BZYET-141 Solved Assignment

1. a) List various innate immune system barriers and protection mechanisms.
   b) Give a brief account of the secondary lymphoid organs of the Immune System.
2. a) What is immune deficiency? Explain how our immune system prevents autoimmunity?
   b) What are the different types of hypersensitivity, according to Gell and Coombs? Briefly explain.
3. Define the following terms:
   i) Mucosa Associated Lymphoid Tissue (MALT)
   ii) Haematopoiesis
   iii) Hinge region of the antibody
   iv) Human Leucocyte Antigen (HLA)
4. Write short notes on the following:
   i) Monoclonal antibodies
   ii) Opsonization
   iii) DNA Vaccines
   iv) Agglutination Reactions
5. Differentiate between the following pairs of terms:
   i) Helper " $T$$T$TT$T$ " cells and cytotoxic " $T$$T$TT$T$ " cells
   ii) Active and Passive immunity
   iii) MHC class-I and II molecules
   iv) Self and non-self antigens
6. What is the vaccine? Explain the mode of action of vaccine. Write about the advantages and disadvantages of vaccination.
7. a) Write the various steps in the establishment of bacterial infection.
   b) Explain the neutralization mechanism of bacteria by antibodies.
8. a) Define autoimmunity. Describe any two autoimmune disorders.

Answer:

a) List various innate immune system barriers and protection mechanisms.

Answer:

1. Physical Barriers

• Skin: The outermost layer of the skin, the epidermis, acts as a tough, impermeable barrier to microorganisms. Its keratinized surface is difficult for bacteria, viruses, and fungi to penetrate.
• Mucous Membranes: The lining of body cavities that open to the outside (e.g., respiratory, gastrointestinal, and urogenital tracts) produces mucus, which traps pathogens. These membranes also contain cilia that help expel microorganisms from the body (e.g., in the respiratory tract).
• Coughing and Sneezing: Reflex actions like coughing and sneezing help expel pathogens from the respiratory tract.

2. Chemical Barriers

• Sebum: Produced by sebaceous glands in the skin, sebum contains fatty acids that inhibit microbial growth and provide a slightly acidic environment.
• Acidic pH: The skin, stomach, and vagina have an acidic pH that is hostile to many microorganisms. For instance, stomach acid (gastric acid) kills most ingested pathogens.
• Lysozyme: An enzyme found in tears, saliva, and mucus, lysozyme breaks down bacterial cell walls, leading to the destruction of certain bacteria.
• Defensins: These small peptides, present in various bodily fluids and tissues, disrupt the membranes of bacteria, fungi, and viruses.
• Acidic Urine: The low pH of urine helps prevent the growth of pathogens in the urinary tract.

3. Cellular Barriers

• Phagocytes: These are immune cells that engulf and digest pathogens, dead cells, and debris.
  • Macrophages: Found throughout the body, macrophages recognize pathogens via pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), and ingest them.
  • Neutrophils: The most abundant white blood cells, neutrophils quickly respond to infections, migrating to the site of infection and engulfing microbes.
  • Dendritic Cells: These cells are important for both the innate immune response and the initiation of the adaptive immune response. They act as antigen-presenting cells that can trigger adaptive immunity after phagocytosis.
• Natural Killer (NK) Cells: NK cells are a subset of lymphocytes that recognize and kill infected or tumor cells by inducing apoptosis (programmed cell death). They are effective against certain viral and cancerous cells.

4. Inflammatory Response

• Vasodilation: Inflammation causes the blood vessels near the site of infection to dilate, increasing blood flow, which allows more immune cells (e.g., neutrophils and macrophages) to reach the site.
• Increased Vascular Permeability: The permeability of blood vessels increases, allowing immune cells and proteins like antibodies and clotting factors to pass into the affected tissue.
• Cytokines and Chemokines: These signaling molecules are released during inflammation and attract immune cells to the site of infection. Interleukins, tumor necrosis factor (TNF), and interferons are examples of cytokines involved in the inflammatory response.

5. Complement System

• Classical Pathway: This is activated by the binding of antibodies to pathogens, leading to the formation of a complex that promotes pathogen destruction.
• Alternative Pathway: This pathway is triggered by pathogen surfaces and leads to the formation of a membrane attack complex (MAC) that creates holes in the pathogen’s membrane, causing lysis.
• Lectin Pathway: This pathway is activated by lectins (carbohydrate-binding proteins) that bind to sugar molecules on pathogens, leading to complement activation.
• Opsonization: Complement proteins bind to the surface of pathogens, tagging them for phagocytosis by immune cells.

6. Acute-Phase Proteins

• C-reactive protein (CRP): CRP levels rise during infections and act as an opsonin to help phagocytes recognize and destroy pathogens.
• Fibrinogen: This protein plays a key role in blood clotting and helps form fibrin clots to limit the spread of pathogens.
• Mannose-binding lectin (MBL): This protein binds to sugars on the surface of pathogens, promoting complement activation and pathogen clearance.

7. Interferons

• Type I Interferons (e.g., interferon-alpha, interferon-beta): These are released by infected cells and bind to receptors on neighboring cells, inducing the expression of antiviral proteins that inhibit viral replication.
• Type II Interferon (interferon-gamma): Produced by immune cells like NK cells and T lymphocytes, interferon-gamma enhances the ability of phagocytes to destroy pathogens.

8. Fever

• Temperature Increase: A higher body temperature creates an environment less favorable for the growth and replication of many pathogens.
• Immune Activation: Fever also enhances the activity of immune cells, such as phagocytes, and increases the production of certain immune molecules like interferons.

9. Molecular Pattern Recognition

• Pattern Recognition Receptors (PRRs): PRRs, such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), are expressed on the surface or inside of immune cells. These receptors detect PAMPs and trigger the activation of immune responses, including the release of cytokines and the recruitment of immune cells.

10. The Role of the Gut Microbiota

• Competitive Exclusion: The normal microbiota competes with pathogenic microbes for nutrients and space, preventing pathogen colonization.
• Production of Antimicrobial Compounds: Certain beneficial microbes produce substances like bacteriocins that directly inhibit the growth of harmful bacteria.

b) Give a brief account of the secondary lymphoid organs of the Immune System.

Answer:

1. Lymph Nodes

• Structure: Lymph nodes are composed of an outer cortex, containing B cells, and an inner medulla, where T cells and other immune cells are found.
• Function: Lymph nodes filter lymph fluid from surrounding tissues, trapping pathogens, debris, and foreign particles. They are sites where B cells can encounter antigens and differentiate into plasma cells, while T cells can be activated to respond to pathogens.

2. Spleen

• Structure: The spleen consists of two main regions: the white pulp, which contains immune cells such as B cells and T cells, and the red pulp, which is involved in filtering blood and recycling iron from red blood cells.
• Function: The spleen filters blood by removing old or damaged red blood cells and pathogens. It is also a major site for the activation of immune responses, especially against blood-borne pathogens.

