Molecular & Cell Biology II - Immune System Primer

Primary Lymphoid Organs

  • Thymus: Encapsulated organ where T cells mature and are selected based on their ability to not recognize the host.

  • Bone Marrow: Site of hematopoiesis.

  • Lymph Nodes: Part of the immune system.

Immune System Overview

  • The immune system functions as a remote pathogen detection system.

  • Different locations are involved:

    • Injury site/point of entry.

    • Lymph nodes.

    • Bone marrow.

Hematopoiesis

  • All cells in the blood are derived from hematopoietic stem cells.

  • Hematopoiesis: The process of diversification of immune cells, primarily occurring in the marrow of long bones.

  • A healthy human adult produces approximately 10^{10} to 10^{11} new blood cells per day.

Diversification of Immune Cells

  • Hematopoietic stem cells produce different blood cells depending on the signals (cytokines) they receive.

  • Examples of cytokines involved: IL3, GM-CSF, M-CSF, SCF, TPO, EPO, IL17, IL15, IL2, IL7.

  • All cells in the immune system are derived from stem cells and differentiate into either myeloid or lymphoid precursors under the control of cytokines.

  • Myeloid cells contribute to innate immunity.

  • Lymphoid cells contribute to adaptive immunity.

Innate vs. Adaptive Immunity

  • Innate Immunity:

    • Immediate/continuous response.

    • Involves mechanical and chemical defenses.

    • Key cells: Macrophages, Dendritic cells, Neutrophils, NK cells.

    • Complement cascade activation.

    • Release of cytokines like IL-1 and IL-6.

  • Adaptive Immunity:

    • Response time: Days.

    • Involves B and T cells.

Immune Events Following a Skin Wound

  • Tissue damage occurs.

  • Vasoactive and chemotactic factors are released.

  • Bacteria enter the wound site.

  • Extravasation (migration of cells out of blood vessels) occurs.

  • Phagocytic cells migrate to the site.

  • Exudate (fluid accumulation) occurs.

  • Margination (adhesion of cells to blood vessel walls) takes place.

  • Complement, antibodies, and C-reactive protein are involved.

Myeloid Cells and Innate Immune Response

  • Granulocytes:

    • Neutrophils, mast cells, basophils, and eosinophils are important granulocytic cells.

    • Involved in phagocytosis or release of innate immune inflammatory mediators.

  • Mast Cells:

    • Release histamine, cytokines, and other inflammatory mediators when IgE (immunoglobulin E) bound to the cell surface is crosslinked by an allergen.

Monocytes, Macrophages, and Dendritic Cells

  • Monocytes:

    • Quiescent precursors to macrophages, found in all tissues.

    • Upon activation by invading pathogens or cytokines, monocytes differentiate into macrophages or dendritic cells.

  • Key Immunological Functions:

    • Detection of pathogens via Toll-like Receptors (TLRs).

    • TLR signaling triggers inflammation.

    • Phagocytosis of pathogens.

    • Antigen presentation.

Inflmesammaso

  • NALP3 Inflammasome: A key component of the innate immune response.

  • Activation:

    • Signal 1 (Priming): Microbial ligand binds to TLR, or endogenous cytokines (TNF) bind to TNFR, leading to gene transcription.

    • Signal 2 (Activation): Triggered by bacterial toxins (e.g., Cholera, pore-forming toxins), Candida albicans, cytosolic bacterial DNA, or Influenza virus M2 protein.

    • NLRP3 inflammasome is activated.

    • Procaspase-1 is processed into Caspase-1.

  • IPAF Inflammasome

  • Caspase-1 cleaves ProIL-1β into active IL-1β.

Phagocytosis

  • Phagocytosis of bacteria is a crucial process in innate immunity.

  • Phagocytosis of viruses "decorated" with antibodies:

    • Neutralizing antibodies bind to the virus, preventing receptor binding and subsequent infection.

    • Phagocytes engulf the antibody-bound virus.

Lymphoid Cells and Adaptive Immunity

  • T and B cells are the main cell types of the adaptive immune system.

  • B cells:

    • Express membrane-bound antibody (IgM) on their surface to recognize intact (unprocessed) antigen.

  • T cells:

    • Express a T cell receptor (TCR) that recognizes processed antigen bound to MHC molecules.

Antigen-Presenting Cells (APCs)

  • Professional APCs: Macrophages, Dendritic cells, B cells.

  • Present antigens via MHCII molecules.

Antigen Presentation

  • APCs (e.g., dendritic cells) take antigens (