Chapter 15 Flashcards
Response to self antigens or antigens associated w/ commensal bacteria is called….
autoimmunity
When immune responses are directed against self antigens, they give rise to auto-reactive effector cells and antibodies (____________) against the self antigen
autoantibodies
What are some common autoimmune diseases?
-psoriasis
-rheumatoid arthritis
-graves disease
-hashimoto’s thyroiditis
-systemic lupus erythematosus
-sjogrens syndrome
-crohns disease
-MS
-type 1 diabetes
Multiple tolerance mechanisms normally _______ autoimmunity
prevent
Immature lymphocytes recognize antigens and lead to negative signal causing lymphocyte death or inactivation. This self tolerance happens when they are developing in thymus and BM (then they can go to secondary lymphoid organs). This is called ________ ______________ (bc its centrally where it happens @ the BM+ thymus)
central tolerance
Tolerance induced to antigens after they have left primary lymphoid organs is called….
peripheral tolerance (away from where tolerance began at the BM/thymus)
Mechanisms to prevent autoimmunity goes through a succession of __________. Together all these ___________ ensure immune system still functions and there is no anti-self response
checkpoints, checkpoints
Autoimmunity results from a combo of different factors. What are they?
-genetic susceptibly
-breakdown of natural tolerance mechanism
-environmental triggers such as infection
what cells undergo central tolerance?
B and T cells
Anytime auto-reactive (reacting to self) T cells are generated, what happens?
they need to be eliminated
What is the first checkpoint of self-tolerance?
central deletion or inactivation of newly formed lymphocytes
Many tissue specific antigens are expressed in the thymus region by __________ _________ cells or ____________ ____________ cells
thymus epithelial, special dendritic
A single transcription factor, ___________, is thought to be responsible for turning on expression of many tissue specific proteins in thymic medullary cells
AIRE (autoimmune regulator)
Peptides are presented to the developing thymocytes as they undergo __________ selection
negative
Individual organs of the body express tissue specific antigens. In the thymus, T cells arise capable of recognizing tissue specific antigens. Under control of the ______ protein, thymic medullary cells express tissue specific proteins leading to deletion of tissue reactive T cells. In the absence of _______, T cells reactive to tissue specific antigens mature and leave the thymus
AIRE, AIRE
Elimination of auto-reactive B cells in germinal centers occurs during ________ ___________.
somatic hypermutation
B cells w/ auto-reactive _____ arises and binds to soluble auto-antigen which induces apoptosis of the auto-reactive B cell
BCR
Antigens in immunologically privileged sites do not induce immune attacks but can serve as targets. These sites are unique in 4 ways:
-communication between privelged site and body extracellular fluid does not pass through conventional lymphatics
-sites are surrounded by tissue barriers that exclude naive lymphocytes (such as BBB)
-anti-inflammatory TGF-beta is produced here, so when antigens are recognized along w/ TGF, then it induces Treg response (NOT TH17 OR OTHERS)
-expression of Fas ligand in theses sites ensures that if Fas-bearing lymphocytes enter, then they will undergo apoptosis
If theres an accumulation of antigen in the privileged sites and auto-reactive T lymphocytes are activated elsewhere, then they can come to these sites and do an….
autoimmune attack
(ex: myelin basic protein in brain and spinal cord, antigens that become targets for autoimmune attack for MS)
What are the immunologically privileged sites (places sterile from immune cells)?
-brain
-eye
-testis
-uterus (fetus)
In sympathetic opthalmia, trauma to one eye results in the release of sequestered intraocular protein antigens. The released intraocular antigen is carried to lymph nodes and activates T cells. Effector T cells return via ___________ and encounter antigen in both eyes
bloodstream
In sympathetic opthalmia, trauma to one eye releases sequestered antigen into surrounding tissues and makes it accessible to T cells. The effector T cells can now come to the traumatized eye area and attack but they will also attack the…..
healthy eye
In sympathetic opthalmia, sequestered antigens do not elicit immune response, but if response is induced elsewhere, then they severe as….
targets
In sympathetic opthalmia, T cells can enter area if the site gets infected. The activated effector T cells can enter ___________ _______ after producing cytokines that alter tissue barriers
privileged areas
What are the 2 classifications of autoimmunity?
