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Final

Microbiology and Immunology 3300B Study Guide - Final Guide: Death Domain, Aldehyde, B Cell


Department
Microbiology and Immunology
Course Code
MICROIMM 3300B
Professor
Prof
Study Guide
Final

Page:
of 9
Microimmune Lecture 21 Study Notes
1. What is tolerance?
-non-responsiveness to an antigen
2. What is self-tolerance?
-non-responsiveness to self-antigens
3. What is acquired or induced tolerance?
-the suppression of a specific, systemic immune response to foreign antigens
induced by the specific actions of lymphocytes
4. What is fetal tolerance?
-the suppression of a specific, systemic immune response to foreign antigens found
within a developing fetus
5. What is oral tolerance?
-the suppression of a specific, systemic immune response against antigens
encountered via the enteric (oral) route
6. What are the layers of self tolerance?
-central tolerance (occurs in the bone marrow and thymus); deletion and editing
-antigen segregation (peripheral organs); physical barrier to self antigens; access to
lymphoid system
-peripheral anergy (secondary lymphoid tissue) cellular inactivation by weak
signaling without co-stimulus
-regulatory T cells (secondary lymphoid tissues and sites of inflammation)
suppression by cytokines, intercellular signals
-functional deviation (secondary lymphoid tissues and sites of inflammation)
differentiation of reg T cells that limit inflammatory cytokine secretion
-activation-induced cell death (secondary lymphoid tissues at sites of inflammation)
apoptosis
7. What is antigen segregation?
-most self antigens are retained outside of the lymphoid system by physical barriers
(cell membranes/endotheliums)
-in the absence of tissue damage these antigens are not encountered by immune
cells (because immune cells don’t see whats inside our cells – intracellular proteins)
8. What are the immune privileged sites?
-brain, testes, placenta and fetus and eyes
-our immune system is actively excluded from these tissues
9. Describe immune privileged sites,
-sites capable of tolerating the introduction of an antigen without eliciting a
damaging immune response
-tissue grafts into these tissues often can survive without immunosuppressive drugs
10. What are the mechanisms of immune privaledged sites?
-restricted entry of immune cells blood brain barrier
-expression of class 1b MHC in preference to classical MHC1 tend to present
formyl peptides not self antigens
-high expression of complement inhibitors
-local production of TGF beta
-minimal or no draining to the lymphatics
-constitutive expression of apoptosis-inducing ligands (FASL and TRAIL)
-tissue-specific immunomodulation (placenta: expression of indolamine 2,3
dioxygenase (IDO) remove tryptophan, preventing T cells from proliferating T
cells cant make their own tryptophan; need it from the outside environment (breaks
down tryp and inhibits T cells within the placenta)
11. What is the FAS/FASL system?
-free floating Fas protein with its death domain
-trimeric Fas ligand binds to and trimerizes Fas
-clustering of the death domains (DD) in the Fas cytoplasmic domains allows Fas to
recruit FADD via its death domain (DED)
-DED and FADD recruit procaspase 8 via similar DEDs in the procaspase
-this allows immune tissue to kill incoming immune cells (on our immune
privaledged membranes)
-on immune privaledged sites: causes death of incoming immune cells
12. Why is a fetus foreign?
-50% of a fetus’s proteome is foreign (from the father)
-some antigens won’t even have “close matches” in the maternal genome
-a male child has over z dozen genes with no homologs/paralogs in the mother
(very unlikely that male and female spouses will have the same MHC molecules)
-because the genes are different; MHC haplotope will be different rejection
similar to a transplanted tissue
13. What are the 3 layers of cells that stand between the mothers and fetus
immune system?
-innermost is the connective tissue, then the cytotrophoblast and the outermost is
the syncytiotrophoblast
14. Which layer is in direct contact with the maternal blood?
-syncytiotrophoblast
15. Does the maternal blood come into contact with the fetal blood?
-no, structure of fetal tissues go into the placenta, arteries/veins/capillaries, blood
perculates through (fetal)
-this tissue is submerged in the placenta which is full of maternal blood
-maternal blood flows into the placenta, contacts the syncytiotrophoblast then
recirculates
16. Discuss the placenta as a physical barrier
-immune cell entry is limited by the syncitium (fused cells) that separate the
mothers blood and the fetus blood
-huge sheet of cells fused together that provide few junctions for immune cells to
enter (would have to drill through them)
17. Discuss the placenta as an immune barrier.
-no HLA-A/B/C expression (no MHC 1)
-HLA-E and G are expressed instead: minimally polymorphic (not much variation);
interact primarily with NK cells (prevent NK cells from attacking the placenta
thorugh missing self mechanism)
-maternal Treg cells present in large number (suppress TH1/2)
-neurokinin B, IDO & phosphocholine suppress immune responses
-high expression of FASL
-all are acting to maintain seperation/non reactiveness between the fetus and
mother
18. Discuss maternal to fetal transfer of antibodies.
-fetus’s don’t have an adaptive immune system (T/B cells)
-getting passive immunization through maternal blood/milk
-fetal placenta and neonatal intestines transport IgG into the fetus/neonate
-there are specialized Fc repcetors(FcRn) that bind IgG and transport it across the
epithelial layers via transcytosis