3. Mucosa-Associated Lymphoid Tissue (MALT)

• Tonsils: Lymphoid tissues located in the pharyngeal region that help protect against pathogens entering through the mouth or nose.
• Peyer’s Patches: Located in the small intestine, these structures contain clusters of lymphoid follicles that help defend against gastrointestinal pathogens.
• Appendix: The appendix is a lymphoid organ located at the junction of the small and large intestines, believed to play a role in immune surveillance in the gastrointestinal system.
• Function: MALT serves as the first line of defense against pathogens that enter through mucosal surfaces. It helps initiate immune responses to pathogens in the respiratory, digestive, and urogenital systems, where most infections begin.

4. Lymphatic Vessels

• Function: Lymphatic vessels provide the means for immune cells to travel between secondary lymphoid organs and to areas of infection or injury, allowing rapid immune responses.

Conclusion

a) What is immune deficiency? Explain how our immune system prevents autoimmunity?

Answer:

• Genetic Mutations: Primary immune deficiencies often stem from inherited genetic mutations that affect the development or function of immune cells. Examples include severe combined immunodeficiency (SCID), in which both T cells and B cells are affected, or X-linked agammaglobulinemia (XLA), a condition that leads to a lack of mature B cells.
• Infections: Certain infections, especially HIV, can lead to acquired immune deficiency. HIV attacks CD4+ T cells, a type of white blood cell crucial for immune function, progressively weakening the immune system and eventually leading to AIDS (Acquired Immunodeficiency Syndrome).
• Medications: Immunosuppressive drugs, often used in organ transplants or to treat autoimmune diseases, can suppress the immune system’s ability to fight infections. Chemotherapy, used to treat cancer, also weakens the immune system by killing rapidly dividing cells, including immune cells.
• Malnutrition: Adequate nutrition is vital for maintaining a strong immune system. Malnutrition, especially deficiencies in vitamins and minerals like vitamin A, C, D, and zinc, can compromise immune function and make the body more susceptible to infections.
• Environmental Factors: Chronic exposure to certain toxins, chemicals, or radiation can also weaken the immune system.

• Primary Immunodeficiencies: These are rare and typically caused by genetic mutations affecting immune cells or proteins.
  • Humoral Immunodeficiencies: These impair B cells and their ability to produce antibodies, making the body more susceptible to bacterial infections.
  • Cellular Immunodeficiencies: These affect T cells, which play a key role in responding to viral infections and in regulating immune responses.
  • Combined Immunodeficiencies: These affect both B and T cells, leading to severe immunodeficiency, as seen in conditions like SCID.
• Secondary Immunodeficiencies: These are more common and result from environmental or external factors.
  • HIV/AIDS: A viral infection that causes immune system dysfunction by targeting and destroying CD4+ T cells.
  • Medications and Cancer Treatment: Drugs or treatments that suppress the immune system, leaving individuals vulnerable to infections.
  • Chronic Diseases: Conditions like diabetes or cancer can lead to weakened immune responses, increasing susceptibility to infections.

Central Tolerance

• T Cell Negative Selection: In the thymus, developing T cells undergo a process called negative selection, where any T cell that strongly binds to self-antigens presented by thymic cells is induced to die (apoptosis). This prevents the release of self-reactive T cells into circulation.
• B Cell Negative Selection: In the bone marrow, developing B cells that bind to self-antigens are either eliminated or rendered inactive. This ensures that mature B cells will produce antibodies only against non-self antigens.

Peripheral Tolerance

• Regulatory T Cells (Tregs): Tregs are specialized T cells that play a crucial role in suppressing immune responses. They can inhibit the activation of self-reactive T cells, preventing them from attacking the body’s own tissues. Tregs maintain immune homeostasis by recognizing self-antigens and regulating immune responses to prevent autoimmunity.
• Clonal Anergy: This occurs when self-reactive T or B cells encounter self-antigens but fail to receive the necessary co-stimulatory signals required for full activation. As a result, these cells become anergic (inactive) and are unable to mount an immune response against self-tissues.
• Activation-Induced Cell Death (AICD): Self-reactive T cells that become activated in the presence of self-antigens undergo programmed cell death (apoptosis). This mechanism ensures that once immune cells respond to a self-antigen, they do not persist and cause damage to healthy tissues.
• Checkpoint Inhibitors: Immune checkpoints are molecules that regulate immune responses to prevent overactivity. For example, the PD-1/PD-L1 pathway helps prevent T cells from attacking self-tissues by inhibiting their activation once they recognize self-antigens.

Immune Privilege Sites

• Blood-Brain Barrier: The blood-brain barrier restricts the entry of immune cells into the brain, limiting the chances of autoimmunity in the central nervous system.
• Immunosuppressive Cytokines: Immune-privileged sites often produce immunosuppressive cytokines that dampen immune responses and prevent inflammation, reducing the likelihood of tissue damage from autoimmune attacks.

• Genetic Predisposition: Certain genetic factors, such as specific alleles of the human leukocyte antigen (HLA) genes, increase the risk of autoimmune diseases by altering immune cell recognition of self-antigens.
• Environmental Triggers: Infections, drugs, or toxins can trigger autoimmune responses by causing changes in self-antigens or by stimulating immune cells in ways that promote autoimmunity. For example, viral infections may mimic self-antigens, leading to molecular mimicry, where the immune system mistakenly targets both the pathogen and the body’s own tissues.
• Failure of Regulatory Mechanisms: If mechanisms like regulatory T cell function or checkpoint inhibition are impaired, self-reactive immune cells may be able to attack the body’s tissues, leading to autoimmune diseases.

b) What are the different types of hypersensitivity, according to Gell and Coombs? Briefly explain.

Answer:

• Mechanism: When an individual is sensitized to an allergen (e.g., pollen, pet dander, or certain foods), the immune system produces IgE antibodies specific to that allergen. Upon subsequent exposure, the allergen binds to the IgE on the surface of mast cells and basophils, triggering the release of histamine and other inflammatory mediators. These mediators cause the symptoms associated with allergic reactions, such as swelling, redness, itching, and bronchoconstriction.
• Clinical Manifestations: Type I hypersensitivity can manifest in a variety of ways, including:
  • Allergic rhinitis (hay fever): Sneezing, nasal congestion, and itching.
  • Asthma: Wheezing, shortness of breath, and coughing due to bronchoconstriction.
  • Urticaria (hives): Raised, red welts on the skin.
  • Anaphylaxis: A severe, systemic reaction that can lead to shock, respiratory failure, and even death if untreated. It requires immediate medical intervention, typically with epinephrine.
• Treatment: Antihistamines, corticosteroids, and allergen immunotherapy (allergy shots) can help manage Type I hypersensitivity. In severe cases, epinephrine is used to reverse anaphylactic reactions.

• Mechanism: In Type II hypersensitivity, antibodies recognize specific antigens on the surface of host cells (such as red blood cells, platelets, or tissue cells). The immune system then mounts a response that can destroy these cells through the activation of the complement system or phagocytosis by macrophages. This can result in cell lysis or dysfunction.
• Clinical Manifestations: Common conditions associated with Type II hypersensitivity include:
  • Autoimmune hemolytic anemia: Destruction of red blood cells leading to anemia.
  • Blood transfusion reactions: If a person receives an incompatible blood type, antibodies attack the transfused red blood cells, leading to hemolysis.
  • Goodpasture syndrome: An autoimmune disorder where antibodies attack the basement membrane of the lungs and kidneys, leading to renal and pulmonary damage.
  • Graves’ disease and Myasthenia gravis: Both are examples of autoimmune disorders where antibodies activate or inhibit normal cellular functions, leading to overactive or underactive organs.
• Treatment: The management of Type II hypersensitivity typically involves removing or neutralizing the offending antibodies (e.g., using plasmapheresis or immunosuppressive therapies) and addressing the symptoms of organ damage.

