Term
| What is antigenic variation? |
|
Definition
| alteration of epitopes displayed by a pathogen that makes the epitopes unrecognizable by an existing immune response |
|
|
Term
|
Definition
| introduction of point mutations that result in minor alterations of the antigenicity of a particular protein |
|
|
Term
|
Definition
| reassortment of genes that results in major changes in the antigenicity of a given protein |
|
|
Term
|
Definition
| a state in the life cycle of some viruses during which they do not replicate and remain hidden from the immune system |
|
|
Term
|
Definition
| molecules that stimulate a subset of CD4 T cells by simultaneously binding to MHC class II molecules and the beta-chain of the TCR; these binding interactions are not specific interactions |
|
|
Term
| How can a pathogen avoid immune surveillance? |
|
Definition
|
|
Term
| In what type of pathogens is altering its antigens particular important? |
|
Definition
| extracelular because principle immune response is production of Ab specific for external structures; also important for viral pathogens that can be effectively neutralized via specific Ab response |
|
|
Term
| In what wayscan antigenic variation occur? |
|
Definition
| Serotypes; antigenic drift and shift; programmed rearrangement of DNA by a pathogen |
|
|
Term
|
Definition
| infectious agents, like Streptococcus pneumoniae, that exist in a wide variety of antigenic types |
|
|
Term
| What is unique about each serotype? |
|
Definition
| antigenically distict polysaccharide capsules |
|
|
Term
| How do serotypes complicate the immune response? |
|
Definition
| infection with one serotype to S. pneumoniae can lead to type-specific immunity that is protective only against the same serotype but not against another serotype of the same organism |
|
|
Term
| What is the end result of serotype variation? |
|
Definition
| same organism can cause disease in the same host multiple times |
|
|
Term
| What is an example of a pathogen exhibiting antigenic drift or shift? |
|
Definition
|
|
Term
| What is true "at any one time" about the influenza virus? |
|
Definition
| Typically, at any one time, a single influenza virus type is responsible for most of the infections throughout the world |
|
|
Term
| How does the human population respond to the single virus type for flu? |
|
Definition
| develops immunity to that specific virus type; immunity is mediated by neutralizing Abs specific for its major surface protein (hemagglutinin) |
|
|
Term
| What happens to influenza once immune response is mounted? |
|
Definition
| cleared rapidly from infected hosts |
|
|
Term
| What does flu depend upon? |
|
Definition
| having a large pool of unprotected hosts among whom it can spread rapidly |
|
|
Term
| How does flu ensure it can have a large pool of unprotected hosts? |
|
Definition
| antigenic drift and antigenic shift |
|
|
Term
| What is antigenic drift caused by? |
|
Definition
| point mutations in the genes encoding hemagglutinin and neuraminadase (a seond surface protein) |
|
|
Term
| What happens every few years with flu? |
|
Definition
| a variant of flu arises with mutations that allow virus to evade Ab neutralization in the population (in those with previous infection)- antigenic drift |
|
|
Term
| What do mutations (antigenic drift) of flu affect? |
|
Definition
| epitopes that are recognized by T cells (esp. CTLs) so that cells infected with the mutant virus also escape destruction |
|
|
Term
| Are people with immunity to the old variant of the flu virus susceptible to the new variant (antigenic drift)? |
|
Definition
|
|
Term
| Do people with immunity to the old variant of flu have any immunization to the new variant? |
|
Definition
| There is usually considerable cross reactivity (Ab and T cells) between old variant and new variant, so most of the population will have some level of immunity with symptoms associated with the new variant being typically mild. |
|
|
Term
| When does antigenic shift arise? |
|
Definition
| through reassortment of segmented negative strand RNA genome (7-8 segments) of influenza virus (and related animal flu viruses) during co-infection of an animal host |
|
|
Term
| What does antigenic shift lead to? |
|
Definition
| major changes in the hemagluttinin protein on the surface of the virus |
|
|
Term
| After antigenic shift, is the virus recognized by people immunized to the old variant? |
|
Definition
