Lecture 16: The Innate Immune System

Overview of the Immune System

What does the Immune system do?

  • immune system function: Protects against pathogens and damaged cells

Cells

  • Key Components:

    • Leukocytes (White Blood Cells): Produced in bone marrow

    • Thymus: where a specific type of white blood cell matures.

    • Lymphatic System: Comprising lymph vessels and lymph node

      • transports lymph fluid (derived from extracellular fluid) and contains white blood cells that check for pathogens.

Divisions of the Immune System

Innate Immune System

  • Innate Immune System: less-specific; blocks against anything foreign

    • innate - present from birth, always have it

    • Includes:

      • Surface defenses: keep foreign things out

        • examples: skin, tears, coughing generally eject and wash away foreign item

      • White blood cells and chemicals that attach broad classes of foreign things

        • examples: phagocytes, defensin proteins attack many broad classes of pathogens (bacteria, viruses, fungi, etc)

Adaptive Immune System

  • Adaptive Immune System: more specific; recognizing specific pathogens

    • white blood cells and antibodies that recognize and attack very specific pathogens

      • examples: lymphocytes attack specific pathogens

    • acquired - developed upon exposure to a particular pathogen

    • Includes memory of prior infection or vaccination

Innate Immunity: Physical, Chemical, and Cellular Defenses

Physical Defenses in Innate Immunity

Surface Barrier: Skin

  • held together by tight junctions

  • act as a tight barrier against pathogens.

  • ALSO PART OF CHEMICAL DEFENSE

Surface Barrier: Mucous Membranes

  • contain mucus that traps pathogens

  • Found in areas such as:

    • mouth

    • nose

    • lungs

    • respiratory tract

    • digestive tract

    • urinary tract

    • reproductive tract

Mechanical Defenses:

  • shedding skin

  • urine

  • tears

  • eye and eyelashes

  • mucocilliary escalator: cilia on cells lining airways that push microbes upward out of airway to be swallowed by digestive system and killed by stomach acid

Microbiome

  • Microbiome: full set of microbes present in a particular environment

    • Occupies space and uses resources to prevent pathogen colonization, makes it harder for microbes to grow

  • Human Microbiome: full set of microbes present in and on a human

  • ALSO PART OF CHEMICAL DEFENSE

Chemical Defenses in Innate Immunity

Skin

  • skin produces:

    • fats

    • acid

    • salt

Microbiome

  • microbiome produces chemicals that hurt pathogens.

Digestive Tract

  • saliva: antimicrobial enzymes

  • stomach: acid

  • intestines: antimicrobial enzymes, bile, antimicrobial peptides

Vagina

  • glycogen converted to lactic acid by Lactobacilli

    • Vaginal produces glycogen that lactobacilli eat and ferment into acid

      • maintains acidic pH in vagina that protects from pathogens

Antimicrobial Peptides:

  • Antimicrobial Peptides: short proteins that can damage microbes

    • Example: Defensins insert into microbial membranes, causing cell lysis.

Complement Proteins:

  • Complement Proteins: found in blood

    • Functions include:

      • Opsonization: complement proteins stick to pathogens and make them more recognizable to white blood cells to be engulfed. (phagocytosis)

      • Inflammation: complement proteins make factors to signal and alert for white blood cells by causing inflammation

      • Lysis: complement proteins form holes in microbial cells to make cells leak and burst

    • Nemonic to remember: favorite “complement” is you look “oil” today

Interferon:

  • Interferon: protein made by virus infected cells

    • cells make interferon as cry for help

      • interferon is sent out of cell for chemical signaling to other cells

    • Neighboring cells receive interferon’s message and respond by:

      1. neighboring uninfected cells destroy RNA and reduce protein synthesis

        • shut down transcription and translation

          • prevents virus from being able to replicate inside of them

      2. neighboring infected cells undergo apoptosis (kill themselves)

      3. activates immune cells

    • Analogy: Interferon functions like a neighborhood watch alerting neighbors of infection.