• Mechanism: When antigen-antibody complexes form in the bloodstream, they can deposit in various tissues, such as the kidneys, joints, and blood vessels. These deposits trigger the activation of the complement system and recruit neutrophils to the site of deposition. The subsequent release of inflammatory mediators (e.g., proteases and reactive oxygen species) leads to tissue injury, inflammation, and the development of disease.
• Clinical Manifestations: Type III hypersensitivity is associated with diseases that involve systemic inflammation and tissue damage. Common examples include:
  • Systemic lupus erythematosus (SLE): A systemic autoimmune disease in which immune complexes deposit in the kidneys, joints, and skin, leading to nephritis, arthritis, and rashes.
  • Rheumatoid arthritis: Chronic inflammation of the joints due to immune complex deposition.
  • Serum sickness: A reaction that occurs after receiving certain medications (e.g., antiserum), where immune complexes deposit in tissues and cause fever, rashes, and joint pain.
  • Polyarteritis nodosa: A vasculitis in which immune complexes deposit in blood vessel walls, causing inflammation and damage.
• Treatment: Type III hypersensitivity reactions are treated with anti-inflammatory drugs, immunosuppressive medications, and plasma exchange in severe cases to remove circulating immune complexes.

• Mechanism: In Type IV hypersensitivity, T cells recognize and respond to an antigen, releasing cytokines that recruit and activate macrophages and other immune cells to the site of exposure. This leads to tissue damage due to the release of inflammatory cytokines, enzymes, and free radicals by macrophages. Unlike other hypersensitivity types, there are no antibodies involved.
• Clinical Manifestations: Type IV hypersensitivity reactions are associated with chronic inflammatory conditions. Examples include:
  • Contact dermatitis: A skin reaction caused by exposure to allergens like poison ivy, nickel, or certain chemicals. It involves CD4+ T cell activation and macrophage infiltration.
  • Tuberculin skin test (Mantoux test): A diagnostic test for tuberculosis that induces a localized Type IV hypersensitivity response in individuals previously exposed to Mycobacterium tuberculosis.
  • Chronic transplant rejection: A delayed immune response to a transplanted organ, where T cells recognize the transplanted tissue as foreign and mount an immune response against it.
• Treatment: Type IV hypersensitivity is typically managed with topical corticosteroids, systemic immunosuppressive agents, and antihistamines in certain cases. The primary focus is to reduce inflammation and control symptoms.

a) Define Mucosa Associated Lymphoid Tissue (MALT).

Answer:

b) Define Haematopoiesis.

Answer:

c) Define the Hinge region of the antibody.

Answer:

d) Define Human Leucocyte Antigen (HLA).

Answer:

a) Write a short note on Monoclonal antibodies.

Answer:

b) Write a short note on Opsonization.

Answer:

c) Write a short note on DNA Vaccines.

Answer:

d) Write a short note on Agglutination Reactions.

Answer:

a) Differentiate between Helper " $T$$T$TT$T$ " cells and cytotoxic " $T$$T$TT$T$ " cells.

Answer:

• Helper T Cells (CD4+ T cells):
  • Role: Helper T cells are crucial for orchestrating the immune response. They do not directly kill infected cells but instead help activate and regulate other immune cells.
  • Function: They assist in the activation of B cells (for antibody production), cytotoxic T cells (for killing infected cells), and macrophages (for enhanced phagocytosis). Helper T cells also promote the production of cytokines, which are signaling molecules that coordinate the immune response.
  • Mechanism: Helper T cells primarily function by recognizing antigens presented by MHC class II molecules on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells. Upon activation, they secrete cytokines that activate other immune components.
• Cytotoxic T Cells (CD8+ T cells):
  • Role: Cytotoxic T cells are responsible for identifying and destroying infected or cancerous cells. They are key players in defending the body against viral infections and tumor cells.
  • Function: Cytotoxic T cells directly kill cells that display foreign antigens (such as viral or tumor antigens) on MHC class I molecules. They release cytotoxins like perforin and granzymes, which induce apoptosis (programmed cell death) in the target cell.
  • Mechanism: Cytotoxic T cells recognize the foreign antigens displayed on MHC class I molecules of infected cells. Upon recognition, cytotoxic T cells release perforin, which creates pores in the target cell membrane, allowing granzymes to enter and trigger apoptosis.

• Helper T Cells (CD4+ T cells):
  • Helper T cells are defined by the CD4+ marker on their surface. CD4 is a co-receptor that assists in binding to MHC class II molecules on antigen-presenting cells.
• Cytotoxic T Cells (CD8+ T cells):
  • Cytotoxic T cells are defined by the CD8+ marker on their surface. CD8 is a co-receptor that assists in binding to MHC class I molecules on infected or abnormal cells.

• Helper T Cells:
  • Helper T cells recognize processed antigen fragments (peptides) presented on MHC class II molecules found on antigen-presenting cells (APCs). The antigen presentation is typically derived from extracellular pathogens (such as bacteria, fungi, or parasites).
• Cytotoxic T Cells:
  • Cytotoxic T cells recognize processed antigen fragments presented on MHC class I molecules of infected or abnormal cells. These antigens are typically derived from intracellular pathogens (such as viruses) or tumor cells.

• Helper T Cells:
  • Upon activation, helper T cells secrete a wide array of cytokines, including interleukins (e.g., IL-2, IL-4, IL-17), which coordinate the immune response by activating other immune cells such as B cells, cytotoxic T cells, and macrophages.
  • Helper T cells are divided into different subsets (Th1, Th2, Th17, Tfh, etc.), each of which produces specific cytokines to target particular immune responses.
• Cytotoxic T Cells:
  • Upon activation, cytotoxic T cells do not primarily produce cytokines. Instead, they focus on releasing cytotoxic molecules such as perforin and granzymes, which are used to kill infected cells.
  • Cytotoxic T cells may also release cytokines (e.g., IFN-γ) that help recruit and activate other immune cells like macrophages.

• Helper T Cells:
  • Helper T cells function as the "commanders" of the immune system, activating other immune cells to respond to pathogens.
  • They do not directly engage in cell killing but instead coordinate the immune response through cytokine signaling and activation of other immune components.
• Cytotoxic T Cells:
  • Cytotoxic T cells are the "killers" in the immune response. They directly target and destroy cells infected with viruses, intracellular bacteria, or cancerous cells through the release of cytotoxins, triggering apoptosis in the target cells.

