NEET MDS Lessons
General Pathology
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.
N. meningiditis
Major cause of fulminant bacteremia and meningitis. Has a unique polysaccharide capsule. It is spread person to person by the respiratory route. Frequently carried in nasopharynx, and carriage rates increased by close quarters. Special risk in closed populations (college dorms) and in people lacking complement. Sub-saharan Africa has a “meningitis belt.”
Pathogenesis is caused by adherence factors that attach to non-ciliated nasopharyngeal epithelium. These factors include pili which promote the intial epithelial (and erythrocyte) attachment, and Opa/Opc surface binding proteins.
Adherence stimulates engulfment of bacteria by epithelial cells. Transported to basolateral surface.
The polysaccharide capsule is a major virulence factor that prevents phagocytosis and lysis.
A lipo-oligosaccharide endotoxin also contributes to sepsis.
Autoimmune(acquired) Haemolytic anaemia
Auto antibodies are usually Ig g type (may be Ig M or Ig A). They may or may not bind complement and may be active in warm or cold temperature They may be complete (agggIutinating) or incomplete. Haemolysis s may be intravascular due to destruction of the antibody coated cells by RE system.
Causes:
a. Idiopathic
b. Secondary to
o Drugs - Methyldopa, Mefanamic acid
o Disease like
-> Infections especially viral.
-> Autoimmune disease especially SLE.
-> Lymphomas and chronic lymphatic leukaemia.
-> Tumours.
Diagnosis : is based on
• Evidences of haemolytic anaemia.
• Demonstration of antibodies
- On red cell surface by direct Coomb’s test
- In serum by indirect Coomb’s test.
Autopsy
Autopsy is examination of the dead body to identify the cause of death. This can be for forensic or clinical purposes.
Bronchiectasis
- Bronchiectasis is abnormal and irreversible dilatation of the bronchi and bronchioles (greater than 2 mm in diameter) secondary to inflammatory weakening of bronchial wall.
- Occur in childhood and early adult life
- Persistent cough with copious amount of foul smelling purulent sputum
Aetiopathogenesis
Bronchial wall destruction is due to:
- Endobronchial obstruction due to foreign body
- Infection due to local obstruction or impaired defence mechanism
Clinical conditions:
- Hereditary and congenital factors
- Obstruction
- Secondary complication
Hereditary and congenital factors:
- Congenital bronchiectasis due to developmental defects
- Cystic fibrosis causing defective secretion resulting in obstruction
- Hereditary immune defiency diseases
- Immotile cilia syndrome- immotile cilia of respiratory tract, sperms causing Kartagener’s syndrome (bronchiectasis, situs inversus and sinusitis) and male infertility
- Allergic bronchial asthma patients
Obstruction:
Localised variety in one part of bronchial system.
Obstruction can be due to
Foreign body
Endobronchial tumors
Hilar lymph nodes
Inflammatory scarring (TB)
Secondary complication:
Necrotizing pneumonia in Staph infection and TB
Morphologic changes
- Affects distal bronchi and bronchioles
- Lower lobes more frequently
- Lungs involved diffusely/segmentally
- Left lower lobe than right
- Pleura fibrotic & thickened adherent to chest wall
C/S lung: Honey-combed appearance
Microscopic examination:
Bronchiole-dilated
Bronchial epithelium-normal, ulcerated, squamous metaplasia
Bronchial wall-infiltration by ac & Ch inflammatory cells,
destruction of muscle, elastic tissue
Lung parenchyma-fibrosis, surrounding tissue pneumonia
Pleura-fibrotic and adherent
Blood-Lymphatic Pathology
Disorders of primary hemostasis
1. General characteristics of disorders of primary hemostasis (due to problems of blood vessels or platelets):
a. Occur early in life.
b. Unlike secondary hemostasis, bleeding occurs in more superficial areas such as skin and mucous membranes rather than in secondary hemostasis.
c. Signs include petechiae.
d. Can be caused by vascular and platelet abnormalities or alterations in the plasma proteins required for adhesion of platelets to vascular subendothelium.
e. Laboratory findings include prolonged bleeding time, as seen in platelet disorders.
