exam 3 Flashcards
mucosal tissues
include components of the GI tract, respiratory tract, and urogenital tract; lined with epithelial cells that secrete mucin (major protein in mucus)
mucin
major protein in mucus; exists in membrane or soluble form; carbohydrates and cysteine residues create cross-linked thick gel
lamina propria
layer below epithelial cell layer
Describe the role of the epithelium in mucosal immunity
Epithelial barrier has tight junctions, adheren junctions, and desmosomes; tightly joined cells block pathogens from entering
MALT
mucosa-associated lymphoid tissues!! they contain specialized cells and structures that enable pathogen delivery to lymphoid tissue and activation of an adaptive immune response
Peyer’s patches
where lymphocytes are activated
M cells
don’t have follicles; responsible for delivering antigen to Peyer’s patches
Intraepithelial lymphocytes
protect the epithelial layer from intracellular infection
Isolated lymphoid follicles
where B cells are activated to produce plasma cells
Immune cells in healthy mucosal tissue include
- activated T cells
-intraepithelial lymphocytes
-plasma cells
-macrophages
-DCs
-innate lymphoid cells
-mast cells - eosinophils
Invasive bacteria trigger production of these three cytokines from intraepithelial cells
IL-1, IL-6, TNF
viruses induce production of these cytokines
Type I interferon
Resident gut macrophages make
IL-10
Gut has a high basal level of active ____ leading to ___ and _____
TGFB; Tregs and IgA
invasive bacteria and viruses can induce ____ and _____ from dendritic cells, leading to _____ and ______ responses
IL-6 and IL-12; Th1 and Th17
Worms damage epithelia and induce these three cytokines
IL25, IL-33, TSLP
Worms damage epithelia and induce cytokines leading to activation of _____ and _____ responses
ILC2s and Th2
How do DCs capture antigen in the gut mucosa?
-uptake via goblet cells; apoptosis dependent transfer; non-specific transport
transcytosis of pathogens by M cells
this is the process by which M cells deliver pathogens to underlying lymphoid tissue; pathogens on phagocytosed by M cells on the luminal side and transported via vesicles toward the basal side. Some of the pathogen is delivered intact and the other is digested via phagolysosome. B cells on the basal side bind to antigen via receptor for antigen processing and presentation. Dendritic cells process pathogen and antigens for presentation to nearby T cells
Sampling of lumen antigens by DCs
DCs extend dendrites bewteen epithelial cells of mucous membranes ot capture antigen on the lumnial side for processing and presentation
Migration of lymphocytes in MALT
After induction, cells leave the PP and mesenteric lymph node and circulate. They re-enter using special receptors induced by mucosal DCs through retinoid production
Extravasation and migration of T cells to mucosal tissue
express L-selecting and a4:B7 (binds to endothelial receptor MAdCAm-1); right binding –> migrate out of bloodstream and into tissue; T cells destined to become intraepithelial cells swtich cell surface integrin to AE:B7 –. promoting binding to epithelial cell receptor E cadherin
IgA structure
exists as a dimer joined by J chain
soluble IgA transport at epithelial surfaces
SlgA binds to mucus
Plasma cells within mucosal tissue secrete IgA and IgE isotypes, which
promote pathogen clearance and neutralization
Protection of mucosal tissue against worm infection
Dendritic cells and mucosal epithelial cells drive detection of a helminth infection. Mucosal epithelial cells secrete IL-33 and (TSLP). These cytokines activate innate lymphoid cell 2 (ILC2) cells and three types of granulocytes found within the lamina propria: mast cells, basophils, and eosinophils. DCs activate naïve T cells to differentiate into TFH cells for B-cell activation and TH2 cells for mast-cell activation. Within the mucosal tissue, B cells switch isotype expression to IgE, which binds to the surface of granulocytes for antigen recognition. TH2 cells secrete the cytokines IL-3, IL-5, and IL-9 to recruit and activate granulocytes. TH2 cells also secrete IL-13 to repair damage to the epithelial cell layer. ILC2 cells secrete the cytokine IL-5 to activate basophils.