| the virus is recognized very poorly or not at all; most people are highly susceptible and severe infection results |
|
|
Term
| What is the most striking example of programmed rearrangement of DNA by a pathogen? |
|
Definition
|
|
Term
|
Definition
| insect-born protozoa that replicate in extracellular tissue spaces in the body, causing sleeping sickness |
|
|
Term
| With what are trypanosomes coated? |
|
Definition
| a single type of glycoprotein, the variant-specific glycoprotein (VSG) |
|
|
Term
| How do infected hosts respond to parasites like trypanosomes? |
|
Definition
| mount a potent anti-VSG antibody response that rapidly clears most of the parasites |
|
|
Term
| Why is producing anti-VSG response to trypanosomes not quite enough? |
|
Definition
| trypanosomes have approx. 1000 different VSG genes that each encode a VSG protein that is antigenically distint |
|
|
Term
| How do trypanosomes encode all these VSG proteins? |
|
Definition
| by utilizing a "cassette system" to express only one of the different VSGs at a time |
|
|
Term
| How do trypanosomes cause recurrence of the disease? |
|
Definition
| a few of the parasites expressing different VSGs can escape the immune response and replicate rapidly |
|
|
Term
| What happens due to the cyclical nature of the trypanosomes VSG switching? |
|
Definition
| chronic cycle of immune complex clearance leads to damage of host tissues, including neurological damage, and eventually resulting coma (sleeping sickness) |
|
|
Term
|
Definition
| evasion of immune response by "playing dead" |
|
|
Term
| What are some examples of viral latency? |
|
Definition
| herpes simplex, varicella zoster (chicken pox), Epstein-Barr (EBV) |
|
|
Term
| What are viral infections usually characterized by? |
|
Definition
| rapid production of viral proteins for replication with some of these proteins being processed so that fragments of them can be displayed on surface MHC I molecules of the infected cell to be recognized by antigen-specific effector CTLs |
|
|
Term
| What happens when latency occurs? |
|
Definition
| viral proteins are not produced in the latent state, so no replication occurs and disease is not caused; virally-infected cells cannot be eliminated by CTLs because there are no viral antigens (peptides) to flag the presence of viral infection |
|
|
Term
|
Definition
| infects epithelia, then spreads to sensory neurons serving the area of infection |
|
|
Term
| What happens after an effective immune response is mounted against herpes? |
|
Definition
| response controls the epithelial infection (cold sores) but the virus persists in the latent phase |
|
|
Term
| How does the virus persist in the latent phase in the sensory neurons? |
|
Definition
| integrates the viral genome into host cell episomal DNA |
|
|
Term
| How can herpes be reactivated? |
|
Definition
| variety of stimuli, like sunlight, bacterial infection, hormonal changes, other stresses |
|
|
Term
| What happens upon reactivation of herpes? |
|
Definition
| travels along the axons of sensory neurons and reinfects the epithelial tissues; immune responses again conrol the infection by killing the infected epitheilial cells (leaving cold sores); the virus again persists in the sensory neurons in latency |
|
|
Term
| Why do sensory neurons remain infected in herpes virus? |
|
Definition
| virus is quiescent in nerve so very few viral peptides are available for presentation to CTLS; also, neurons express very low levels of MHC class I molecules |
|
|
Term
| Why is low expression of MHC I molecules an important feature of neurons? |
|
Definition
| neurons cannot be regenerated, so a lack of MHC class I molecules helps prevent unnecessary killing |
|
|
Term
| What is the downside of low MHC class I expression on neurons? |
|
Definition
| also makes them susceptible to persistent infections |
|
|
Term
| Where does the chicken pox virus remain latent? |
|
Definition
| dorsal root ganglia (in one or a few) |
|
|
Term
| How can chicken pox be reactivated? |
|
Definition
| stress (or immunosuppression) to spread down nerve and reinfect skin |
|
|
Term
| What is the name of the characteristic rash caused by chicken pox reactivation? |
|
Definition
|
|
Term
| How often does reactivation of varicella zoster occur? |
|
Definition
| once in a lifetime of an immunocompetent host |
|
|
Term
| What does EBV cause in children? |
|
Definition
|
|
Term
| what does EBV cause in adolescents/adults? |
|
Definition
| infectious mononucleosis upon initial infection |
|
|
Term
