3. Biology Notes 05

Elaborate Notes

Immunity and its Types

The human body’s ability to resist disease-causing organisms or pathogens is known as immunity. It is broadly categorized into innate (non-specific) and adaptive (acquired/specific) immunity. The provided summary focuses on adaptive immunity, which is pathogen-specific and characterized by immunological memory.

• Discussion of PYQ on B cells and T cells: The question correctly identifies the primary function of B and T cells. These are types of lymphocytes (a subset of white blood cells) and are the principal agents of the adaptive immune system.

  • B cells (B lymphocytes): They are responsible for humoral immunity (or antibody-mediated immunity). Upon encountering a specific antigen, B cells differentiate into plasma cells, which produce and secrete large quantities of antibodies. These antibodies circulate in the blood and lymph (body humors), binding to pathogens and marking them for destruction. A subset of B cells becomes memory B cells, providing long-term immunity. This principle was foundational to the work of Paul Ehrlich (early 20th century), who proposed the “side-chain theory” to explain antibody formation.
  • T cells (T lymphocytes): They are responsible for cell-mediated immunity. They mature in the thymus gland. T cells do not produce antibodies but act directly against infected cells or help orchestrate the immune response. There are several types, including Helper T cells (which activate B cells and other T cells) and Cytotoxic T cells (which identify and kill pathogen-infected host cells). This dual nature of adaptive immunity was elucidated by researchers like Robert A. Good in the mid-20th century.

• Adaptive/Acquired Immunity: This immunity is acquired during an individual’s lifetime.

  • I. Active Immunity: The body’s own immune system is stimulated to produce antibodies and memory cells.
    • Natural Active Immunity: This develops after a person is infected with a pathogen, recovers, and develops long-lasting immunity. For example, recovering from chickenpox (caused by the Varicella-zoster virus) usually confers lifelong immunity.
    • Artificial Active Immunity: This is induced through vaccination. A vaccine introduces a harmless form of a pathogen or its antigen (e.g., inactivated virus, attenuated virus, protein subunit) into the body. This stimulates an immune response without causing the disease. The concept of vaccination was pioneered by Edward Jenner in 1796 when he used cowpox material to protect against smallpox.
  • II. Passive Immunity: The body receives pre-formed antibodies from an external source. It provides immediate but temporary protection as the body does not produce its own memory cells.
    • Natural Passive Immunity: This occurs when antibodies are transferred from mother to fetus across the placenta (IgG antibodies) or to the infant through breast milk, particularly colostrum (the first milk), which is rich in IgA antibodies.
    • Artificial Passive Immunity: This involves the administration of antibodies from an immune person or animal. Examples include:
      • Plasma Therapy (Convalescent Plasma Therapy): Plasma from individuals who have recovered from a disease (e.g., COVID-19) is transfused to a sick patient. This plasma contains antibodies against the specific pathogen.
      • Monoclonal Antibodies: These are laboratory-produced antibodies designed to target a specific antigen. They are used to treat various diseases, including some cancers and viral infections. The technology for their production was developed by Georges Köhler and César Milstein in 1975, for which they won a Nobel Prize.
      • Antitoxins: Administration of antivenom for a snakebite is a classic example. The antivenom contains antibodies against the snake’s venom. Emil von Behring developed an antitoxin for diphtheria in the 1890s, earning him the first Nobel Prize in Physiology or Medicine in 1901.

Blood and its Components

Blood is a specialized fluid connective tissue essential for transporting oxygen, nutrients, hormones, and waste products. It comprises plasma and formed elements (cells).

• Plasma: This is the straw-colored liquid matrix of blood, constituting about 55% of blood volume. It is primarily water (about 92%) but also contains vital proteins, glucose, clotting factors, hormones, and electrolytes.