IELs recognizing peptides from viruses/intracellualr
use CD8 a:B heterodimer; IEL releases perforin and granzyme or binding of Fas ligand
IELs that have been stressed
express MIC-A, MIC-B to produce IL-15. Nearby cells are activated and They kill the epithelial cells by releasing perforin and granzyme; these carry CD8 a:a homodimer
inducible protective mechanisms at mucosal sites
1) inflammation (immune response recruits monocytes, neutrophils, eosinophils to control infection) 2) IgA (transported across mucosal epithelium)
constitutive mechansims at mucosal sites
1) mucus production by goblet cells 2) Paneth secretaion of anti-microbial peptides 3) low pH & lysozyme 4) microbiome - primes development of MALT; compete for nutrients and produce own anti-microbials
immunoglobulin structure
2 heavy & 2 light chains; covalently linked by disulfide bonds; AG binding site between variable regions
Fc region
constant regions (4 bottom) of heavy and light
Fab
fragment antigen binding
Variation in hypervariable loops/CDRs is important because
it allows for immunoglobulins with different CDRs to bind to unique antigens
immunoglobulins can bind to macromolecules including
protein, carbohydrate, and nucleic acid
Linear epitope
close in primary sequence (such as adjacent amino acids in the primary sequence of a protein). Linear epitopes are not destroyed if the three-dimensional structure of the antigen is destroyed, as long as the primary sequence is still intact.
conformational epitope
dictated by the structure of the antigen. Conformational epitopes may or may not be driven by functional groups or atoms that are farther apart in the primary sequence, and they are always destroyed if the three-dimensional structure of the antigen is no longer intact
What are the five immunoglobulin isotypes?
IgM, IgD, IgG, IgA, IgE
IgG subclasses
IgG1-4; differ in hinge regions & these different classes exist because of class switch recombination
igM structure
assembles as a pentameric structure & associates with the J chain
IgA structure
exists as a dimer and associates with J chain; secreted in saliva, teaers, gut, mucus
IgM is made in response to
carbohydrate antigens
Effector functions of Igs
1) neutralization 2) opsonization 3) complement activation 4) activation of innate immune cells
IgM is involved in which effector functions
neutralization & complement activation
IgA is involved in which effector functions
neutralization, opsonization, complement activation
IgG is involved in which effector functions
ALL
IgD is involved in which effector functions
activation of innate immune cells
What does it mean for an antigen to be multivalent?
having multiple epitopes, each allowing the binding of a different immunoglobulin
What does it mean for an antigen to have repeating epitopes?
allows binding of more than one immunoglobulin of the same type
recombination in Ig happens with
heavy chain is subject to somatic recombination
IgM production
determined by alternative splicing; includes Cu region
IgD production
determined by alternative splicing; includes Cs region
What determines whether membrane bound or soluble Ig is produced?
poly A early - transmembrane region is removed
Poly A later - incorporates transmembrane region
How does class switch recombination work
Within activated B cells, transcription of different immunoglobulin heavy chain constant regions exposes the associated switch regions to cytosine deamination by AID. Repair mechanisms remove the uracil from the switch regions and create nicked DNA. Because of the sequence similarity among the switch regions and the breaks within the DNA, repair proteins facilitate recombination at the nicked switch regions. This results in recombination of the new constant region to a location for use during heavy chain transcription and removal of the intervening sequence in a manner similar to V(D)J recombination.
AID
is expressed in activated B cells and catalyzes the deamination of cytosine and the formation of uracil in DNA
deanimation of cytosine to uracil in DNA produces mutations
1) DNA rep 2) base excision repair 3) mismatch repair
IFN-y intiaties isotope switch of
IG1, IG3
IL-4 intitiates isotype swtich of
IG2, IGE
IL-5 intitiates isotype swtich of
IgA
TGF-B intitiates isotype swtich of
IgA, IgG4
