IMMUNITY AND RESISTANCE TO INFECTION

Body's resistance to infection depends upon:

I. Defence mechanisms at surfaces and portals of entry.

II. Nonspecific or innate immunity

Ill. Specific immune response.

I.  Surface Defence Mechanisms

1. Skin:

(i) Mechanical barrier of keratin and desquamation.

(ii) Resident commensal organisms

(iii)Acidity of sweat.

(iv) Unsaturated fatty acids of sebum

2. Oropharyngeal

(i)Resident flora

(ii) Saliva, rich in lysozyme, mucin and Immunoglobulins (lgA).

3. Gastrointestinal tract.-

(i) Gastric HCI

(ii) Commensal organisms in Intestine

(iii) Bile salts

(iv) IgA.

(v) Diarrhoeal expulsion of irritants.

4. Respiratory tract:

(i) Trapping in turbinates

(ii) Mucus trapping

(iii) Expulsion by coughing and sneezing.

(iv) Ciliary propulsion.

(V) Lysozymes and antibodies in secretion.

(vi) Phagocytosis by alveolar macrophages.

5. Urinary tract:

(i) Flushing action.

(ii) Acidity

(iii) Phagocytosis by urothelial cells.

6. Vagina.-

(i) Desquamation.

(ii) Acid barrier.

(iii) Doderlein's bacilli (Lactobacilli)

7. Conjunctiva:

Lysozymes and IgA in tears

II. 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) 

III. The Specific Immune Response

Definition

The immune response comprises all the phenomenon resulting from specific interaction

of cells of the immune-system with antigen. As a consequence of this interaction cells

, appear that mediate cellular immune response as well cells that synthesis and secrete

immunoglobulins

Hence the immune response has 2 components.

1. Cell mediated immunity (CMI).

2:. Humoral immunity (antibodies)

(I) Macrophages. Constituent of the M. P. S. These engulf the antigenic material.

(i) Most of the engulfed antigen is destroyed to' prevent a high dose paralysis of the Immune competent cells.

(ii) Some of it persists in the macrophage, retaining immunogenecity for continued stimulus to the immune system.

(iii)The antigenic information is passed on to  effectors cells. There are two proposed mechanisms for this:

(a) As messenger RNA with code for the specific antibody.

(b) As antigen-RNA complexes.

(2) Lymphocytes. There are 2 main classes recognized by surface characteristics.

(A) T-Lymyhocytes (thymus dependant) :- These are responsible for cellular immunity . On exposure to antigen

• They transform to immunoblasts  which divide to form the effectors cells.
• They secrete lymphokines These are
  • Monocyte migration inhibition factor
  • Macrophage activation factor
  • Chemotactic factor
  • Mitogenic factor
  • Transfer factor
  • Lymphotoxin which kills target cell
  • Interferon.
  • Inflammatory factor which increases permeability. .
• Some remain as 1onglived memory cell for a  quicker recognition on re-exposure
• They also modify immune response by other lymphocytes in the form of “T – helper cells “ and “T-suppressor” cells
• They are responsible for graft rejection

(B) B-Lymphocytes (Bursa dependent). In birds the Bursa of Fabricious controls these cells. In man, its role is taken up by," gut associated lymphoid tissue)

(i) They are responsible for antibody synthesis. On stimulation they undergo blastic transformation and then differentiation to plasma cells, the site of immunoglobulin synthesis.

(ii) They also form memory cells. But these are probably short lived.

(C) In addition to T & B lymphocytes, there are some lymphocytes without the surface markers of either of them. These are 'null' cells-the-natural Killer (N,K.) cells and cells responsible for antibody dependent cellular-cytotoxicity.

(3) Plasma cells. These are the effectors cells of humoral immunity. They produce the immunoglobins, which are the effector molecules.

Langerhans cell granulomatosis (histocytosis X)
a. A group of diseases that are caused by the proliferation of Langerhans’ cells (previously known as histocytes).
b. Most commonly causes bone lesions; however, other tissues can be affected.
c. Histologic findings include Langerhans’ cells containing Birbeck granules and eosinophils.

d. Three types:
(1) Letterer-Siwe disease—an acute, disseminated form that is fatal in infants.
(2) Hand-Schüller-Christian disease—a chronic, disseminated form that has a better prognosis than LettererSiwe disease. It usually presents
before the age of 5 and is characterized by a triad of symptoms:
(a) Bone lesions—found in skull, mandible (loose teeth).
(b) Exophthalmos.
(c) Diabetes insipidus.
(3) Eosinophilic granuloma of bone—a localized, least severe form of the three. Lesions may heal without treatment.
(a) Most commonly occurs in young adults.
(b) Lesions in the mandible may cause loose teeth.