2. Vascular abnormalities
Scurvy
(1) Caused by a vitamin C deficiency leading to decreased synthesis of collagen. Note: vitamin C is necessary for the formation of collagen via hydroxylation of lysine and proline.
(2) Symptoms include:
- Delayed wound healing.
- Petechiae and ecchymosis.
- Gingival bleeding, swelling, and ulcerations.
3. Platelet abnormalities
a. Thrombocytopenia
(1) Characterized by a decreased number of platelets.
(2) The most common type of bleeding disorder.
(3) Can be caused by a number of diseases, such as irradiation, acute leukemia, disseminated intravascular coagulation (DIC), or idiopathic thrombocytopenic purpura (ITP).
b. Thrombocytopenic purpura
(1) Idiopathic: An autoimmune disease characterized by the presence of autoantibodies against platelets, resulting in the removal of platelets by splenic macrophages.
(2) May also be drug-induced.
Disorders of secondary hemostasis
1. General characteristics of disorders of secondary hemostasis (due to problems with clotting factors):
a. Symptoms occur later in life.
b. As compared to disorders of primary hemostasis, bleeding occurs in deeper areas and larger vessels (i.e., joint spaces).
c. Laboratory findings include abnormal:
- Partial thromboplastin time (PTT)—measures the intrinsic and common clotting pathway (i.e., tests all coagulation factors except factor 7).
- Prothrombin time (PT)—measures the extrinsic pathway.
- Does not affect the bleeding time.
Hemophilia
a. Caused by a deficiency of particular clotting factor(s).
b. All types of hemophilia affect the intrinsic pathway of the clotting cascade.
c. Signs and symptoms include:
- Prolonged PTT.
- Continuous bleeding from cuts or trauma, which can lead to excessive blood loss.
- Bleeding into joint cavities (hemarthroses) and muscle.
Two types:
(1) Hemophilia A (classic hemophilia)
- Caused by a deficiency of factor 8 (antihemophilic factor).
- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.
(2) Hemophilia B (Christmas disease)
- Caused by a deficiency of factor 9 (plasma thromboplastin).
- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.
- Lower incidence rate than hemophilia A.
(3). Vitamin K deficiency
- Causes include malnutrition and malabsorption of fats.
- A decrease in clotting factors 2, 7, 9, and 10 and prothrombin is observed.
- Prolonged PT.
Disorders of both primary and secondary hemostasis
1. von Willebrand’s disease
a. Characterized by a defective von Willebrand’s factor (vWF). Defective vWF affects both primary hemostasis by affecting platelet adhesion to
endothelium, and secondary hemostasis, by a defective factor 8.
b. Genetic transmission: autosomal dominant.
It is the most common hereditary bleeding disorder.
2. Liver disease—disease of the liver results in a decreased production of coagulation factors and therefore can lead to problems with hemostasis.
3. Disseminated intravascular coagulation a condition in which clots form throughout the vasculature. This uses up all available clotting factors and platelets, resulting in problems with bleeding.
Diseases from Str. pyogenes (Group A strep)
1. Streptococcal pharyngitis. Most frequent Group A infection. Throat has gray-white exudate. Infection may become systemic into blood, sinuses, jugular vein, meninges. In less than a week the M-protein and capsule production decrease, and transmission declines.
2. Skin infections, such as impetigo. Especially in children. Different M-proteins than in pharyngitis. Skin infections associated with edema and red streaking (characteristic).
3. Necrotizing fasciitis/myositis. Infection of deeper tissue advances despite antibiotics.
4. Scarlet fever. Caused by phage-associated erythrogenic toxin-producing strains. Toxins cause cardiac, renal, and other systemic failures. Rash is very red with a sand-papery feel and shedding of superficial skin.
5. Toxic Shock Syndrome. Parallels the toxic shock caused by TSST-carrying Staph. aureus.
6. Non-suppurative, post-infection diseases.
Rheumatic fever (myocarditis, cardiac valve disease, polyarthralgia, rashes. Occurs two weeks after a pharyngeal infection)
Glomerulonephritis (Occurs two weeks after pharyngeal or skin infections. Often due to immunologic reaction to M-protein type 12)