human bio week 12 lecture 2

General Features and Functions of the Innate Immune System

• The immune system's primary function is to:

  • Detect pathogens or foreign entities.

  • Prevent infection.

  • Eradicate established infections.

• Two major divisions:

  • Innate Immune System:

    • First line of defense.

    • Blocks pathogen entry.

    • Removes pathogens that enter.

    • General response; acts the same way every time a specific pathogen is encountered.

  • Adaptive Immune System:

    • Specific response against each particular pathogen.

    • Antibodies are produced by lymphocytes (B cells).

    • Antibodies are specific to each pathogen.

    • Adapts upon repeated exposure.

Innate Immunity: Activation and Components

• Innate immunity activates quickly (within hours).

• First line of defense: Physical and chemical barriers (epithelial cells, hydrochloric acid).

• Epithelial cells line various tracts (skin, GI, respiratory, urinary, reproductive) and prevent pathogen entry.

• Immune cell recruitment occurs when pathogens breach barriers.

• Phagocytes:

  • Engulf and destroy pathogens via phagocytosis (cell eating).

  • Neutrophils and monocytes are the first phagocytes to arrive.

  • Monocytes mature into macrophages upon entering tissue.

• Other immune cells:

  • Dendritic cells: Stimulate the adaptive immune response.

  • Mast cells: Induce vasodilation, increasing blood flow to the affected area and allowing more immune cells to infiltrate.

  • Natural killer cells: Recognize and kill infected cells.

Features of Innate Immunity

• Fast activation (hours).

• Short-lived (days), compared to the adaptive immune system (months/years).

• Provides time to activate the adaptive immune response.

• Nonspecific: No memory of previous encounters; responds the same way each time it encounters the same pathogen.

• Leukocytes (white blood cells) circulate in the bloodstream and migrate into tissues when signaled.

• Tissue-resident immune cells act as surveillance (e.g., Langerhans cells in the epidermis).

Key Immune Cells: Neutrophils and Monocytes

• Neutrophils and monocytes are crucial for phagocytosing pathogens.

Detection of Foreign Entities by the Innate Immune System

• Innate immunity follows the same general process upon encountering the same pathogen.

• Pathogen-associated molecular patterns (PAMPs):

  • Molecules (proteins, nucleic acids) expressed by pathogens.

  • Recognized as foreign by the immune system.

• Damage-associated molecular patterns (DAMPs):

  • Molecules released by infected, damaged, or dying cells.

• Pattern recognition receptors (PRRs):

  • Receptors on immune cells that recognize and bind to PAMPs and DAMPs.

  • Activation leads to activation of the innate immune response.

• PAMPs are essential for pathogen survival and infectivity.

• Approximately 100 types of PRRs can detect over 1,000 different PAMPs and DAMPs.

Pattern Recognition Receptors (PRRs)

• Expressed by various cell types (epithelial cells, phagocytes, dendritic cells).

• Expressed in different parts of the cell:

  • Cell surface: Detect extracellular pathogens.

  • Cytoplasm: Detect cytoplasmic PAMPs and DAMPs.

  • Endosomes: Detect pathogens internalized into endosomes.

• Advantage: Detect pathogens at various stages of their life cycle.

Types of Pattern Recognition Receptors (PRRs)

• Toll-like receptors (TLRs).

• Inflammasomes.

• RIG-like receptors.

• Cytosolic DNA sensors.

Toll-Like Receptors (TLRs)

• Major PRRs that recognize foreign proteins and nucleic acids (DNA and RNA).

• Different types are scattered throughout the cell:

  • Cell surface TLRs: Detect various pathogens.

  • Endosomal TLRs: Detect nucleic acids after engulfment.

• A range of TLRs detect both RNA and DNA.

• Equip cells to detect pathogens at different stages of their life cycle.

Signaling Pathways Activated by PRRs

• Most PRRs (but not all) activate signaling cascades that activate key factors:

  • NF-κB (Nuclear Factor kappa B):

    • Usually inactive in the cytoplasm, bound to IκB.

    • TLR activation causes IκB degradation, releasing NF-κB.

    • NF-κB translocates to the nucleus, binds to DNA, and induces transcription of genes encoding cytokines, enzymes, and proteins important for inflammation and stimulation of the adaptive immune system.

  • Interferon Regulatory Factors (IRFs):

    • Inactive in the cytoplasm.

    • TLR activation leads to IRF activation.

    • IRFs move to the nucleus, bind to DNA, and trigger transcription and translation of type I interferons.

    • Interferons establish an antiviral state within the cell.

Summary of Innate Immune System Key Points

• First line of defense against invading pathogens; fast activation (hours).

• Responds the same way each time it encounters the same pathogen (no memory).

• Activates key cytokines and proteins, leading to:

  • Inflammation.

  • Defense mechanisms.

  • Clearing the infection.

  • Activating the adaptive immune response.