Term
| Are autoimmune diseases common or uncommon? What percentage of the population Western countries do they affect? |
|
Definition
|
|
Term
| Autoimmunity results from what? What is it thought to be a combination of? |
|
Definition
-a breakdown in the ability of the immune system to recognize self from non-self
-genetic susceptibility of the individual, breakdown in nautral tolerance mechanism, environmental triggers such as infections |
|
|
Term
| What must individuals express to predispose them to autoimmune diseases? |
|
Definition
| -certain MHC II molecules |
|
|
Term
| What are the 6 types of self-tolerance? |
|
Definition
-central tolerance
-antigen segregation
-peripheral anergy
-regulatory cells
-cytokine deviation
-clonal deletion |
|
|
Term
| What is the mechanism and site of action of central tolerance? |
|
Definition
-deletion, editing
-thymus, bone marrow |
|
|
Term
| What is the mechanism and site of action of antigen segregation? |
|
Definition
-physical barrier to self antigen access to lymph system
-peripheral organs |
|
|
Term
| What is the mechanism and site of action ofperipheral anergy? |
|
Definition
-cellular inactivation by weak signaling without co-stimulus
-secondary lymphoid tissue |
|
|
Term
| What is the mechanism and site of action of regulator cells? |
|
Definition
-suppression by cytokines, intercellar signals
-secondary lymphoid tissue and sites of inflammation |
|
|
Term
| What is the mechanism and site of action of cytokine deviation? |
|
Definition
-differentiation to Th2 cells, limiting inflammatory cytokine secretion
-secondary lymphoid tissue and sites of inflammation |
|
|
Term
| What is the mechanism and site of action of clonal deletion? |
|
Definition
-apoptosis post-activation
-secondary lymphoid tissue and sites of inflammation |
|
|
Term
| What happens during central tolerance? |
|
Definition
-in thymus, T cells react with self Ag presented by MHC molecules on DCs in medullary thymic epi cells in the thymus medulla undergo apoptosis
-in bone marrow, B cells whose BCR bind to soluble self Ag secreted by stromal cells in the bone marrow also undergo apoptosis |
|
|
Term
| How is it possible for DCs in the thymus to present every possible self antigen to T-cells? |
|
Definition
-AIRE (auto immune regulatory gene) gene is turned on in thymic medullary epi cells
-AIRE gene elps transcribe many enes that code for self peptides, peptides that DCs from the bone marrow cannot bring into the thymus |
|
|
Term
| Explain how peripheral tolerance is aided by restricted traffic patterns. |
|
Definition
-naïve T cells do not see self proteins in tissues b/c of their restricted traffic patterns
-naïve T cells are only allowed to exit through HEV in lymphoid organs |
|
|
Term
| What happens in the case of trauma or surgery in which the self-reacting T cells escape into normal tissue? |
|
Definition
-a naïve CD8+ CTL, with TCRs that recognize a cardiac peptide presented by MHC I may escape the re-circulation pattern and gain access into heart tissues during a heart attach
-cardiac cells cannot activate a naïve CTL since they lack B7- the naïve CTL will be anergized
-same thing happens with B cells due to lack of Th cells to activate them |
|
|
Term
Definition: immunologically privileged sites
-give some examples |
|
Definition
-organs that are sequestered, their extracelluar fluid does not drain into lymphnodes are some are surrounded by barriers
-ex: thyroid gland, testis, eye, pancreas, uterus, brain |
|
|
Term
| Cells within immunologically privileged sites secrete _____. What does it do? |
|
Definition
-TGF-beta (transforing growth factor)
-induces immune suppression when Th cells that recognize peptides derived from these cells become activated