| How is mononucleosis characterized? |
|
Definition
| B cell becomes infected and proliferates, producing lots of new virus; T cells are activated |
|
|
Term
| How is mononucleosis infection controlled? |
|
Definition
| CD8 effector cells that kill infected B cells |
|
|
Term
| How does EBV become latent? |
|
Definition
| inserts genome into host DNA |
|
|
Term
| Does reactivation of EBV cause symtpoms? |
|
Definition
| rarely in immunocompetent people |
|
|
Term
| What time of mechanisms do pathogens use to subvert host cell defense mechanisms? |
|
Definition
| capturing cellular genes for cytokines or cytokine receptors; synthesizing complement regulatory proteins; inhibiting MHC class I molecule synthesis of assembly |
|
|
Term
| What type of bacteria "trick" the immune system? |
|
Definition
| Mycobacterium tuberculosis; Listeria monocytogenes; Taxoplasma gondii |
|
|
Term
| How do Mycobacterium tb. subvert the immune system? |
|
Definition
| taken up by macrophages but the bacterium prevents phagosome-lysosome fusion, enabling the bacterium to survive inside the lysosome |
|
|
Term
| How do Listeria evade the immune system? |
|
Definition
| bacterium that can escape the phagosome and replicate freely in cytoplasm of the infected macrophage; can be spread via cell-to-cell contact, allowing its entire life cycle to be intracellular |
|
|
Term
| How can you clear a Listeria infection? |
|
Definition
| antigen-specific effector CTLs |
|
|
Term
| How do Taxoplasma (a protozoan parasite) subvert the immune system? |
|
Definition
| generate own vesicle following phagocytosis; vesicle isolates the parasite from rest of cell and prevents presentation of peptides- remains invisible to the immune system |
|
|
Term
| Can pathogens suppress the immune response? |
|
Definition
| yes, by various mechanisms |
|
|
Term
| What do staphylococcal bacteria do? |
|
Definition
| produce toxins that act as superantigens (staphylococcal enterotoxins) |
|
|
Term
|
Definition
| massive production of cytokines by CD4 cells; induces a state of immune suppression and/or systemic toxicity |
|
|
Term
| What is different about superantigens? |
|
Definition
| an antigen that binds to outer surface of both MHC class I molecules and Vbeta region of TCR; does not bind in binding groove |
|
|
Term
| How many Vbetas can superantigens bind and how does that affect T cell stimulation? |
|
Definition
| 20-50 gene segments, stimulating 2-20% of T cells |
|
|
Term
| Does binding of superantigen to MHC class II and TCR simultaneously prime an antigen-specific immune repsonse? |
|
Definition
| no, it causes massive prodution of cytokines by CD4 T cells, causing systemic toxicity and/or immunosuppression |
|
|
Term
|
Definition
| induces immunosuppression by its pathogenic mechanism |
|
|
Term
|
Definition
|
|
Term
|
Definition
| either suppression of cell-mediated acquired resopnses or induction of a very potent cell-mediated anti-bacterial response |
|
|
Term
| What are the two major forms of leprosy? |
|
Definition
| lepromatous and tuberculoid |
|
|
Term
| What typifies lepromatous leprosy? |
|
Definition
| profound depression of cell-mediated immunity without infection control; bacteria is highly infectious and replicates freely in macrophages, disseminating infection widely in the body; hypergammaglobulinemia; low/absent T cell responsiveness (no response to M. leprae antigens); anergic state in host (cannot respond to antigens) |
|
|
Term
| What is hypergammaglobulinemia? |
|
Definition
| elevated levels of immunoglobulins or antibodies in the circulation |
|
|
Term
| Describe tuberculoid leprosy. |
|
Definition
| potent cell-mediated immunity with macrophage activation which controls but does not eradicate infection; not very infectious bacteria present at low to detectable levels; granulomas and local inflammation observed; normal serum levels of Ig; normal T cell responsiveness and specific resopnsiveness to M. leprae antigens |
|
|
Term
| What might cause the difference in the two types of leprosy? |
|
Definition
| difference in ratio of TH1 and TH2 cells- therefore, a cytokine issue |
|
|
Term
| What causes inherited immunodeficiency and with what are they associated? |
|
Definition
| recessive gene effects, affecting both adaptive and innate immune system (potentially) |
|
|
Term
| What sort of defects have been observed with inherited immunodeficiency diseases? |
|
Definition