  • Plasma Proteins: These are typically globular (functional) proteins.
    • Albumin: The most abundant plasma protein, it is crucial for maintaining the colloid osmotic pressure (oncotic pressure) of the blood, which prevents fluid from leaking out of the blood vessels.
    • Globulin: This group includes alpha, beta, and gamma globulins. The gamma globulins are the immunoglobulins, i.e., antibodies, and are central to the body’s defense mechanism.
    • Fibrinogen: A key protein in the blood clotting cascade. It is converted into insoluble fibrin threads to form a clot at the site of an injury.

• Red Blood Cells (RBCs) or Erythrocytes:

  • These are biconcave, anucleated (in mammals) discs specialized for oxygen transport. Their primary component is hemoglobin, an iron-containing protein.
  • The iron atom in the heme group of hemoglobin binds to oxygen in the lungs and releases it in the tissues. This iron is what gives blood its characteristic red color.
  • The oxygen delivered to cells is used in cellular respiration to produce Adenosine Triphosphate (ATP), the primary energy currency of the cell.

• Platelets or Thrombocytes:

  • These are not true cells but small, irregular fragments of large cells called megakaryocytes, found in the bone marrow.
  • They play a critical role in hemostasis (stopping bleeding). When a blood vessel is damaged, platelets adhere to the site, form a temporary plug, and release factors that initiate the clotting cascade.
  • This cascade involves a series of enzymatic reactions culminating in the conversion of fibrinogen to fibrin, which forms a mesh to trap RBCs and form a stable clot. Vitamin K is essential for the synthesis of several clotting factors in the liver.
  • In diseases like Dengue, the virus can suppress bone marrow and lead to antibody-mediated destruction of platelets, causing a sharp drop in platelet count (thrombocytopenia), which can lead to life-threatening hemorrhages.

• White Blood Cells (WBCs) or Leucocytes:

  • These are the mobile units of the body’s immune system. They are classified based on the presence or absence of granules in their cytoplasm.
  • I. Agranulocytes (no granules):
    • Lymphocytes: Comprise B cells and T cells, the main players in adaptive immunity.
    • Monocytes: The largest WBCs, they are phagocytic. They circulate in the blood for a few days before migrating into tissues, where they differentiate into macrophages, which engulf pathogens and cellular debris as part of innate immunity.
  • II. Granulocytes (with granules):
    • Neutrophils: The most abundant type of WBC. They are highly phagocytic and are typically the first responders to the site of an infection or inflammation (innate immunity).
    • Basophils: Release histamine and other mediators of inflammation; involved in allergic responses.
    • Eosinophils: Combat multicellular parasites and are also involved in allergic reactions.

Blood Groups

• The classification of blood is based on inherited antigenic substances on the surface of RBCs.
  • Antigen: A molecule (usually a protein or polysaccharide) on the surface of a cell that can trigger an immune response.
  • Antibody: A Y-shaped protein produced by plasma cells that identifies and neutralizes foreign objects like pathogens and their antigens.
• ABO System: Discovered by Karl Landsteiner in 1901. It is based on the presence or absence of two antigens, A and B, on the RBC surface. The plasma contains naturally occurring antibodies against the antigens that are absent on the RBCs.
  • Blood Group A: Has A antigen on RBCs and Anti-B antibody in plasma.
  • Blood Group B: Has B antigen on RBCs and Anti-A antibody in plasma.
  • Blood Group AB: Has both A and B antigens on RBCs and no antibodies in plasma.
  • Blood Group O: Has no antigens on RBCs and both Anti-A and Anti-B antibodies in plasma.
• Rhesus (Rh) Factor: An additional antigen (Antigen D) on the RBC surface. It was co-discovered by Landsteiner and Alexander Wiener in 1940 in Rhesus monkeys.
  • Rh-positive (Rh+): The Rh antigen is present.
  • Rh-negative (Rh-): The Rh antigen is absent. Unlike the ABO system, anti-Rh antibodies are not naturally present; they are produced only upon exposure to Rh+ blood.
• Blood Transfusion:
  • The core principle is to avoid a reaction between the donor’s antigens and the recipient’s antibodies.
  • Universal Donor: O negative (O-) blood is considered the universal donor because its RBCs have no A, B, or Rh antigens to be attacked by the recipient’s antibodies.
  • Universal Recipient: AB positive (AB+) is considered the universal recipient because their plasma contains no Anti-A, Anti-B, or Anti-Rh antibodies to attack the donor’s RBCs.
• Golden Blood Group (Rh-null): An extremely rare blood type where individuals lack all antigens within the Rh system. First identified in an Aboriginal Australian woman in 1961. Its rarity makes it precious for transfusions but also makes it very difficult for individuals with this blood type to find a compatible donor.
• Rh Incompatibility in Pregnancy (Erythroblastosis Fetalis):
  • This condition can arise if an Rh-negative mother carries an Rh-positive fetus.
  • During the first pregnancy, there is typically no issue. However, at delivery, some of the fetus’s Rh+ blood can enter the mother’s circulation, sensitizing her immune system to produce anti-Rh antibodies.
  • In subsequent pregnancies with an Rh+ fetus, these maternal anti-Rh antibodies (being IgG) can cross the placenta and attack the fetus’s RBCs, leading to severe anemia, jaundice, and potential fetal death.
  • This is now preventable by administering an injection of RhoGAM (anti-Rh antibodies) to the Rh- mother shortly after the delivery of an Rh+ baby. This injection destroys any fetal Rh+ cells in her system before she can produce her own antibodies and memory cells.