-therefore T cells that encounter this dev into Treg cells that secrete TGR-beta and IL-10, immunosuppressive and anti-inflammatory cytokines |
|
|
Term
| What happens if antigens leave immunologically privileged sites during inflammation? Ex= eye |
|
Definition
-trauma to one eye releases the sequestered eye Ag's to surrounding tissues, that will be taken into the lymph tissues along with inflammatory cytokines IL-12, IFN-gamma, TNF-alpha
-DC will present the peptides to Th cells and one may recognize and become activated by the eye protein
-the Th then circulates back into both eyes and induces inflammation |
|
|
Term
| Tregs are ____+, ____+, and ____+ cells. |
|
Definition
|
|
Term
| What do Tregs do when they encounter their self peptide presented by MHC II molecules on APCs? |
|
Definition
| -they secrete suppressor cytokines IL-10 and TGF-beta that suppress the activation of all other Th cells |
|
|
Term
| Going from a Th1 to a Th2 cell response will switch the response from an (anti-inflammatory/inflammatory) cell response to a (anti-inflammatory/inflammatory) cell response. |
|
Definition
-inflammatory Th1
-non-inflammatory Th2 |
|
|
Term
| A Th17 response initiated by (cell type) secreting TGF-beta PLUS IL-6 could switch to a Treg response if _____ secretion is stopped and only _____ continues to be secreted. |
|
Definition
|
|
Term
| Repeated stimulation of an activated T cell will result in an increase in the number of ___ molecules on its surface. When this molecule reaches a certain concentration, they trimerize, resulting in what? |
|
Definition
|
|
Term
| Which cells have FasL that can bind to T cell Fas? |
|
Definition
|
|
Term
| What is the most important factor in turning off the immune system at the end of an infection? What is another means of deactivation? |
|
Definition
-the removal of antigen
-binding of B7 to CTLA-4 that accumulate the surface of activated T cells |
|
|
Term
| In a primary immune response after vaccination with an inactivated vaccine, how long does it take for Ab to appear in the serum? |
|
Definition
|
|
Term
| Which Ab is the first detected in an immune response? |
|
Definition
|
|
Term
| In a secondary or anamnestic immune response, how soon is an Ab response observed? Do you see IgM or IgG first? |
|
Definition
-2-3 days after re-vaccination
-IgM is seen first, but it is rapidly overrun by a massive IgG spike |
|
|
Term
| True or False: IgG titers are relatively the same after a live virus vaccine as they are after an inactivated vaccine. |
|
Definition
| FALSE, the are significantly higher in a vaccination with a live virus |
|
|
Term
| How long after infection with BHV-1 will you start to see clinical signs in a calf? What are the clinical signs? |
|
Definition
-5 days
-fever, nasal secretions, necrotic nasal mucosa, bronchitis, cough |
|
|
Term
| IFN-alpha and IFN-beta are detected in NS within ___hrs post infection. What else is noted at this time? |
|
Definition
-24 hours
-NK cell activation and activity in the lungs and blood |
|
|
Term
| CTLS specific for BHV-1 appear about ___days PI in the lung tissue and in the blood. |
|
Definition
|
|
Term
| In respone to BHV-1, IgM appears in the serum at about ___ days PI, then there is isotype switching and a strong _____ appears 2-3 days later. |
|
Definition
|
|
Term
| When does IgG2 show up in the serum after BHV-1? |
|
Definition
|
|
Term
| In cases of canine distemper virus (CDV), there is a/an (direct/inverse) relationship between Ab response and severity of disease. |
|
Definition
|
|
Term
In CDV, if the dog dev anti-CDV Ab by 9d PI and the lvl inc by 14d, what will happen to the dog?
-what if it dev anti-CDV Ab after 9d but there is no significant inc by 14 d?