• Helper T Cells:
  • Helper T cells are involved in both autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis) and allergic reactions. Dysregulation of helper T cells can lead to chronic inflammation and tissue damage.
  • They also play a role in HIV infection, where the virus specifically targets and destroys CD4+ T cells, weakening the immune response.
• Cytotoxic T Cells:
  • Cytotoxic T cells are essential in combating viral infections and tumors. They can become dysfunctional in certain conditions, such as autoimmunity (where they might attack healthy cells) or in the presence of immune evasion mechanisms by pathogens or cancer cells.
  • Cytotoxic T cells are also implicated in graft rejection during organ transplants, where they attack transplanted tissues recognized as foreign.

b) Differentiate between Active and Passive immunity.

Answer:

• Active Immunity: Active immunity occurs when an individual’s immune system is exposed to a pathogen or its antigens and subsequently produces an immune response, including the production of antibodies and memory cells. This type of immunity is typically long-lasting, as it involves the body’s own immune system developing a defense.
• Passive Immunity: Passive immunity refers to the transfer of pre-formed antibodies or immune cells from another individual or organism, providing immediate but temporary protection. The recipient’s immune system does not actively participate in generating the immune response.

• Active Immunity:
  • Process: In active immunity, exposure to a pathogen (via infection or vaccination) stimulates the immune system to produce antibodies and activate T cells. The immune system also generates memory cells (B cells and T cells), which "remember" the pathogen, leading to a quicker and more effective response upon future exposures.
  • Response: The body’s immune system actively produces antibodies and induces a cell-mediated response (including helper T cells and cytotoxic T cells) to fight the infection or disease.
• Passive Immunity:
  • Process: Passive immunity involves the transfer of antibodies from an external source. These antibodies can be acquired naturally (e.g., through the placenta or breast milk) or artificially (e.g., through antibody-containing blood products such as immune globulin).
  • Response: The recipient’s immune system does not generate any new antibodies or immune memory; it only benefits from the antibodies provided by another source.

• Active Immunity:
  • Duration: Active immunity is generally long-lasting, often providing years or even lifetime protection. This is because memory cells persist in the body, allowing the immune system to mount a rapid and effective response if the pathogen is encountered again.
• Passive Immunity:
  • Duration: Passive immunity provides temporary protection, usually lasting only a few weeks to a few months. This is because the transferred antibodies eventually degrade over time, and no memory cells are formed in the recipient’s immune system.

• Active Immunity:
  • Vaccination: Vaccines, such as those for measles, influenza, or COVID-19, stimulate the body to produce antibodies and memory cells without causing the disease itself.
  • Natural Infection: After recovery from an infection (e.g., chickenpox or influenza), the immune system has developed immunity against future infections by the same pathogen.
• Passive Immunity:
  • Natural: Maternal antibodies passed from mother to fetus through the placenta during pregnancy, or through breast milk, provide temporary protection to the infant against infections during the early months of life.
  • Artificial: The administration of immunoglobulins (antibody-rich blood products) to individuals who have been exposed to specific pathogens, such as in cases of tetanus, rabies, or hepatitis B exposure, to provide immediate protection.

• Active Immunity:
  • Memory Formation: Active immunity involves the creation of memory B and T cells. These cells remain in the body long after the infection or vaccination, enabling the immune system to respond more rapidly and effectively if the pathogen is encountered again.
• Passive Immunity:
  • No Memory Formation: In passive immunity, the immune system does not create memory cells, meaning that there is no long-term immune defense once the transferred antibodies degrade.

• Active Immunity:
  • Onset of Protection: Active immunity takes time to develop. After exposure to the pathogen or vaccination, it typically takes several days to weeks for the immune system to generate an effective response, including the production of antibodies and the activation of memory cells.
• Passive Immunity:
  • Onset of Protection: Passive immunity provides immediate protection since the antibodies are already present in the recipient. This makes it useful in situations where immediate defense against infection is needed, such as after exposure to certain viruses or bacteria.

• Active Immunity:
  • Advantages: Long-lasting protection, development of immune memory, and no need for repeated treatments.
  • Disadvantages: Takes time to develop protection, and there is a risk of side effects (e.g., mild symptoms from vaccines or illness from natural infection).
• Passive Immunity:
  • Advantages: Provides immediate protection, ideal in emergency situations or for individuals who cannot mount their own immune response (e.g., immunocompromised patients).
  • Disadvantages: Temporary protection with no long-term immunity, and the potential for allergic reactions to the foreign antibodies.

c) Differentiate between MHC class-I and II molecules.

Answer:

• MHC Class I Molecules:
  • MHC class I molecules consist of a single alpha chain and a beta-2 microglobulin (β2m). The alpha chain is divided into three domains (α1, α2, and α3), with the α1 and α2 domains forming a groove that holds the antigenic peptide. The α3 domain binds to CD8 co-receptors on cytotoxic T cells.
• MHC Class II Molecules:
  • MHC class II molecules are composed of two polypeptide chains: an alpha chain and a beta chain. Both chains are integral to forming the antigen-binding groove, which holds the antigenic peptide. The CD4 co-receptor on helper T cells binds to the β2 domain of MHC class II molecules.

• MHC Class I Molecules:
  • MHC class I molecules are expressed on the surface of all nucleated cells, including epithelial cells, muscle cells, and neurons. These molecules are crucial for displaying intracellular antigens such as those from viruses or tumors.
• MHC Class II Molecules:
  • MHC class II molecules are predominantly expressed on antigen-presenting cells (APCs), including dendritic cells, macrophages, and B cells. These cells are specialized in capturing, processing, and presenting extracellular antigens.

• MHC Class I Molecules:
  • MHC class I molecules primarily present endogenous antigens, which are peptides derived from proteins synthesized inside the cell. These proteins can be viral proteins, mutated tumor proteins, or self-proteins that are abnormal. The presented peptides are typically 8-10 amino acids in length.
• MHC Class II Molecules:
  • MHC class II molecules present exogenous antigens derived from extracellular sources, such as bacteria, fungi, and parasites. These antigens are taken up by the APCs through phagocytosis or endocytosis, processed, and displayed. The peptides are usually longer (13-25 amino acids in length).

• MHC Class I Molecules:
  • MHC class I molecules interact with CD8+ cytotoxic T cells (also known as killer T cells). The CD8 co-receptor on cytotoxic T cells binds to the α3 domain of the MHC class I molecule, facilitating the recognition and killing of infected or tumor cells that present foreign peptides.
• MHC Class II Molecules:
  • MHC class II molecules interact with CD4+ helper T cells. The CD4 co-receptor on helper T cells binds to the β2 domain of the MHC class II molecule. This interaction helps activate helper T cells, which in turn stimulate B cells to produce antibodies and macrophages to phagocytize pathogens.

• MHC Class I Molecules:
  • The antigen processing pathway for MHC class I involves the cytosolic degradation of proteins by the proteasome. These degraded peptides are transported into the endoplasmic reticulum (ER) by the TAP (Transporter Associated with Antigen Processing) complex, where they bind to MHC class I molecules. The peptide-MHC class I complex is then transported to the cell surface via the Golgi apparatus.
• MHC Class II Molecules:
  • MHC class II molecules are processed in endosomal compartments within antigen-presenting cells. The antigens are taken up from the extracellular environment, degraded in phagosomes or endosomes, and the peptides are then loaded onto the MHC class II molecules. The peptide-MHC class II complex is subsequently transported to the cell surface for presentation to CD4+ T cells.

