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 (