-what if it does not dev anti-CDV Ab by 9d PI? |
|
Definition
-dog will clear the virus and recover
-dev clinical disease and may recover
-dev severe clinical disease and die |
|
|
Term
| True or false: If we give dogs the measles vaccine, they are protected from canine distemper. |
|
Definition
|
|
Term
| Which cytokine causes isotype switching from IgM to IgG? |
|
Definition
|
|
Term
| Why is it that a puppy can only be properly immunized against CPV-2 if there are no more maternal Abs in its system? |
|
Definition
-If there are maternal Abs, they will bind to CPV-2 and cause its death, thus their is no need for the puppy to develop its own Abs
-However, if these maternal Ab's are absent, then the puppy will develop its own immune response to the vaccine |
|
|
Term
| Between the skin and mucosal surfaces, which is more fragile? |
|
Definition
|
|
Term
| ___% of pathogens gain entry into the body by way of the mucosa. |
|
Definition
|
|
Term
| What is the specialized function of mucosal epi cells? |
|
Definition
| -absorption of nutrients and gas exchange |
|
|
Term
| Mucosal surfaces are covered by _________ produced by _________ cells. This has what function? |
|
Definition
-mucus
-most important non-specific barrier to pathogens |
|
|
Term
| What does mucus contain? Its purpose? |
|
Definition
-lysozyme and secretory IgA
-to trap, neutralize, and inactivate pathogens |
|
|
Term
| True or False: Resident microflora in the intestinal, upper respiratory, and urogenital tracts are very important in protecting the mucosa against pathogens. |
|
Definition
|
|
Term
| How do resident microflora protect against pathogens on mucosal surfaces? |
|
Definition
| -they out-compete pathogenic bacteria for space and nutrients |
|
|
Term
| True or False: Normal microflora is irrelevant in the normal development of the immune system. |
|
Definition
FALSE, it is very important
-germ-free animals have hypoplastic lymph nodes, no germinal centers, and only 1/50th of the Abs normally present in formal animals |
|
|
Term
| Concerning adaptive immunity, the mucosa is rich in which two cell types? |
|
Definition
| -macrophages and dendritic cells |
|
|
Term
| What is the purpose of macrophages and dendritic cells on mucosal surfaces? |
|
Definition
-to pick up pathogens from the mucosal surfaces and present them to T-cells and B-cells in the submucosal lymphoid tissues
-also, if a pathogen breaks through the mucosal epi and enters the intestinal or resp submucosa, it will be phagocytosed by macrophages and presented to the immune cells in the lymph node by DC |
|
|
Term
| What happens to IgG secreted onto mucosal surfaces? |
|
Definition
| -it is broken down and digested by protease present on the mucosal surface and in the nasal passages |
|
|
Term
| Describe the two main characteristics of fighting off non-invasive pathogens that stay in the lumen or on the mucosal epi cells. |
|
Definition
1) manufacturing and secretion of specialized Ab called IgA
2) system that grabs pathogens from the mucosal surface and presents them to T and B cells in the submucosal lymphoid tissue |
|
|
Term
| Name the mucosal compartments. Are they linked? |
|
Definition
-esophagus
-GI tract
-resp tract
-urogenital tract
-mammary glands
-lachrymal system
-they are all immunologically linked in a common mucosal immune system |
|
|
Term
| How are the mucosal compartments immunologically linked? |
|
Definition
| -immune cells activated in one compartment will not only home back to that compartment, but will also migrate to other compartments to secrete IgA |
|
|
Term
| What is lactogenic immunity? |
|
Definition
| -animals that suckle milk are protected form enteric viruses through IgA in the milk |
|
|
Term
| What are the inductive sites within the GALT? |
|
Definition