• MHC Class I Molecules:
  • The primary role of MHC class I molecules is to present antigens to cytotoxic T cells (CD8+) for the detection and destruction of infected or cancerous cells. This is crucial for the immune system’s response to viruses, intracellular pathogens, and tumors.
• MHC Class II Molecules:
  • MHC class II molecules are involved in the activation of helper T cells (CD4+). Once activated, helper T cells assist in the immune response by stimulating other immune cells, including B cells (for antibody production) and macrophages (for enhanced pathogen clearance), to fight off extracellular pathogens like bacteria and fungi.

• MHC Class I Molecules:
  • The genes encoding MHC class I molecules are part of the human leukocyte antigen (HLA) complex, specifically HLA-A, HLA-B, and HLA-C loci. These molecules are highly polymorphic, meaning they have many different versions (alleles) within the population, which enhances the ability of the immune system to recognize a wide variety of pathogens.
• MHC Class II Molecules:
  • MHC class II molecules are encoded by the HLA-D region of the genome, which includes HLA-DP, HLA-DQ, and HLA-DR genes. Like MHC class I, MHC class II molecules are also polymorphic, allowing for a broad range of antigen presentation.

d) Differentiate between Self and non-self antigens.

Answer:

• Self Antigens:
  • Self antigens are molecules or markers that are naturally present on the cells and tissues of an individual’s own body. These molecules are recognized as "self" by the immune system and are typically tolerated by the immune system, meaning the body does not mount an immune response against them under normal circumstances.
• Non-Self Antigens:
  • Non-self antigens are molecules or markers that originate from external sources such as pathogens (viruses, bacteria, fungi, parasites), foreign cells (e.g., from organ transplants), or environmental agents. The immune system recognizes these as "foreign" and mounts an immune response to eliminate them.

• Self Antigens:
  • Self antigens are produced by the body itself, including proteins, lipids, and other molecules that are naturally expressed by the cells and tissues of an individual.
• Non-Self Antigens:
  • Non-self antigens are derived from external sources, such as microbes (bacteria, viruses, etc.), allergens (e.g., pollen or dust), or even foreign tissues (e.g., during organ transplantation).

• Self Antigens:
  • The immune system typically does not react to self antigens because the body has mechanisms for recognizing its own molecules. This recognition involves immune tolerance, which prevents the immune system from attacking its own cells and tissues.
• Non-Self Antigens:
  • The immune system recognizes non-self antigens as foreign and dangerous, initiating an immune response to neutralize or eliminate the threat. This involves the activation of various immune components, such as T cells, B cells, and antibodies.

• Self Antigens:
  • Under normal, healthy conditions, self antigens do not induce an immune response. However, if the immune system fails to recognize self antigens due to immune dysregulation or malfunction, it may result in autoimmune diseases where the body attacks its own tissues (e.g., rheumatoid arthritis, type 1 diabetes, multiple sclerosis).
• Non-Self Antigens:
  • Non-self antigens trigger an immune response, which typically involves the production of antibodies, activation of cytotoxic T cells, and other immune cells designed to neutralize or eliminate the foreign antigen. This response is crucial for fighting infections and preventing the spread of disease.

• Self Antigens:
  • Major Histocompatibility Complex (MHC) molecules on the surface of cells, which help the immune system recognize "self."
  • Blood group antigens (e.g., ABO antigens).
  • Self proteins in tissues like collagen or enzymes involved in metabolism.
• Non-Self Antigens:
  • Pathogen-derived antigens: such as viral proteins (e.g., influenza hemagglutinin), bacterial toxins (e.g., tetanus toxin), and fungal components.
  • Transplanted organ cells or tissue, which express foreign antigens not recognized by the recipient’s immune system.
  • Allergens: environmental substances like pollen, dust mites, or pet dander that trigger allergic reactions.

• Self Antigens:
  • In autoimmune diseases, the immune system mistakenly recognizes self antigens as foreign, leading to an attack on its own tissues. For example, in Systemic Lupus Erythematosus (SLE), the immune system attacks the body’s own DNA, and in Hashimoto’s thyroiditis, the immune system targets the thyroid gland.
• Non-Self Antigens:
  • Non-self antigens are normally targeted by the immune system in a protective response. However, in hypersensitivity reactions, the immune system may overreact to non-harmful non-self antigens (e.g., pollen or peanuts), resulting in allergic reactions.

• Self Antigens:
  • The immune system develops tolerance to self antigens through processes such as central tolerance (where self-reactive T and B cells are eliminated in the thymus and bone marrow) and peripheral tolerance (where self-reactive cells are inactivated or suppressed in peripheral tissues). These mechanisms prevent the immune system from attacking the body’s own cells.
• Non-Self Antigens:
  • The immune system does not develop tolerance to non-self antigens; rather, it actively recognizes and targets them as foreign. This recognition triggers a cascade of immune responses aimed at neutralizing or removing the foreign invader.

What is the vaccine? Explain the mode of action of vaccine. Write about the advantages and disadvantages of vaccination.

Answer:

• Exposure to Antigen: When a person is vaccinated, they are exposed to a harmless part of the pathogen, known as an antigen. This can be a whole microorganism (such as a virus or bacterium), a piece of the microorganism (such as a protein or sugar), or a toxin that the microorganism produces.
• Activation of Immune Response: The immune system recognizes the antigen as foreign and responds by activating the innate immune system. This includes the production of phagocytes, which engulf the foreign particles. The adaptive immune system is then triggered, involving T cells (which coordinate the immune response) and B cells (which produce antibodies).
• Production of Antibodies: B cells, once activated, produce specific antibodies tailored to recognize and neutralize the pathogen. These antibodies remain in circulation for a period of time, offering passive immunity.
• Formation of Memory Cells: After the immune system successfully responds to the pathogen, it forms memory cells—both memory B cells and memory T cells. These cells “remember” the pathogen and remain in the body for years or even a lifetime. In case of future exposure, the immune system can rapidly recognize and attack the pathogen, often preventing illness from occurring.
• Neutralization of Future Infection: Upon subsequent exposure to the same pathogen, the immune system is able to quickly respond due to the presence of the memory cells, leading to a much faster and more efficient immune response. This rapid response often prevents the disease from taking hold, or at least significantly reduces its severity.

• Inactivated or Killed Vaccines: These vaccines contain pathogens that have been killed or inactivated so they cannot cause disease. Examples include the polio vaccine (IPV) and the hepatitis A vaccine.
• Live Attenuated Vaccines: These vaccines contain live pathogens that have been weakened so that they cannot cause illness in healthy individuals. They closely mimic a natural infection and produce a strong and lasting immune response. Examples include the measles, mumps, rubella (MMR) vaccine and the yellow fever vaccine.
• Subunit, Recombinant, or Conjugate Vaccines: These vaccines contain pieces of the pathogen, such as proteins or sugars, that trigger an immune response without containing the entire pathogen. Examples include the Hepatitis B vaccine and the Haemophilus influenzae type b (Hib) vaccine.
• Toxoid Vaccines: These vaccines are made from inactivated toxins produced by the pathogen. They help protect against diseases caused by bacterial toxins. Examples include the diphtheria and tetanus vaccines.