Genetics

• Genetic Material: The material responsible for heredity, passing traits from one generation to the next.

  • The discovery that DNA is the genetic material was a culmination of work, including the Avery–MacLeod–McCarty experiment (1944) and the Hershey–Chase experiment (1952).

• Nucleic Acids (DNA and RNA):

  • Polymers made of repeating monomer units called nucleotides. Each nucleotide has three components:
    1. Phosphate Group
    2. Pentose Sugar: Deoxyribose in DNA, Ribose in RNA.
    3. Nitrogenous Base:
       • Purines: Adenine (A), Guanine (G).
       • Pyrimidines: Cytosine (C), Thymine (T) in DNA, Uracil (U) in RNA.

• DNA (Deoxyribonucleic Acid):

  • Typically a double-stranded helix.
  • The structure was famously elucidated by James Watson and Francis Crick in 1953, based on the X-ray diffraction images produced by Rosalind Franklin and the base-pairing rules discovered by Erwin Chargaff.
  • Structure: Two polynucleotide chains are coiled around each other. The “backbone” of each chain is made of alternating sugar and phosphate groups. The nitrogenous bases are attached to the sugar and project inwards.
  • Complementary Base Pairing: Adenine (A) always pairs with Thymine (T) via two hydrogen bonds. Guanine (G) always pairs with Cytosine (C) via three hydrogen bonds. This specific pairing is the key to DNA’s ability to replicate accurately.

• RNA (Ribonucleic Acid):

  • Typically single-stranded.
  • Contains the sugar ribose and the base Uracil (U) instead of Thymine. Uracil pairs with Adenine.

• Gene Expression (The Central Dogma):

  • The process by which information from a gene is used to synthesize a functional product, like a protein. This concept was articulated by Francis Crick in 1958.
  • A gene is a specific sequence of DNA that codes for a functional molecule.
  • 1. Transcription: The DNA sequence of a gene is copied into a complementary messenger RNA (mRNA) molecule. This occurs in the nucleus of eukaryotic cells.
  • 2. Translation: The genetic code on the mRNA molecule is read by ribosomes in the cytoplasm. The ribosome facilitates the synthesis of a specific protein by linking amino acids in the correct order as dictated by the mRNA sequence.

• Viruses and Genetic Material:

  • Viruses are obligate intracellular parasites that can have either DNA or RNA as their genetic material.
    • DNA Viruses: Adenovirus, Herpesvirus (Chickenpox).
    • RNA Viruses:
      • Non-Retrovirus: Their RNA genome can often act directly as mRNA for translation into proteins. Examples include Coronaviruses (SARS-CoV-2), Dengue virus, Influenza virus.
      • Retrovirus: These are special RNA viruses (e.g., HIV). They possess an enzyme called reverse transcriptase, which synthesizes a DNA copy of their RNA genome. This DNA is then integrated into the host cell’s genome, from where it is transcribed and translated. The discovery of reverse transcriptase by Howard Temin and David Baltimore in 1970 was a landmark finding.

