Innate Immunity: The Induced Response to Infection

Overview: The immune system is categorized into immediate innate immune response, induced innate immune response, and adaptive immune response based on the time courses and mechanisms involved in responding to pathogens.

Initial Response:
- Occurs immediately after pathogen invasion.
- Involves recognition of pathogens by preformed soluble effector molecules and resident effector cells within infected tissues.
Outcomes:
- Pathogen is eliminated, leading to the end of infection.
- Very minor tissue damage occurs, which is rapidly repaired.
Components:
- Involves the complement system and other antimicrobial molecules.
- If the pathogen persists:
- The body proceeds with the induced innate immune response.

Process:
- Involves further pathogen recognition by activating resident cells and recruiting effector cells to the infected tissue, resulting in inflammation, fever, and the acute-phase response.
Mechanisms:
- Soluble effector molecules and effector cells arrive to recognize and attack the pathogen.
Outcomes:
- Pathogen is resolved, leading to the end of the infection.
- Minor tissue damage is soon repaired.

Characteristics:
- If pathogens are not cleared, the adaptive immune response is initiated.
Indicators:
- Secondary lymphoid tissues become aware of the infection.
- Pathogen-reactive B and T cells are identified and proliferate and mature into effector cells.
Outcome:
- Effector molecules (such as antibodies) and effector T cells migrate to the infection site to eliminate the pathogen.
- Major tissue damage is gradually repaired.

Physical and chemical barriers and their normal flora
Molecules of Innate Immunity:
- Complement system
- Coagulation system
- Kinin system
- Protease inhibitors
- Antimicrobial peptides
Cellular Components:
- Macrophages
- Neutrophils
- Natural Killer Cells (NK cells)

Functionality:
- Cellular receptors are critical for distinguishing 'non-self' from 'self'.
- Examples include macrophage receptors recognizing bacterial cell-surface carbohydrates but not those of human cells.
- Natural Killer (NK) Cell Receptors:
- Recognize alterations on human cell surfaces caused by viral infections.

Role in Phagocytosis and Signaling:
- Carry a variety of phagocytic and signaling receptors to identify and respond to pathogens.
Specific Receptors Include:
- Scavenger Receptors (e.g., SR-A1, SR-A6, SR-B2):
- Recognize various pathogens, including bacteria and viruses.
- Toll-like receptors (TLRs):
- Family of signaling receptors recognizing different microbial products (e.g., LPS, peptidoglycan).
- Each TLR signals the nucleus for inflammation cytokine production.

LRR and TLR4 Activation:
- TLR4 is specific for LPS (lipopolysaccharides) and upon activation signals the nucleus for inflammatory responses.
- Complexes with CD14, MD2, and TLR4 lead to TIR activation.
- Activation due to LPS involves modulation of gene expression related to inflammation.

Characteristics of Inflammation:
- Marked by swelling, pain, heat, and redness at the affected area.

Types and Ligands:
- TLRs recognize various pathogen-associated molecular patterns (PAMPs) found in microorganisms like bacteria and viruses.
- Information on specific TLRs includes their ligands and cell types expressing them, as well as the cellular localization of these receptors (plasma membrane vs. endosomes).

Function of Inflammatory Cytokines:
- Raise body temperature, activate the liver, and induce the acute-phase response (e.g., acute-phase proteins like C-reactive protein and mannose-binding lectin).
- Cytokines such as IL-1, IL-6, and TNF-α play crucial roles in mobilizing immune responses through effects on the hypothalamus and bone marrow.

Mechanism of Interferon Action:
- Interferons (IFN) are crucial for inhibiting viral replication and alerting nearby uninfected cells.
- The interferon response includes positive feedback mechanisms to enhance production and is important in antiviral therapies (e.g., HBV, HCV).

Functionality of Inflammasomes:
- Inflammasomes amplify the innate immune response by increasing IL-1β production, a critical cytokine for inflammation.
  - We know IL-B is important because when given suppressant, inflammatory response is decreased.
- Inflammasome: a combination of several proteins
- Balance of inflammatory and antiinflammatory is lost in inflammatory diseases.
- This process is characterized by pyroptosis, underlining the connection between cytokine secretion and cell death mechanics.

Key Characteristics:
- Neutrophils are the first responders, programmed to kill pathogens via various granules containing antimicrobial substances.
  - Recruited from the bloodstream by the cytokine CXCL8,
- Interaction between endothelium and neutrophils slow down endothelium in blood stream and allow them to stop flowing in blood and migrate into the tissue
  - I-CAM1, CXCL8
- They undergo processes involving phagocytosis, respiratory bursts, and inflammation regulation, ultimately leading to cell death due to exhaustion of granule content.

Complement Pathways:
- Activation pathways include the classical, alternative, and lectin pathways.
- Key players include C-reactive protein during the classical pathway and mannose-binding lectin as well as their associated serine proteases (MASP).

Overview and Function:
- NK cells participate in the innate immune response analogous to cytotoxic T cells, recognizing and killing infected cells.
- Activation requires interaction with target cells and can modify local immune responses through cytokine secretion (e.g., IL-12 and IFN-gamma interactions with macrophages).

Modulation of Immune Responses:
- The balance between NK cells and dendritic cells determines the outcome of immune responses, either leading to NK-mediated cell killing or initiating adaptive immunity through dendritic cell maturation.