Innate Immunity Flashcards
Which lung surfactants agglutinate pathogens and induce phagocytosis by alveolar macrophages?
- SP-A
- SP-D
Are complement proteins produced by the liver only produced during active infection or constitutively?
Constitutively
What is the function of the complement system?
- Opsonsize pathogens
- Produces proteases and zymogens
- Simple, effective way to distinguish human from microbial cells
What is the common step that links the alternative, lectin, and classical pathways of complement activation?
Cleavage of C3 to C3a and C3b
At the start of an infection, complement activation proceeds by the _____ pathway.
Alternative
In the alternative pathway of complement activation, which soluble convertase is responsible for the cleavage of C3 into C3a and C3b?
iC3Bb
Where does the alternative pathway occur?
At the cell surface of a pathogen
Which pathways come first, second, and third respectively during complement activation?
- Alternative
- Lectin
- Classical
What is the function of properdin in the alternative pathway?
- Binds C3bBb to prevent its degradation
- Overall, upregulates the alternative pathway
What are the functions of Factor H and Factor I in the alternative pathway?
- Factor H binds C3b and induces cleavage to iC3b by Factor I
- Factor I decrease the amount of C3b on the pathogen surface
- Overall downregulates alternative pathway
What are the functions of DAF and MCP in the alternative pathway?
- DAF - binds C3b and causes dissociation and inactivation
- MCP - binds C3b and makes it susceptible to cleavage by factor I
- Overall, downregulates alternative pathway at the human cell surface
What is the function of CR1 in complement activation?
- Receptor on macrophages that recognize C3b
- Makes C3b susceptible to cleavage by factor I
- Prevents C3b form opsonizing macrophages
What is the function of the membrane attack complex?
Lysis of pathogens by forming membrane pores
What are the functions of the components of the membrane attack complex? C5, C6, C7, C8, & C9.
- C5 - soluble C5b fragment initiates MAC assembly
- C6 - stabilizes C5b and forms binding size for C7
- C7 - binds C5b6 and exposes a hydrophobic region that permits attachment to the cell membrane
- C8 - Binds C5b67 and exposes a hydrophobic region that inserts into the cell membrane
- C9 - polymerization on the C5b678 complex to form a membrane-spanning channel that results in lysis
What is the function of CD59 during formation of the MAC?
On human cells, binds to C5b678 complex and prevents recruitment of C9 to form a pore
Paroxysman nocturnal hemoglobinuria is caused by ______
Destruction of RBCs due to faulty CD59 gene
________ act on blood vessels to increase vascular permeability and induce local inflammation.
Anaphylatoxins (C3a and C5a)
What is the function of plasma protein α2-macroglobulin?
Enshroud proteases to limit spread of infection
______ is secreted at mucosal surfaces by epithelial cells and neutrophils, which kills pathogens by perturbing their membranes
Human β1-defensin
Explain how defensins disrupt a pathogen cell membrane.
______ are plasma proteins of innate immunity that bind microorganisms and target them for phagocytosis (unspecific).
Pentraxins
______ patterns on cell membranes help macrophages determine self from non-self.
Carbohydrates
What is the function of carbohydrate-recognition domains (CTLD) of macrophages?
- Binds C-type lectin domains on pathogen
- Requires calcium
What is the function of Ricin-type lectin domains (RTLD) of macrophages?
- Binds sulfated galactosamine residues on pathogens
What is the function of scavenger receptors (SR) of macrophages?
- Binds negatively charged microbial ligands
Toll-like receptors (TLR) are a family of how many genes?
- Ten
- TLR1-10
Recognition of LPS by ______ induces changes in macrophage gene expression.
TLR4
What are the functions of CD14 and MD2?
- CD14: co-receptor for TLR4; binds LPS
- MD2: protein that binds TLR4 and LPS
What is the result of activation of TLR4 by pathogens on macrophages?
Transcription and secretion of inflammatory cytokines
What is X-linked hypohidrotic ectodermal dysplasia and immunodeficiency (NEMO)?
- Lack of an IKK subunit in the TLR4 cascade
- Impairs inflammatory cytokine production
- Abnormalities in tissues that arise from ectoderm (skin, teeth, and hair)
Activation of _____ induces inflammation at sites of infection by secretion of cytokines.
Macrophages
What are the functions of each inflammatory cytokine? IL-1β, TNF-α, IL-6, CXCL8, and IL-12
- IL-1β and TNF-α: increase blood vessel permeability, enabling effector cells and molecules to enter infected tissue
- IL-6: Fat and muscle cell metabolism, which makes heat and raises temperature in infected tissue
- CXCL8: Recruits neutrophils from blood and guides them to infected tissue
- IL-12: Recruits and activates NK cells, which secrete more cytokines and strengthen macrophage response
_____ recognize bacterial degradation produces in the cytoplasm
Nucleotide-binding oligomerization domain (NOD)-like receptors
What is the function of the leucine-rich region (LRR) of a NOD domain?
Recognition of degradation products of bacteria (specifically peptidoglycan)
What is the function of the CARD domain of NOD receptors?
Recruitment of caspases
Inflammasomes amplify the innate immune response by increasing the production of ____ by positive feedback.
IL-1β
______ are dedicated phagocytes and first effector cells recruited to sites of infection.
Neutrophils
How does fever affect adaptive immunity?
- Increases activity
- More potent at higher temperatures
The _____ is the sum of changes in the change of plasma proteins during infection, which is initiated by inflammatory cytokines acting on the liver.
Acute-phase response
What is the function of C-reactive protein (CRP)?
- Opsonization; triggers innate immune response
- Binds to phosphocholine
- May deliver pathogens to phagocytes
What is the function of serum amyloid A?
- Interacts with HDL
- Binds TLRs and CD36
- Induces cytokines
The lectin pathway of complement activation is initiated by ______
Mannose-binding lectin (MBL)
What is the function of MBL?
Binds mannose-containing carbohydrates on pathogens
Opsonization by MBL induces monocytes in blood to _____
uptake bacteria
Describe the cascade of events that occurs in the lectin pathway of complement activation
- MBL binds to pathogen surface
- MASP-2 domain of MBL cleaves C4 into C4a and C4b; Cleaves C2 into C2a and C2b
- C4b binds covalently to microbial surface
- C2a binds to C4b, forming the classical C3 convertase, C4b2a
- C4b2a cleaves C3b and C3a
What is the function of C4a from the lectin pathway?
Recruitment of leukocytes (weaker than C3a and C5a)
Of the two convertases, which is classical and which is alternative?
- C3b2Bb
- C4bC2a
- Classical: C4bC2a
- Alternative: C3b2Bb
The classical pathway of complement activation is initiated by ______
- Binding of CRP to phosphorylcholine
- Bound C1 becomes active protease the cleaves C4
Internal detection of viral infection induces cells to make a _______ response
interferon
A type 1 interferon response is initiated by ______ infection
Viral