Immunology: Immune Cell Function

Natural Immunity

• Natural immunity is a crucial part of the immune system
• It has cellular components and a mode of action
• The immune system has three main functions: recognition, communication and elimination (effector functions)
• Natural immunity involves cells, recognition mechanisms, killing mechanisms, and other effector functions

Immune System Cells

• Monocytes/Macrophages: Originate from bone marrow pluripotent progenitors, myeloid progenitors. Size 10-15µm, bean-shaped nucleus, in circulation. Become macrophages when exiting the circulation.
• Granulocytes: Major participant in inflammatory processes but not an initiator
• NK cells (Natural Killer): Originate from bone marrow and lymphoid progenitors, 5-10% are in the circulation amongst lymphocytes. Contain cytotoxic granules and lack antigen-binding cell membrane receptors. Destroy infected or tumor cells.
• Mast cells: Originate from myeloid progenitor cells and differentiate in tissue, mostly around small blood vessels. Release substances that regulate vascular permeability during activation, in both natural and adaptive immune responses, and help with allergic reactions (FcERI on cell surface). Produce histamine.
• Complement System: A cooperative chain of proteins that protects cells through inhibitors. Activation can occur in three pathways: alternative, classical, and lectin (often activated by MBL).

Macrophages

• Types based on tissue location: microglia (brain), Kupffer cells (liver), histiocytes (connective tissue), osteoclasts (bone), alveolar macrophages (lung)
• Phagocytic cells, one of the first cell types to recognize a pathogen.
• Function: recognition, destruction, communication, and restoration

Dendritic Cells

• Originate from myeloid or lymphoid progenitors.
• Immature cells migrate from blood to tissue where they undergo phagocytosis and mature
• Migrate to lymph nodes.
• Professional antigen-presenting cells (APCs) . One of the first cell types to recognize a pathogen

Neutrophil Granulocytes

• Most abundant leukocyte (68%–99%), found in the blood, but not normal healthy tissue
• Capable of phagocytosis and destroying pathogens
• Major participant in inflammatory processes, but not an initiator
• Invade tissues in response to injury

Basophil & Eosinophil Granulocytes

• Basophils (1%): Large granules (cytoplasm), 2-lobed nucleus. Involved in allergic reactions, histamine release, and defence against parasites. High affinity IgE receptors.
• Eosinophils (2-3%): Involved in protection against parasites, allergic reactions.

Mast Cells

• Originate from myeloid progenitor cells, found in tissue, mainly around small blood vessels
• Release substances during activation to regulate vascular permeability. Crucial to both natural and adaptive immune responses. Play a key role in allergic processes (FcERI on cell surface).
• Produce histamine. One of the first cell types to recognize a pathogen.

NK Cells (Natural Killer)

• Originate from bone marrow pluripotent progenitors and lymphoid progenitors
• In circulation around 5-10% of lymphocytes.
• Have cytotoxic granules in cytoplasm, lack antigen binding cell membrane receptors.
• Destroy infected or tumor cells

Professional Antigen-Presenting Cells (APCs)

• Cells capable of antigen presentation:
  • Macrophages -Dendritic cells -B lymphocytes

Recognition Mechanisms

• The goal is to identify structures and danger signals common in pathogens but not in humans (e.g., bacterial cell wall, flagellin, double-stranded RNA).
• Recognition can't be avoided, covers all pathogen types targeted by their characteristic structures
• Includes pattern recognition receptors (PRR), pathogen-associated molecular patterns (PAMPs), and threat-associated molecular patterns (DAMPs).

Receptor Types

• TLR-like receptors
• RIG-like receptors
• NOD-like receptors
• Scavenger receptors
• C-type lectin receptors
• Mannose recognition receptors

Danger Signals

• Natural immune system recognises molecules from damaged or necrotic cells (DAMPs)
  • Examples include extracellular ATP, actin.

Recognition Mechanisms of NK cells

• NK cell activity boosted by cytokines that activate receptors.
• Inhibitory receptors prevent lysis of healthy cells (KIR receptors bind to MHC I).
• Activating receptors (KAR) on NK cells trigger immune response.

Opsonisation

• Opsonisation aids natural immune cells in identifying pathogens.
• Recognition is quicker with the presence of opsonins. Opsonins bind to pathogens for better identification.
• Antibodies, complement fragments, and acute phase proteins are examples of opsonins that form a bridge between pathogen and the responding cell

Killing Mechanisms

• Mechanisms of killing include phagocytosis, production of soluble mediators, complement system, and NK cells.

Phagocytosis

• Cell killing and antigen presentation in macrophages
• Degradation and cell killing in dendritic cells and neutrophil granulocytes

Production of Soluble Mediators

• Reactive oxygen radicals (ROS)
• Nitric oxide (NO)
• Proteolytic enzymes
• Antimicrobial peptides

Complement System

• Cooperative chain of proteins (protease cascade).
• Protects cells via inhibitors on cell surfaces or dissolved in the plasma.
• Activation pathways: alternative (continuously active, inhibited by cell structures), classical (activated by antibody molecule), and lectin (activated by mannose-binding lectin).

Complement System Functions

• Destroys pathogens, opsonises pathogens (makes them easier targets), attracts phagocytes (chemotactic), clears immune complexes

NK Cells

• NK cells can eliminate infected or tumor cells by secreting cytotoxic granules or activating cell death receptors.
• Antibody-dependent cellular cytotoxicity (ADCC) is another way that immune system cells can activate NK cells
• Fc receptors on NK cells recognize antibodies on pathogens

Other effector functions

• Antiviral response
• Inflammation
• Opsonisation
• Antigen presentation

Antiviral Response

• Type I interferons (α and β)
• NK cells
• Cytotoxic T cells
• Neutralizing antibodies

Virus Induced Interferon Production

• Intracellular PRRs detect viruses, triggering IFN-β expression and IFN I production.
• Autocrine and paracrine action.
• All nucleated cells can be infected and contain intracellular PRRs and produce type I IFN.
• Plasmacytoid dendritic cells produce very large amounts of type I interferon.
• They cluster to the T-cell areas of lymph nodes following viral infection.

Function of Type I interferons

• Inhibition of RNA synthesis
• RNA degradation
• Inhibition of protein synthesis
• Degradation of viral proteins
• Induction of apoptosis
• Activation of NK cells and cytotoxic T cells (activation of DCs)

Acute Inflammation

• Body's rapid response to tissue damage, delivering defense elements (leukocytes and plasma proteins).
• Components: increased blood vessel diameter, increased permeability, and leukocyte migration.
• Important for fighting microbes, developing immune response, and activating immune cells.

Acute Inflammation Continued

• Inflammation isolates heavily-infected areas, preventing microbes from entering bloodstream
• Cytokines, like IL-6, TNF, and IL-1 trigger immune response.
• Increase hypotension, antimicrobial protein production, and white blood cell formation

Opsonisation

• Main opsonins are antibodies, complement fragments, and acute-phase proteins. They facilitate pathogen recognition by natural immune cells and influence the response.

Antigen Presentation

• Professional antigen-presenting cells (APCs): macrophages, B lymphocytes, and dendritic cells expressing MHCII for activation of T-helper and naive T cells.

Test your knowledge of immune cells! This quiz covers pathogen recognition, macrophage functions, dendritic cell migration, cell origins, and the roles of neutrophils, NK cells, and mast cells in immune responses.