| development of lymphocytes or surface molecule expression important for lymphocyte function; phagocytes, compement, cytokines/cytokine receptors and in molecules mediating effector mechanisms |
|
|
Term
| What is the principle effect of deficiencies in Ab production? |
|
Definition
| inability to control extracellular bacteria that produce polysaccharide capsules (resistant to phagocytosis) |
|
|
Term
| What does Ab deficiency do? |
|
Definition
| increase susceptibility to viruss (enteroviruses) that are sensitive to neutralizing antibodies |
|
|
Term
| What is Broton's X-linked agammaglobulinemia? |
|
Definition
| 1st described immunodeficiency disease characterized by absence of Ig in serum |
|
|
Term
| What does the defective gene target in Bruton's? |
|
Definition
| gene codes for tyrosine kinase protein that is expressed by B cells and neutrophils (only B cell function affected by defect in this gene) |
|
|
Term
| What is Btk (Bruton's tyrosine kinase) invlved in? |
|
Definition
| signal transductino of signals from cell-surface receptors during B cell development |
|
|
Term
| What happens to B cells in Bruton's? |
|
Definition
| B cells are defective (and you won't have any) because B cell maturation is halted at the pre-B cell stage |
|
|
Term
| What is Pre-B cell receptor (gamma5) deficiency? |
|
Definition
|
|
Term
| What is the lambda5 gene? |
|
Definition
| component of surrogate light chain that pairs with mu heavy chain during somatic recombination of light chain genes |
|
|
Term
| What does the non-functional surrogate light chain cuase? |
|
Definition
| inability of developing B cells to produce a pre-B cell receptor and they all undergo apoptotic death; profound B cell deficiency |
|
|
Term
| What susceptibilities are associated with lambda5 deficiency? |
|
Definition
| extracellular bacteria and many viral pathogens |
|
|
Term
| What is selective IgA deficiency and is it a problem? |
|
Definition
| likely heterogenous genetic defect; 1 in 500 Caucasians are affected by this disease where you make little to no IgA; in developed countries, most people are healthy; a problem in countries with common parasite infections |
|
|
Term
| Why is IgA deficiency (mostly) not a problem? |
|
Definition
| IgM can be transported across mucosal epithilia to perform IgA function (though not as efficiently) |
|
|
Term
| What do people with IgA deficiency do? |
|
Definition
| make higher levels of Ab isotypes |
|
|
Term
| What is selective IgG deficiency? |
|
Definition
| likely heterogenous problem with deficiency is each of the IgG subtypes possible |
|
|
Term
|
Definition
| very rare and includes increased susceptibility to many bacterial and viral pathogens |
|
|
Term
|
Definition
| most common in kids; susceptbility to encapsulated bacteria |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What is the breakdown of IgG that circulates in normal adults? |
|
Definition
| 60-70% IgG1, 20-30% IgG2, 5-8% IgG3, 1-3% IgG4 |
|
|
Term
| What is X-linked hyper IgM syndrome? |
|
Definition
| inherited disease with no B cell activation (no germinal centers); highl evels of IgM but very low concentrations of other Ab isotypes |
|
|
Term
| What is the common defect causing hyper IgM syndrome? |
|
Definition
| CD40 ligand on T cells cannot interact CD40 on B cells, so helper T cells cannot deliver the 2nd signal of B cell activation |
|
|
Term
| What else is a problem in hyper IgM (caused as a result of inability of CD40:CD40L to bind? |
|
Definition
| TH1 cells cannot activate macrophages so you have defective cell-mediated immunity contributes to profound immunodeficiency in this disease |
|
|
Term
| What is another cause of hyper IgM syndrome? |
|
Definition
| genetic defect in expression of activation-induced cytidine deaminase (AID)? |
|
|
Term
|
Definition
| enzyme is required for isotype switching and somatic hypermutation; defect has nother to do with lack of T cell help |
|
|
Term
| How does AID deficiency and class hyper IgM syndrome differ? |
|
Definition
| in hyper IgM, you could have some IgG but without AID, you have absolutely no class switching (though you may have germinal centers) |
|
|
Term
| What are defects in C3 (or activation of C3) associated with? |
|
Definition
| wide range of infections by encapsulated bacteria, emphasizing important role in C3b opsonization which promotes phagocytosis |
|
|
Term
| What do defects in membrane-attack components of complement (C5-C9) affect? |
|
Definition
| limited effects, exclusively in susceptbility to Neisseria species |
|
|
