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Immuno questions, Block 5, set 2
questions from prestudy 14 only- no lecture questions (yet)
186
Immunology
Professional
03/12/2011

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Term
What is antigenic variation?
Definition
alteration of epitopes displayed by a pathogen that makes the epitopes unrecognizable by an existing immune response
Term
What is antigenic drift?
Definition
introduction of point mutations that result in minor alterations of the antigenicity of a particular protein
Term
What is antigenic shift?
Definition
reassortment of genes that results in major changes in the antigenicity of a given protein
Term
What is latency?
Definition
a state in the life cycle of some viruses during which they do not replicate and remain hidden from the immune system
Term
What is a superantigen?
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
Altering its antigens
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
What is a serotype?
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
influenza virus
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
yes
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
African trypanosomes
Term
What are trypanosomes?
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
What is viral latency?
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
what does herpes infect?
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
shingles
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
cold-like symptoms
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
What are superantigens?
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
What does leprosy do?
Definition
induces immunosuppression by its pathogenic mechanism
Term
what causes leprosy?
Definition
Mycobacterium leprae
Term
What does M. leprae do?
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
mutation of gamma5 gene
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
What is IgG1 deficiency?
Definition
very rare and includes increased susceptibility to many bacterial and viral pathogens
Term
What is IgG2 deficiency?
Definition
most common in kids; susceptbility to encapsulated bacteria
Term
What is IgG3 dfeiciency?
Definition
most common in adults
Term
What is IgG4 defiency?
Definition
of unknown significance
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
What does AID do?
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
no
Term
What is Omenn syndrome?
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
signaling via the TCR
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
bone marrow transplant
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
What is AIRE?
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
How does IPEX present?
Definition
clinical triad: watery diarrhea, eczematous dermatitis, endocrinopathy (type I diabetes); may also express Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, tubular nephropathy
Term
How do you treat IPEX?
Definition
aggressive immunosuppression and/or bone marrow transplant
Term
What is autoimmune lymphoproliferative syndrome (ALPS)?
Definition
genetic disease characterized by lymphadenopathy and splenomegaly
Term
How does ALPS manifest?
Definition
results from immune cells failing to undergo apoptotic death following an immune response, causing overpopulation of secondary lymphoid tissues
Term
What causes ALPS?
Definition
mutation that prevents expression of either Fas, FasLigand, or capsase 10
Term
How does ALPS present?
Definition
autoimmune hemolytic anemia and neutropenia, thrombocytopenia (decreased platelets in the blood), lymphadenopathy, splenomegaly, large number of CD4-CD8- T cells
Term
How do you treat ALPS?
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
What occurs in GVHD?
Definition
caused by mature T cells from the transplant (from donor) attacking recipient's tissues
Term
What does GVHD attack?
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?
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
Term
What happens following the transplant?
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
Term
Why is gene therapy an attractive idea for treating immunodeficiencies?
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
Term
What is a chemokine?
Definition
small cytokines that are involved in the migration and activation of cells (macrophages and lymphocytes)
Term
What is seroconversion?
Definition
phase of an immune response when antigen-specific antibody production is 1st detectable
Term
What is Human Immunodeficiency Virus (HIV)?
Definition
lentivirus (slow) that infects humans and causes acquired immunodeficiency syndrome (AIDS)
Term
What is HIV chracterized by?
Definition
susceptibilty to opportunistic infection (notably Kaposi's sarcoma and B cell lymphoma)
Term
What accompanies HIV?
Definition
profound decrease in CD4 T cells
Term
How many people are infected with HIV?
Definition
world pandemic: 11.7 million have died from AIDS complications; 33 million infected with most in sub-Saharan Africa
Term
How has HIV evolved?
Definition
to take advantage of human behavior and components of the immune system, in addition to evading the immune response
Term
How is HIV transmitted?
Definition
via blood usually, most commonly in sexual activity, IV drug use, therapeutic use of blood products
Term
Describe the tropism of HIV.
Definition
the envelope protein complex of HIV (gp120:gp41) binds with high affinity to CD4 molecules
Term
Where are CD4 molecules expressed?
Definition
CD4+ T cells, macrophages, dendtritic cells
Term
what happens once HIV is bound to CD4?
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
Term
What happens in HIV infected patients?
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
Term
When does seroconversion occur in HIV?
Definition
2-6 weeks post-infection
Term
When does the asymptomatic/latency phase of HIV begin?
Definition
about the same time seroconversion occurs and lasts about 10 years
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
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
Term
What is AIDS?
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
Term
Do immune responses do anything for HIV?
Definition
yes, they control but do not clear the infection
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
Term
When is T cell mediated immunity observed in HIV?
Definition
early in infection, persisiting through the asymptomatic phase, waning during AIDS phase
Term
How does HIV use antigenic variation to evade the immune response?
Definition
HIV uses reveres transcriptase to transcribe its RNA genome into DNA that can integrate into host cell DNA
Term
What is interesting about reverse transcriptase?
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
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
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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