Genes and the Immune System

Genes and the Immune System

Introduction

• The immune system defends the body against infections by attacking foreign molecules and organisms (pathogens).
• Pathogens include viruses (e.g., Ebola, HIV), bacteria, fungi, and parasites.

Levels of Immune Protection

• First Level:
  • Skin: Physical barrier.
  • Mucosal membranes: Line the nose and respiratory tract (nonspecific defense).
  • Flushing mechanisms: Tears, saliva, diarrhea.
• Innate Immune System:
  • Nonspecific: Responds to all types of pathogens.
  • Components:
    • Phagocytes (macrophages, neutrophils): White blood cells that engulf pathogens.
    • Antimicrobial proteins.
    • Inflammatory response.
• Adaptive (Acquired) Immunity:
  • Specific: Targets particular pathogens.
  • Components:
    • B cells (B lymphocytes): Produce antibodies and memory cells; mature in the bone marrow.
    • T cells (T lymphocytes): Include T helper cells (stimulate the immune system) and cytotoxic T cells (kill infected/cancer cells); mature in the thymus.

The Innate Immune Response

• Macrophages engulf bacteria via phagocytosis.
• Other components:
  • Antimicrobial proteins
  • Complement system
  • Cytokines (interferon, interleukins, tumor necrosis factor)
  • Inflammatory response
  • Fever

Inflammatory Response

• Occurs when the skin is breached (e.g., by a nail), leading to bacterial infection.
• Macrophages and neutrophils phagocytize bacteria.
• Mast cells secrete histamines which makes blood vessels leaky.
• Leakiness allows immune cells to enter the interstitial fluids to fight infection.

Cells of the Immune System

• All blood cells originate in the red bone marrow.
• Lymphocytes (B and T cells) are key players.

Humoral vs. Cell-Mediated Immunity

• B cells: Mediate humoral immunity.
• T cells: Mediate cell-mediated immunity.

Antigen Presentation and T Helper Cells

• Macrophages engulf pathogens and present antigens (surface proteins) to the immune system.
• Antigen presentation involves:
  • Digesting the pathogen with hydrolytic enzymes.
  • Displaying pathogen fragments (antigens) on the cell surface via the self and non-self complex, also called MHC (major histocompatibility complex) number one.
• T helper cells recognize the MHC complex and stimulate both B cells and cytotoxic T cells.
• T helper cells secrete interleukin two to stimulate B cells and cytotoxic T cells, and also stimulate their own production.
• Antigens are molecules that elicit an immune response and can be detected by antibodies.
• B lymphocytes mature into plasma cells, which are dedicated antibody-producing cells.

Antibodies

• Antibodies are custom-made to fit specific antigens.
• Composed of proteins assembled into a Y-shaped structure.
• Types of antibodies:
  • IgG: Major antibody; fights bacteria, viruses, and toxins; can cross the placenta.
  • IgA: Found in breast milk, saliva, and tears.
  • IgE: Involved in allergic reactions and responses to parasites; can cause anaphylactic shock.
  • IgD: Found in B cells in the blood.
  • IgM: Found in blood plasma; appears soon after vaccination.

Humoral Immune Response

• Involves antigens activating B cells.
• Clonal selection leads to proliferation of specific B cells with the right antigens into antibody factories (plasma cells).

Cellular Immune Response

• Involves T cells.
• T helper cells stimulate the humoral response (B cells) and cytotoxic T cells.
• Cytotoxic T cells:
  • Destroy virus-infected cells and cancer cells.
  • Bind to target cells via T cell receptors.
  • Secrete perforins to perforate the cell membrane and kill the target cell.

Overview of Immune Cells

• Macrophages: Nonspecific; engulf and break up bacteria.
• Mast cells: Nonspecific; release histamines, dilating blood vessels during infection.
• B cells (B lymphocytes): Mature in bone marrow; produce antibodies; some become memory cells.
• T cells (T lymphocytes):
  • T helper cells: Stimulate B cells and cytotoxic T cells.
  • Cytotoxic T cells: Kill virus-infected and cancer cells.
• Natural killer cells: Attack cancer cells and virus-infected cells.
• Suppressor cells: Inhibit antibody production.

Immune Memory and Vaccination

• The immune system builds memory for rapid response upon second exposure to a pathogen.
• Vaccines: Expose the immune system to weakened viruses or viral components (antigens), stimulating antibody production and memory cell formation.
• Vaccination protects against illness upon subsequent exposure to the real virus.

Blood Type Testing

• Involves interactions between antigens (surface proteins) and antibodies.
• ABO blood type system: Three alleles (A, B, O) lead to blood types A, B, O, AB.
• Blood type A can donate to A or AB.
• Mismatched blood transfusions can cause agglutination (clumping) and death.
• Antigens are membrane glycoproteins with sugar chains attached.
• Rh System: Membrane proteins determine Rh+ or Rh- blood type.
• Rh incompatibility during pregnancy: Rh- mother carrying Rh+ fetus can develop antibodies against Rh+ factor, potentially harming subsequent Rh+ fetuses. RhoGAM is administered to prevent antibody production.

Immune Deficiencies and Disorders

• Diseases associated with abnormalities in human leukocyte antigen alleles: Type one diabetes, celiac disease, rheumatoid arthritis, multiple sclerosis, and lupus.
• Inherited immune deficiencies: SCIDs (severe combined immunodeficiency syndrome).
• Allergies: Immune system overreacts to harmless antigens (e.g., pollen), causing histamine release and symptoms like sneezing and tearing.

Historical Perspective on Vaccination

• Edward Jenner: Pioneered vaccination in 1796 using cowpox virus to protect against smallpox.
• Variolation: Similar procedures practiced in China a thousand years prior.

Monoclonal Antibodies for Diagnostics

• Pregnancy tests use monoclonal antibodies to detect human chorionic gonadotropin (HCG) in urine.
• Production of monoclonal antibodies:
  • Inject antigen (HCG) into a mouse.
  • Harvest B cells from the spleen.
  • Fuse B cells with tumor cells to create hybridoma cells.
  • Culture hybridoma cells to continuously produce antibodies.

Organ Transplantation

• Types of grafts:
  • Isograft: From identical twin (ideal).
  • Allograft: From another human (related if possible, or immunocompatible).
  • Xenograft: From another species (e.g., pig).
  • Autograft: Tissue taken from and returned to the same patient (immunocompatible).
• Xenografts (e.g., pig organs) elicit strong immune responses in humans.
• Transgenic pigs: Genetically engineered pigs with human leukocyte antigens to reduce rejection in xenotransplantation.

HIV and AIDS

• HIV (human immunodeficiency virus) leads to AIDS (acquired immunodeficiency syndrome).
• HIV infects T cells which are responsible for stimulating the humoral response and cell mediated response within the adaptive immune system
• HIV is an RNA virus that uses reverse transcriptase to convert its RNA into DNA, integrating into the host cell's genome.
• The virus hijacks cellular machinery to produce new viruses, then buds from the cell, acquiring membrane proteins.
• The rapidly changing viral surface makes vaccine development challenging.