Mycobacterium leprae 

- tuberculoid type has intact cellular immunity
 - forms granulomas and kill the organisms (very few present).
 - evokes a positive lepromin skin test
 - localized skin lesions that lack symmetry
 - nerve involvement (organisms invade Schwann cells) that dominates the clinical picture and leads to skin anesthesia, muscle atrophy and autoamputation.
 - lepromatous leprosy patients lack cellular immunity
 - no granulomas
 - organisms readily identified
 - negative lepromin skin test
 - Bacteremia disseminates to cooler areas like the digits.
 - symmetrical, skin lesions that produce the classic leonine facies; biopsy reveals grentz zone in superficial dermis and then organisms in macrophages.
 - neural involvement is a late feature of the disease.
 - lepromin skin test is to determine host immunity; not a diagnostic test.
 - treatment: dapsone + rifampin

Tuberculosis

Causative organism

-Mycobacterium tuberculosis 
-Strict aerobe 
-Pathogenic strains
-hominis, bovis, avium, murine& cold blooded vertebrate strain 

Koch’s bacillus
-small slender, rod like bacillus, 4umnon-motile, aerobic -high lipid content 
-divides every 16 to 20 hours, an extremely slow rate 
-stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolicacid content of its cell wall 
-can withstand weak disinfectant and survive in a dry state for weeks. 

Demonstrated by 
-ZiehlNeelsenstaining 
-Fluorescent dye method 
-Culture in LJ media 
-Guinea pig inoculation

Modes of transmission

Inhalation , Ingestion, Inoculation , Transplacental

Route Spread 
Local , Lymphatic , Haematogenous , By natural passages, 

Pathogenesis 

- Anti‐mycobacterial CMI, confers resistance to bacteria → dev. of HS to tubercular Ag 
- Bacilli enters macrophages 
- Replicates in phagosomeby blocking fusion of phagosome&  lysosome, continues for 3 weeks →bacteremiabut  asymptomatic 
- After 3 wks, T helper response is mounted by  IL‐12 produced  by macrophages 
- T cells produce IFN, activates macrophages → bactericidal  activity, structural changes 
- Macrophages secrete TNF→ macrophage recruitment,  granuloma& necrosis

Fate of granuloma 
- Caseousmaterial undergo liquefaction---cold abscess 
- Bones, joints, lymph nodes & epididymis---sinuses are formed & sinus tract lined by tuberculousgranulation tissue 
- Dystrophic calcification

Types of TB

1. Primary Pulmonary TB 
2. secondary TB (miliary, fibrocaseous, cavitary) 
3. Extra-pulmonary TB (bone, joints, renal, adrenal, skin… )

Primary TB
Infection in an individual who has not been previously infected or immunised 
Primary complex 
Sites
    -lungs, hilarlymph nodes 
    -tonsils, cervical lymph nodes 
    -small intestine, mesenteric lymph nodes

Primary TB
In the lung, Ghon’scomplex has 3 components: 
1. Pulmonary component -Inhalation of airborne droplet ~ 3 microns. 
    -Bacilli locate in the subpleuralmid zone of lung 
    -Brief acute inflammation –neutrophils. 
    -5-6 days-invoke granulomaformation. 
    -2 to 8 weeks –healing –single round ;1-1.5 cm-Ghon focus. 
2. Lymphatic vessel component 
3. Lymph node component

Fate of primary tuberculosis

- Lesions heal by fibrosis, may undergo calcification, ossification 
    -a few viable bacilli may remain in these areas  
    -bacteria goes into a dormant state, as long as the person's immune system remains active 
- Progressive primary tuberculosis: primary focus continues to grow & caseousmaterial disseminated to other parts of lung 
- Primary miliarytuberculosis: bacilli may enter circulation through erosion of blood vessel 
- Progressive secondary tuberculosis: healed lesions are reactivated, in children & in lower resistance

Secondary tuberculosis

-Post-primary/ reinfection/ chronic TB 
-Occurs in immunized individuals. 
-Infection acquired from 