• Prevention of Disease: Vaccines prevent a variety of diseases, many of which can cause severe illness or death. For example, the measles vaccine prevents measles, which can lead to complications like pneumonia, brain swelling, and death.
• Herd Immunity: When a significant portion of the population is vaccinated, it creates herd immunity, which makes it difficult for a disease to spread. This protects individuals who cannot be vaccinated, such as those with weakened immune systems (e.g., chemotherapy patients or infants who are too young for certain vaccines).
• Eradication of Diseases: Vaccines have contributed to the eradication of diseases like smallpox and the near-eradication of polio. Through widespread vaccination, the goal is to completely eliminate the disease from the population.
• Cost-Effective: Vaccination is a cost-effective way to prevent diseases compared to treating the disease once it occurs. It helps reduce the financial burden on healthcare systems by avoiding hospitalizations, long-term treatments, and lost productivity.
• Reduction of Disease Spread: By preventing the spread of infectious diseases, vaccination helps reduce the burden on healthcare systems and decreases the overall prevalence of diseases in the community.
• Protection Against Emerging Threats: Vaccines are developed in response to emerging infectious diseases, as seen with the rapid development of the COVID-19 vaccines. This allows for a quick response to new pandemics.

• Side Effects and Reactions: Most vaccines have mild side effects, such as fever, pain at the injection site, or fatigue. Rarely, vaccines may cause more severe reactions, such as allergic responses. However, these reactions are generally much less common than the adverse effects caused by the diseases the vaccines prevent.
• Incomplete Protection: While vaccines provide protection against many diseases, they may not provide 100% immunity. Some individuals may not develop full immunity after vaccination, and they may remain vulnerable to the disease. For example, the influenza vaccine is not always perfectly matched to circulating strains, which can reduce its effectiveness in some years.
• Vaccine Hesitancy: There is a growing issue of vaccine hesitancy in certain populations, driven by misinformation, fear, and distrust in medical institutions. This can lead to lower vaccination rates and outbreaks of vaccine-preventable diseases.
• Access and Availability: Vaccines may not be readily available or accessible in all regions, especially in low-income countries or areas with poor healthcare infrastructure. This can limit the effectiveness of global vaccination efforts, leaving some populations vulnerable to preventable diseases.
• Cost of Vaccines: While vaccines are generally cost-effective in the long run, the initial development, production, and distribution costs can be high. This may create financial barriers to widespread vaccination, particularly in developing countries.
• Potential for Misuse: There is the potential for vaccines to be used improperly, for example, when vaccine schedules are not followed, or vaccines are not stored properly, reducing their efficacy.

a) Write the various steps in the establishment of bacterial infection.

Answer:

• Respiratory tract: Bacteria can be inhaled through airborne droplets (e.g., in pneumonia or tuberculosis).
• Gastrointestinal tract: Ingested contaminated food or water (e.g., in foodborne infections like Salmonella or E. coli).
• Skin or mucous membranes: Direct contact with contaminated surfaces or injury (e.g., in wound infections, cellulitis).
• Genitourinary tract: Bacteria can enter through sexual contact or improper hygiene (e.g., in urinary tract infections).

• Pili (fimbriae): Hair-like structures on bacterial surfaces that allow attachment to host cell receptors.
• Adhesins: Surface proteins that bind to specific molecules on host cells, facilitating attachment.
• Capsules: Some bacteria have a slimy outer coating that helps them adhere to surfaces, as well as evade immune detection.

• Proteases: Enzymes that break down proteins and allow bacteria to penetrate tissue barriers.
• Hyaluronidase: An enzyme that breaks down the hyaluronic acid in connective tissues, enabling bacterial spread.
• Collagenase: An enzyme that degrades collagen, a major structural component of connective tissues.

• Capsules: Some bacteria produce capsules that prevent phagocytosis by immune cells like macrophages and neutrophils.
• Antigenic variation: Bacteria can change their surface proteins to avoid recognition by the host’s antibodies.
• Toxins: Many bacteria secrete toxins that damage immune cells or suppress immune responses. For example, staphylococcal enterotoxins can interfere with the functioning of immune cells.
• Immune suppression: Some bacteria, like Mycobacterium tuberculosis, can survive within host cells, preventing the host immune system from effectively targeting them.

• Exotoxins: These are toxic proteins secreted by bacteria into the host’s tissues. Examples include diphtheria toxin and botulinum toxin.
• Endotoxins: Found in the outer membrane of Gram-negative bacteria, these toxins can trigger severe inflammatory responses when released into the bloodstream, leading to conditions like sepsis.

• Resolution: If the immune response is successful, the bacteria are cleared, and the infection resolves. This often leads to the development of immunity, as memory cells are formed to recognize the pathogen in future encounters.
• Chronic Infection: In some cases, the bacteria evade immune clearance or overwhelm the immune system, leading to a chronic infection. Chronic infections can result in persistent inflammation, tissue damage, and long-term health problems. Examples include chronic urinary tract infections or chronic tuberculosis.

b) Explain the neutralization mechanism of bacteria by antibodies.

Answer:

• Variable Region: This region of the antibody is responsible for binding to the specific antigen. It is highly variable between different antibodies, allowing the immune system to recognize a vast array of pathogens.
• Constant Region: This part of the antibody remains the same across different antibodies of the same class. The constant region interacts with other components of the immune system, such as phagocytes and complement proteins, to help clear the pathogen.

• Inhibition of Adhesion: Many bacteria cause infection by adhering to host cells. Antibodies can block adhesion molecules on the bacterial surface, preventing the bacteria from attaching to host tissues and gaining access to the cells.
• Blocking Receptors: Some bacteria have receptors that allow them to interact with host cells. Antibodies can block these receptors, preventing the bacteria from entering the cells and causing infection.
• Inhibition of Toxin Activity: Some bacteria release toxins that damage tissues or interfere with cellular functions. Antibodies can bind to these toxins, neutralizing their harmful effects. For example, the diphtheria toxin can be neutralized by antibodies, rendering it incapable of interfering with host cell functions.

• Direct Binding to Toxins: Antibodies can bind to the active sites of bacterial toxins, preventing them from interacting with host cells. For example, antibodies to botulinum toxin bind to the toxin and prevent it from binding to the neuromuscular junction, thereby preventing paralysis.
• Blocking Toxin Receptors: Some toxins need to bind to specific receptors on the surface of host cells to be effective. By blocking the receptor binding site, antibodies prevent the toxin from interacting with its target cells, neutralizing its effect.
• Preventing Toxin Internalization: Many bacterial toxins enter host cells by being endocytosed into vesicles. Antibodies can prevent this internalization process by binding to the toxin and blocking the necessary receptors involved in this uptake.

• Opsonization: Antibodies that bind to bacteria act as "tags" that signal for phagocytes (like macrophages and neutrophils) to engulf and destroy the bacteria. This process is known as opsonization. The Fc region of the antibody interacts with complement proteins and receptors on phagocytes, facilitating the clearance of the bacteria.
• Membrane Attack Complex: The complement system can be activated by the classical pathway, where antibodies bound to the pathogen initiate a cascade of complement activation. This leads to the formation of a membrane attack complex (MAC), which can create pores in the bacterial cell membrane, leading to bacterial lysis and death.
• Enhancement of Antibody Functions: The complement system can also enhance the ability of antibodies to neutralize pathogens by making the pathogens more "visible" to the immune system.

