First Aid, Chapter 1 Immune Mechanisms, Innate Immunity and Toll-Like Receptors Flashcards
What are the innate mechanisms used on extracellular bacteria?
Complement activation Phagocytosis: Recognition by pattern recognition receptors (PRR)
What are the innate mechanisms used on intracellular bacteria?
Nucleotide binding oligomerization domain-like receptors (NLRs)
What are the innate mechanisms used on fungi?
Neutrophil phagocytosis Complement activation
What are the innate mechanisms used on viruses?
Phagocytosis: Toll-like receptors (TLRs) and NK cells
What are the innate mechanisms used on parasites?
Phagocytosis; Complement (alternative pathway)
What is the difference in the genetics of innate immunity vs. adaptive immunity?
Innate immunity: Response encoded in host germ line DNA
Adaptive immunity: somatic gene rearrangement
What does the innate immune system recognize in pathogens?
Recognize conserved sequences such as pathogen-associated molecular patterns (PAMPs)
What does the adaptive immune system recognize in pathogens?
Recognize unique antigenic determinants: TCR and (MHC restricted-) Ig receptors
What are the components of the innate immune system?
Complement Pattern recognition receptors (PRRs) on immune cells Phagocytes Mast cell or basophils NK cells
What are the components of the adaptive immune system?
T lymphocytes, B lymphocytes, and complement
What are antimicrobial peptides (AMPs)? What are they produced by?
AMP are ubiquitous cationic proteins that play a role in innate immunity. They provide defense against bacteria and fungi viruses. Produced by keratinocytes.
What are the families of AMPs in humans?
Two families in humans:
o Human β defensins: HBD1, 2, 3
o Human cathelicidins: LL37 o Lactoferrins: hLF1-11
o Histatins
How do AMPs work?
Interact with phospholipids of microbial membranes, enter cell and mediate antiproliferative effects
Why are atopic dermatitis patients susceptible to staph aureas infections?
AMPs are decreased in a Th2 environment. Atopic dermatitis patients are susceptible to Staphylococcus aureus infection due to a decrease in AMP.
What environment are AMPs decreased in?
Th2 environment.
What is the function of neutrophils?
Phagocytosis and oxidative burst or free radical production
What is the function of monocytes or macrophages?
Phagocytosis and secretion of proinflammatory cytokines
What are two types of dendritic cells?
APCs (conventional) and antiviral (plasmacytoid)
What are the functions of eosinophils?
Antihelminthic, antibacterial, and secretion of proinflammatory mediators or free radicals
What are the functions of mast cells?
Antibacterial, antiviral, and secretion of proinflammatory cytokines
What are the functions of basophils?
Antibacterial, antiviral, and secretion of proinflammatory cytokines
What are the functions of NK cells?
Eliminates virus-infected cells and tumor cells (missing “self” hypothesis), and secretion of cytokines
What are the function of intraepithelial lymphocytes?
Secretion of proinflammatory cytokines (phagocyte activation and killing of infected cells)
What is the function of B-1 B lymphocytes?
Produce natural serum antibodies.
What are PAMPs?
Pathogen associated molecular patterns (PAMPs) are conserved microbial sequences found on microorganims. Their strucutres are consistent and conserved.
What are examples of PAMPs?
LPS on gran-negative bacteria on teichoic acid on gram on gram positive bacteria
What are PRRs? Where are they found? What do they recognize?
Pattern recognition receptors on APCs (conventional dendritic cells, B lymphocytes, and macrophages).
-PRRs identify PAMPs on microorganisms to detect infection.
Name some pattern recognition receptors?
- fMLP (N-formyl met-leu-phe receptors)
- CARD (Caspase activation and recruitment domains eg retinoic acid inducible gene-I-like receptors)
- CLR C-type lectin receptors: mannose-binding lectin and macrophage mannose receptor)
- NLR (Nucleotide-binding oligomerization domains NODs)
- NACT-LRR and pyrin domain-containing proteins (NALPS)
- TLR (toll-like receptors)
Where are fMLP (N0formyl Met-Leu-Phe) receptors found? What class are they? What is their structure? What is their function?
- cell surface
- signalling
- G protein-coupled 7-transmembrane domain receptor
- antibacterial
Where are CARD (Caspase activation and recruitment domains eg retinoic acid inducible gene-l-like receptors) found? What class are they? What is their structure? What is their function?
-cytoplasm
-signalling
RNA helicase and caspase recruitment domains, component of inflammasome
-cytoplasmic virus detection and to induce type 1 IFN production
Where are CLRs (C-type lectin receptors mannose binding lectin and macrophage mannose receptors) found? What class are they? What is their structure? What is their function?
