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.
Diagnostic techniques used in pathology
The pathologist uses the following techniques to the diagnose diseases:
a. Histopathology
b. Cytopathology
c. Hematopathology
d. Immunohistochemistry
e. Microbiological examination
f. Biochemical examination
g. Cytogenetics
h. Molecular techniques
i. Autopsy
Sickle Cell Disease
Sickle cell anemia is a autosomal recessive genetic disorder. It affects the BETA GLOBIN gene on the CHROMOSOME 16. In sickle cell anemia, the hemoglobin abnormality consists of a point mutation in the beta chain gene for hemoglobin; the resulting abnormal gene product is denoted HbS. If you are heterozygous for the HbS gene you will have what is called sickle trait, which is asymptomatic .
If you are homozygous for the HbS gene you will get sickle cell disease, which is symptomatic in most patients.
The problem with HbS is that as it releases oxygen, it polymerizes and aggregates with other HbS molecules, making the red cell stiff and distorted. These distorted, sickle-shaped red cells are fragile so the patient can end up with a hemolytic anemia.
This can occur as pure disease (homozygous) or trait (heterozygous) or with other haemoglobinopathies. It is common. in Negroes. It is due to Hb-s which is much less soluble than Hb-A hence deoxygenation insoluble form sickling of RBC.
This causes:
• Removal by RE system.
• Blockage of microvessels causing ischaemia.
Immunoglobulins. (Ig)
These are made up of polypeptide chains. Each molecule is constituted by two heavy and two light chains, linked by disulfide (S-S) bonds. The h~ chains are of 5 types, with corresponding, types or immunoglobulin. IgG (gamma), IgM (mu µ ), IgA(alpha α), IgD(delta ), IgE(epsilon)
Each of these can have light chains of either kappa (k) or lambda type.Each chain has a constant portion (constant for the subtype) land a variable portion (antigen specific).
Enzyme digestion can split the Ig molecule into.2 Fab (antibody binding) fragments and one Fc (crystallisable, complement binding ) fragment.
Hepatitis D virus—can only infect cells previously infected with hepatitis B.
Delta hepatitis (HDV) is associated with a 35-nm RNA virus composed of a delta antigen-bearing core surrounded by HBV's Ag coat;
HDV requires HBV for replication.
Delta hepatitis can cause quiescent HBV states to suddenly worsened . Its transmission is the same as that of HBV.
Hepatitis E virus—a high mortality rate in infected pregnant women.
Hepatitis E (HEV) is caused by a single-stranded RNA virus. The disease is typically self-limited and does not evolve into chronic hepatitis; it may, however, be cholestatic.
Pregnant women may develop fulminant disease.
Transmission is by the fecal oral route.
HEV occurs mainly in India, Nepal, Pakistan, and Southeast Asia.
HYPERPLASIA
It is the increase in the size of an organ or tissue due to increase in the number of its constituent cells. This is seen in organs made up of labile and stable cells.
Causes
I. Increased demand:
- Bone marrow in hypoxia and haemolytic states.
- Thyroid gland in puberty
2. Persistant Trauma:
- Acanthosis of the epidermis in chronic inflammations and in warts.
- Hyperplasia of oral mucosa due tooth and denture trauma.
- Mucosa at the edges of a gastric ulcer.
3. Endocrine target organ:
- Pregnancy hyperplasia of breast.
- Prostatic hyperplasia.
4. Compensatory:
Hyperplasia of kidney when the other kidney has been removed.
5. Idiopathic:
Endocrine organs like thyroid, adrenals, pituitary etc. can undergo hyperplasia with no detectable stimulus. .
Cytopathologic techniques
Cytopathology is the study of cells from various body sites to determine the cause or nature of disease.
Applications of cytopathology:
- Screening for the early detection of asymptomatic cancer
2. Diagnosis of symptomatic cancer
3. Surveillance of patients treated for cancer
Cytopathologic methods
There are different cytopathologic methods including:
1. Fine-needle aspiration cytology (FNAC) -In FNAC, cells are obtained by aspirating the diseased organ using a very thin needle under negative pressure.
Superficial organs (e.g. thyroid, breast, lymph nodes, skin and soft tissues) can be easily aspirated.
Deep organs, such as the lung, mediastinum, liver, pancreas, kidney, adrenal gland, and retroperitoneum are aspirated with guidance by fluoroscopy, ultrasound or CT scan.
- Exfoliative cytology
Refers to the examination of cells that are shed spontaneously into body fluids or secretions. Examples include sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.
- Abrasive cytology
Refers to methods by which cells are dislodged by various tools from body surfaces (skin, mucous membranes, and serous membranes). E.g. preparation of cervical smears with a spatula or a small brush to detect cancer of the uterine cervix at early stages.