1) organ specific
2) systemic disease
What are some examples of organ specific autoimmune diseases
-type 1 diabetes
-MS
-crohns disease
-psoriasis
-graves disease
-hashimotos thyroiditis
-autoimmune hemoltyic anemia
-autoimmune Addison’s disease
-vitiligo
MG
What are some examples of systemic autoimmune diseases?
-rheumatoid arthritis
-scleroderma
-systemic lupus erythematous
-primary sjogrens syndrome
What are the 3 main ways autoimmunity happens?
1) autoantibodies produced against ACh receptor blocks receptor function at NMJ and results in muscle weakness (MG)
2) In other cases, Abs in the form of immune complexes are deposited into tissues and cause tissue damage from inflammation
3) effector cells are the main destructive agents in these cases and T cells recognize self peptides or those from self bacteria in complex w/ MHC. Local inflammation and direct damage from T cells (more common) or NK cells can lead to diabetes, psoriasis IBD, MS, etc
Autoantibodies can cross the placenta and leads to disease in the fetus. The symptoms of disease disappear fast as the maternal IgG Ab is catabolized approx 6 months after birth. Sometimes however, the Ab can cause ________ _________
organ injury
What are some autoimmune diseases that are transferred across the placenta to the fetus/newborn infant?
A pt w/ Graves disease makes _________ antibodies. This is caused primarily from the Abs passed on from mom that were transferred across placenta into the fetus. Newborn infant will then also suffer from Graves disease. Plasmapheresis can remove maternal _________ antibodies and cure the disease
anti-TSHR, anti-TSHR
Maternal IgG crosses the placenta. If the mother has IgG mediated autoimmune disease then the infant will most likely show symptoms in the first few weeks of life. Symptoms will disappear when maternal Abs disappear. Children born to such mothers have ______________ and this can be corrected by replacing plasma and removing maternal Abs
hyperthyroidism
In Graves disease, symptoms caused by antibodies against…
thyroid stimulating hormone receptor (TSHR)
What are the 3 mechanisms of tissue damage in autoimmune diseases?
1) antibody against cell-surface or matrix antigens
2) immune complex disease
3) T cell mediated disease
In type 1 diabetes and RA, both T cell and Ab mediated pathways cause….
tissue injury
Autoantibodies IgM and IgG against the blood cells promotes their destruction and causes _________ ___________
auto-hemolytic anemia (Abs made on surface of RBCs)
Autoantibodies IgM and IgG against the blood cells promotes their destruction and causes auto-hemolytic anemia. RBCs w/ IgG/IgM Ab bound, are cleared from circulation by interaction w/ Fc receptor on ____________ or complement
phagocytes
What is the treatment for auto-hemolytic anemia?
-put in new RBCs
-try not to get rid of the RBCs that pt already has/prevent Abs from being produced
-remove spleen (stop RBC destruction)
-large quantities of nonspecific IgG (IVIG) which inhibits Fc receptor mediated uptake of Ab coated cells and suppresses inflammation
What is the immunological function of the spleen?
organ where there is the main clearance of RBCs, platelets, and leukocytes
Binding of IgG and IgM Abs to cells in tissues causes….
