B-I Innate immunity and complement Flashcards
Types of barriers
Anatomical, mechanical, chemical, microbiological
Describe the anatomical barrier
Prevents pathogen entry physically. Examples include the skin, epithelium in lungs, gut
Describe the mechanical barrier
Also physically prevents entry by pathogens. Examples include tight junctions between cells, flow of air and fluid (mucus, tears) over the anatomical barrier
Describe the chemical barrier
Breaks down or destroy pathogens. Low pH in the stomach, antimicrobial proteins and toxic chemicals
Lysozyme
An antimicrobial glycosidase that breaks down a chemical bond in peptidoglycan in the bacterial cell wall. Produced by neutrophils
Defensin
Peptide that is electrostatically attracted to bacterial membrane and form pores in them, destroying the cell
How does the microbiota help with the immune system?
Fights for space with pathogenic bacteria, can kill them. Producing antimicrobial substances. Stimulates epithelial cells to produce antimicrobial substances as well
Macrophage
Activated monocytes. Round nucleus with massive vacuoles. Does phagocytosis, activated bactericidal mechanisms, APC, produces cytokines
What cytokines do macrophages produce?
IL-1β, TNF-α, IL-6, CXCLβ, IL-12
Dendritic Cell - DC
Has long arms so it can present a lot of MHC Class II. Does antigen uptake in peripheral tissue, APC, cytokine production
Neutrophil
Granulocyte. Vesicles. Does phagocytosis and activates bactericidal mechanisms
Mast cell
Releases histamines
Basophil
Granulocyte. Promotes allergic responses and is responsible for anti-parasitic immunity
Eosinophil
Kills parasite coated with antibodies
Natural Killer cell (NK cell)
Releases granules that induces apoptosis in virus infected and tumor cells. Has both activating and inhibitory receptors, activates when there’s an imbalance of receptors bound.
Innate lymphoid cells (ILCs)
A class of lymphoid cells (which includes NK cells). Produces cytokinins?
Pattern recognizing receptors (PRRs)
Sensors for immune cells to detect microbes. Expressed by epithelial cells also. Recognizes PAMPs and DAMPs.
Toll-like receptors (TLRs)
Transmembrane receptors. Can detect both extracellular bacteria but also bacteria taken in by vesicles, and they sit in the membrane in the vesicle.
NOD-like receptors (NLRs)
Not membrane bound, dimerize when they come in contact with ligand
Inflammasome
Oligomerized NLRs that cleaves and activates caspase 1 which in turn cleaves gasdermin D, pro-IL-1β and pro-IL-18. Gasdermin D creates pore so that IL-1β and IL-18 can get out of the cell
PAMPs
Conserved, microbe specific patterns
DAMPs
Endogenous molecules from damaged or dying cells that should not be in the extracellular space. Ex. nuclear proteins
Phagocytosis
Engulfment of large particles, energy dependent. Can be done by multiple immune cells such as macrophages, neutrophils
Process of phagocytosis
PRRs bind and identify microbe. Enclose the particle in a vacuole inside the cell. This vacuole fuses with the lysosome, where the particle is killed with toxic compounds, pH, enzymes, etc
What is the complement system?
Proteolytic enzymes that circulate through the blood. Can recognize certain classes of antibodies, surface proteins, or whole microbes, and causes a cascade amplification. Stimulates phagocytes, induces inflammation, and creates the MAC which is a pore that kills the bacteria
What are the pathways of activation for the complement system?
Lectin, classical, alternative
Lectin pathway
Activating proteins binds to carbohydrates on surface of microbes
Classical pathway
Activating proteins interact with antibody bound to the surface of the microbe
Alternative pathway
Activating protein will spontaneously hydrolyze and bind directly to the microbe(?)
C3 convertase
Key part of the complement system. Cleaves C3 into C3a and C3b. Is made out of different components depending on which activating pathway was used.
C3A
Soluble. With C5A it will recruit phagocytic cells and promote inflammation
C3B
Stuck to surface of microbe. Will bind to C3 convertase to form C5 convertase. Furthermore, it can cause phagocytes to engulf the pathogen as it can bind to C3B receptors on them.
C5 convertase
Cleaves C5 to C5a and C5b. Made out of different components depending on which pathways was used.
C5a
Together with C3a to recruit phagocytic cells and promote inflammation. Stronger than C3a.
C5b
Key to creating MAC pores that disrupts the cell membrane which kills the cell.