elevated blood levels of catecholamines and elevated urine levels of catecholamine metabolites such as vanillylmandelic acid [VMA] and homovanillic acid [HVA]). 

Urticaria (hives) refers to the presence of edema within the dermis and itchy elevations of the skin which may relate to either a Type I (MC) or Type III hypersensitivity reaction.

Type III hypersensitivity reaction.

 - exaggerated venular permeability MC related to IgE mediated disease and release of histamine from mast cells.

 IMMUNO PATHOLOGY

Abnormalities of immune reactions are of 3 main groups

• Hypersensitivity,
• Immuno deficiency,
• Auto immunity.

Hypersensitivity (ALLERGY)

This is an exaggerated or altered immune response resulting in adverse effects

They are classified into 4 main types.

I. Type I-(reaginic, anaphylactic). This is mediated by cytophylic Ig E antibodies, which get bound to mast cells. On re-exposure, the Ag-Ab reaction occurs on the mast cell surface releasing histamine.

Clinical  situations

I. Systemic anaphylaxis, presenting with bronchospasm oedema hypertension, and even death.

2. Local (atopic) allergy.

• Allergic rhinitis (hay fever)
• Asthma
• Urticaria.
• Food allergies.

2. Type II. (cytotoxic). Antibody combines with antigen present on-cell surface. The antigen may be naturally present on the surface or an extrinsic substance (e.g.drug) attached to cell surface.

The cell is then destroyed by complement mediated lysis (C89) or phagocytosis of the antibody coated cell.

Clinical situations

• Haemolytic anemia.
• Transfusion reaction
• Auto immune haemolytic anemia.
• Haemolysis due to some drugs like Alpha methyl dopa

Drug induced thrombocytopenia (especially sedormid).

Agranulocytosis due to sensitivity to some drugs.

Goodpasture’s syndrome-glomermerulonephritis due to anti basement membrane antibodies.

3. Type III. (Immune complex disease). Circulating immune complexes especially

small soluble complexes tend to deposit in tissues especially kidney, joints, heart and

arteries.

These then cause clumping of platelets with subsequent release of histamine. and

serotonin resulting in increased permeability. Also, complement activation occurs which

being chemotactic results in aggregation of polymorphs and necrotising vasculitis due to

release of lysosmal enzymes

Clinical situations

• Serum sickness.
• Immune complex glomerulonephritis.
• Systemic lupus erythematosus.
• Allergic alveolitis.
• Immune based vasculitis like
  • Drug induced vasculitis.
  • Henoch – Schonlein purpura

4. Type IV. (Cell mediated). The sensitized lymphocytes may cause damage by

cytotoxicity or by lymphokines and secondarily involving macrophages in the reaction.

Clinical situations

I. Caseation necrosis in tuberculosis.

2. Contact dermatitis to

• Metals.
• Rubber.
• Drugs (topical).
• Dinitrochlorbenzene (DNCB).

5. Type V. (stimulatory) This is classed by some workers separately and by other with

cytotoxic type (Type II) with a stimulatory instead of toxic effect

Clinical Situations :

LATS (long acting thyroid stimulator) results in thyrotoxicosis (Grave’s disease)