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

Microbiology and Immunology
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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)
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?
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
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
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