Innate Immunity and Complement Flashcards
What are the protective features of the Epithelial cells?
They form a physical barrier
-protective mucus layer
-some secrete antimicrobial peptides (AMPs)
-beating cilia to sweep pathogens away
-damaged epithelial cells send signals to immune cells for inflammatory response
What are the different epithelial cell types contributing to immunity in the intestine?
-Microfold (M) cells: transcytosis of antigens across epithelium to Peyer’s patches (GALT)
-Enterocytes: recognize microbial PRRs and alert the immune system
Intraepithelial lymphocytes (IELs): respond to memory cells
-Goblet cells: transport Ag to APCs -> they secrete cytokines
-Paneth cells: sustain stem cells for layer replenishment
-Tuft cells: cytokines to initiate a response to worms
What are the protective features of the Respiratory Epithelia?
-Cilia to sweep microbes away
-Alveolar macrophages (dust cells) -regulate tolerogenic and inflammatory response
-Tonsils and adenoids: NALTs
How does the skin contribute to immunity?
-Keratinocytes produce antimicrobial molecules and recognize PAMPs
-Epidermis: Langerhans cells + memory T cells communicating with dermis immune cells
-Dermis: most immune cells, along with lymphatic vessel, sending antigens to lymph nodes
What are PAMPs?
-Represent motifs of recurring patterns on bacteria, yeast, and parasites
-They have to be broad, and not self
-Receptors for PAMPs are PRRs (in the membrane or intracellular)
What are the features of PRR: Toll-like receptors (TLRs)?
-Dimer with leucine-rich (LRR) domain on the outside
-in endosomes they are flipped inside to look for PAMPs
What are the features of PRR: C-Like receptors (CLRs)
-Recognize carbohydrate components of fungi, viruses, mycobacteria, parasites, allergens -> activate signaling pathways
What are the features of PRR: Nucleotide Oligomerization Domain-Receptors (NLRs)
-Not membrane-bound but present in the cytoplasm
->initiate autophagy (cell degrade damaged proteins)
->form autophagosomes around pathogenes -> fuse with lysosome
What is the role of the Inflammasomes?
multimerization of inflammosomes induces self-cleavage and activation of protease activity
->cytokine secretion
->pyroptosis (cell death)
Name other cytosolic PRRs:
-RIG-I-like receptors (RLRs): recognize cytosolic viral ds RNA
->activation of IFN α and β
-AIM-like rec. (ALRs): bacterial and viral ds DNA -> binding of multiple ALRs to dsDNA forms inflammasomes
-Cyclic-GMP-AMP- synthase (cGAS): cytosolic dsDNA, generating cGAMP -> activation STING receptor -> activates transcription factors
What is the antiviral response of Type-1 Interferons (IFN-α and IFN-β)?
-Translation inhibition, mRNA degradation, viral assembly inhibition
-infected cells secreting IFN-α and β to neighbor cells
What are the possible outcomes of TNF-α?
Depending on the cell TNF-α can have different outcomes
-MAPK and NF-κB pathways induce survival and inflammation
-in other cells: caspase-8 activation -> cell death
What is the function of Innate Lymphoid cells (ILC)?
-They lack PRRs
absorb cytokines and amplify the signal into a broader cytokine response
What is the function of NK cells?
-NK cells are cytotoxic lymphocytes (similar to cytotoxic T cells) with innate immune functions
-activated NK cells also kill altered self-cells)
How does phagocytosis work?
Performed by macrophages, DCs, and neutrophils)
-PRRs interact with surface PAMPs through opsonized pathogen surface (complement or antibodies)
-Engulfment and internalization (also damaged host cells)
-Inside: Phagosomes fuse with lysosomes -> destruction through enzyme degradation, reactive oxygen (ROS), and nitrogen (RNS)