Alcoholic (nutritional, Laennec’s) cirrhosis

Pathology
 
Liver is at first enlarged (fatty change), then return to normal size and lastly, it becomes slightly reduced in size (1.2 kg or more).
- Cirrhosis is micronodular then macronodular then mixed.   

M/E  
Hepatocytes:-  show fatty change that decreases progressively. Few hepatocytes show increased intracytoplasmic haemochromatosis. 
b. Fibrous septa:-  Regular margins between it and regenerating nodules.
 -Moderate lymphocytic infiltrate.      
 – Slight bile ductular proliferation.
 
Prognosis:-   It Progresses slowly over few years. 

Valvular disease
A. Generally, there are three types:
1. Stenosis—fibrotic, stiff, and thickened valves, resulting in reduced blood flow through the valve.

2. Regurgitation or valvular insufficiency— valves are unable to close completely, allowing blood to regurgitate.

3. Prolapse—“floppy” valves; may occur with or without regurgitation. The most common valvular defect.

THE PITUITARY GLAND 

This is a small, bean-shaped structure that lies at the base of the brain within the confines of the sella turcica. It is connected to the hypothalamus by a "stalk," composed of axons extending from the hypothalamus. The  pituitary is composed of two morphologically and functionally distinct components: the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). The adenohypophysis, in H&E stained sections, shows a colorful collection of cells with basophilic, eosinophilic or poorly staining ("chromophobic") cytoplasm.

Fibrous and Fibro-Osseous Tumors

Fibrous tumors of bone are common and comprise several morphological variants.
1. Fibrous Cortical Defect and Nonossifying Fibroma 
Fibrous cortical defects occur in 30% to 50% of all children older than 2 years of age; they are probably developmental rather than true neoplasms. The vast majority are smaller than 0.5 cm and arise in the metaphysis of the distal femur or proximal tibia; almost half are bilateral or multiple. They may enlarge in size (5-6 cm) to form nonossifying fibromas. Both lesions present as sharply demarcated radiolucencies surrounded by a thin zone of sclerosis. Microscopically are cellular and composed of benign fibroblasts and macrophages, including multinucleated forms. The fibroblasts classically exhibit a storiform pattern. Fibrous cortical defects are asymptomatic and are usually only detected as incidental radiographic lesions. Most undergo spontaneous differentiation into normal cortical bone. The few that enlarge into nonossifying fibromas can present with pathologic fracture; in such cases biopsy is necessary to rule out other tumors.

2. Fibrous Dysplasia 

is a benign mass lesion in which all components of normal bone are present, but they fail to differentiate into mature structures. Fibrous dysplasia occurs as one of three clinical patterns:
A. Involvement of a single bone (monostotic)
B. nvolvement of multiple bones (polyostotic)
C. Polyostotic disease, associated with café au lait skin pigmentations and endocrine abnormalities, especially precocious puberty (Albright syndrome).

Monostotic fibrous dysplasia accounts for 70% of cases. It usually begins in early adolescence, and ceases with epiphyseal closure. It frequently involves ribs, femur, tibia & jawbones. Lesions are asymptomatic and usually discovered incidentally. However, fibrous dysplasia can cause marked enlargement and distortion of bone, so that if the face or skull is involved, disfigurement can occur.

Polyostotic fibrous dysplasia without endocrine dysfunction accounts for the majority of the remaining cases. 
It tends to involve the shoulder and pelvic girdles, resulting in severe deformities and spontaneous fractures.

Albright syndrome accounts for 3% of all cases. The bone lesions are often unilateral, and the skin pigmentation is usually limited to the same side of the body. The cutaneous macules are classically large, dark to light brown (café au lait), and irregular.

Gross features

• The lesion is well-circumscribed, intramedullary; large masses expand and distort the bone.
On section it is tan-white and gritty.

Microscopic features

• There are curved trabeculae of woven bone (mimicking Chinese characters), without osteoblastic rimming
• The above are set within fibroblastic proliferation
Individuals with monostotic disease usually have minimal symptoms. By x-ray, lesions exhibit a characteristic ground-glass appearance with well-defined margins. Polyostotic involvement is frequently associated with progressive disease, and more severe skeletal complications (e.g., fractures, long bone deformities, and craniofacial distortion). Rarely, polyostotic disease can transform into osteosarcoma, especially following radiotherapy.