| -tonsils and adenoids in the pharynx, Peyer's patches and isolated lymphoid follicles in the ileum and jejunum, lymphoepithelial glands in LI, and the appendix |
|
|
Term
| True or False: Peyer's Patches and isolated lymphoid follicles are truly isolated. |
|
Definition
| FALSE, they are all connected by lymphatics, which drain in the mesenteric lymph nodes |
|
|
Term
| In which cell layer can you find Peyer's Patches and isolated lymphoid follicles? |
|
Definition
| -in the lamina propria within the submucosa |
|
|
Term
| What specialized cells form a dome over Peyer's patches in the gut? |
|
Definition
|
|
Term
| Lymphoid tissue consists primarily of ___-cells, with a ring of ___-cells encircling. |
|
Definition
|
|
Term
| In the gut, DCs are situated in the lymphoid follicles just below ___-cells in order to perform what function? |
|
Definition
-M-cells
-capture antigen for presentation to the T-cells and B-cells |
|
|
Term
| What is the function of M-cells in the gut? Their special form of Ag transport is called what? |
|
Definition
-take in Ags (proteins, partcles, pthogens) from the lumen by endocytosis, transport them across the cell within vesicles, and dump them across the basal membrane into the lymphoid follicles where they are taken up by DC and presented to lymphocytes
-transcytosis |
|
|
Term
| Naïve T-cells and B-cells enter the Peyer's patch by way of the ____. |
|
Definition
|
|
Term
| B-cells in the gut become activated by presentation of their cognate Ag by __ cells and then move into the _________ where they will proliferate through stimulation by the surrounding __ cells. |
|
Definition
|
|
Term
| True or False: Although both Th1 and Th2 cells can differentiate as a result of Ag presentation, it is primarily Th2 and Tregs that are observed in normal mucosal lymphoid tissues. |
|
Definition
|
|
Term
| Which cytokines do Th2 cells secrete? |
|
Definition
| -IL-4, IL-5, IL-10, IL-13, TGR-beta |
|
|
Term
| Which cytokine activates Tregs? What do they secrete when activated? |
|
Definition
|
|
Term
| Which cytokines are responsible for isotype switching from IgM to IgA? |
|
Definition
-TGF-beta from Th2
-IL-10 from Th2 and Tregs |
|
|
Term
| What is IL-5 produced by Th2 cells in the gut responsible for? |
|
Definition
| -the continued expansion and proliferation of the IgA producing B-cell |
|
|
Term
| In Peyer's patches, DCs secrete __-__ when activated, which plays an important role in inducing Th2 cells and Tregs. |
|
Definition
|
|
Term
| What happens after lymphocytes are activated in Peyer's patches? |
|
Definition
| -they move to the mesenteric lymph nodes, they acquire integrin adhesive molecules that allows them to home back only to the mucosa and MALT. |
|
|
Term
| Integrin molecules recognize special addressins on cells of the HEV called _________. |
|
Definition
|
|
Term
| True or False: In addition to the Peyer's patches and organized lymphoid follicles, the mucosal immune system contains a large number of effector lymphocytes even in the absence of disease. |
|
Definition
|
|
Term
| True or False: The healthy intestinal mucosa actually displays the characteristic of a chronic inflammatory response. |
|
Definition
|
|
Term
| When activated by inflammatory cytokines, DCs in the gut will produce _____ and _____ that will cause a Th1 response and inflammatory response. |
|
Definition
|
|
Term
| IgA is secreted in its ___-meric form. |
|
Definition
|
|
Term
| IgA dimers will bind to special receptors referred to as _____ present on the basement membrane of enterocytes. What happens to the complexes formed here? |
|
Definition
-pIgR
-the pIgR:IgA complex is then transported through the cytoplasm of the enterocytes and released into the lumen of the gut as secretory IgA |
|
|
Term
| What is the purpose of the secretory piece on IgA? |
|
Definition
