Term
| What are the main mechanisms behind the development of an autoimmune response? |
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Definition
| Type II-IV hypersensitivity, spontaneous autoreactive ab production, lymphatic leukemia, molecular mimicry |
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Term
| What mechanisms lead to cell and tissue damage in autoimmune conditions? |
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Definition
| Ab-mediated cell destruction, cytoxic activity (T and NK cells) - molecular mimicry-driven, immune complex deposition, cytokine storm and inflammatory damage, bystander effect (e.g. superantigens), complement activation |
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Term
| What can cause a primary immunodeficiency? |
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Definition
| Genetic/developmental defects (recessive alleles) |
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Term
| What kinds of agents are involved in a secondary immunodeficiency? |
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Definition
| Chemical, physical, or biological agent |
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Term
| Immature B cells present in the blood are indicative of what? |
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Definition
| Secondary immunodeficiency |
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Term
| What are the molecular symptoms of X-linked agammaglobulinemia? |
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Definition
| Reduced/absent B cells in blood and lymphoid tissues-->low/undetectable Ig (all 5 isotypes); lack of germinal centers in lymph nodes; absence of tonsils/adenoids; lack of T cell activation |
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Term
| What kind of infections are increased with B-cell deficiency? |
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Definition
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Term
| What kind of infections are increased with T-cell deficiency? |
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Definition
| Viral, mycobacterial, and fungal |
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Term
| What may cause B cells to fail to differentiate into IgA-secreting plama cells? |
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Definition
|
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Term
| What is the function of IL-12? |
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Definition
| Stimulate T cells to differentiate |
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Term
| What is DiGeorge syndrome? |
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Definition
| T cell deficiency, athymic, deletion on chromosome 22 |
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Term
| What kind of genetic disorder leads to lack of isotype switching and memory cell differentiation? |
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Definition
| Mutation in X-linked CD40L gene - X-linked hyper-IgM syndrome |
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Term
| Are RAG-1, RAG-2, or DSB proteins (responsible for VDJ recombination) involved in isotype switching? |
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Definition
| No, these processes are RAG-independent |
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Term
| How does CD40L stimulate B cells to proliferate and differentiate? |
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Definition
| TCR:MHC interaction on the surface of the T cell specific to the antigen causes release of CD40L by the T cell. Binding of CD40L to CD40 on the B cell is a costimulatory signal with the MHC:TCR binding, causing proliferation and differentiation |
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Term
| Why would we see reduced neutrophil count and increased monocyte count in hyper-IgM syndrome? |
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Definition
| IL released by T cells stimulate production and chemotaxis of PMNs and differentiation of monocytes into macrophages |
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Term
| What kind of B cells would be found in the paracortex in hyper-IgM syndrome? |
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Definition
| Mature, undifferentiated B cells |
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Term
| How can lack of CD40L activity lead to defects in cell-mediated immunity? |
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Definition
| Lack of stimulation for production of PMNs and differentiation of MMNs into macrophages --> reduced specificity of cell-mediated immunity |
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Term
| How does leukocyte infiltration differ in hyper-IgM syndrome? |
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Definition
| Limited chemotaxis still occurs, but takes a long time to get up to a level capable of dealing with the injurious agent - necrotic death of monocytes would be primary inflammation feedback mechanism |
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Term
| Why could you see development of Ab's for blood group antigens in hyper-IgM syndrome, but not (for e.g.) bacterial antigens? |
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Definition
| Blood group A and B are sugars - only one possible epitope; in virulence factors of infectious agents, multiple epitopes possible, so affinity maturation is critical to the development of an effective immune response. |
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Term
| What kind of pathogenesis is seen in complement protein defects? |
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Definition
| Impaired phagocytosis, increased susceptibility to G- bacteria, lack of clearance of Ag:Ab complexes, non-specific host tissue damage |
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Term
| Describe the general pathogenesis of SCID. |
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Definition
| Defects in lymphoid development - affects either T or T + B cells |
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Term
| Describe the general etiology of SCID. |
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Definition
| Homozygous recessiveness in X-linked gene encoding gamma chain (shared by IL-2, IL-4, IL-7, IL-9, and IL-15 receptors); possibly also faulty adenosine deaminase (build-up of toxic molecules in lymphocytes); or defects in JAK-3 (lack of signalling from IL-2 receptor) |