Term
| How is the host defense to Neisseria mediated? |
|
Definition
| Neisseria is incapable of intracellular survival and host defense is mediated by extracelular lysis by the membrane attack complex |
|
|
Term
| What happens when you have defects in the classical complement pathway, especially in early components? |
|
Definition
| early components are particularly important in elimination of immune complexes and defects leads to accumulation of immune complexes, eventually causing tissue damage |
|
|
Term
| What happens if C3b deposition cannot be activated via the classical pathway? |
|
Definition
| small immune complexes of antigen-specific antibody will be difficult for phagocytes to recognize |
|
|
Term
| What do deficiencies in proteins regulating complement activation cause? |
|
Definition
| immunodeficiency or auto-immune-like disease |
|
|
Term
| What happens in Properdin P defects? |
|
Definition
| Properdin P enhances activity of alternative pathway and defects lead to heightened senstiivty to Neisseria |
|
|
Term
| What happens in patients lacking decay accelerating factor (DAF) and CD59? |
|
Definition
| DAF and CD59 protect host cell surfaces from alternative pathway activation; defects destroy their own red blood cells; aka "paroxysmal nocturnal hemoglobulinuria" |
|
|
Term
| What happens in patients with C1-inhibitor defects (hereditary angioneurotic edema-HANE)? |
|
Definition
| defects fail to control inappropriate activation of classical cascade and uncontrolled cleavage of C2 allows generation of vasoactive fragment (anaphylatoxin C2a); causes fluid accumulation in tissues and epiglootal swelling (suffocation-->death) |
|
|
Term
| What do defects in recruitment of phagocytes to extravascular sites of infection cause and why? |
|
Definition
| causes severe immunodeficiency because phagocytes should reach these extracellular sites by emigrating from blood vessels, mediated by cell adhesion molecules |
|
|
Term
| What do phagocytic deficiencies result in? |
|
Definition
| infections that are antibiotic resistance and persist in spite of apparently effective cellular and humoral immune responses |
|
|
Term
| What happens in chronic granulomatous disease? |
|
Definition
| phagocytes cannot produce reactive oxygen compounds (**superoxide radical), resulting in impaired ability to kill bacteria |
|
|
Term
| How is chronic granulomatous disease caused and how does it present? |
|
Definition
| non-functional gp91 protein (P91-PHOX); patients have chronic bacterial infection, sometimes leading to granulomas |
|
|
Term
| What is Chediak-Higashi syndrome? |
|
Definition
| complex syndrome characterized by partial albinism, abnormal platelet function, severe immunodeficiency |
|
|
Term
| What causes Chediak-Higashi? |
|
Definition
| defective gene encoding a protein involved in intracellular vesicle formation that causes a failure of lysosome:phagosome fusion (impaired ability of phagocytes to kill bacteria) |
|
|
Term
| What do defects in T cell function cause? |
|
Definition
| severe combined immunodefiency diseases (SCID); high susceptbility to broad range of infectious agents |
|
|
Term
| What happens in patients who lack T cell fucntion? |
|
Definition
| cannot produce T-dependent antibody responses and cannot mount cell-mediated responses; cannot mount protective immune responses |
|
|
Term
| What is adenosine deaminase (ADA) deficiency and purine nucleotide phsophorylase (PNP) deficiency? |
|
Definition
| result in SCID phenotype; accumulation of nucleotide catabolites that are particularly toxic to developing T and B cells |
|
|
Term
| What is bare lymphocyte syndrome? |
|
Definition
| lack of expression of MHC class II or II molecules (2 types of bare lymphocyte syndrome) |
|
|
Term
| What happens in classical bare lymphocyte syndrome? |
|
Definition
| lack of expression of all MHC class II molecules, resulting in an inability of CD4 T cells to be positively selected in the thymus (few develop; the ones that do cannot be activated because APCs lack MHC class II as well) |
|
|
Term
| What happens in the other bare lymphocyte syndrome? |
|
Definition
| lack of MHC class I expression from non-functional TAP1 or TAP2, deficiency of Beta2-microglobulin etc |
|
|
Term
| What is DiGeorge syndrome? |
|
Definition
| 1/4000 incidence resulting from sall delition in chromosome 22 with congenital heart disease (40%), palatal abnormalities (50%), learning disabilities (90%), hypocalcemia (50%), mile differences in facial features |
