Lec 04- Innate Immunity (Part 1) Flashcards
What is the function of innate immunity?
- Initial host defense response to pathogens that prevents, controls, or eliminates infection
- Eliminates damaged cells and initiates tissue repair process
- Controls adaptive responses
Innate immunity may keep the infection in check until _______.
more specialized adaptive immune responses are activated
Steps of damaged cell elimination
1- RECOGNIZES and responds to host molecules that are stressed, damaged, and dead host cells
2- CLEARS cell debris by phagocytosis
3- STIMULATES and controls tissue remodeling
How does innate immunity control adaptive responses to intracellular vs. extracellular pathogens?
- Provides danger signals»_space; alert adaptive immune system to respond
- Reacts in distinct ways to different microbes»_space; influences the type of adaptive immune response
Innate Immunity component:
Cellular and chemical barriers
- skin
- mucosal epithelia
- antimicrobial molecules
Innate immunity component:
Blood proteins
- complement
- acute phase proteins
- cytokines
- others
Innate immunity component:
Cells
- phagocytes (macrophages/neutrophils)
- dendritic cells
- natural killer cells
- innate lymphoid cells
3 Major Type of Defenses of Innate Immunity
-Inflammation
> Leukocytes and plasma proteins
-Physical barriers
> Skin and epithelial cells
-Anti-viral responses
> Inhibition of viral replication
Specificity:
Innate vs. Adaptive
Innate:
- Pathogen-associated molecular patterns (PAMPs)
- Damage-associatd molecular patterns (DAMPs)
Adaptive:
-Fine structures of microbial and non microbial Ags
Receptors:
Innate vs. Adaptive
Innate = Pattern recognition receptors (PRRs)
Adaptive = Greater diversity of BCRs and TCRs generated by somatic recombination
Distribution of receptors:
Innate vs. Adaptive
Innate = NONCLONAL (identical receptors on various cells)
Adaptive = CLONAL (identical on a single cell, but different between 2 cells)
Discrimination of self and non-self:
Innate vs. Adaptive
Innate = YES
Adaptive = YES
Where are PRRs located?
- extracellularly
- endosomes
- cytosol
What are the 5 families of microbial PRRS?
1- TLR family (surface and endosomal) 2- CLRs family 3- NOD-like receptors (NLRs) family 4- RIG-like receptors (RLRs) family 5- Cytosolic DNA sensors (CNS) family
PRRs on the cell surface bind PAMPs from __________.
extracellular pathogens
What do endosomal TLRs recognize?
nucleic acids of phagocytized microbes
Which family of PRRs is an evolutionarily conserved family?
TLRs
TLRs can form _______ or ________.
homodimers or heterodimers
What do TLRs recognize?
Both PAMPs and DAMPs
Which TLRs are expressed on the cell surface?
TLRs: 1 2 4 5 6
Which TLRs are expressed in endosomes?
TLRs: 3 7 8 9
Which TLRs use the adapter protein MyD88 and activate the transcription factors NF-kB and AP-1?
TLRs: 1 2 5 6
Which TLR uses the adaptor protein TRIF and activates the IRF3 and IRF7 transcription factors?
TLR3
Which TLR can activate both pathways?
TLR4
Which TLRs in the endosome use My D88 and activate both NF-kB and IRF7?
TLRs:
7
9
All TLRs signal through MyD88 except _______.
TLR3
Which TLRs also engage TIRAP?
TLR4 and the TLR2 subfamily (TLR 1,2,6)
Which TLR signals through TRIF?
TLR3
What is used in conjunction with TRAM in the TLR4-MyD88 independent pathway?
TRIF
TLRs are expressed on ______ cells
Immune cells
including macrophages and dendritic cells
Microbial lipoproteins activate mammalian immune cells through ________.
TLR2
LPS activates cells via ______.
TLR4
Through which TLR do bacterial DNA sequences containing unmethylated cytosine-guanosine dinucleotides (CpGs) work?
TLR9
TLR-dependent signaling pathways activate ______ which results in transcription of pro-inflammatory genes.
NF-kB
Which cytokine controls the adaptive T cell immune response?
IL-12
Activation of TLRs triggers ____.
antimicrobial pathways that directly kill the pathogen