Immune System Dysfunction and Discoveries

Immune System Dysfunction

• SCID (Severe Combined Immune Deficiency Syndrome) is a genetic disorder in which the immune system is severely impaired. Individuals with SCID have a reduced ability to fight infections.
• AIDS (Acquired Immune Deficiency Syndrome) is caused by the HIV (Human Immunodeficiency Virus) virus. HIV destroys T Helper cells, which are crucial for the immune system's ability to fight off infections.

Harnessing the Power of the Immune System

• Immunization is the process of introducing a weakened or inactive form of a pathogen into the body to stimulate an immune response without causing disease. This allows the body to develop immunity to the pathogen.

Discoveries in Science

• Penicillin G (benzylpenicillin) is an antibiotic discovered by Alexander Fleming. He observed that the mold Penicillium chrysogenum produced a substance that killed Staphylococcus aureus bacteria.

Smallpox and Vaccination

• Smallpox is a highly contagious and deadly viral disease that was responsible for millions of deaths throughout history.
• Pharaoh Ramses V died of smallpox in 1157 BCE.
• The last known case of smallpox in the wild occurred in 1977 in Merca, Somalia. Ali Maow Maalin, a hospital cook, survived with treatment.
• Dr. Edward Jenner developed the first successful vaccine against smallpox in 1796 in London.
• The World Health Organization (WHO) declared smallpox eradicated in 1980.

Components of the Immune System

• The immune system consists of lymphoid organs, immune cells, and secretions of immune cells.

Lymphoid Organs

• Primary lymphoid organs are where stem cells divide and immune cells develop. These include:
  • Bone Marrow: responsible for producing blood cells, including B cells and immature T cells. Mature B cells develop here.
  • Thymus: located above the heart, this organ contains T cells, dendritic cells, epithelial cells, and macrophages. This is where T cells mature. It atrophies after maturity.
• Secondary lymphoid organs are where most immune responses occur. These include:
  • Lymph Nodes: scattered throughout the body, they filter microbes and contain macrophages that phagocytize microbes entering the lymph.
  • Spleen: the largest lymphoid organ, it removes microbes and old erythrocytes.
  • Lymphoid Nodules: these are small, localized collections of immune cells.
  • Tonsils: located in the throat, they help to protect against infections.
  • Peyer's Patches and MALT (Mucosal-Associated Lymphoid Tissues): found in the digestive tract, they provide immune protection against ingested pathogens.
  • Appendix: although its function is not fully understood, it is believed to be part of the immune system.

Immune Cells

• Leukocytes (white blood cells) are the primary cells of the immune system.
  • Lymphoid Cells:
    • T cells: these cells are responsible for cell-mediated immunity. There are several types of T cells:
      • Cytotoxic T cells (CD8+): destroy infected cells.
      • Helper T cells (CD4+): activate B cells, cytotoxic T cells, NK cells, and macrophages.
      • Regulatory T cells (CD4+): suppress the immune system and help to prevent autoimmune diseases.
    • B cells: responsible for antibody-mediated immunity. They transform into plasma cells, which produce antibodies.
    • NK cells (Natural Killer cells): kill cells that are infected with viruses or are cancerous.
  • Myeloid Cells:
    • Macrophages: phagocytize microbes and other debris.
    • Dendritic cells: phagocytize microbes and present antigens to T cells.

Myeloid Cells

• Eosinophils: destroy parasites.
• Basophils: release chemicals such as histamine and prostaglandins.
• Mast Cells: release chemicals, primarily histamine.
• Neutrophils: phagocytes that are the most abundant type of white blood cell in the blood.
• Monocytes: mature into macrophages and dendritic cells.

Antibodies

• Antibodies are proteins produced by B cells that bind to specific antigens. They are crucial for the body's ability to fight off infections.

Host Defenses

• The body has two major lines of defense against pathogens: non-specific/innate immunity and specific/adaptive immunity.

