BIOL2022 Innate Immunity

INNATE IMMUNITY

Overview of Innate Immunity

  • Innate immunity serves as the first line of defense against pathogens.

  • It operates through a variety of mechanisms that recognize and eliminate invading microbes and toxins.

Components of Innate Immunity

  • Pathogens: Disease-causing organisms, such as bacteria, viruses, and fungi.

  • PAMPs (Pathogen-Associated Molecular Patterns): Molecular signatures found on pathogens (e.g., lipids, proteins).

  • Cytokines: Signaling proteins that modulate immune responses.

Immune Response Mechanisms

  • Macrophages: Engulf and digest pathogens (phagocytosis).

    • Utilize Toll-like Receptors (TLRs) for pathogen recognition.

  • Dendritic Cells: Present antigens to T-cells and produce cytokines, bridging innate and adaptive immunity.

  • Natural Killer (NK) Cells: Attack and destroy virally infected cells or tumor cells.

  • Cytotoxic T Cells: Recognize and kill virally infected cells.

  • B Cells: Part of adaptive immunity; produce antibodies against specific antigens.

TOLL-LIKE RECEPTORS (TLRs)

Discovery of TLRs

  • Medzhitov and Janeway (1997): Proposed that immune responses begin with sensing 'danger' from pathogens.

  • Christiane Nusslein-Volhard (1985): Identified Toll genes in Drosophila melanogaster, linking them to developmental processes.

  • Jules Hoffmann (1996): Found that Toll plays a role in immune responses against infections in flies, leading to further discoveries of TLRs in vertebrates.

Role of TLRs in Innate Immunity

  • TLRs detect PAMPs, initiating immune responses such as inflammation and phagocytosis.

  • Example: TLR4 recognizes lipopolysaccharides (LPS) from bacterial membranes.

Mechanisms of TLR Signaling

  • Activation triggers intracellular signaling cascades to activate immune responses, including:

    • MyD88: A key adaptor protein that initiates pathways leading to inflammatory gene expression.

    • NF-kB: Transcription factor that promotes the expression of cytokines and other inflammatory mediators.

    • IRFs (Interferon Response Factors): Induce expression of Type I interferons critical for antiviral responses.

Effect of TLR Activation on Immune Cells

  • Macrophages: Produce inflammatory cytokines and initiate phagocytosis.

  • Dendritic Cells: Maturation and antigen presentation lead to T-cell activation.

CYTOKINES AND INTERFERONS

Key Functions of Cytokines

  • Recruit immune cells to sites of infection.

  • Induce fever and activate the acute-phase response.

  • Contribute to the resolution of infections by promoting tissue repair.

Classification of Immune Cells

  • NK Cells: Provide immunological surveillance and kill infected or cancerous cells.

  • Dendritic Cells: Antigen presenting cells that link innate and adaptive immunity.

  • Macrophages and Neutrophils: Primary phagocytic cells involved in the initial response to infection.

JAK-STAT Signaling Pathway

  • JAKs (Janus Kinases): Activate responses by phosphorylating receptors in response to cytokines.

  • STATs (Signal Transducers and Activators of Transcription): Function as transcription factors that mediate downstream signaling in immunity.

Systemic Effects of Cytokines

  • Cytokines like IL-1, TNF-alpha, and IL-6 exert both local and systemic effects by regulating immune responses and influencing fever.

  • They play a critical role in the acute phase response, facilitating immune activation and mobilization of immune cells.

ADAPTIVE IMMUNE SYSTEM VS INNATE IMMUNE SYSTEM

  • Adaptive Immunity: Involves T and B lymphocytes, providing specific responses and memory against pathogens.

  • Innate Immunity: Rapid responses utilizing physical barriers, phagocytes, and the complement system to combat pathogens without prior exposure.