Innate Immunity Flashcards
What Ig would be found in the urinary tract, vagina tears, saliva
IgA
List 4 potent vasodilators
Prostaglandins, leukotrienes, histamine, bradykinin
What are potent inducers of fever
TNF, IL-1, IL-6
How do innate immune cells distinguish self from non self Ags
Pathogen associated molecular patterns (PAMPs) are recognized by specialized receptors (PRRs, TLRs)
Mannose receptors
Recognizes glycans with terminal mannose, which are not found on human cells
Innate cells have a nonclonal distribution of receptors, what does this mean
All cells have receptors with identical specificities
Which TLRs recognize extracellular pathogens (bacteria)
1, 2, 4, 5, 6
What TLR recognizes dsRNA
3
What TLR recognizes ssRNA
7, 8
What TLR recognizes CpG DNA
9
What are two important transcription factors activated by TLRs
NF-kB- promotes expression of cytokines and endothelial adhesion molecules (most important TF for inflammation)
Interferon regulatory factors IRFs- stimulate production of antiviral cytokines IFN-a/b (type I interferons)
Which TLRs recognize fungi
2, 6
MyD88 and IRAK4 deficiency
TLR disorders that lead to increased susceptibility to infection by bacteria or viruses
PAMPs and inflammasomes
PAMPs activate inflammasomes which contain NLR. NLRs trigger activation of NF-kB and MAPK, which activates caspase-1
Caspase 1 processes precursor forms of IL-1B and IL-18 to active forms (IL-1B and IL-18 are potent proinflammatory cytokines)
DAMPs
Endogenous danger molecules released from damaged or necrotic cells. Induce potent inflammatory responses by activating innate immune system during non-infections inflammation
List 3 DAMPs released by necrotic cells
HMGB1
Uric Acid
Heat shock proteins
DAMPs and autoimmunity
DAMPs instigate innate immune pathways that promote adaptive autoimmune responses against self-Ags which manifest as severe clinical symptoms
List some inflammatory mediators that macrophages produce
Cytokines/chemokines ROSs NO Prostaglandins Defensins
What preformed mediators are released by mast cells
Proteases
Histamine
Which type of signaling can cytokines participate
Endocrine, paracrine, autocrine
Macrophages may secrete which anti-inflammatory cytokines
IL-10, TGF-b
What is the function of IL-8
Chemotactic factor for neutrophils, basophils, T cells
What is the function of IL-12
Activate NK cells
Induce T cell differentiation of CD4–>Th1 cells
Classical pathway is initiated by what
Binding of IgM or two IgG on a molecules surface
Explain classical pathway steps
C1 binds to IgM or 2x IgG on microbe
C1 cleaves C2 and C4
C4b attaches to microbe, C2a attaches to C4b forming C3 convertase– C4bC2a
C3 convertase cleaves C3–> C3a, C3b
C3b binds microbe and C3 convertase forming C5 convertase C4bC2aC3b
C5 convertase cleaves C5 into C5a/C5b
C5b initiates MAC formation consisting of C5b, C6-C9 (multiple C9 molecules)
What induces the secretion of acute phase proteins
TNF-a, IL-1, IL-6
High blood concentrations of ___ and ____ allow more accurate laboratory detection of inflammation
CRP and SAA
Where do neutrophils/monocytes enter tissue
Through post-capillary venules, except parenchymal tissues (liver, lung, kidneys- all blood enters through capillaries)
TNF-a and IL-1 have what effect on endothelial cells
They active them, increasing surface expression of P-selectin and E-selectin, which bind PSGL-1 and ESL-1, respectively. These are constitutively expressed on neutrophils
LFA-1 and VLA-4 method of action
Both are expressed in low affinity state on neutrophils. Once rolling of neutrophil on endothelium occurs, chemokines bind receptors on neutrophil and activate LFA-1/VLA-4 which bind with high affinity to ICAM-1 and VCAM-1 on endothelial cells
Rolling is ____ dependent, while adhesion, crawling and transmigration are ____ dependent
Rolling- Selectin dependent
Adhesion/crawling/transmigration- Integrin dependent
What is the most important chemokine that regulates migration/infiltration of monocytes into tissues
Monocyte chemoattractant protein 1 MCP-1
M1 vs M2 macrophages
M1 are classically activate macrophages, induced by microbial products binding TLRs, and cytokines like IFN-y
M2 are alternatively activated Macrophages, induced by IL-4, IL-13 and involved in tissue repair/fibrosis
Interferons trigger the killing of viruses by what methods
Inhibition of protein synthesis
Degradation of viral RNA
Inhibition of viral gene expression
Activation of NK cells
NK cell activating receptors
KIRs, recognize stress associated molecules such as MICA and MICB
NK cell inhibiting receptors
Recognize Class I MHC and inhibit the activation signal
How do NK cells kill
Release perforins, then granzymes from NK cell enter hole and activate apoptosis
Macrophage then digests dying cells
