Lecture 5: Innate Immunity (part 2) Flashcards
C3a, C4a, and C5a have what effects
inflammation
C3b main function is
opsonization and phagocytosis
Although the 3 pathways of complement activation differ in how they are initiated, all of them result in the generation of enzyme complexes that are able to cleave the most abundant complement protein, ___
- C3
The 3 complement pathwyas differ in how C3b is produced but follow a common sequence of reactions after the cleave of
C5
What is the function of Properdin in complement
- Properdin stabilizes C3 convertases (C3bBb) on microbial surfaces
The classical pathway is initiated by binding of the complement protein ____ to the CH2 domains of IgG ro the CH3 domains of IgM molecules that have bound antigen
C1
C4 is homologous to ____
C3
Soluble C3a fragment stimulates ____ by acting as a chemoattractant for ____
inflammation, neutrophils
Soluble C5a is a very potent _____ that also induces changes in
chemoattractant, permeability of blood vessels
The classical activation pathway requires
- IgM or IgG and C1
What is C3 convertase and C5 convertase in the lectin and classical activation pathways
- C4bC2a (C3 convertase)
- C4b2aC3b (C5 convertase)
What is the C3 and C5 convertase in alternative pathways
- C3bBb (C3 convertase)
- C3bBbC3b (C5 convertase)
C1q binds to ___ portion of antibody
Fc
In the alternative pathway C3b is capable of binding factor B that can be cleaved into Ba and Bb by the constitutively active serum protease
factor D
Mannose-binding lectin has a hexametric structure similar to the ___ component of the classical pathway
C1q (which makes sense because they begin similar and have the same C3 convertase components)
After mannose-binding lectin (MBL) binds to microbes, two zymogens called _____ and _____ (mannose-associated serine protease) are activated they have similar functions to ____ and _____ and initiate downstream proteolytic steps identical to the classical pathway
- MASP1 and MASP2
- C1r anC1s
Pulmonary surfactant proteins SP-A and SP-D are members of the ____ family. fxn?
- collectins
- act as opsonins, facilitating phagocytosis by alveolar macrophages
What are Ficolins
humoral molecules (PRRs) of the innate immune systems which recognize N-acetylglucosamine and lipoteichoic acid on pathogens, apoptotic, and necrotic cells (activate the lectin pathway)
Complement is not activated on the surface of mammalian cells because they express regulatory proteins that inhibit, disassemble, or cleave the convertases. Examples?
- Decay-Accelerating Factor (DAF)
- blocks C2:C4b interaction
- enhance dissociation of C4bC2a interaction
- Complement receptor 1 (CR1)
- enhanc dissociation of C4bC2a
- cleave C4b and C3b
- Factor I (FI)
- clave C4b and C3b
What is the strongest anaphylatoxin of the complement cascade
C5a (it has the strongest effects and it is the only one that effects Chemotaxis, release of O2 radicals and lysosomal enzymes
____, ____, and ___ mediate protective systemic effects of inflammation, including induction of fever, acute-phase protein synthesis by the liver, and increased production of leukocytes by the bone marrow
- TNF
- IL-1
- IL-6
Acute phase proteins are several plasma proteins that recognize microbial structures and participate in innate immunity belong ot the ____ family. Examples:
- pentraxin
- Ex: C-reactive protein (CRP) and Serum amyloid P (SAP)
CRP and SAP recognize ____ and ____ respectively, which are found on bacteria and apoptotic cells
- CRP recognizes phosphorylcholine
- SAP recognizes Phosphatidylethanolamine
The increased levels of CRP and SAP are a result of increased synthesis by the liver induced by the cytokines ___ and ____
IL-6 and IL-1
CRP and SAP can activate the complement by binding ____ and initiating the ___ pathway
C1q and initiating the classical pathway
IFN-alpha and IFN-beta bind to receptors on neighboring uninfected cells and activate _______ signaling pathways
JAK-STAT
Inactive JAK (Janus kinases) are non-covalently attached to the cytoplasmic domains of Type ___ and Type ____ cytokine receptors
Type I and Type II
IFN-alpha and IFN-beta bind to receptors on neighboring unifected cells and activate ____ signaling pathways
JAK-STAT
Type I interfeurons bind to receptors on unifected cells and activate JAK-STAT signaling pathways meanwhile they also bind to receptor on infected cells and
induce expression of genes whose products enhance the cell’s susceptibility to CTL-mediated killing
