Nonspecific or Innate Immunity

1. Genetic factors

• Species: Guinea pig is very susceptible to tuberculosis.
• Race: Negroes are more susceptible to tuberculosis than whites
• Sickle cells (HbS-a genetic determined Haemoglobinopathy resistant to Malarial parasite.

2. Age Extremes of age are more susceptible.

3. Hormonal status. Low resistance in:

• Diabetes Mellitus.
• Increased corticosteroid levels.
• Hypothyroidism

4. Phagocytosis. Infections can Occur in :

• Qualitative  or quantitative defects in neutrophils and monocytes.
• Diseases of mononuclear phagocytic system (Reticuloendothelial cells-RES).
• Overload blockade of RES.

5. Humoral factors

• Lysozyme.
• Opsonins.
• Complement
• Interferon (antiviral agent secreted by cells infected by virus)

FUNGAL INFECTION

Histoplasmosis

A disease caused by Histoplasma capsulatum, causing primary pulmonary lesions and hematogenous dissemination.

Symptoms and Signs

The disease has three main forms. Acute primary histoplasmosis is usually asymptomatic

Progressive disseminated histoplasmosis follows hematogenous spread from the lungs that is not controlled by normal cell-mediated host defense mechanisms. Characteristically, generalized involvement of the reticuloendothelial system, with hepatosplenomegaly, lymphadenopathy, bone marrow involvement, and sometimes oral or GI ulcerations occurs, particularly in chronic cases

Progressive disseminated histoplasmosis is one of the defining opportunistic infections for AIDS.

Chronic cavitary histoplasmosis is characterized by pulmonary lesions that are often apical and resemble cavitary TB. The manifestations are worsening cough and dyspnea, progressing eventually to disabling respiratory dysfunction. Dissemination does not occur

Diagnosis

Culture of H. capsulatum from sputum, lymph nodes, bone marrow, liver biopsy, blood, urine, or oral ulcerations confirms the diagnosis

Pneumoconioses—are environmentally related lung diseases that result from chronic inhalation of various substances.

1. Silicosis (stone mason’s disease) 
a. Inhalant: silica dust.
b. Associated with extensive fibrosis of the lungs.
c. Patients have a higher susceptibility to tuberculosis infections.

2. Asbestosis
a. Inhalant: asbestos fibers.
b. Associated with the presence of pleural plaques.
c. Consequences include:
(1) Mesothelioma (malignant mesothelial tumor).
(2) Bronchogenic carcinoma.

3. Anthracosis
a. Inhalant: carbon dust.
b. Usually not as harmful as silicosis or asbestosis.
c. Associated with the presence of macrophages containing carbon.

Liver cirrhosis

It is a chronic, progressive diffuse process characterized by 
a. Hepatocellular necrosis           
b. Replacement by fibrosis and inflammation 
c. Hyperplasia of surviving liver cells forming regenerating nodules 
d. Vascular derangement. 

All these changes lead to loss of the normal liver architecture. 

Pathology of cirrhosis
At first the liver is enlarged or of normal size. Late in the disease, it is reduced in size and weight. 
Consistency- Firm. 
Colour -May be yellow (fatty change), red (congestion), green (cholestaisis), or pale gray (recent nodules due to absence of pigment). 

Morphologically  According to the size of these nodules, cirrhosis can be classified
    
    Micronodular (regular) cirrhosis. Small nodules 2-3 mm.in diameter.
    Macronodular (irregular) cirrhosis, nodules up to one cm in diameter.
    Mixed cirrhosis is the end stage of all types of cirrhosis
    
Microscopic picture 

1 Regenerating nodulesn- Proliferated hepatocytes arranged in thick plates and separated by blood sinusoids.  Central vein in abnormal sites (eccentric) - Hepatocytes may be small , large , or binucleated 

2- Fibrosis- It replaces damaged hepatocytes. It develops at certain sites:-
a-perivenular    b -perisinusoidal    c -pericellular  and d -in relation to portal tracts.

- It may be young, cellular and highly vascular or mature with diminished vasculsarity. It encloses groups of hepatocytes, lobules or regenerating nodules.

-As a result of hepatocyte injury and fibrosis, there’s loss of normal liver architecture including the lobular and acinar pattern as well as the liver cell plates 

3- Bile ductular proliferation:- Occurs in the fibrous septa.Focal choestaisis with feathery degeneration of hepatocytes occur at the margins of regenerating nodules. It becomes diffuse terminally.  

4- Inflammatory cells:-   Lymphocytes, macrophages and plasma cells infiltrate the fibrous septa and regenerating nodules 

Etiological classification of cirrhosis

Congenital Occurs at childhood
- congenital syphilis   
  
Hereditary diseases:- 
a. Primary idiopathic haemochromatosis      b. Thalassemia      c. Wilson’s disease      d.α 1-antitrypsin deficien e. glycogen storage disease

Acquired

-Cryptogenic (10-50%).             
-Alcoholic (30-70%)
-Post viral  (15-20%)                
- Biliary cirrhosis (16%) primary or secondary. 