inflammatory response
Binding of IgG and IgM Abs to cells in tissues causes inflammatory response. Complement is unleashed, MAC is formed on cell surface, and cytokines are released. Nucleated cells are resistant to lysis by complement, but MAC accumulation on surface can be a stimulus for action. Depending on cell type interaction, it can result in cytokine release, respiratory burst, or membrane phospholipids mobilize to generate arachidonic acid. ____ is released and other inflammatory leukocytes arrive and cause tissue damage
C5a
In Graves disease, the pituitary gland secretes _____ which acts on the thyroid to induce the release of thyroid hormones. Thyroid hormones act on the hypothalamus and the pituitary gland to shut down production of TSH, suppressing further thyroid hormone synthesis (_________ ___________). Autoimmune B cells make Abs against TSH receptor that also stimulates thyroid hormone production. Thyroid hormones shuts down TSH production but has no effect on autoantibody production, which continues to cause excessive thyroid hormone production
TSH, feedback suppression
Thyroid hormone is produced in response to…
TSH (thyroid stimulating hormone)
In normal situations, Ach is released from stimulated neurons and bind to AChR on skeletal muscles and triggers muscle contraction. In MG, however, autoantibodies against the AChR is present on the NMJ in the skeletal muscle cells. The system internalizes the AChR bound to ACh and degrades it, so AChR is gone. ACh will still be released but it doesn’t bind to anything because there is no longer a receptor, and so there will be no response from muscle cells. As the number of receptors decrease, muscles become __________
unresponsive
In streptococcal glomerulonephritis, there is immune complex deposition in the glomerulus of the kidneys. The kidneys are unable to filter like they should and this is bc Abs showed up there because _____ was made against the strep infection prior. Abs can also be made against the basement membrane of the renal glomeruli and cause rapidly fatal disease if not treated (secondary). The autoantibodies bound to the basement membrane ligate to Fc receptor on ___________ and _____________ activating them. Chemokines are released and call more cells to show up and cause tissue injury
IgG, monocytes, neutrophils
In systemic lupus erythematosus (SLE), there is a defective clearance of nucleic acids bound immune complexes. This comes from dying cells. ssRNA or dsDNA from dead cells are bound by Fc receptors on ____________ cells. This is internalized and TLRs are activated which causes the cell to release ________. This in tern asks monocytes and other cells to produce BAFF (B cell activating factor, a part of TNF family). BAFF interacts w/ B cells and it can increase auto-reactivity of B cells and increased Ab production. More and more immune complexes form and T cells get activated which will result in tissue damage
dendritic, IFN-alpha
The islets of langerhans contain several cell types secreting distinct hormones. Each cell expresses different tissue specific proteins. In type 1 diabetes, an effector T cell recognizes peptides from a beta cell specific protein and kills the beta cell. Glucagon and somatostatin are still produced by the alpha and delta cells but no ________ can be made
insulin
In MS, there is an unknown trigger that sets up initial focus of inflammation in the brain and BBB and becomes locally permeable to leukocytes and blood proteins. T cells are specific for CNS antigen and are activated in the peripheral lymphoid tissues that reencounter antigen presented on the _________ or DCs in the brain. An inflammatory reaction occurs in the brain due to mast cell activation, complement activation, antibodies, and cytokines. Demyelination of neurons occurs.
microglia
What is the inflammatory cascade of MS?
In RA, there is an unknown trigger that sets up initial focus of inflammation in the synovial membrane attracting leukocytes into the tissue. Auto-reactive _________ cells activate macrophages, resulting in the production of pro-inflammatory cytokines and sustained inflammation. Cytokines induce production of MMP and RANK ligand by fibroblasts. MMPs attack tissues. Activation of bone-destroying osteoclasts by RANK ligand results in joint destruction
CD4 T
Innate and adaptive immune systems cooperate to limit inflammatory responses of intestinal bacteria in crohns disease by…..
hint: theres 4 bullet points
-mucus from goblet cells
-tight junctions between epithelial cells
-Paneth cells release antimicrobial peptides
-induction of t reg cells which promote IgA production and inhibit CD4 T cell development
Autoimmune syndromes involve molecular mimicry, for example, ________ ___________ following step infection will have antibodies against bacterial cell surface and can cross react w/ heart valves
rheumatic fever
Graft rejection is an immunological response mediated primarily by…..
T cells
Self proteins are routinely digested by the proteasome and loaded onto MHC class ___. If the proteins are polymorphic then the peptides made will be different in the donor and recipient of graft. These are called minor H antigens. There is a large fraction of cells in grafts that express minor H. Additionally, there is virtual certainty of mismatches in minor H
1
Direct allorejection is when organ grafts carry w/ them APCs of the donors origin. These leave the graft and go to secondary lymphoid organs in the recipient and activates host T cells. Then, they move through the circulatory system since lymphatic drainage is interrupted in transplantation. The T cells can now directly attack the….
graft!
Indirect allorejection is where there is an uptake of allogenic proteins by the hosts own _______ and their presentation to T cells by self MHC
APCs
