Hepatitis C virus.

 It is most often mild and anicteric but occasionally severe with fulminant hepatic failure. It is caused an RNA virus, which may be transmitted parenterally (a cause of post-transfusion hepatitis); the route of transmission undetermined in 40%-50% of cases
a. 90% of blood transfusion-related hepatitis is caused by hepatitis C.
b. 50% progress to chronic disease.
c. Increased risk for hepatocellular carcinoma.

d. Incubation period: ranges from 2 to 26 weeks, but averages 8 weeks.
-  Antibody is detected by enzyme-linked immunosorbent,assay (ELISA). The incubation period is between 2 and weeks with peak onset of illness 6-8 weeks after infection 
- Most patients progress to chronic liver disease, specifically chronic persistent hepatitis or chronic active hepatitis 
- Cirrhosis is common in patients with chronic active hepatitis and occurs in 20%-25% of infected patients. HCV is also associated with hepatocellular carcinoma.

e. Treatment and prevention: α-interferon is used to treat chronic hepatitis C. There is currently no vaccine available.

Smallpox (variola)
 - vesicles are well synchronized (same stage of development) and cover the skin and mucous membranes.
 - vesicles rupture and leave pock marks with permanent scarring.

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]). 

Lymphocytosis:
Causes
-Infections in children and the neutropenic infections in adults.
-Lymphocytic leukaemia.
-Infectious mononucleosis.
-Toxdplasmosis.
-Myast'henia gravis.

Autoimmune Diseases
These are a group of disease where antibodies  (or CMI) are produced against self antigens, causing disease process.

Normally one's immune competent cells do not react against one's own tissues. This is due to self tolerance acquired during embryogenesis. Any antigen encountered at that stage is recognized as self and the clone of cells capable of forming the corresponding antibody is suppressed.

Mechanism of autoimmunity

(1) Alteration of antigen

-Physicochemical denaturation by UV light, drugs etc. e.g. SLE.
- Native protein may turn antigenic  when a foreign hapten combines with it, e.g. Haemolytic anemia with Alpha methyl dopa.

(2) Cross reaction: Antibody produced against foreign antigen may cross react with native protein because of partial similarity e.g. Rheumatic fever.

(3) Exposure of sequestered antigens: Antigens not normally exposed to immune competent cells are not accepted as self as tolerance has not been developed to them. e.g. thyroglobulin, lens protein, sperms.

(4) Breakdown of tolerance : 
Emergence of forbidden clones (due to neoplasia of immune system as in lymphomas and lymphocytic leukaemia)
Loss of suppressor T cells as in old age and CMI defects

Autoimmunity may be
Organ specific.
Non organ specific (multisystemic)

I. Organ specific

(1) Hemolytic anaemia:

Warm or cold antibodies (active at 37° C or at colder temperature)
They may lyse the RBC by complement activation or coat them and make them vulnerable to phagocytosis

(2) Hashimoto's thyroiditis:
 
Antibodies to thyroglobulin and microsomal antigens.
Cell mediated immunity.
Leads to chronic. destructive thyroiditis.

(3) Pernicious anemia

Antibodies to gastric parietal cells and to intrinsic factor.

2. Non organ specific.

Lesions are seen in more than one system but principally affect blood vessels and
connective tissue (collagen diseases).

1. Systemic lupus erythematosus  (SLE). Antibodies to varied antigens are seen. Hence it is possible that there is abnormal reactivity of the immune system in self recognition.

Antibodies have been demonstrated against:

Nuclear material (antinuclear I antibodies) including DNA. nucleoprotein etc. Anti nuclear antibodies are demonstrated by LE cell test.
Cytoplasmic organelles- mitochondria, rib osomes, Iysosomes.
Blood constituents like RBC, WBC. platelets, coagulation factors.