Cartilage-Forming Tumors

1. Osteochondroma (Exostosis) is a relatively common benign cartilage-capped outgrowth attached by a bony stalk to the underlying skeleton. Solitary osteochondromas are usually first diagnosed in late adolescence and early adulthood (male-to-female ratio of 3:1); multiple osteochondromas become apparent during childhood, occurring as multiple hereditary exostosis, an autosomal dominant disorder. Inactivation of both copies of the EXT gene (a tumor suppressor gne) in chondrocytes is implicated in both sporadic and hereditary osteochondromas. Osteochondromas develop only in bones of endochondral origin arising at the metaphysis near the growth plate of long tubular bones, especially about the knee. They tend to stop growing once the normal growth of the skeleton is completed. Occasionally they develop from flat bones (pelvis, scapula, and ribs). Rarely, exostoses involve the short tubular bones of hands and feet.

Pathological features

• Osteochondromas vary from 1-20cm in size.
• The cap is benign hyaline cartilage. 
• Newly formed bone forms the inner portion of the head and stalk, with the stalk cortex merging with cortex of the host bone.
Osteochondromas are slow-growing masses that may be painful. Osteochondromas rarely progress to chondrosarcoma or other sarcoma, although patients with the multiple hereditary exostoses are at increased risk of malignant transformation. 

2. Chondroma 

It is a benign tumor of hyaline cartilage. When it arises within the medullary cavity, it is termed enchondroma; when on the bone surface it is called juxtacortical chondroma. Enchondromas are usually diagnosed in persons between ages 20 and 50 years; they are typically solitary and located in the metaphyseal region of tubular bones, the favored sites being the short tubular bones of the hands and feet. Ollier disease is characterized by multiple chondromas preferentially involving one side of the body. Chondromas probably develop from slowly proliferating rests of growth plate cartilage.

Pathological features 

• Enchondromas are gray-blue, translucent nodules usually smaller than 3 cm.
• Microscopically, there is well-circumscribed hyaline matrix and cytologically benign chondrocytes.
Most enchondromas are detected as incidental findings; occasionally they are painful or cause pathologic fractures. Solitary chondromas rarely undergo malignant transformation, but those associated with enchondromatosis are at increased risk. 

3. Chondrosarcomas are malignant tumors of cartilage forming tissues. They are divided into conventional chondrosarcomas and chondrosarcoma variants. Each of these categories comprises several distinct types, some defined on microscopic grounds & others on the basis of location within the affected bone, for e.g. they are divided into central (medullary), peripheral (cortical), and juxtacortical (periosteal). The common denominator of chondrosarcoma is the production of a cartilaginous matrix and the lack of direct bone formation by the tumor cells (cf osteosarcoma). Chondrosarcomas occur roughly half as frequently as osteosarcomas; most patients age 40 years or more, with men affected twice as frequently as women 

Pathological features 
Conventional chondrosarcomas arise within the medullary cavity of the bone to form an expansile glistening mass that often erodes the cortex. They exhibit malignant hyaline or myxoid stroma. Spotty calcifications are typically present. The tumor grows with broad pushing fronts into marrow spaces and the surrounding soft tissue. Tumor grade is determined by cellularity, cytologic atypia, and mitotic activity. Low-grade tumors resemble normal cartilage. Higher grade lesions contain pleomorphic chondrocytes with frequent mitotic figures with multinucleate cells and lacunae containing two or more chondrocytes. Dedifferentiated chondrosarcomas refers to the presence of a poorly differentiated sarcomatous component at the periphery of an otherwise typical low-grade chondrosarcoma. Other histologic variants include myxoid, clear-cell and mesenchymal chondrosarcomas. Chondrosarcomas commonly arise in the pelvis, shoulder, and ribs. A slowly growing lowgrade tumor causes reactive thickening of the cortex, whereas a more aggressive high-grade neoplasm destroys the cortex and forms a soft tissue mass. There is also a direct correlation between grade and biologic behavior. 
Size is another prognostic feature, with tumors larger than 10 cm being significantly more aggressive than smaller tumors. High-grade Chondrosarcomas metastasize hematogenously, preferentially to the lungs and skeleton.

Rocky Mountain Spotted Fever (Spotted Fever; Tick Fever; Tick Typhus)

An acute febrile disease caused by Rickettsia rickettsii and transmitted by ixodid ticks, producing high fever, cough, and rash.

Symptoms and Signs

The incubation period averages 7 days but varies from 3 to 12 days; the shorter the incubation period, the more severe the infection. Onset is abrupt, with severe headache, chills, prostration, and muscular pains. Fever reaches 39.5 or 40° C (103 or 104° F) within several days and remains high (for 15 to 20 days in severe cases),

Between the 1st and 6th day of fever, most patients develop a rash on the wrists, ankles, palms, soles, and forearms that rapidly extends to the neck, face, axilla, buttocks, and trunk. Often, a warm water or alcohol compress brings out the rash. Initially macular and pink, it becomes maculopapular and darker. In about 4 days, the lesions become petechial and may coalesce to form large hemorrhagic areas that later ulcerate

Neurologic symptoms include headache, restlessness, insomnia, delirium, and coma, all indicative of encephalitis. Hypotension develops in severe cases. Hepatomegaly may be present, but jaundice is infrequent. Localized pneumonitis may occur. Untreated patients may develop pneumonia, tissue necrosis, and circulatory failure, with such sequelae as brain and heart damage. Cardiac arrest with sudden death occasionally occurs in fulminant cases.