• Genetic Material-based Vaccines:

  • I. DNA Vaccine: A plasmid containing the DNA sequence for a specific antigen is injected. The host cells take up this DNA, transcribe it to mRNA, and then translate it into the antigen protein, triggering an immune response. Example: Zydus Cadila’s ZyCoV-D for COVID-19.
  • II. mRNA Vaccine: An mRNA sequence coding for the antigen is encapsulated in a lipid nanoparticle and injected. The host cells’ ribosomes directly translate this mRNA into the antigen, eliciting an immune response. This bypasses the transcription step, potentially leading to a faster response. Examples: Pfizer-BioNTech and Moderna COVID-19 vaccines.

• Replication and Mutation:

  • Replication: The process of copying DNA before cell division. DNA replication is remarkably accurate because the enzyme DNA polymerase has a “proofreading” function, correcting most errors.
  • Most RNA viruses lack this proofreading mechanism in their replication process. This leads to a much higher mutation rate. This high rate of mutation is responsible for the emergence of new variants of viruses like influenza and SARS-CoV-2.
  • The high mutation rate of HIV, a retrovirus, is a primary reason for the difficulty in developing a vaccine. The virus changes its surface antigens so rapidly that the immune system (and any vaccine-induced response) cannot keep up.

• Genome and Genome Sequencing:

  • Genome: The entire set of genetic material (DNA) in an organism.
  • Genome Sequencing: The process of determining the precise order of nucleotides (A, T, C, G) within a genome. This allows scientists to identify genes, understand their function, and pinpoint mutations associated with diseases. The Human Genome Project, an international research effort completed in 2003, was a monumental achievement that sequenced the entire human genome.

Prelims Pointers

• B cells: Responsible for antibody-mediated (humoral) immunity. They produce antibodies.
• T cells: Responsible for cell-mediated immunity. They attack infected cells directly.
• Active Immunity: The body produces its own antibodies. It is long-lasting. Examples: Post-infection immunity, Vaccination.
• Passive Immunity: The body receives ready-made antibodies. It is short-lived. Examples: Mother to fetus/infant, Antivenom injection.
• Colostrum: The first milk produced after birth, rich in IgA antibodies.
• Plasma Proteins:
  • Albumin: Maintains blood osmotic pressure.
  • Globulin: Defense mechanism (antibodies).
  • Fibrinogen: Blood clotting.
• RBCs (Erythrocytes): Transport oxygen via hemoglobin, which contains iron.
• ATP (Adenosine Triphosphate): The energy currency of the cell.
• Platelets (Thrombocytes): Cell fragments essential for initiating blood clotting.
• Vitamin K: Essential for the synthesis of clotting factors.
• WBCs (Leucocytes):
  • Agranulocytes: Lymphocytes (B and T cells), Monocytes (become macrophages).
  • Granulocytes: Neutrophils, Basophils, Eosinophils.
• Blood Group Antigens: Located on the surface of Red Blood Cells.
• Blood Group Antibodies: Located in the Blood Plasma.
• ABO Blood Group System: Discovered by Karl Landsteiner (1901).
• Universal Donor: Blood group O-negative. Reason: No A, B, or Rh antigens on RBCs.
• Universal Recipient: Blood group AB-positive. Reason: No anti-A, anti-B, or anti-Rh antibodies in plasma.
• Rh-null Blood Group: Known as “Golden Blood,” it lacks all Rh antigens. It is the rarest blood type.
• Erythroblastosis Fetalis: A condition in an Rh+ fetus due to antibodies from an Rh- mother.
• Genetic Material: DNA (in most organisms), RNA (in some viruses).
• DNA Bases: Adenine (A), Guanine (G), Cytosine (C), Thymine (T).
• RNA Bases: Adenine (A), Guanine (G), Cytosine (C), Uracil (U).
• DNA Base Pairing Rule: A pairs with T; G pairs with C.
• RNA Base Pairing Rule: A pairs with U; G pairs with C.
• DNA Structure: Double Helix model proposed by Watson and Crick (1953).
• Central Dogma of Molecular Biology: DNA → (Transcription) → RNA → (Translation) → Protein.
• Retrovirus: An RNA virus that replicates via a DNA intermediate using an enzyme called reverse transcriptase. Example: HIV.
• DNA Vaccine Example (COVID-19): ZyCoV-D by Zydus Cadila.
• mRNA Vaccine Examples (COVID-19): Pfizer-BioNTech, Moderna.
• Genome: The complete set of an organism’s DNA.