|
|
Term
| What is complete DiGeorge syndrome? |
|
Definition
| much more rare than DiGeorge; absence or underdeveloped (nonfunctional) thymus and can therefore make very few T cells; patients develop fungal, bacterial and viral infections typical of SCID |
|
|
Term
| How do you treat a Complete DiGeorge patient? |
|
Definition
| thymic transplant to treat immunodeficiency but nothing for others |
|
|
Term
| What is a common gamma chain deficiency and what deficiency has the same phenotype? |
|
Definition
| Jak3 deficiency and Omenn have same phenotype; common gamma chain (X-linked) is the signaling component of a number of cytokine receptors that interacts with Jak3 to initate signaling once cytokine receptor has been engaged by binding |
|
|
Term
| What cytokine receptors are affected by common gamma chain deficiency? |
|
Definition
| IL-2, IL-4, IL-7, IL-9, IL-15 |
|
|
Term
| Can patients with common gamma chain deficiency or Jak3 deficiency initate signaling of cytokine receptors? |
|
Definition
|
|
Term
|
Definition
| missense mutations that result in partially active RAG enzymes |
|
|
Term
| What happens when there is lack of RAG activity? |
|
Definition
| absence of B cells and low numbers of oligoclonal autoreactive T cells |
|
|
Term
| What do patients develop in Omenn syndrome? |
|
Definition
| fungal, bacterial, viral infections typical of SCID; essentially same phenotype as common gamma chain deficiency |
|
|
Term
| What are the symptoms of Omenn syndrome? |
|
Definition
| erythroderma, desquamation, alopecia, chronic diarrhea, failure to thrive, lymphadenopathy, hepatosplenomegaly |
|
|
Term
| What is ZAP-70 deficiency? |
|
Definition
| genetic defect that prevents expression of functional ZAP-70, a tyrosine kinase that associates with phosphorylated ITAMS during signaling via TCR complex |
|
|
Term
| What is ZAP-70 required for? |
|
Definition
|
|
Term
| What occurs in patients with ZAP-70 deficiency? |
|
Definition
| absence of CD8 T cells but normal numbers of NONFUNCTIONAL CD4 T cells; SCID |
|
|
Term
| How doe you treat ZAP-70 deficiency? |
|
Definition
|
|
Term
| What is autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED)? |
|
Definition
| genetic immunodeficiency resulting in a number of autoimmune syndromes and caused by genetic deficiency of a gene encoding autimmune regulator (AIRE) |
|
|
Term
|
Definition
| transcription factor that regulates expression of several hundred host-tissue specific genes by epithelial cells in the thymic medulla |
|
|
Term
| What do host-specific proteins that AIRE regulates do? |
|
Definition
| serve as a source of self-proteins for presentation during thymic negative selection |
|
|
Term
| What are the characteristics of APECED? |
|
Definition
| Problems in numerous glands (polyglandular) including: hypoparathyroidism, hypogonadism, adrenal insuficiency, type I diabetes, laten hypothyroidism, total baldness (alopecia totalis), keratoconjunctivitis, tooth enamel hypoplasia, candidiasis (yeast) infection, juvenile-onset pernicious anemia, GI problems such as malabsorption, diarrhea |
|
|
Term
| What is Immune Dysregulation Polyendocrinopathy, Enteropathy, X-linked syndrome (IPEX)? |
|
Definition
| genetic deficiency of FoxP3 expression in regulatory CD4 T cells, resulting in early onset (1st year) autoimmunity to a variety of host tissues due to lack of Treg cell function |
|
|
Term
|
Definition
| clinical triad: watery diarrhea, eczematous dermatitis, endocrinopathy (type I diabetes); may also express Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, tubular nephropathy |
|
|
Term
|
Definition
| aggressive immunosuppression and/or bone marrow transplant |
|
|
Term
| What is autoimmune lymphoproliferative syndrome (ALPS)? |
|
Definition
| genetic disease characterized by lymphadenopathy and splenomegaly |
|
|
Term
|
Definition
| results from immune cells failing to undergo apoptotic death following an immune response, causing overpopulation of secondary lymphoid tissues |
|
|
Term
|
Definition
| mutation that prevents expression of either Fas, FasLigand, or capsase 10 |
|
|
Term
|
Definition
| autoimmune hemolytic anemia and neutropenia, thrombocytopenia (decreased platelets in the blood), lymphadenopathy, splenomegaly, large number of CD4-CD8- T cells |
|
|
Term
|
Definition
| immunosuppression and IV Ig |
|
|
Term
| how can you treat immunodeficiencies? |
|
Definition
| often with bone marrow transplantation (via replacement therapy) |