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Term
| What kind of cells are responsible for a) positive T selection and b) negative T selection? |
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Definition
| a) Cortical epithelial cells, b) medullary epithelial cells |
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Term
| Why do we see 97% of T lymphocytes undergo apoptosis during maturation in SCID? |
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Definition
| Since they lack the gamma chain, the TCR is not functional, so they are kicked into the apoptotic pathway during negative selection when they attempt to bind MHC molecules |
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Term
| Why are SCID patients' MMNs unresponsive to PHA, ConA, and pokeweed mitogen? |
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Definition
| Lack of interleukin stimulation, lack of TCR reactions |
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Term
| What makes giving a patient cyclosporin and prednisone following bone marrow transplantation paradoxical? |
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Definition
| The bone marrow transplant is meant to supplement the patient's immune system, but the drugs work to suppress it. |
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Term
| What is the etiology/pathogenesis of bare lymphocyte syndrome? |
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Definition
| Failure to display MHC II molecules --> similar symptoms as SCID |
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Term
| What are the advantages and disadvantages in using maternal or paternal-derived bone marrow? |
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Definition
| Mother contains a unique marker with the XX karyotype (Xx genotype); father contains only "good" gamma gene, but has an extra antigen (H-Y antigen) that may result in immune response |
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|
Term
|
Definition
| Cleavage into C3a and C3b |
|
|
Term
| How can factor I deficiency lead to C3 deficiency? |
|
Definition
| Factor I degrades C3b. Lacking factor I will mean that C3b will not be degraded, and will continue to cause spontaneous C3 tickover |
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Term
| Why might we see a deficiency in factor B in a patient with factor I deficiency? |
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Definition
| Factor B is used in the alternative pathway, and its rate of consumption would mimic that of C3 |
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|
Term
| Why would we see the development of hives in patients with factor I deficiency? |
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Definition
| C3a binds to mast cells and induces degranulation. |
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Term
| Why would we see an increase in susceptibility to infection with Neisseria spp in C8 complement deficiency? |
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Definition
| Late complement component deficiency causes an inability of the immune system to develop membrane attack complexes |
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Term
| What is the CH50 test and how is it significant? |
|
Definition
| Quantity of component needed to lyse 50% of sensitized sheep RBCs. It gives a general overview/evaluation of the functionality of the complement cascade in a patient |
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|
Term
| What is the significance of the double-diffusion assay (in terms of complement protein)? |
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Definition
| Determines which component of complement is missing/non-functional |
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|
Term
| What is the relationship between MHC and complement? |
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Definition
| The genes encoding C2 and C4 proteins are in the MHC complex; MHC haplotyping may indicate if a complement protein is missing, and which one it is |
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Term
| How can encapsulated gram(-) bacterial cells be susceptible to MAC-mediated damage? |
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Definition
| Mannose-binding-lectin pathway: mannose is only present the membranes of lower-level organisms |
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Term
| How can C1, C4, and C2 deficiencies lead to susceptibility to immune complex damage? |
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Definition
| These proteins facilitate the uptake and removal of immune complexes from the blood. In their absence, the immune complexes are not removed from the site of deposition, and bystander effect damage occurs |
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|
Term
| What leads to whether T or T + B cells are deficient in SCID? |
|
Definition
| T cells deficient in X-linked disorder, T + B cells deficient in autosomal disorder |
|
|
Term
| How can actin filament:microtubule interactions contribute to T cell activity? |
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Definition
| Draws T cells towards target cells in order to locally release cytokines |
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|
Term
| Why do T cells in WAS patients respond poorly to mitogens? |
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Definition
| The white-blood-cell-specific actin filament malfunctions cause numerous errors during mitotic division |
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Term
| Why might we see the development of a peanut allergy in a liver transplant recipient? |
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Definition
| The liver holds a large store of (differentiated) B and T lymphocytes - leading to the generation of anti-peanut IgE |
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|
Term
| General treatment methods of immunodeficiencies. |
|
Definition
| Bone marrow transplants, stem cell injections, recombinate cytokine delivery, gene therapy |
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Term
| What are two ways of blocking HIV from entering T cells and which one is the "better" choice? |
|
Definition
| Injection of either gp120 (tie up CD4 on T cells) or CD4 (tie up gp120): CD4 is the better bet, since gp120 is a neurotoxin |
|
|
Term
| How does HIV activity lead to AIDS dementia? |
|
Definition