- Cell surface
- secreted or endocytic
- calcium-dependent carbohydrate binding domain
- antifungal immunity
Where are NLR or NACT-LRRs found? What class are they? What is their structure? What is their function?
- cytoplasm
- signalling
- c-terminal leucine-rich repeat and nucleotide-binding domain, central proteins of inflammasome
- IL-1B and IL-18 secretion
Where are TLRs found? What class are they? What is their function?
- cell surface and cytoplasm (TLR3)
- signalling
- antibacterial, antifungal, and antiviral immunity
What is the inflammasome? What cytokines does it cause secretion of? What provides a platform for adaptor proteins SC and caspases to bind?
The inflammasome is multiprotein complex located in the cytoplasm that activates caspases 1 and 5, leading to production and secretion of IL-1 and IL-18. NALPs provide a platform to which the adaptor protein ASC and caspases bind
What diseases are activating mutations in cold-induced autoinflammatory syndrome 1 (CIAS1) seen in?
Activating mutations in cold-induced autoinflammatory syndrome 1(CIAS1) is seen in Muckle-Wells syndrome (MWS), familial cold urticaria, and chronic infantile neurologic, cutaneous, and articular autoinflammatory disease (CINCA).
Where are TLRs found?
TLRs are found on the cell surface or intracellularly.
-TLR 3, 7, 8, and 9 are found in the intracellular compartment and detect nucleic acids.
What adapter protein plays a role in TLR signalling?
MyD88
What is the ligand for TLR1? What is the source?
Ligand: lipoarabinomannan
Source: mycobacteria
What is the ligand for TLR2? What is the source?
Ligand: Zymosan
Source: Fungi
What is the ligand for TLR3? What is the source?
Ligand: dsRNA
Source: Virus
What is the ligand for TLR4? What is the source?
Ligand: Lipopolysaccharide, peptidoglycan, RSV fusion protein, and HSP (heat shock protein) 70 and HSP 90
Source: Gram-negative bacteria, gram-positive bacteria, RSV, and endogenous acute phase proteins
What is the ligand for TLR5? What is the source?
Ligand: Flagellin
Source: Flagellated bacteria
What is the ligand for TLR6? What is the source?
Ligand: Diacyl lipopeptides
Source: Mycoplasma
What is the ligand for TLR7? What is the source?
Ligand: Imidazolquinolones
Source: Synthetic
What is the ligand for TLR8? What is the source?
Ligand: ssRNA
Source: Virus
What is the ligand for TLR9? What is the source?
Ligand: Unmethylated CpG (cytosine-phosphate-guanosine) motifs
Source: Bacteria and DNA viruses
What is the ligand for TLR10? What is the source?
Ligand and source: unknown
What is the ligand for TLR11? What is the source?
Ligand: Profilin
Source: Toxoplasma gondii
What is signalling through MyD88 dependent pathways similar to?
Similar to signalling through IL-1.
What TLR-signalling pathways are MyD88 involved in?
All except TLR3
What is TLR3 signaling mediated through?
TLR3 signaling is mediated by the Toll-interleukin-1-receptor domain containing adapter-inducing interferon β (TRIF) and is MyD88 independent.
What signaling pathways does TLR4 signal thorugh?
TLR4 can signal through both MyD88-dependent and -independent pathways (Figure 1-18).TLR 4 binds to lipopolysaccharide (LPS) via lipopolysaccharide-binding protein (LBP), MD2 (lymphocyte antigen 96), and CD14.
What are TLR agonists 7 and 8 agonists? What are they used for?
TLR agonists, such as imiquimod (TLR 7) and resiquimod (TLR 7 and 8), are used topically for its antiviral and antitumor effects.
What TLR mutations are associated with HSV1 encephalitis?
TLR 3, 7, 8, and 9
What TLR mutations are associated with aspergillosis?
TLR4
What TLR mutations are associated with adrenal insufficiency?
TLR 2, 4
What innate signalling pathway mutations are associated with Crohn’s disease or Blau’s syndrome?
NOD2 (nucleotide oligomerization domain)
What TLR mutation is associated with leprosy and TB?
TLR2
What does IRAK4 or MyD88 deficieny cause?
Recurrent infections with pyogenic bacteria
What does mutations in NEMO (NFkB essential modifier) cause?
Primary immune deficiency with infectious and mycobacterial susceptibilities
Which TLR binds lipopolysaccharide (LPS) on gram-negative bacteria?
TLR4
Which TLRs are present in the intracellular compartment and implicated in HSV1 encephalitis?
TLR 3, 7, 8, 9