|
|
Term
| What is the goal of bone marrow transplantation from a healthy donor? |
|
Definition
| Transfer pluripotent stem cells from the healthy donor to the recipient so that stem cells can affect reconstitution of patient's immune system |
|
|
Term
| What is cord blood and what is it used for? |
|
Definition
| fetal blood extracted from placenta after birth that can be used as an alternative source of stem cells for transplantation |
|
|
Term
| What is the advantage of using cord blood? Disadvantage? |
|
Definition
| Advantage: no invasive procedure on donor; disadvantage: fewer stem cells are obtained from cord blood samples than from bone marrow samples |
|
|
Term
| What is the major complication of bone marrow transplantation? |
|
Definition
| graft vs host disease (GVHD) |
|
|
Term
|
Definition
| caused by mature T cells from the transplant (from donor) attacking recipient's tissues |
|
|
Term
|
Definition
| donor T cells can attack almost any host tissue but mainly involves skin, intestines, and liver |
|
|
Term
| How can you reduce the incidence of GVHD? |
|
Definition
| depletion of T cells from graft prior to transplantation though this procedure can increase frequency of graft rejection by host (**if host has SCID, their immune system is unable to mount a graft-specific immune response) |
|
|
Term
| What is bone marrow transplantation dependent upon and why? |
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Definition
| Good HLA matching: good match ensures lower incidence of alloreactions that cause graft rejection or GVHD; good match also ensures that APCs from transplant will be able to effectively present antigens |
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Term
| What happens following the transplant? |
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Definition
| all bone-marrow derived cells in the recipient are of donor HLA haplotype, whereas all other cells are of the recipient's haplotype; positive selection of T cells occurs exclusively on thymic epithelial cells having the receipient's HLA type; ability of T cells that mature (receive positive selection from host thymic cells) to be activated by donor-derived APCs is dependent on degree of HLA haplotype match |
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Term
| Why is gene therapy an attractive idea for treating immunodeficiencies? |
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Definition
| functional copy of defective gene can be introduced into stem cells derived from patient's bone marrow, fixing the stem cells to express the defective gene; cells can be re-infused to patient; protocols are in early developmental stages though |
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Term
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Definition
| small cytokines that are involved in the migration and activation of cells (macrophages and lymphocytes) |
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Term
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Definition
| phase of an immune response when antigen-specific antibody production is 1st detectable |
|
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Term
| What is Human Immunodeficiency Virus (HIV)? |
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Definition
| lentivirus (slow) that infects humans and causes acquired immunodeficiency syndrome (AIDS) |
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Term
| What is HIV chracterized by? |
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Definition
| susceptibilty to opportunistic infection (notably Kaposi's sarcoma and B cell lymphoma) |
|
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Term
|
Definition
| profound decrease in CD4 T cells |
|
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Term
| How many people are infected with HIV? |
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Definition
| world pandemic: 11.7 million have died from AIDS complications; 33 million infected with most in sub-Saharan Africa |
|
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Term
|
Definition
| to take advantage of human behavior and components of the immune system, in addition to evading the immune response |
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Term
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Definition
| via blood usually, most commonly in sexual activity, IV drug use, therapeutic use of blood products |