Mechanism. Immune complexes of body proteins and auto antibodies deposit in various
organs and cause damage as in type III hypersensitivity

Organs involved
Skin- basal dissolution and collagen degeneration with fibrinoid vasculitis.
Heart- pancarditis.
Kidneys- glomerulonephritis of focal, diffuse or membranous type 
Joints- arthritis. 
Spleen- perisplenitis and vascular thickening (onion skin).
Lymph nodes- focal necrosis and follicular hyperplasia.
Vasculitis in other organs like liver, central or peripheral nervous system etc,

2. Polyarteritis nodosa. Remittant .disseminated necrotising vasculitis of small and medium sized arteries

Mechanism :- Not definitely known. Proposed immune reaction to exogenous or auto antigens 

Lesion : Focal panarteritis- a segment of vessel is involved. There is fibrinoid necrosis
with initially acute and later chronic inflammatory cells. This may result in haemorrhage
and aneurysm.

Organs involved. No organ or tissue is exempt but commonly involved organs are :
- Kidneys.
- Heart.
- Spleen.
- GIT

3. Rheumatoid arthritis. A disease primarily of females in young adult life. 

Antibodies
- Rheumatoid factor (An IgM antibody to self IgG)
- Antinuclear antibodies in 20% patients.

Lesions

- Arthritis which may progress on to a crippling deformity.
- Arteritis in various organs- heart, GIT, muscles.
- Pleuritis and fibrosing alveolitis.
- Amyloidosis is an important complication.

4. Sjogren's  Syndrome. This is constituted by 

- Kerato conjunctivitis sicca
-Xerostomia
-Rheumatoid arthritis. 

Antibodies

- Rheumatoid factor
- Antinuclear factors (70%).
- Other antibodies like antithyroid, complement fixing Ab etc
- Functional defects in lymphocytes. There is a higher incidence of lymphoma

5. Scleroderma (Progressive systemic sclerosis)
Inflammation and progressive sclerosis of connective tissue of skin and viscera.

Antibodies

- Antinuclear antibodies.
- Rheumatoid factor. .
- Defect is cell mediated.

lesions

Skin- depigmentation, sclerotic atrophy followed by cakinosis-claw fingers and mask face.
Joints-synovitis with fibrosis
Muscles- myositis.
GIT- diffuse fibrous replacement of muscularis resulting in hypomotility and malabsorption
Kidneys changes as in SLE and necrotising vasculitis.
Lungs – fibrosing alveolitis.
Vasculitis in any organ or tissue.

6.Wegener’s granulomatosis. A complex of:
Necrotising lesions in upper respiratory tract.
Disseminated necrotising vasculitis.
Focal or diffuse glomerulitis.

Mechanism. Not known. It is classed with  autoimmune diseases because of the vasculitis  resembling other immune based disorders.
 

PARASITIC DISEASES

AMEBIASIS (Entamebiasis)

Infection of the colon with Entamoeba histolytica, which is commonly asymptomatic but may produce clinical manifestations ranging from mild diarrhea to severe dysentery.

Etiology and Pathogenesis 

Amebiasis is a protozoan infection of the lower GI tract. E. histolytica exists in two forms: the trophozoite and the cyst.

Two species of Entamoeba are morphologically indistinguishable: E. histolytica is pathogenic and E. dispar harmlessly colonizes the colon. Amebas adhere to and kill colonic epithelial cells and cause dysentery with blood and mucus in the stool. Amebas also secrete proteases that degrade the extracellular matrix and permit invasion into the bowel wall and beyond. Amebas can spread via the portal circulation and cause necrotic liver abscesses.

Symptoms and Signs 

Most infected persons are asymptomatic but chronically pass cysts in stools. Symptoms that occur with tissue invasion include intermittent diarrhea and constipation, flatulence, and cramping abdominal pain. There may be tenderness over the liver and ascending colon, and the stools may contain mucus and blood.

Amebic dysentery, common in the tropics but uncommon in temperate climates, is characterized by episodes of frequent (semi)liquid stools that often contain blood, mucus, and live trophozoites.

Chronic infection commonly mimics inflammatory bowel disease and presents as intermittent nondysenteric diarrhea with abdominal pain, mucus, flatulence, and weight loss.

Metastatic disease originates in the colon and can involve any organ, but a liver abscess, usually single and in the right lobe, is the most common