Cytokines for Hematopoietic Stem Cell –> Myeloid Precursor
IL-3
GM-CSF
Cytokines for Myeloid Precursor –>
Basophil Progenitor
Eosinophil Progenitor
Granulocyte-Macrophage Progenitor
IL-3
GM-CSF
Cytokines for Basophil Progenitor –> Basophil
IL-3
GM-CSF
IL-4
Cytokines for Eosinophil Progenitor –> Eosinophil
IL-3
GM-CSF
IL-5
Cytokines for Granulocyte-Macrophage Progenitor –> Neutrophil
IL-3
GM-CSF
G-CSF
Cytokines for Granulocyte-Macrophage Progenitor –> Monocyte
IL-3
GM-CSF
M-CSF
Cytokines for Monocyte –> Dendritic Cells
GM-CSF
IL-4
Cytokines for Monocyte –> Macrophage
GM-CSF
M-CSF
Cytokine for Monocyte –> Neutrophil (occasionally)
IL-8
Types of Granulocytes
Neutrophils
Basophils
Eosinophils
Monocytes can differentiate to form…
Macrophages
Dendritic Cells
Neutrophils (sometimes)
Resident macrophages phagocytose PAMPs or DAMPs and then display the peptides on what?
MCH II
Resident macrophages will release what cytokines to elicit an innate immune response?
TNFalpha
IL-1
Cytokine inputs for Macrophages
GM-SCF
IL-3 (early on in differentiation)
M-CSF (later in differentiation)
Resident macrophages will release what cytokines after transcriptional reprogramming to elicit an innate immune response?
TNF-alpha
IL-1
FcR
Binds to constant region of Antibody
CR3
Complement Receptor and I-CAM-1
FcR and CR3 are what type of receptors?
Opsonic Receptors
Cytokines for classical activation of the M1 “angry” Macrophage
IFN-gamma
TNF-alpha
Cytokines for activation of the M2 “healing” Macrophage
IL-4
IL-13
Cytokine for deactivation of the macrophage
IL-10
Endothelial cells respond to INF-alpha by producing…
E-Selectins
Leukocytes in the capillaries undergo a 4 step process for recruitment to the site of infection.
- Rolling
- Tethering
- Adhesion
- Migration
Leukocytes will tether to E-selectin via…
CD15 (releasing cytokine IL-8 as well)
Endothelial cells will make I-CAM-1 to interact with the Leukocyte’s
CR3/LFA-1
I-CAM-1 and CR3/LFA1 interaction makes it possible for the Leukocyte to…
Migrate into the tissue from the blood vessel
Vascular Permeability can be stimulated if you activate the ________ system.
Kinen
Resident Macrophages will display peptides on MHC II to activate…
CD4+ T-Cells
If the CD4+ T-Cell is a Th1 class that attaches to the MHC II, then it can release…
IFN-gamma to activate the macrophage to an M1 macrophage.
What cells are the link between the innate and adaptive immune system?
Antigen Presenting Cells:
Macrophages
Dendritic Cells
B-Cells
What does the innate immune response recognize?
PAMPs
DAMPs
Absence of “self” molecules
What is the role of antimicrobial peptides such as defensins and cathelidins?
Interact with microbial cell membrane components to increase cellular permeability resulting in cell death through antimicrobial, chemotactic and regulatory activities.
What are Defensins?
B-strand peptides connected by disulfide bonds
What are Cathelicidins?
Cationic Helical Bactericidal Protein = alpha-helical peptides expressed by PMNs and epithelial cells
Human Neutrophil Peptide (HNP) 1-4 are expressed where?
Alpha Defensins produced in PMNs, Monocytes, lymphocytes, NK Cells
Human Defensins (HD) 5-6 are expressed where?
Alpha Defensins produced in Paneth cells of small intestine
Human Beta Defensing (HBD) 1-4 are expressed where?
Beta Defensins produced in epithelial tissues, monocytes, macrophages, dendritic cells
Types of PAMPs
LPS, PGN, Lipopeptides, Flagellin, bacterial DNA, viral dsRNA
Types of DAMPs
Intracellular proteins and protein fragments from extracellular matrix
The signaling cascades from TLRs activate what?
Interferon Regulatory Factors, AP-1, NF-kB
dsRNA binding to TLR3/TLR4 signaling results in…
IRF3 transcribing Type 1 IFN-B
Lipoprotein binding to TLR 1, 2, or 6 or Flagellin binding to TLR 5 signaling results in…
AP-1 and NF-kB transcribing pro-inflammatory cytokines TNF-alpha, IL-6, IL-12
ssRNA binding to TLR7/8 and CpG-DNA binding to TLR9
IRF7 transcribing Type 1 IFN-alpha
Hallmarks of Inflammation
Edema
Hyperthermia
Local Hypoxia
Extravasation
3 principle changes to tissue during acute inflammation
Increase blood supply
Increase capillary permeability
Increase leukocyte migration
Sites of Acute inflammation have:
Neutrophils and T-helper cells
Sites of Chronic inflammation have:
Macrophages, Cytotoxic T-cells and B-Cells
TNF-alpha
Produced by macrophages and mediates acute infmallation
IL-1B, IL-6, TNF-alpha
Produced by macrophages and mediates fever
IL-8 (CXCL8)
Produced by macrophages and chemotactic factor for PMNs, Basophils, T-cells
IL-12
Produced by macrophages to activate NK cells and CD4+ Th1 T-cells
What are the 3 types of myeloid DCs?
Langerhan’s Cells
Dermal/Interstitial DCs
Monocyte-derived DCs
Describe Myeloid DC1s:
Diffuse
Produce IL-8 and IL-12
Describe Lymphoid DC2s:
Restricted to T-cell areas
Produce Type I IFNs
What cytokines activate NK cells?
IL-12 and TNF-alpha
What cytokines do NK cells produce?
INFgamma
Hematopoietic Stem Cell –> Lymphoid Progenitor
IL-3
Lymphoid Progenitor –> NK Cell
IL-2
SCF
Congenital Neutropenia
Lack of GM-CSF (No myeloid progenitor cells)
Frequent bacterial infections (NK and CD8+ provide protection from viral infections –> lyphoid progenitors)
Chronic Granulomatous Disease
Inability to kill phagocytosed bacteria
Leukocyte Adhesion Deficiency (LAD)
Lack of integrin subunit, the common B-chain
Increased susceptibility to fungal, bacterial, viral infections
Complement defects
Increased susceptibility to bacterial infections
Chediak-Higashi Syndrome
Defect in gene LYST (CHS1) –> Lysosomal trafficking gene
Increased susceptibility to bacterial infections