• Immune Complexes: The binding of multiple antibodies to antigens on the bacterial surface leads to the formation of immune complexes, which can be cleared from the bloodstream by macrophages and other phagocytic cells.
• Precipitation: In some cases, the immune complexes formed by antibodies and bacterial antigens may precipitate (settle out of solution), which also helps in their removal from the host body.
• Phagocytosis: Immune complexes make bacteria more prone to being ingested and destroyed by phagocytes. The Fc region of the antibody facilitates recognition and ingestion by phagocytes through interactions with receptors on these immune cells.

a) Define autoimmunity. Describe any two autoimmune disorders.

Answer:

• Loss of Immune Tolerance: The immune system usually has mechanisms that prevent it from attacking the body’s own tissues. This is known as self-tolerance. In autoimmune diseases, these mechanisms fail, and immune cells that normally ignore self-antigens begin to attack them.
• Autoantibodies: In many autoimmune disorders, the immune system produces antibodies that target self-antigens. These antibodies are referred to as autoantibodies. They can bind to healthy tissues and cause inflammation and tissue damage.
• T-cell Dysregulation: T-cells play a critical role in the immune system. In autoimmune diseases, autoreactive T-cells can attack self-tissues, leading to immune-mediated damage.

• Symptoms: The symptoms of SLE can be highly variable and can range from mild to severe. Common symptoms include:
  • Butterfly-shaped rash across the cheeks and nose.
  • Fatigue, joint pain, and muscle aches.
  • Photosensitivity (sensitivity to sunlight).
  • Kidney damage (lupus nephritis) in some cases.
  • Raynaud’s phenomenon (reduced blood flow to fingers and toes).
  • Chest pain, headaches, and cognitive issues.
• Pathogenesis: The pathogenesis of SLE involves the formation of immune complexes (antibody-antigen complexes) that deposit in various tissues, triggering an inflammatory response. These immune complexes activate complement proteins, leading to inflammation, tissue damage, and the symptoms of the disease. The kidneys are particularly vulnerable, and untreated lupus can lead to renal failure.
• Diagnosis: The diagnosis of SLE is based on clinical symptoms, laboratory findings (including the presence of ANA and anti-dsDNA antibodies), and organ involvement. Imaging studies and biopsy may be required to assess the extent of organ damage.
• Treatment: There is no cure for SLE, but treatments focus on controlling symptoms, reducing inflammation, and preventing flares. Nonsteroidal anti-inflammatory drugs (NSAIDs), antimalarials (like hydroxychloroquine), and immunosuppressive drugs (like corticosteroids and methotrexate) are commonly used. In severe cases, biologic therapies targeting specific immune pathways (such as B-cell depletion therapies) may be recommended.

• Symptoms: The hallmark symptoms of RA include:
  • Joint pain and swelling, particularly in the smaller joints (e.g., fingers, wrists).
  • Morning stiffness, lasting for at least 30 minutes.
  • Fatigue, low-grade fever, and weight loss.
  • In some cases, rheumatoid nodules (firm lumps under the skin) can develop.
• Pathogenesis: The autoimmune attack in RA is primarily directed against the synovial membrane, which lines the joints. Autoantibodies, particularly rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), bind to citrullinated proteins in the joints, forming immune complexes that trigger inflammation. This leads to the activation of T-cells and the release of pro-inflammatory cytokines, such as TNF-alpha, which further amplify the immune response and cause damage to the cartilage and bone.
• Diagnosis: Diagnosis is based on clinical symptoms, laboratory tests for rheumatoid factor and anti-CCP antibodies, and imaging studies showing joint erosion or inflammation.
• Treatment: Early diagnosis and treatment are crucial to preventing long-term joint damage. Treatment options for RA include disease-modifying antirheumatic drugs (DMARDs) like methotrexate, which help reduce disease progression. Biologic agents that target specific immune molecules, such as TNF inhibitors, are also commonly used to control inflammation.

b) Describe the steps involved in the immunoelectrophoresis technique.

Answer:

• Electrophoresis: When the electric field is applied, proteins in the sample begin to migrate through the gel. The migration occurs according to the charge of the proteins; positively charged proteins will migrate towards the negative electrode (anode), while negatively charged proteins will migrate towards the positive electrode (cathode). Proteins with a neutral charge will not migrate significantly.

• Antiserum Application: A well or trough is created next to the protein bands, and a small amount of antisera is placed into the well. The antibodies in the antiserum will diffuse out from the well into the gel.
• Antigen-Antibody Reaction: As the antibodies diffuse into the gel, they encounter the proteins separated by electrophoresis. If there are proteins in the sample that correspond to the antibodies in the antiserum, a precipitation line will form at the site where the antibody and antigen meet. This reaction is based on the formation of an immune complex, where the antibody binds to its specific antigen.

• Normal Patterns: In a healthy individual, the immunoelectrophoresis gel will show distinct bands that correspond to the different types of proteins in the serum, including albumin, alpha-1-globulins, alpha-2-globulins, beta-globulins, and gamma-globulins.
• Abnormal Patterns: In cases of disease, such as multiple myeloma or nephrotic syndrome, the patterns may show abnormal spikes or monoclonal bands indicating an overproduction of a specific protein or immunoglobulin. The presence of monoclonal gammopathy or other abnormal patterns can be indicative of a disease.

a) Define antibodies and draw the structure of immunoglobulin.

Answer:

• Variable Region: The top portion of the Y-shaped antibody consists of the variable regions of both the heavy and light chains. This is the part of the antibody that binds to the antigen. The variability in this region allows antibodies to recognize a wide variety of antigens.
• Constant Region: The bottom portion of the antibody, known as the constant region, does not vary between different antibodies of the same class. This region is involved in interactions with other components of the immune system, such as phagocytes and complement proteins, to trigger immune responses like phagocytosis or the activation of the complement cascade.

• IgG: The most common antibody in the blood, IgG is involved in the secondary immune response and provides long-term immunity after infection or vaccination. It is the only antibody class that can cross the placenta to provide passive immunity to the fetus.
• IgA: Found primarily in mucosal areas, such as the respiratory and gastrointestinal tracts, as well as in secretions like saliva, tears, and breast milk, IgA plays a key role in protecting mucosal surfaces from pathogens.
• IgM: The first antibody produced during an immune response, IgM is highly effective in forming immune complexes and activating the complement system. It is usually the first antibody produced upon initial exposure to an antigen.
• IgE: Associated with allergic reactions, IgE binds to allergens and triggers the release of histamine from mast cells and basophils. It plays a central role in the immune response to parasitic infections.
• IgD: Found on the surface of B cells, IgD is involved in the activation and regulation of B cells. Its exact role is less understood but is thought to be important in initiating immune responses.