Mains Insights

GS Paper III: Science & Technology in Everyday Life, Biotechnology, Public Health

1. Vaccine Technology and Public Health Strategy:

   • Cause-Effect: The development of novel vaccine platforms like mRNA and DNA vaccines (as seen with COVID-19) has drastically reduced vaccine development timelines. This rapid development capability is crucial for pandemic preparedness.
   • Analysis: India’s vaccine strategy (e.g., using traditional inactivated virus vaccines like Covaxin, viral vector vaccines like Covishield, and now DNA vaccines like ZyCoV-D) reflects a diversified approach. This diversification mitigates risks associated with a single technology and addresses different logistical needs (e.g., mRNA vaccines require ultra-cold storage, which is a challenge in rural India).
   • Debate: The debate over intellectual property rights (IPR) and the TRIPS waiver for COVID-19 vaccines highlights the tension between incentivizing innovation (through patents) and ensuring global vaccine equity. The technology behind mRNA vaccines is a focal point of this debate.

2. Blood Safety and Management:

   • Analysis: Understanding blood groups, the Rh factor, and transfusion principles is fundamental to public health. The concept of a “universal donor” (O-) is critical in emergency medicine. This underscores the need for robust blood donation programs, efficient blood banking systems, and public awareness campaigns to maintain a safe and adequate blood supply.
   • Challenges: Despite scientific understanding, challenges in India include a fragmented blood transfusion service, lack of centralized data, and reliance on replacement donors over voluntary donors, which can compromise blood safety.

3. Genomics and its Applications:

   • Cause-Effect: Genome sequencing allows for a deeper understanding of genetic diseases, pathogen evolution, and personalized medicine. Sequencing viral genomes (like SARS-CoV-2) helps track the emergence and spread of new variants, informing public health responses and vaccine updates.
   • Future Perspective: The application of genomics in India (e.g., IndiGen program) can revolutionize healthcare by enabling predictive diagnosis, targeted therapies, and a better understanding of the genetic basis of diseases prevalent in the Indian population. However, it requires significant investment in infrastructure and skilled human resources.

GS Paper II: Social Justice, Health

1. Health Equity and Access:
   • Analysis: The case of Rh incompatibility (Erythroblastosis fetalis) and its prevention through RhoGAM injections exemplifies how medical advancements can prevent disease. However, access to such essential antenatal care is a matter of health equity. Disparities in access between urban and rural areas, or rich and poor, can lead to preventable infant mortality.
   • Connection: The high cost of advanced treatments like monoclonal antibodies or future gene therapies raises critical questions about accessibility and affordability, potentially widening the health gap in society.

GS Paper IV: Ethics

1. Ethical Dilemmas in Genetics:
   • Debate: Genome sequencing, while beneficial, raises profound ethical questions. The “right to know” versus the “right not to know” one’s genetic predispositions is a major dilemma.
   • Concerns: There is a significant risk of genetic discrimination by employers or insurance companies. The privacy and security of vast amounts of personal genetic data are paramount concerns, necessitating strong regulatory frameworks like the proposed DNA Technology (Use and Application) Regulation Bill.
   • Human Enhancement: The potential to move from treating genetic diseases to enhancing human traits (“designer babies”) opens a Pandora’s box of ethical, social, and philosophical issues that society must grapple with.