How immune cells recognize pathogens:

  • 3 types of Innate Immune Cells:

    1. natural killer cells

    2. granulocytes

    3. phagocytes

  • granulocytes and phagocytes both recognize pathogens chemically:

    • pathogen recognition receptors (PRRs): receptors that allow them to recognize pathogens

      • PRRs bind to molecules called pathogen-associated molecular patterns (PAMPs) and respond to fight pathogen

        • pathogen-associated molecular patterns (PAMPs): foreign molecules, found in microbes

          • examples of PAMPs:

            • lipopepetide on cell walls

            • flagellin in flagella

            • peptidoglycan on cell walls

Natural Killer Cells (NKC’s)

  • Natural Killer Cells (NKC’s): detect infected cells that do not have MHC I and kill them

    • MCH 1 (major histocompatability complex 1): found on nearly all cells, displaying samples of molecules found inside cell so pathogen can check for pathogens

      • some intracellular pathogens remove MHC I from cell they are infecting

        • Natural Killer Cells recognize infected cells that are missing the MHC I and destroy them

Cellular Defenses in Innate Immunity

Granulocytes

  • Granulocytes: contain granules filled with chemicals that hurt microbes

    • Basophils, eosinophils, and neutrophils are granulocytes

      • Nemonic to remember: Granulocytes = BEN with pockets full of poison

    • Basophils and Mast cells:

      • Basophils are found in blood

      • mast cells are present in most tissues

      • both basophils and mast cells contain granules release histamine (don’t directly attack microbes)

      • involved in allergic response and inflammation

    • Eosinophils:

      • found mainly in tissues below mucous membranes

      • attack parasitic worms

      • involved in allergic responses

    • Neutrophils:

      • granules contain antimicrobial substances

        • can release intracellularly or extracellularly

          • if bump into pathogen, can dump granules to kill pathogen OR can engulf microbe and kill it when inside cell

Phagocytes

  • Phagocytes: cells that eat microbes

    • incude:

      • macrophages

      • neutrophils

        • Neutrophils are BOTH granulocytes and phagocytes

      • Nemonic to remember: Phagocyte = NoM (Neutrophil OR Macrophage)

    • STEPS:

      1. phagyocyte engulf bacterium

      2. forms phagosome (vesicle of membrane)

      3. phagosome fuse with lysosome containing digestive enzymes

      4. digest bacteria into little pieces and kill it

      5. cell can use some pieces

      6. unused pieces are released from cell as waste

Innate Immune Processes:

Inflammation:

  • Inflammation: innate immune response to infection or injury

    • blood vessels become leaky, delivering blood and WBCs to specific area

    • Signs of Inflammation: (acronym: SHARP)

      • Swelling

      • heat

      • altered function

      • redness

      • pain

    • Acute vs. Chronic Inflammation:

      • Acute inflammation - short-term

        • resolves within days as infection clears and damage is repaired

        • helpful

      • Chronic inflammation - long term

        • two cases:

          1. infection doesn’t clear and inflammation continues for months or years

          2. causes damage healthy tissues as well as fight infection

            • inflammation is inappropriate - white blood cells damage own tissue if inflammation continues for too long

              • example: auto-immune response, allergy

    • Response Mechanism:

      1. pathogen enters the body

      2. macrophage and mast cells detect pathogen and release chemicals into bloodstream (into blood vessels)

      3. phagocytes are attracted to chemical released, and squeeze between capillary walls, following chemical signals to where they are most concentrated

        • extravasation: phagocytes move outside blood vessels to where chemical signal is most concentrated

          • “extra-” means outside

          • “vasa” means vessel

            • outside vessel

      4. within damaged tissue, neutrophils release chemicals that break apart pathogens

      5. macrophages and neutrophils phagocytize pathogens and cellular debris

Fever:

  • Fever: Indicates an increase in body temperature above 37.8°C/101°F (normal: 37°C)

    • fever is caused by pyrogens

      • pyrogens: chemical messengers that cause hypothalamus to increase temperature, causing a fever

        • hypothalamus receives signals (pyrogens) from body and increases temperature

        • chemicals come from:

          • microbes infecting cells

          • white blood cells that detect infection

    • Benefits of Fever:

      • Prevents some microbial growth

      • enhances immune system function (increased enzymatic activity rate)

    • Risks:

      • Extremely high fever (42°C) can be life threatening

        • lead to enzyme denaturation and cell death.