• Fab Region (Fragment antigen-binding): The Fab region is the arms of the Y-shaped antibody and is composed of the variable regions of both the heavy and light chains. This is the site where the antibody binds to the antigen. The unique sequence of amino acids in the variable regions of the light and heavy chains allows for the recognition of a specific antigen.
• Fc Region (Fragment crystallizable): The Fc region is the stem of the Y-shaped structure and consists of the constant regions of the heavy chains. This region does not bind to antigens but interacts with various components of the immune system. For example, it can bind to receptors on phagocytes, triggering the process of phagocytosis, or activate the complement system to enhance the immune response.

• Neutralization: By binding to pathogens or their toxins, antibodies can neutralize their ability to cause harm. For example, antibodies can bind to a virus and prevent it from entering host cells.
• Opsonization: Antibodies mark pathogens for destruction by phagocytes through a process called opsonization. The Fc region of the antibody binds to receptors on phagocytes, facilitating their engulfment and destruction of the pathogen.
• Activation of the Complement System: The binding of antibodies to pathogens can trigger the complement system, a series of proteins that help destroy pathogens by creating pores in their membranes or by enhancing phagocytosis.
• Agglutination and Precipitation: Antibodies can cross-link pathogens or antigens, causing them to clump together (agglutination) or form insoluble complexes (precipitation), which can then be cleared by the immune system.

• Heavy Chain: Each immunoglobulin molecule has two heavy chains (H). These chains are long and contain both variable and constant regions.
• Light Chain: Each immunoglobulin molecule has two light chains (L), which are shorter than the heavy chains and also consist of variable and constant regions.
• Variable Region: This is the top part of the Y-shaped structure and includes the antigen-binding sites, which are formed by parts of both the heavy and light chains. The variability in these regions allows antibodies to bind specifically to a diverse range of antigens.
• Constant Region: The stem and the lower parts of the arms of the Y-shape consist of the constant region, which interacts with immune cells and other components of the immune system.

b) Explain the significance of the different classes of antibodies.

Answer:

• Function: IgG antibodies are highly effective in neutralizing toxins and viruses. They are capable of crossing the placenta, providing passive immunity to the fetus, which is crucial in the early stages of life before the infant’s immune system is fully developed. IgG can also activate the complement system, enhancing the immune response by triggering inflammation and the destruction of pathogens.
• Significance: The presence of IgG antibodies in the blood can indicate prior exposure to an infection or vaccination, making them useful in diagnostic tests for immune memory.

• Function: IgA helps to neutralize pathogens, such as viruses and bacteria, by preventing their attachment to mucosal surfaces. It also plays a role in preventing the invasion of harmful microorganisms into the body’s internal tissues by blocking their adherence to epithelial cells.
• Significance: Because IgA is secreted into mucosal areas, it is essential for protecting the body’s first line of defense against pathogens that enter through the respiratory or gastrointestinal tracts. The presence of IgA in breast milk provides newborns with passive immunity, protecting them against infections in the early months of life.

• Function: IgM is highly effective in forming immune complexes, which are clusters of antigens bound to antibodies. These complexes are essential for activating the complement system, which enhances the immune response and helps clear pathogens. IgM can bind to multiple antigens simultaneously, forming large complexes that can effectively neutralize pathogens.
• Significance: The presence of IgM in the blood indicates an acute or recent infection. It is used in diagnostic tests to detect new or current infections, as it is the antibody produced during the first phase of the immune response.

• Function: When IgE binds to specific allergens, it triggers the release of histamine and other inflammatory mediators from mast cells and basophils, leading to the characteristic symptoms of allergies, such as itching, swelling, and bronchoconstriction. IgE also plays a role in defending against parasitic infections by promoting eosinophil activation.
• Significance: IgE-mediated immune responses are central to allergic diseases like hay fever, asthma, and anaphylaxis. Elevated levels of IgE are often seen in individuals with these conditions. In parasitic infections, IgE helps mobilize the immune system to combat helminths and other parasites.

• Function: The primary role of IgD is to assist in the activation of B cells. When B cells encounter an antigen, the binding of IgD to the antigen helps signal the cell to initiate an immune response. IgD also plays a role in regulating the balance of immune responses and in the early stages of the immune response.
• Significance: IgD is important in the activation and differentiation of B cells into antibody-secreting plasma cells. It is also involved in fine-tuning the immune response to ensure that the body reacts appropriately to pathogens without causing excessive inflammation.

How is the classical complement pathway activated? Discuss with a suitable diagram.

Answer:

• C1 Complex: The first component of the classical pathway, C1 is composed of three subunits: C1q, C1r, and C1s. C1q binds to the antibody-antigen complex, and this binding activates the C1r subunit, which in turn activates C1s.
• C2 and C4: Once activated, C1s cleaves the C2 and C4 proteins, forming the C3 convertase, a crucial step in the complement cascade.
• C3: The central molecule in the complement system, C3 is cleaved into C3a and C3b. C3b binds to the pathogen surface and promotes phagocytosis, while C3a promotes inflammation by acting as a potent anaphylatoxin.
• C5, C6, C7, C8, and C9: These components come together to form the membrane attack complex (MAC), which creates pores in the pathogen’s membrane, leading to its destruction.

• Step 1: Antigen Recognition and Antibody Binding: The classical complement pathway begins when an antibody, typically IgM or IgG, binds to a specific antigen on the surface of a pathogen. This binding occurs through the variable region of the antibody, which recognizes a unique structure on the antigen.
• Step 2: Binding of C1q to the Antibody-Antigen Complex: The next step involves the C1 complex, which consists of three subunits: C1q, C1r, and C1s. C1q binds to the Fc region of the antibody that is bound to the antigen. This interaction causes a conformational change in C1q, activating the associated C1r and C1s subunits.
• Step 3: Activation of C1r and C1s: Upon activation, C1r cleaves and activates C1s. Activated C1s then cleaves C4 into C4a and C4b. C4b binds to the pathogen surface, while C4a acts as a potent anaphylatoxin, contributing to inflammation.
• Step 4: Formation of C3 Convertase (C4b2a): Activated C1s also cleaves C2 into C2a and C2b. C2a binds to C4b on the pathogen surface to form the C3 convertase complex (C4b2a). This enzyme complex is responsible for cleaving C3 into C3a and C3b.
• Step 5: Cleavage of C3 and Formation of C3b: The cleavage of C3 into C3a and C3b is a critical step in the classical pathway. C3a acts as a chemotactic factor and an anaphylatoxin, promoting inflammation and recruiting immune cells like neutrophils to the site of infection. C3b binds to the pathogen surface, opsonizing it for phagocytosis and also forming the C5 convertase.
• Step 6: Formation of C5 Convertase (C4b2a3b): The next step involves the assembly of the C5 convertase, which consists of C4b2a3b. This enzyme cleaves C5 into C5a and C5b. C5a is another anaphylatoxin that promotes inflammation, while C5b plays a key role in the formation of the membrane attack complex (MAC).
• Step 7: Formation of the Membrane Attack Complex (MAC): The final step in the classical complement pathway is the assembly of the membrane attack complex (MAC). C5b binds to C6 and C7, forming a complex that attaches to the pathogen surface. The C5b-7 complex then binds to C8, which initiates the polymerization of C9 molecules. The C9 molecules form a pore in the pathogen’s membrane, leading to its lysis and death.