Non-specific/Innate Immunity

• The body's first line of defense, it provides a general barrier against pathogens.
  • Physical Barriers: these include the skin, mucous membranes, and cilia.
  • Chemical Barriers: these include stomach acid, lysozyme, and sebum.
  • Microbiological Barriers: these include the normal flora of the body.

Second Line of Defense - Innate Immunity

• This line of defense is activated when pathogens breach the first line of defense.
  • Cellular Factors:
    • Phagocytic Cells: These include neutrophils, macrophages, and dendritic cells.
    • Cells with Inflammatory Mediators: These include basophils, mast cells, and eosinophils.
    • Natural Killer Cells: These cells kill infected or cancerous cells.
  • Humoral Factors:
    • Inflammation and Fever: These are non-specific responses to tissue damage that help to fight off infection.
    • Antimicrobial Substances: These include complement, cytokines, and acute phase reactants.
    • Interferons: These are proteins that interfere with viral replication.

Inflammation

• Is a non-specific response to tissue damage. It involves four distinct signs and symptoms: redness, heat, pain, and swelling.
• Has three stages:
  • First, the body releases chemicals that cause the blood vessels to dilate, increasing blood flow to the area. This causes redness and heat.
  • Second, fluid leaks from the blood vessels into the tissues, causing swelling.
  • Third, white blood cells migrate to the area to remove pathogens and debris.

Extracellular Traps (NETs)

• Are structures released by neutrophils that trap and kill pathogens outside of the cell.

Antigen-Presenting Cells (APCs)

• APCs are cells that present antigens to T cells to activate an adaptive immune response. This is a critical step in linking innate and adaptive immunity.
  • Professional APCs include dendritic cells and macrophages.
  • Neutrophils are an example of a cell that can release NETs to trap pathogens outside of the cell.

Antigen

• A substance capable of inducing an immune response.
  • Immunogen: a material that induces an immune response.
  • Allergen: an antigen that causes an allergic reaction.
  • Ligand: any molecule that binds to a specific receptor.

Antigen-Presenting Cells (APCs)

• Present exogenous antigens with MHC II.
  • Steps involved:
    • Ingest the antigen
    • Digest the antigen into peptide fragments
    • Synthesize and package MHC-II molecules
    • Bind peptide fragments to MHC-II
    • Insert the antigen–MHC-II complexes on the plasma membrane

Adaptive Immune Response (Acquired, Specific)

• Reactivity: An antibody binds specifically to the antigen that provoked it.
• Immunogenicity: The antigen can provoke an immune response by stimulating antibody production to that antigen.
• Antigen Presenting Cells (APCs) (MHC II + antigen):
  • Dendritic cells (Interdigitating Dendritic Cells) / “Professional APC”
  • Macrophages
  • B lymphocytes (B cells)

Specific/Adaptive Immunity

• This line of defense is specific to particular pathogens and provides long-lasting immunity.
• B cells and T cells are involved.
• Memory for previously encountered antigens.

Major Histocompatibility Complex (MHC)

• MHC I: expressed on all nucleated cells; responsible for presenting self-antigens and signaling to the immune system that the cell is healthy.
• MHC II: expressed on all antigen-presenting cells (macrophages, dendritic cells, and B cells); responsible for presenting foreign antigens to T cells to activate an immune response.
• HLA: Human Leukocyte Antigen (the human MHC) - different HLA types are defined by their antigen-binding areas.
  • Only identical twins have the same MHCs on their cells.

T-cell Receptor Recognition

• T-cell receptors only recognize antigens when they are associated with MHC II proteins.

MHC and Cell Death

• Recall, natural killer (NK) cells can destroy cells with altered or missing MHC I on their surface. This means the cell is acting strangely/suspiciously.

PHGY 209 Midterm Exam

• Date: Tuesday, October 8, 2024
• Time: 7:00 - 8:30 pm
• Location: TBA - Check myCourses the morning of the exam
• Format: 35 Multiple Choice Questions (MCQs), approximately 2-3 MCQs per lecture
• Content: Body fluids, transport mechanisms, blood, and immunology
• Note: Tutorial with Dr. [Name of Dr. for tutorial, if available]