How to React to Danger

Page 1: Overview of Immunology

  • Context: Summary of immunology in four lectures

    • Lectures 1-2: General design of the immune system

    • Lectures 3-4: Diseases of immune excess and immune deficiency

Page 2: Immune Response

  • Four key points:

    1. How immune responses start

    2. Development of immune responses

    3. Immune-mediated diseases and therapies

    4. Enhancing the immune response through vaccination

Page 3: Understanding Danger

  • Concept of danger:

    • Damage recognized by the immune system

Page 4: Reacting to Danger

  • Recognizing danger molecules

  • The anatomy of the immune response:

    • Highlighting key immune components

  • Innate immune cells as the body’s heroes:

    • Role of innate immune cells in response

Page 5: Immunological Danger

  • Key pathogens and diseases:

    • SARS-CoV-2 (COVID-19)

    • Plasmodium falciparum (malaria)

    • Salmonella typhimurium (infection)

Page 6: Under Attack!

  • External Epithelia

    • wounds

    • insect bites

    • Skin surface interactions

  • Mucosal Surface

    • Airway

    • Gastrointestinal Tract

    • Reproductive Tract

Page 7: Defenses

  • Main defense mechanisms:

    • Mucus secretion

    • Ciliary action

    • Production of defensins (antimicrobial peptides)

Page 8: The Response - Inflammation

  • Introduction to inflammation:

    • Role of Pattern Recognition Receptors (PRRs) on immune cells

    • Importance of toll-like receptors (TLRs) in immune recognition

  • If something goes wrong - barrier breach, pattern recognition receptors recognise patterns of potential danger. This is called inflammation

Page 9: Initiation of Inflammation

  • Key triggers of inflammation:

    • Various molecules from pathogens (e.g., lipoproteins, lipid A, flagellin)

    • Recognition through TLRs (e.g., TLR2, TLR4, TLR6)

    • Additional receptors like NOD1 and NOD2

Page 10: The Start of Inflammation

  • Key inflammatory mediators:

    • Histamines, peptides, cytokines, chemokines

Page 11: Inflammation Symptoms

  • Clinical signs of inflammation:

    • Scab formation, rubor (redness), calor (heat), tumor (swelling), dolor (pain)

    • Loss of function associated with inflammatory response

Page 13: The Lymphatic System Map

  • Overview of the lymphatic system - like the subway

  • Lymphatic vessels as connecting pathways

    • the lines that connect the system

  • Lymph nodes is a point in a network at which lines or pathways intersect or branch

    • the stations

  • Lymph is a colourless fluid containing white blood cells that drains through the lymphatic system into the bloodstream

    • the train carriages

Page 14: Key Lymphatic Components

  • Notable lymphatic locations:

    • thymus, spleen, lymph nodes

  • lymph nodes immune system also has more specialised lymphoid organs

  • thymus is where T cells are made

  • spleen responsible for filtering blood.

Page 15: Lymph nodes

  • Anatomical details:

    • Various veins and lymph glands involved in lymphatic drainage

    • the lymphatic system is similar to the blood vessel system. Lymph nodes, are often found where blood vessels meet or join together.

Page 16: Lymphatic Anatomy

  • blood enters through arteries and exits through veins

  • Lymph coming in through lymphatic vessels and leaves through lymphatic vessels.

  • Lymph nodes are points for meeting of cells, they connect everything.

Page 17: Next Steps: Molecules and Anatomy

  • Focus areas for understanding the immune response:

    1. Molecules involved (PRRs) - inflammation

    2. Lymphatic anatomy and its role in immunity

Page 18: Blood Cells Overview

  • Importance of blood cells:

    • Function of red blood cells (oxygen transport)

    • Function of white blood cells (immune cells)

Page 19: Red Blood Cells Facts

  • Key facts about red blood cells:

    • Normal count: 5-6 million cells/µl

    • Lifespan: ~110 days

    • Role in transporting O2 and CO2

Page 20: White Blood Cells

  • Types of white blood cells:

    • Innate immune cells

      • neutrophils, macrophages, dendritic cells

      • basophils, eosinophils, mast cells, monocytes

    • Adaptive immune cells

      • B cells, T cells,

Page 21: Innate vs Adaptive Immunity

  • Comparison of immune responses:

    • Innate immunity: Immediate response, non-specific

      • epithelial barriers

      • phagocytes

      • dendritic cells

      • complement

      • NK cells

    • Adaptive immunity: Delayed response, specific, involving B and T lymphocytes

  • innate immunity for first 12 hours, adaptive for 1-5 days

Page 22: Complement System

  • Overview of complement system:

    • Initial complement protein activation through antibodies

    • Importance of complement cascade in immune function

  • antigen binds to antibody - first compliment protein is activated, leading to a series of further complement proteins - compliment cascade

  • Complement is not a cell. It is a cascade of protein that senses danger

Page 23: Function of Complement

  • Key roles of complement:

    • amplifying inflammatory response

    • directly killing pathogens and recruiting immune cells

Page 24: Key Cells in Blood

  • Important blood immune cells:

    • Neutrophils, macrophages, and dendritic cells

Page 25: Neutrophils - Key Facts

  • Characteristics of neutrophils:

    • Most abundant white blood cells

    • Phagocytic activity against pathogens

    • consume and kill pathogens, using NETs

    • Recruitment to sites of inflammation

    • act fast and die fast

Page 26: Macrophages - Key Facts

  • Characteristics of macrophages:

    • Develop from tissue precursors

    • also consume and kill pathogens

    • Active phagocytic cells with long lifespan

    • always there - activated by inflammation

  • Tattoo - barrier breach and activates the macrophages and eats the ink and holds it. If macrophage dies, another one eats the ink.

Page 27: Dendritic Cells - Key Facts

  • Characteristics of dendritic cells:

    • Development in tissues from precursors

    • active phagocytic cells

    • Migrate out of peripheral tissues

    • Carry proteins to lymph nodes to Activate adaptive immune responses

    • unlike other, main job is not to eliminate but to pick up danger molecules and migrate to lymph codes where it meets T-cells and B-cells

Page 28: Reacting to Danger

  • Key components in responding to danger:

    • Recognizing danger via pattern recognition receptors (PRRs)

    • Mapping of immune response through lymph nodes and innate immune cells (neutrophils, macrophages, dendritic cells)