Innate Immunity
Chapter 14: The Innate Immune Response
Overview
Source: Nester's Microbiology: A Human Perspective, 10th Edition by Denise Anderson, Sarah Salm, Mira Beins, © 2022 McGraw Hill, LLC
Comparison of Innate vs. Adaptive Immunity
Innate Immunity
Non-Specific: Acts as an alarm system to pathogens and damaged or stressed cells.
Features:
First responders in the immune response, also referred to as acute inflammatory response.
Duration of response: dissipates in 2 to 14 days.
Key Components:
Cells: Macrophages, Natural Killer (NK) cells, Dendritic cells, Mast cells, Basophils, Eosinophils, Neutrophils (Granulocytes).
Actions: Phagocytosis, complement activation, interferon response, inflammatory response, and fever.
Adaptive Immunity
Features:
Lag time exists between exposure and maximal immune response.
Long-lasting effects, with immunological memory; responses can last years, dependent on the initial insult.
Key Components:
Cells: B cells, T cells (CD4+, CD8+), Plasma cells, Natural Killer T cells.
Responses are developed further through seroconversion and production of neutralizing antibodies.
Mechanisms of Innate Immunity
Physical and Physiological Barriers
First Line of Defense: Skin and mucous membranes act as barriers against microbial invasion.
Skin: Multi-layered epidermis, dead cells filled with keratin repel moisture.
Mucosal membranes: Line organs in the digestive, respiratory, and urogenital tracts, aiding in the movement and elimination of microbes.
Innate Immune Defenses (Analogy)
Security Walls: Prevent entry of pathogens.
Security Cameras: Detect invaders through sensor systems.
Security Teams: Consist of immune cells that eliminate threats through various actions mentioned earlier.
Cells of the Immune System
Hematopoiesis
Definition: Production of blood cells within the bone marrow, initiated from Hematopoietic stem cells.
Factors: Colony-stimulating factors (CSFs) are secreted by bone marrow to promote cell growth and differentiation.
Types of Blood Cells
Three General Categories:
Erythrocytes (Red Blood Cells): Responsible for oxygen transport.
Platelets (Thrombocytes): Involved in clotting.
Leukocytes (White Blood Cells):
Granulocytes: Include Basophils, Eosinophils, Neutrophils. They participate mainly in inflammation and allergic responses.
Mononuclear Phagocytes: Macrophages and Dendritic cells are derived from Monocytes; essential for pathogen digestion and the presentation to T cells.
Lymphocytes: B cells and T cells involved primarily in adaptive immunity.
Immune System Communication
Cell Surface Receptors
Function: Connect to the exterior of the cell, allowing them to sense environmental changes and coordinate responses.
Cytokines: Chemical signals produced by immune cells that bind to specific receptors to induce changes in the cell's behaviors, such as growth and movement.
Cytokine Storm
Definition: Overproduction of cytokines during an immune response, potentially leading to systemic inflammation and tissue damage.
Pattern Recognition Receptors (PRRs)
Definition: Receptors located on immune cell surfaces that recognize specific molecular patterns, triggering immune responses.
Types:
Microbe-associated molecular patterns (MAMPs) which include cell wall components and nucleic acids.
Pathogen-associated molecular patterns (PAMPs) and Damage-associated molecular patterns (DAMPs).
Common Types:
Toll-like receptors (TLRs): Located on cell membranes, detecting extracellular and ingested materials.
NOD-like receptors (NLRs): Found in the cytoplasm, recognizing microbial components or damage signals.
Innate Immune Proteins
Defensins
Action: Induced by TLR recognition, these proteins block microbial entry and inhibit viral lifecycle processes.
Cellular Proteins
SAMHD1: Depletes dNTP pools in the cell, may degrade ssDNA or RNA/DNA.
Tetherin: Prevents the release of budding enveloped viruses.
RIG-I and MDA5: Recognize dsRNA, activating responses to viral infections.
Protein Kinase R: Halts translation upon detection of dsRNA.
The Complement System
Overview
Function: Enhances the activities of the adaptive immune system, composed of small proteins (C1-C9) circulating in blood in inactive form.
Activation: Processes like the complement cascade resulting in the cleavage of proteins, particularly C3 into C3a and C3b.
Pathways of Activation
Alternative Pathway: Initiated by C3b binding to foreign cell surfaces.
Lectin Pathway: Triggered by pattern recognition molecules binding to mannose on microbial cells.
Classical Pathway: Activated by antibodies binding to antigens.
Results of Complement Activation
Opsonization: C3b binds to bacterial cells, promoting phagocytosis.
Lysis of Foreign Cells: Membrane attack complexes (MACs) formed by complement proteins destroy foreign cell membranes.
Inflammatory Response: C3a and C5a promote vascular permeability and recruit phagocytes.
Regulation of the Complement System
Host Cell Regulation: Regulatory proteins bind to host cell membranes, inactivating C3b to prevent inappropriate activation.
Interferon Response
Definition: Anti-viral cytokines released in response to viral RNA detection, encouraging neighboring cells to produce inactive antiviral proteins (iAVPs).
These mechanisms include degradation of mRNA and shutting down protein synthesis, ultimately leading to cell death in infected cells.
Phagocytosis
Mechanism
Chemotaxis: Phagocytes are drawn to sites of infection by chemoattractants.
Recognition and Attachment: Adaptive mechanisms involving direct receptor binding or opsonization.
Engulfment: Formation of a phagosome as pseudopods wrap around the pathogen.
Phagosome Maturation: Phagosome fuses with lysosomes to become a phagolysosome.
Destruction and Digestion: Enzymes and ROS (Reactive Oxygen Species) within the phagolysosome work to degrade pathogens.
Exocytosis: Remaining waste is expelled from the phagocyte.
Characteristics of Immune Cells
Macrophages: Phagocytize debris and pathogens; can activate into M1 (pro-inflammatory) or M2 (anti-inflammatory) states.
Neutrophils: The first responder, capable of NET formation for trapping and destroying pathogens.
The Inflammatory Response
Overview
Triggered by infection or tissue damage to localize and eliminate invaders while restoring tissue.
Symptoms include swelling, redness, heat, and pain.
Mechanisms
Vasodilation: Increased blood flow due to histamines and other mediators, enhancing the influx of immune cells.
Cellular Changes:
Diapedesis: Phagocytes exit blood vessels into tissues to respond to the infection.
Clotting factors prevent bleeding and contain the infection.
Pus Formation: Accumulation of dead cells and debris produced during the immune response.
Abscess Formation: Localized areas of pus within tissues.
Consequences of Inflammation
Can be damaging if chronic or excessive (e.g., cytokine storms, autoimmune diseases).