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Term
| Describe the tropism of HIV. |
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Definition
| the envelope protein complex of HIV (gp120:gp41) binds with high affinity to CD4 molecules |
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Term
| Where are CD4 molecules expressed? |
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Definition
| CD4+ T cells, macrophages, dendtritic cells |
|
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Term
| what happens once HIV is bound to CD4? |
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Definition
| must interact with co-receptor on the host cell (chemokine receptor) to gain entry into cell; after infection, HIV replicates rapidly in the blood, causing a marked reduction in circulating CD4 T cell numbers |
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Term
| What happens in HIV infected patients? |
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Definition
| CD8 T cells are activated to become HIV antigen-specific effector CTLs primed to kill HIV infected cells, particular those that are CD4 T cells; also, seroconversion |
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Term
| When does seroconversion occur in HIV? |
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Definition
|
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Term
| When does the asymptomatic/latency phase of HIV begin? |
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Definition
| about the same time seroconversion occurs and lasts about 10 years |
|
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Term
| What happens to circulating CD4 T cells during progression of HIV? |
|
Definition
| numbers circulating rebound to about 50% of normal numbers, but numbers gradually decline during asymptomatic stage of disease |
|
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Term
| When does the symptomatic phase of HIV start and what is typical of it? |
|
Definition
| when numbers of functional circulating CD4 T cells gets very low; disease phase is chracterized by high incidence of opportunistic infections |
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Term
|
Definition
| The final stage of HIV; clinically defined by very low number of circulating CD4 T cells (less than or equal too 200/microliter); always results in death |
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Term
| Do immune responses do anything for HIV? |
|
Definition
| yes, they control but do not clear the infection |
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Term
| What is the initial response to HIV? |
|
Definition
| observed during seroconversion and is when the Ab specific for the envelope and core proteins are easily detectable within 4-8 weeks of initial infection |
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Term
| When is T cell mediated immunity observed in HIV? |
|
Definition
| early in infection, persisiting through the asymptomatic phase, waning during AIDS phase |
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Term
| How does HIV use antigenic variation to evade the immune response? |
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Definition
| HIV uses reveres transcriptase to transcribe its RNA genome into DNA that can integrate into host cell DNA |
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Term
| What is interesting about reverse transcriptase? |
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Definition
| very error-prone and introduces numerous point mutations during every replicative cycle |
|
|
Term
| What do point mutations from HIV reverse transcriptase result in? |
|
Definition
| antigenic changes in the envelope protein that facilitates evasion of immune responses |
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Term
| How do changes in HIV interact with drug treatments to HIV? |
|
Definition
| HIV rapidly acquires resistance to anti-viral drugs; immediately following adminstration of protease inhibitors, vial loads decrease rapidly and CD4 cell numbers increase but within a few weeks, mutant viruses begin to appear with CD4 cells numbers decreasing again |
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|
Term
| What is zidovudine (AZT)? |
|
Definition
| a reverse transcriptase inhibitor; resistance to it takes months to develop because several (3-4) mutations are required to confer resistance |
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