| -makes IgA resistant to digestion by proteases |
|
|
Term
| What is the most important function of IgA? |
|
Definition
-neutralize pathogens on mucosa surfaces including the lumen of the gut; they bind to and agglutinating bacteria and viruses, preventing them from attaching to the mucosa
-in addition, IgA can inactivate pathogens in the submucosa and intracellularyly |
|
|
Term
| Describe how IgA binds to pathogens INTRACELLULARYLY in the wall of the gut. |
|
Definition
| -IgA can bind to the pathogen in the submucosa before it binds ot the pIgR, and is thus transported to the mucosal surface |
|
|
Term
|
Definition
|
|
Term
| In addition to the conventional alpha-beta TCR bearing T-cells carrying either CD4 or CD8, a second class of T-cells exist which carry __:__ TCR. |
|
Definition
|
|
Term
| Unique gama-delta TCR-carrying T-cells include what special type of T-cell that is abundant in the epi of the gut? |
|
Definition
| -intraepithelial lymphocytes (IEL) |
|
|
Term
| IELs bind only to MHC class ___ molecules that are only expressed on intestinal epi enterocytes that have been injured or stressed via what mechanism? |
|
Definition
|
|
Term
| Definition: Oral Tolerance |
|
Definition
| -a state of active and specific unresponsiveness induced by antigenic food proteins that we have ingested |
|
|
Term
| Th cells and B-cells that recognize the food antigens in the absence of costimulation undergo _________. |
|
Definition
|
|
Term
| True or False: The development of immune capabilities depends on antigenic stimulation. |
|
Definition
|
|
Term
| Most mammals are born with a strong tendency towards Th1 or Th2 responses? Bacterial infections acquired after birth will shift the immune response towards Th1 or Th2? |
|
Definition
|
|
Term
| True or False: The fetsuses of most domestic animals cannot overcome viral infections if they are infected in utero because their immune system is not fully functional until a few weeks after birth. |
|
Definition
| -FALSE, they can overcome some viral ifections if they are infected in utero during the last third of gestation |
|
|
Term
| During the development of immune system in the bovine fetus, the _________ is the first lymphoid organ/aggregate to develop at 40 days post-conception. |
|
Definition
|
|
Term
| When do IgM-positive cells appear in the development of the immune system in the bovine fetus? |
|
Definition
| -two weeks after lymphoctyes (40d+5d+2w) |
|
|
Term
| True or false: During the immune development of a bovine fetus, all the primary lymphoid organs and the most important secondary lymphoid organs are fully developed by the end of the second trimester. |
|
Definition
| FALSE, by the end of the first (90days) |
|
|
Term
| By the end of the (first/second/third) trimester, the bovine fetus is able to mount both humoral and cell mediated immune (CMI) responses to pathogens such as viruses and to kill and eliminate such athogens. |
|
Definition
|
|
Term
| Which of the domestic animals has the fetus that is the slowest in developing a functional immune system? |
|
Definition
|
|
Term
| What are the three reasons that newborn animals have an increased susceptibility to certain infections when compared to older animals? |
|
Definition
-deficiency in the phagocytic capability of macrophages and neutrophils in the newborn animal, including in the ability to phagocytoze and in killing phagocytosed pathogens
-the macrophage's inability to fully respond to IFN gamma
-the level of glucorticoids in the fetus is very high at time of birth with an immunosuppressive effect |
|
|
Term
| The (active/passive) transfer of Ab allows the newborn to resist most infections to which its mother is immune. |
|
Definition
|
|
Term
In the following animals, are maternal Ab's transferred via yolk, placenta, or colostrum?
