Seminar (Pregnancy) Flashcards
The Issue: a fetus is an allograft
Minimally, a fetus is a ____ but in the case of a surrogate mother, can be totally ____.
semi-allograft
allogeneic
Antigens
Virtually any molecule, including those derived from non-pathogenic entities, can function as an ____ and/or ____.
What are the consequences of the responses induced by different types of antigens?
- Protective
- “Harmless”
- Pathogenic
antigen
immunogen
Genes Encoding Lymphocyte An’gen Receptors
initially, germ theory proposed that every L/H chain protein that B cells can produce is coated by an individual gene… BUT, in actuality it is somewhere in between (involving mutations)
each chain has their own locus of genes; the variable of a L chain protein is encoded by V and J region segment (for kappa, 85 V region segment, 5 J region segment); these two segments can ____ amongst themselves; and within the junctions can also differ
once a cell chooses a ____, it never changes throughout the life of the cell (and if it chooses kappa, and that also doesn’t change
also applies to heavy chain, they also have a D region segment (among the antibodies produced (A v. D. etc.), it is also maintains the same V, D and J segments)
can only class switch to groupings that are located ____
rearrange
combination
downstream
Recombination of the gene segments encoding the light/heavy and α/β chain proteins of antibodies and T cell antigen receptors, respectively, occurs in a ____ manner. As a result, B and T cells are generated that can be specific for foreign and self antigens.
random
History
Burnet proposed that antigens encountered by an “immature” immune system tolerized the relevant lymphocytes.
Medawar transferred histoincompa’ble hematopoietic cells into recipient mice at different times after birth. Skin grafting experiments showed that mice who received cells in the first few days of life (but not later) acquired ____ tolerance to antgens of the donor.
injection of initial mouse (0 weeks, not beyond a few days) with histoincompatible cells > induce immunoloigcal tolerance with the red MHC molecules, and then it ____ the red skin graft (accepts it as self), another type of mouse it would reject
lifelong
accepts
Immunologic Tolerance
Specific immunological non-reac’vity to an an’gen induced by a previous exposure to the same an’gen.
The most important form of immunologic tolerance is ___; under certain condi’ons, non-self antigens can induce tolerance ___.
Maintenance of immunologic tolerance requires ___ of antigen. It can be broken naturally (autoimmune disease) or artificially (irradiation, drug treatment or expose to cross reactive antigens.
Autoreac’ve B cells and T cells are present in the ___ of healthy individuals.
tolergons
non-reactivity to self-antigens
persistence
peripheral circulation
Immunologic Ignorance
A form of self tolerance in which self reac’ve lymphocytes and their an’gens are both detectable within an individual, yet no autoimmune attack occurs. This can be attributed to:
- the concentration of antgen being too ___ to induce activation of potentially autoreactive cells.
- sequestration of the antigen in ___ sites (i.e., brain, eyes, [fetus?]).
low
immunologically privelaged
gene segments that ecnode ___ have the highest level of mutation out of any gene
LPS is a classic ___ antigen
light and heavy chain proteins
T-independent
Mechanisms of Tolerance Induc’on
Central Tolerance – induction of immunologic tolerance during lymphocyte development in ___ (for B cells) and ___ (for T cells).
Peripheral Tolerance – induction of immunologic tolerance in ___ that have made it out of the primary lymphoid issues.
in peripheral circulation you want B and T cells that have the capacity to identify an epitope of a conventional antigen
T/B cell can acquire a high affinity receptor for self molecule > you do not want these cells in peripheral > induction of apoptosis within ___ tissue > induction of central tolerance (during antigen-independent stages)
B cells develop that do not have high reactivity and are not deleted by self, enter the circulation and have potential of becoming ___ > but they are kept in a quiescent state (do not want them activating) > peripheral tolerance, induction within a SECONDARY lymphoid tissue
bone marrow
thymus
autoreactive B and T cells
primary lymphoid
reactive
AIRE > autoimmune regulator protein; expressed by ___ cells > induces transcription of non-thymic proteins, all the ___ seen in all proteins
medullary thymic epithelial
non-self proteins
Central B Cell Tolerance
if b cells express receptor for high affinity for self > ___ the V, D, J and can escape the apoptotic signal and express a receptor that has an entirely different specificity, and if it’s not self- receptive it’ll exit into the circulation
rearrange
Peripheral B Cell Tolerance
interaction of ___ on the B cells
Fc receptors
The maternal immune system is exposed to paternal antigens derived from the fetus that can induce both ___ and ___ immune responses.
Interactions between the fetal tissues and maternal innate immune system are thought to promote ___ of an embryo and facilitate ___.
humoral
cell-mediated
implantation
successful pregnancy
Immune “Protective” Mechanisms in Pregnancy
Old Paradigms
- The placenta acts as a mechanical barrier that prevents movement of cells and an’gens from the fetus to the mother and mother to fetus.
- Pregnancy is characterized by a state of maternal immune ____.
- Inflammation is ___ to a successful pregnancy.
OLD NEWS
suppression
detrimental
Immune “Protec’ve” Mechanisms in Pregnancy
Placenta-Associated Mechanisms
- Strictly regulated expression of ____ molecules to protect against maternal cytotoxic T cells.
- extravillous trophoblasts migrating into the decidua do not express ____ molecules considered to be major stimulators of graft rejection
- non-classical MHC class I molecules including ____ that may inhibit the “killer” activity of ____, macrophages and T cells
- HLA-G may activate pathways in NK cells, macrophages and T cells that facilitates ____.
- syncytiotrophoblasts forming the outermost aspect of the placental villi exposed to maternal blood do not express ____ proteins - Trophoblasts do not express ____ molecules.
MHC Class I MHC Class I HLA-G NK cells placentation MHC Class I
MHC Class II
