Innate immunity, acute inflammation Flashcards
PAMPS/MAMPS
Pathogen/Microbe Associated Molecular Pattern
A conserved structural component of microbes/fungi/viruses that is sensed by the innate immune system
Pattern Recognistion Molecules
Component of the innate immunse system that binds to and recognizes PAMPS
What happens upon recognition/binding of PAMPS by the Pattern Recognition Molecules of the innate immune system?
- Phagocytosis (eg mannose receptor)
- Opsonization (eg. soluble lectins)
- Killing and breakdwon (eg lysozyme)
- Production of inflammatory mediators (eg TLRs, NLRs, RLRs)
What do macrophages release when activated and what does this initiate?
- Cytokines (TNF-a and IL-1B)
- Chemokines (IL-8)
This initiates the inflammatory response by causing vasodilation and increased vascular permeability (Causing redness/heat/edema)
Inflammatory cells can now migrate into tissues and release inflammatory mediators that cause pain
Cell surface TLR (Toll-Like Receptor) action
When activated (primarily by bacteria and fungi):
- Increase expression of Cytokines, adhesion molecules, and costimulators
- Cause acute inflammation
- Stimulate adaptive immunity
What type of cells have Toll-Like Receptors?
TLRs are primarily on innate immune cells like Macrphages and Dendritic Cells as well as non-immune cells such as fibroblast cells and epithelial cells
Endosomal Toll-Like Receptor (TLR) action
When activated (primarily by bacterial and viral particles):
- Produce type 1 interferon (IFN a, b)
- Activate antiviral state
Where are NOD-Like Receptors (NLRs) located?
In the cytoplasm
NOD-Like Receptor (NLR) action
When activated by bacteria or tissue damage:
- Leads to the secretion of IL-1B
- IL-1B then causes acute inflammation
Process of Leukocyte Migration (eg Neutrophils)
What cell produces histamine?
Basophils and Mast Cells
What does histamine do?
Histamine increases the permeability of the capillaries to WBCs and some proteins, to allow them to engage pathogens in the infected tissues
Cytokines
A broad category of small proteins important in cell signaling
Chemokines
Class of cytokines with functions that include attracting WBCs to sites of infection
Prostaglandins
Group of compounds with varying hormone-like effects; control processes such as inflammation, blood flow, blood clots formation, and the induction of labour
TNF-a
(Tumor Necrosis Factor-alpha)
A cytokine that causes:
- Endothelium vascular leakage and WBC recruitment
- Fever
Which cytokines act on the brain to cause fever?
IL-1
IL-6
TNF-a
IL-1
(Interleukin-1)
A cytokine that causes:
- Fever
- Acute inflammation
- Endothelium to express adhesion molecules
- Induction of chemokine secretion that recruits WBCs
IL-6
(Interleukin-6)
A cytokine that causes:
- Fever
- Production of acute-phase proteins
What cytokines act on the liver to cause acute phase protein production?
- IL-1
- IL-6
What cytokines act on the bone marrow causing leukocyte production?
- TNF
- IL-1
- IL-6
IL-8
(Interleukin-8)
A cytokine that acts as the major chemotactic factor for neutrophils
Phagosome
A vacuole in the cytoplasm of a cell, containing a phagocytosed particle enclosed within a part of the cell membrane.
How do cells kill the microbes within the phagosomes after phagocytosis?
- Phagosome fuses with lysosome
- The microbe is killed by:
- ROS (Reactive Oxygen SSpecies)
- NO (Nitric Oxide)
- Lysosomal Enzymes
The Complement System (General Info)
- System of host blood proteins
- Generates cascade of enzymatic reactions leading to opsonization or destruction of a pathogen
Opsonization
Mechanism whereby pathogenic molecules, microbes, or apoptotic cells (antigenic substances) are connected to antibodies, complements, or other proteins to attach to the cell surface receptors on phagocytes and NK cells
Complement System 3 Activation Pathways
- Classic: IgG or IgM mediated
- Alternative: Microbe surface molecules
- Lectin: Mannose on microbe surface binds lectin
C3b
Component of the complement system that causes opsonization and phagocytosis of microbes
C3a and C4a
Components of the complement system that cause anaphylaxis/inflammation
C5a
Components of the complement system that causes anaphlyaxis and neutrophil chemotaxis
C5b-9
(MAC) Membrane Attack Complex
Forms transmembrane channels that disrupt the cell membrane of target cells, leading to cell lysis and death
Selectins
Family of cell adhesion molecules
How do cells react to viruses?
- RIG-llike receptors (RLRs), Cytosolic DNA Sensors (CDSs), and Endosomal TLRs bind to viral particles and release type 1 intererons (IFN a or b)
- Type 1 INF binds to receptors on nearby cells which causes them to have an antiviral state that inhibits viral replication via:
- Inhibiting proetin synthesis
- Inhibiting viral genome expression and virion assembly
- Producing RNAase which degrades viral RNA
What signals NK cells to kill virally infected cells?
Lack of MCH 1 expression
Where are RIG-like receptors (RLRs) located and what do they sense/react to?
- Location: cytoplasm
- Sense/react to: viral replication intermediates
Where are NLRs (NOD-like receptors) and what do they sense/react to?
- Location: cystoplasm
- Sense/React to: Bacterial components
Where are CDSs (Cystosolic DNA sensors) located and what do they sense/react to?
- Location: Cytoplasm
- Sense/React to: DNA released from microbes or from cellular damage
What are the cardinal signs of inflammation?
- Heat
- Redness
- Pain
- Swelling
- Loss of Function
Integrins
Transmembrane receptors that facilitate cell-extracellular matrix (ECM) adhesio
What increases the expression of integrin?
Cytokines can increase the production of integrin to aid with WBC migration