| Accumulated neuron damage due to neurotoxic gene products (gp-120, tat, nef, rev) |
|
|
Term
| How can HIV evade immune system clearance? |
|
Definition
| High mutation rate, latency of infection, cell-to-cell spread |
|
|
Term
| What is thought to be responsible for the weight loss seen in AIDS patients? |
|
Definition
| Binding of gp120 to macrophages-->production of TNF-alpha |
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Term
| How can an individual's MHC-encoding genes confer susceptibility to infection-induced autoimmunity? |
|
Definition
| Activated T cells (due to infection) that failed to undergo negative selection in the thymus recognize self-MHC as non-self Ag. |
|
|
Term
| How could cold agglutinins produce a Raynaud's-like syndrome? |
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Definition
| Since the phalanges are generally cooler than the rest of the body, the cold agglutinins could be activated in the phalanges, causing a discoloration and hypoxia. |
|
|
Term
| How can the direct and indirect Coombs test be used to identify autoantibody? |
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Definition
| Since Coombs test is used to identify bound antibody to self-cells, a positive result means that there was an autoimmune antibody present. |
|
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Term
| How might an indirect Coombs test be useful in practice? |
|
Definition
| Mix mother's serum (with Ab) with fetal blood and test for agglutination to see if mother possesses anti-fetal Abs (surrogate) |
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|
Term
| What options are available with a Rh- mother carrying an Rh+ fetus. |
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Definition
| Primary option is Rhogam - anti-Rh antibody, designed to tie up the antigen and prevent a secondary immune response from being mounted against the Rh antigen. Complete transfusion of fetal blood is the next choice if this fails. |
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|
Term
| A positive western blot result for one of each of these gene families is considered a (+) HIV result? |
|
Definition
|
|
Term
| What helps HIV to avoid infecting already-infected T lymphocytes? |
|
Definition
| Nef gene down-regulates CD4 and MHC class I expression |
|
|
Term
| What kind of activity is seen by HIV in macrophages (including astrocytes)? |
|
Definition
| Latent and chronic infection, rather than lytic infection - cause the cell to secrete nef, tat, and rev (neurotoxic agents) |
|
|
Term
| What mechanisms does HIV use to evade the immune system? |
|
Definition
| High mutation rate, latency in macrophages and Th cells, cell-to-cell spread (including directed release) |
|
|
Term
| What is the ultimate cause of AIDS dementia? |
|
Definition
| Increase in the production of neurotoxic gene products --> disruption of neuronal connections --> decrease in patient's cognition |
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|
Term
| Why might patients with SLE display a reduced level of serum C3? |
|
Definition
| SLE is a type III hypersensitivity - meaning it involves immune complexes. Immune complexes use complement as an opsonization signaller, so the deposition of immune complexes would cause a great deal of complement fixation |
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|
Term
| How can the argument that SLE might be due to loss of T cell tolerance be supported? |
|
Definition
| The variety of anti-self Ab specificities indicates a lack of affinity maturation, which is seen with a lack of T cell activity |
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|
Term
| How might an anti-TNF-alpha-antibody result in the development of skin lesions? |
|
Definition
| Deposition of immune complexes (type III-like reaction) |
|
|
Term
| Why is the liver fairly resistant to host tissue rejection? |
|
Definition
| Kupffer cells seem capable of phagocytosing both antibody and complement |
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|
Term
| What would be the first target in the donor organ during a rejection? |
|
Definition
| Response to ABO antigens on endothelial cells of blood vessels within the transplanted organs |
|
|
Term
| Why might there be pre-made anti-ABO antibodies, even before a primary exposure to the antigen (e.g. transfusion)? |
|
Definition
| The pre-existing antibody may be the result of stimulation by bacterial carbohydrates/glycoproteins, or due to a blood exchange of some kind (pregnancy, injury) |
|
|
Term
| Why does tissue rejection take several days to develop? |
|
Definition
| Tissue rejection seems to be mostly Ab-based, with MHC being a target epitope. Primary ab-based immune responses take several days to reach maximum effectiveness |
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|
Term
| What's the difference between direct and indirect allorecognition of MHC molecules? |
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Definition
| In direct, CTLs recognize the donor MHC directly. In indirect, donor MHCs are uptaken and proteolytically processed and packaged into self MHC, then presented to CTLs |
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|
Term
| What is the relevance of minor histocompatility? |
|
Definition
| Conservative changes in amino acid sequence - do not affect protein structure or function, but are recognized as foreign antigens in recipient's body - slow rejection rather than fast rejection |
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|
Term
| How does chronic rejection differ from acute rejection? |
|
Definition
| Mechanism of damage is due to blood vessel occlusion or decrease in size, resulting in oxidative stress, hypoxic conditions, and eventual organ death |
|
|
Term
| In graft-versus-host disease, why are conventional immunosuppresive methods often not enough? |
|
Definition
| Participation of NK cells - failure to recognize recipient MHC molecules |
|
|
Term
| What cytokines are targets in graft-versus-host disease as a treatment method? |
|
Definition
|
|
Term
| How can IFN-gamma release increase the severity of graft-versus-host disease? |
|
Definition
| IFN-gamma up-regulates the expression of MHC I and II molecules - the chief target molecule in GVHD |
|
|
Term
| How could MHC makeup be influential in the development of insulin-dependent diabeetus? |
|
Definition
| Certain types of MHC molecules are more efficient at presenting beta-cell peptides |
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