Innate Immune System Flashcards
Functions of Innate IS:
- Complement Activation
- Inflammation
- Cell Activation
- -cytokine & chemokine production
- -phagocytosis
- Priming of adaptive immune response
Defensins and Cathelicidins functions/MOA
Antimicrobial peptides. (short) Associated with physical barriers. Expressed in epithelial cells
MOA: membrane destruction by integrating into microbial membrane, aggregating, and poking holes in membrane
- chemokine role to bring in other IS cells to infection site.
- slows down pathogen
Defensins
2 classes:
Alpha–
Beta–
Beta stand peptides connected by disulfide bonds
Alpha: in granules of PMNs and Paneth cells
Beta: secreted by mucosal surface epithelia
Cathelicidins
Alpha helical peptides
Defensins: Alpha
- -Human neutrophil peptide (HNP):
- -Human Definsins (HD):
–Human neutrophil peptide (HNP) 1-4 :
PMNs, monocytes, and lymphocytes
–Human Definsins (HD) 5-6: paneth cells of s. intestines
Defensins: Beta
–Human beta defensing (HBD):
epithelial tissues mostly
sometimes: monocytes, macrophages, and dendritic cells.
HSC–> Myeloid progenitor cells
GM-CSF
IL-3
Myeloid Pro–> basophil, eosinophil pro, granulocyte-macropahge pro?
GM-CSF
IL-3
Basophil pro –> basophil
GM-CSF
IL-3
IL-4
Eosinophil pro–> eosinophil
GM-CSF
IL-3
IL-5
granulocyte-macropahge pro –> Neutrophil
GM-CSF
IL-3
G-CSF
granulocyte-macropahge pro –> monocyte
GM-CSF
IL-3
M-CSF
Monocyte–> Dendritic cell
GM-CSF
IL-4
Monocyte –> Macrophage
GM-CSF
M-CSF
Monocyte –> Neutrophil
IL-8
Congenital neutropenia
- Lack of GM-CSF–so you can’t produce any cells downstream of myeloid precursor
- Frequent bacterial infections
Name the cells that form the bridge between innate and adaptive immunity.
APCs!
TLR1+
TLR2
PAMPS Recognized:
- –Triacylated lipoproteins (PAM3CSK4)
- –Peptidoglycans
- –Lipopolysaccharides
Production: AP-1 & NF-kB Inflammatory Cytokines (IC)
TLR2+
TLR6
PAMPS Recognized: Diacylated lipoproteins (FSL-1)
Production: AP-1 & NF-kB –>IC
TLR3
PAMPS Recognized:
- dsRNA (poly I:C)
- tRNA
- siRNA
Production: IC & IFN-beta
TLR4
PAMPS Recognized:
- -Lipopolysaccharides (LPS)
- -Paclitaxel
Production: IC & IFN-Beta
TLR5
PAMPS Recognized: Flagellin
Production: IC
TLR7
PAMPS Recognized:
- -ssRNA
- -Imidazoquinolines (R8
- -Guanosine analogs
Production: IC & IFN-alpha
TLR8
PAMPS Recognized:
- -ssRNA
- -Imidazoquinolines
Production: IC & IFN-alpha
TLR9
PAMPS Recognized:
- -CpG DNA
- -CPG ODNs
Production: IC & IFN-alpha
TLR10
PAMPS Recognized: Profilin-like proteins
Production: IC
TRLs that produce both IC and Type1 IFN?
3, 4, 7-9
Beta: 3-4
Alpha: 7-9
“Mother of all immune system transcription factors”?
NF-kappaB
Stimulation of TLRs initiates cascades that lead to activation of…
AP-1
NF-kappaB
Interferon regulatory factors
–IRFs 3 and 7
Proinflammatory cytokines?
TNF-alpha
IL-6
IL-12
Pro-inflammatory cytokines?
TNF-alpha
IL-6
IL-12
Activation of NF-kappaB:
- Expression of pro-inflammatory genes (TNF alpha)
- Increased phagocytosis
- Increased efficiency of antigen presentation
C5b
byproduct of complement activation and opsonization
-acts as focal point for deposition of membrane attack complex
Hallmarks of inflammation
- Influx of fluid (edema)
- Increased temp (hyperthermia)
- Decreased oxygenation
- Influx of WBCs
Triggers of inflammation:
- Complements C5a stimulation of basophils and mast cell degranulation
- Macrophages
- NK cells
Changes in acute inflammation:
- increased blood supply to affected area
- Increase capillary permeability
- Increase in leukocyte migration into affected tissue.
Pro-inflammatory cytokines?
TNF-alpha: produced by macs
IL-1
IFN-gamma
Cells of acute vs chronic inflammation
Acute: Neutrophils and activated helper T cells
Chronic: macrophages, cytotoxic T cells, and B cells.
granulocyte-macropahge pro –> Neutrophil
GM-CSF
IL-3
G-CSF
PMNs
- Granules
- First responders (phagocytic)
- Have FcR to bind antibodies
GM-CSF
IL-3
G-CSF
Eosinophils
-bilobed nucleus
-phagocytic
-Granules contain Major Basic Protein
MBP is toxic to HELMINTHS
GM-CSF, IL3, IL5
Basophils
- Multilobed nucleus
- Express FcR1 receptors for IgE so IgE is always on their surface
- release histamine–>allergic response
- activated by complement C5a and C3a
GM-CSF, IL3, IL4
Monocytes:
Form macrophages
Horseshoe shaped nucleus
long lived
Macrophages
Major producer of cytokines
Highly activated by IFNs
APC
Dendritic Cells
Classical vs Follicular
Classical: process and present foreign protein antigens to T cells
Follicular: form immune complexes to B cells in LYMPHOID FOLLICLES
Dendritic Cells
Classical vs Follicular
Classical: process and present foreign protein antigens to T cells
Follicular: form immune complexes to B cells in LYMPHOID FOLLICLES
*Take naive T cells and activate them
DC1
Location?
Produces?
From myeloid precursor
Location? Diffuse
Produces: IL-8
DC2
Location?
Produces?
Lymphoid precursor
Location? restricted to T cell areas of secondary lymphoid organs and tissues
Produces? mainly type I interferons
NK Cells
Innate immunity
- IFNs ramp up granule production in NKs
- Look for missing MHC I molecules on cell surfaces
Lymphoid progenitor cell –> NK
IL-3 SCF and IL-2
Chronic Granulomatous Disease
- Inability to produce hydrogen peroxide and hypochlorous acid
- Inability to kill phagocytosed bacteria
Leukocyte Adhesion Deficiency (LAD)
- Lack of INTEGRIN subunit, the common beta chain
- Inability to RECRUIT innate immune cells to site of inflammation
- Increased susceptibility to bacterial, fungal, and viral infections
Complement Defects
Increased susceptibility to bacterial infections
-Reduced ability to remove immunocomplexes
Chediak-Higashi Syndrome
Defect in gene LYST (CHS1), a lysosomal trafficking gene that affects lysosomes and meanosomes
-Increased susceptibility for bacterial infections.
