Muscle pathology
1. Myasthenia gravis
a. An autoimmune disease caused by autoantibodies to acetylcholine receptors at the neuromuscular junctions.
b. Characterized by muscle weakness or the inability to maintain long durations of muscle contractions; this worsens during exercise but recovers after rest.
c. Affects various muscle groups, including:
(1) Eyes—diplopia, ptosis.
(2) Neck—dysphagia, problems swallowing or speaking.
(3) Extremities—arms and legs.
d. Treatment: cholinesterase inhibitors(neostigmine), anti-immune therapy.

2. Muscle tumors
a. Rhabdomyoma—benign tumor of skeletal muscle.
b. Leiomyoma
(1) Benign tumor of smooth muscle.
(2) Most common tumor found in women.
(3) Usually affects the uterus, although it can occur anywhere.
c. Rhabdomyosarcoma
(1) Malignant tumor of skeletal muscle.
(2) Most common sarcoma found in children.
(3) Usually affects head and neck region—orbit, nasal cavity, and nasopharynx.

Autopsy

Autopsy is examination of the dead body to identify the cause of death. This can be for forensic or clinical purposes.

Nevus
1. Commonly known as moles.
2. A benign, pigmented tumor of melanocytes, found deep within connective tissue.
3. Types of skin nevi:
a. Junctional nevus—found in the epidermis.
It is the only type of nevus that may be considered to be premalignant.
b. Compound nevus—found in both the epidermis and underlying dermis.
c. Intraepidermal nevus—found in the dermis.

 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

2. Drug induced thrombocytopenia (especially sedormid).
3 Agranulocytosis due to sensitivity to some drugs.
4 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
    o    Drug induced vasculitis.
    o    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)
 

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.

Cells Of  The Exudate

Granulocytes (Neutrophils, eosinophils, and basophils)

Monocytes (and tissue macrophages)

Lymphocytes

Neutrophils (polymorphs).

Characteristics

(1) Cell of acute inflammation.

(2) Actively motile.

(3) Phagocytic.

(4) Respond to chemotactic agents like.

Complement products.

Bacterial products.

Tissue breakdown

Lysosomal enzymes of other polymorphs

Functions

(1) Phagocytosis and intracellular digestion of bacteria.

(2) Exocytosis of lysosomal enzymes to digest dead tissue as the first step in the process of repair.

Eosinophils

Characteristics

(I) Cell of allergjc and immunologic inflammation.

(2) Motile and phagocytic but less so than a neutrophil.

(3) Response to chemotaxis similar to neutrophil. In addition, it is also responsive to antigens and antigen-antibody complexes.

(4) Steroids cause depletion of eosinophils.

Functions

(1) Contain most of the lysosomal enzymes that polymorphs have

(2) control of Histamine release and degradation in inflammation

Basophils (and mast cells)

Characteristics

(1) Contain coarse metachromatic granules.

(2) Contain, histamine and proteolytic enzymes

Functions

Histamine: release which causes some of the changes of inflammation and allergic

reactions. .

Monocytes .

Blood monocytes form a component of. the mononuclear phagocytic system (MPS), the other being tissue macrophages The tissue macrophages may be :

(a) Fixed phagocytic. cells:

• Kuffer cell of liver.
• Sinusoidal lining cells of spleen and lymph nodes.
• Pleural and peritoneal macrophages
• Alveolar macrophages.
• Microglial cells.

(b) Wandering macrophages or tissue histiocytes.

The tissue histiocytes are derived from blood monocytes.

Characteristics

.(1)Seen in inflammation of some duration, as they -outlive polymorphs.

(2) Actively phagocytic and motile.

(3) Fuse readily to from giant cells in certain situations.

Function

(1) Phagocytosis.

(2) Lysosomal enzyme secretion.

(3) Site of synthesis of some components of complement.

(4) Antigen handling and processing before presenting it to the Immune  competent cell.

(5) Secretion of lysosyme and interferon.

Giant cells can be

(A) Physiological

Syncytiotrophoblast, megakatyocytes, striated muscle, osteoclast.

(B) Pathological:

Foreign body: in the presence of particulate foreign matter like talc, suture material etc. and in certain infections_e g fungal.

Langhan's type: a variant of foreign body giant cell seen in tuberculosis.

Touton type in lipid rich situations like Xanthomas, lipid granulomas etc.

(iv) Aschoff cell in rheumatic carditis.

(v) Tumour gjant cells e.g. Reid-Sternberg cell in Hodgkin's Lymphoma, giant cells in any malignancy.

Lymphocytes and Plasma cells

These are the small mononuclear cell comprising the immune system

They are less motile than_macrophages and  neutrophils and are seen in chronic inflammation and immune based diseases.