Innate Immunity: Barriers and Sensing Flashcards
Examples of Innate Immunity?
•External barriers
(Skin and mucosal surfaces)
•Surveillance/sensing
•Phagocytosis
(Neutrophils & macrophages)
•Natural Killer (NK) cells
Defensins, Histanin, Dermicidin, and Cathelicidin are examples of what?
Anti-microbial peptides (AMPs)
_________
•Small cationic peptides
•Disrupt lipid membranes
•Directly toxic to bacteria, fungi, and encapsulated viruses
Defensins
•Small cationic peptides
•Disrupt lipid membranes
•Directly toxic to bacteria, fungi, and encapsulated viruses
______________:
•Cationic antimicrobial protein in saliva
Histatin
•Cationic antimicrobial protein in saliva
_______________
•Anti bacterial secreted in sweat
Dermicidin
•Anti bacterial secreted in sweat
_____________
•Cationic anti-bacterial
•LL 37 form binds LPS
Cathelicidin
•Cationic anti-bacterial
•LL 37 form binds LPS
Keratinocytes “sense” ________
Keratinocytes “sense” Infection
LL37 expressed at ________ levels while healthy, _______ when immune system active
LL37 expressed at low levels while healthy, upregulated highly when immune system active
________ has largest surface area of all organs
GI tract has largest surface area of all organs = 400m
Significance of Mucosa-associated lymphoid tissue (MALT)?
Epithelial surfaces of the airways and gastrointestinal tract
- Scattered lymphoid tissue/immune effector sites
- 2 compartments
- Epithelial layer
- Lamina propria
- Contain mature effector T cells and B cells (IgA producing plasma cells)
- Intraepithelial lymphocytes (IEL)
- Mainly lymphocytes, predominantly CD8+CTLs
- Lamina propria lymphocytes (LPL)
- CD4 and CD8 T cells, dendritic cells, plasma cells, macrophages
Dominant class of antibody at the mucosal surface?
Where is it synthesized? How transported?
- Dominant class of antibody at mucosal surface is IgA
- Synthesized in plasma cells lying just beneath epithelial basement membranes
- Undergoes transcytosis across the cell to the apical surface
- Carbohydrate on the secretory component binds to mucins in mucus and holds the IgA at the epithelial surface
Role of IgA at mucosal surfaces?
- Prevents adherence of bacteria and neutralizes toxins
- Main function is to limit access of pathogens to mucosal surface without causing inflammation
Pathogen Associated Molecular Patterns (PAMPs) and
Microbe Associated Molecular Patterns (MAMPs)
- Produced only by microbes: Self/non-self
- Essential for microbial survival: Mutants not generated
- Invariant between microorganisms of a given class: Limited number of germ-line encoded PRRs can detect any microbial infection
Pattern Recognition Receptors Roles?
- Endocytic: Promotes phagocytosis
- Signalling: Toll-like receptors (TLRs)
- Secretion: Lectins, Complement (Opsonin’s), C reactive protein
Pattern Recognition Receptors Roles?
- Endocytic: Promotes phagocytosis
- Signalling: Toll-like receptors (TLRs)
- Secretion: Lectins, Complement (Opsonin’s), C reactive protein
Role of Toll-like receptors in mammalian immunity. Number in Humans?
Recognize ligands leading to signal cascasde12 total, 10 in humans. Detect dozens of ligands inclu:
- Peptidoglycan
- Lipoprotein
- Flagellin
- Zymosan (yeast)
- Bacterial DNA
- Viral RNA
What is the role of NF-kB?
Master regulator of inflammatory gene expression
Damage Associated Molecular Patterns (DAMP):
- Molecules that are not normally present in the extracellular environment
- Necrotic cell death releases intracellular contents
- Examples of Nuclear and Cytosolic?
Molecules that are not normally present in the extracellular environment
- Necrotic cell death releases intracellular contents
- Nuclear DAMPs: Histones, Genomic DNA, HMGB1
- Cytosolic DAMPs: ATP, F-actin, Heat shock proteins (HSPs)
What kind of inflamation are DAMPS associated with?
Damage Associated Molecular Patterns are associated with Sterile Inflammation
PAMPs vs. DAMPs vs. MAMPs