    -endogenous source/ reactivation 
    -exogenous source/ reinfection 

Reactivation
-when immune system is depressed 
-Common in low prevalence areas. 
-Occurs in 10-15% of patients 
-Slowly progressive (several months) 

Re-infection 
-when large innoculum of bacteria occurs 
-In areas with increased personal contact

Secondary TB

-Sites-Lungs 1-2 cm apical consolidation with caseation 
-Other sites -tonsils, pharynx, larynx, small intestine & skin

Fate of secondary tuberculosis

•Heal with fibrous scarring & calcification 
•Progressive secondary pulmonary tuberculosis: 
    -fibrocaseoustuberculosis 
    -tuberculouscaseouspneumonia 
    -miliarytuberculosis

Complications: 
a) aneurysm of arteries–hemoptysis 
b) bronchopleuralfistula 
c) tuberculousempyema 

MiliaryTB

• Millet like, yellowish, firm areas without caseation 
• Extensive spread through lympho-hematogenousroute 
• Low immunity 
• Pulmonary involvement via pulmonary artery 
• Systemic through pulmonary vein: 
    -LN: scrofula, most common 
    -kidney, spleen, adrenal, brain, bone marrow

Signs and Symptoms of Active TB

• Pulmonary-cough, hemoptysis, dyspnea 
• Systemic: 
• fever 
• night sweats 
• loss of appetite 
• weight loss 
• chest pain,fatigue 

•If symptoms persist for at least 2 weeks, evaluate for possible TB infection

Diagnosis

•Sputum-Ziehl Neelsen stain –10,000 bacilli, 60% sensitivity 
    -release of acid-fast bacilli from cavities intermittent. 
    -3 negative smears : low infectivity 

•Culture most sensitive and specific test.
     -Conventional Lowenstein Jensen media-10 wks. 
     -Liquid culture: 2 weeks 

•Automated techniques within days 
    should only be performed by experienced laboratories (10 bacilli) 

•PPD for clinical activity / exposure sometime in life 
•X-ray chest 
•FNAC

PPD Tuberculin Testing

- Read after 72 hours. 
- Indurationsize -5-10 mm 
- Does not d/s b/w active and latent infection 
- False +: atypical mycobacterium 
- False -: malnutrition, HD, viral, overwhelming infection, immunosuppression 
- BCG gives + result.

Tuberculosis Atypical mycobacteria 

- Photochromogens---M.kansasii 
- Scotochromogens---M.scrofulaceum 
- Non-chromogens---M.avium-intracellulare 
- Rapid growers---M.fortuitum, M.chelonei

5 patterns of disease 

- Pulmonary—M.kansasii, M.avium-intracellulare 
- Lymphadenitis----M.avium-intracellulare, M.scrofulaceum 
- Ulcerated skin lesions----M.ulcerans, M.marinum 
- Abscess----M.fortuitum, M.chelonei 
- Bacteraemias----M.avium-intracellulare as in AIDS

A dermatofibroma is a benign tumor of the dermis, MC located on the lower extremity, where it has a nodular, pigmented appearance.
 - composed of benign histiocytes.

Immunohistochemistry

 This is a method is used to detect a specific antigen in the tissue in order to identify the type of disease.

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]). 

Immunodeficiency

This may be :- 
- Congenital (Primary)
- Acquired (Secondary)

Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.

T Cell Defects :

- Thymic dysplasia
- Digeorge’s syndrome
- Nazelof’s syndrome
- Ataxia teltngiectaisa
- Wiscott Aldrich’s syndrome

These  lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.

C. Humoral immunity defects.
Bruron type- aggammaglobulinaemia.
- Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.

Acquired deficiency

A. Immuno suppression by :
- Irradiation.
- Corticoids.
- Anti metabolites.
- Anti lymphocyte serum.

B. Neaplasia  of lymphoid system :

- Hodgkin's and Non Hodgkin's lymphomas.
- Chronic lymphocytic leukaemia..
- Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).

c. excessive protein loss.
- Nephrotic Syndrome.
- Protein losing enteropathy.