a) birds
b) ungulates
c) carnivores
d) primates/rodents |
|
Definition
a) yolk
b) colostrum
c) mostly colostrum
d) placenta |
|
|
Term
| Ig in the colostrum is made up of Ig_ predominately (>80%) with some Ig_ and IgM. |
|
Definition
|
|
Term
| What happens to Ig in colostrum when it reaches the stomach? How does it survive the trypsin? |
|
Definition
-the Ig binds to specialized Fc receptors on the intestinal epi cells called FcRn
-trypsin levels in newborn are low and colostrum contains trypsin inhibitors |
|
|
Term
| Ig_ is the isotype preferentially transferred across the gut epi. |
|
Definition
|
|
Term
| Describe the change in gut permeability in the newborn. |
|
Definition
| -perm is highest immediately after birth and declines after about 6 hrs b/c the cells that absorb colostrum are replaced by more mature intestinal epi cells |
|
|
Term
| What is the most important aspect of colostrum from a management perspective? |
|
Definition
| -must make sure that the newborn ingests enough colostrum within the first 6 hrs after birth |
|
|
Term
| Passively acquired Ig have a half-life of __ days in cattle/horses and __ days in dogs/cats. |
|
Definition
|
|
Term
| Failure of Passive Transfer (FPT)can be due to failure of the dam to produce enough colostrum. What are a few factors that can lead to this issue? |
|
Definition
| -malnutrition, mastitis, excessive dripping of colostrum from udder during parturition, failure of Ig transfer into the udder |
|
|
Term
| What is the most common cause of FPT? |
|
Definition
| -failure of absorption by the newborn |
|
|
Term
| What is the only way to ensure that enough colostrum and Ig have been absorbed by the newborn? |
|
Definition
| -to measure levels of IgG in the newborn serum at about 18 hours after birth |
|
|
Term
| In foals, an IgG level of between ___ mg/dl and ___ mg/dl is considered adequate for protection of the foal against infections. |
|
Definition
|
|
Term
| True or False: Mortality rate in calves with FOT is almost double that of calves that have obtained adequate amaounts of colostrum. |
|
Definition
|
|
Term
| How do we treat foals with FPT? |
|
Definition
-feed them colostrum obtained commercially or collected from mares
-if foal is older than 15 hrs, it should be infused IV with good quality plasma obtained from the blood of an older mare |
|
|
Term
| Animals that have suckled are (faster/slower) to mount an immune response than those that have not suckled. Why? |
|
Definition
-slower
-masking and sequestration of the Ag by the passively acquired IgG and the maternal IgG/Ag complex blocking the proliferation of B-cells whose BCR have bound the same Ag |
|
|
Term
| Fetal immune response to intrauterine infection depends on what two factors? |
|
Definition
-stage of fetal development at time of infection
-virulence of the pathogen |
|
|
Term
| True or False: Pregnant sows infected with PPV show no signs of clinical illness. |
|
Definition
|
|
Term
|
Definition
| -Stillbirth, Mummification, Embryonic Death, and Infertility |
|
|
Term
| If sows are infected with PPV early during gestation, what happens to the developing fetus? |
|
Definition
| -it is reabsorbed and the sow comes back into estrus infertile |
|
|
Term
| If the pregnant sow becomes infected with PPV after the formation of bones, skin, and fair, what happens to the developing fetus? |
|
Definition
| -the fetus is killed and partially reabsorbed, resulting in a mummy |
|
|
Term
| If the pregnant sow is infected with PPV after the 70th day of pregnancy, what happens to the developing fetus? |
|
Definition
| mounts an immune response and clears the infection, born with circulating Ab's to PPV |
|
|
Term
| The results of a pregnant cow being infected with BVD depend on what two factors? |
|
Definition
1) the stage of fetal development
2) whetehr the BVD strain si cytopathic or non-cytopathic |
|
|
Term
| What is the difference between the cytopathic and non-cytopathic strains of BVD? |
|
Definition
-non-cytopathic will not kill cells in which they replicate unless an immune response is directed at the infected cell
-cytopathic will always kill cells in which they replicate |
|
|
Term
| Infection of pregnant cow with BVD earlier than day 45 results in what? From day 45-125 of CP strain? Day 125-175 of CP? After 175? |
|
Definition
-<45d: death of embryo
-45-125d: fetal death and abortion
-125-175d: fetal survival with congenital defects, cerebellar hypoplasia
->175d: full recovery |
|
|
Term
| What happens when a pregnant cow gets infected with NCP strain of BCD b/n 45-125d of gestation? |
|
Definition
| -fetus becomes infected and will recognize the BVD as self and will possess no circulating Ab to BVE (called persistently infected) and will die within the first two years of life |
|
|
Term
| True or False: A PI cow will only occasionally produce a PI calf. |
|
Definition
| FALSE, a PI cow will always produce PI calves. |
|
|
