Term
| What developed that caused the death rate of AIDS to go down? |
|
Definition
|
|
Term
| Where was HIV thought to originate and is still very high? |
|
Definition
|
|
Term
| When the HIV virus enters the cell, it causes binding of what? |
|
Definition
|
|
Term
HIV contains __(#) molecules of RNA
What is the essential step that is the first target for antiviral drugs?
Is that antiviral drug high toxicity? |
|
Definition
2 molecules of RNA
Reverse Transcriptase
No, drugs that inhibit reverse transcription have relatively low toxicity, since it is a viral specific enzyme. |
|
|
Term
| After entering the cell, binding CD4 and co-receptors, and reverse transcription, what does the HIV cDNA do? |
|
Definition
| cDNA integrates into host chromatin --> transcriptional activation |
|
|
Term
| Protease ghrelins block what step in HIV replication? |
|
Definition
|
|
Term
| What step in HIV replication CAN NOT be targeted by drugs? why? |
|
Definition
| the transcription step uses the same enzyme that the host uses for transcription; a drug targeting this would be very toxic |
|
|
Term
What part of the HIV virus binds CD4 and chemokine receptors (gp120 or gp41) and what part binds to (gp120 or gp41) penetrates the membrane?
Can this be targeted? |
|
Definition
gp 120 binds to CD4 and chemokine receptors
gp 41 penetrates membrane
Yes-If cells don’t express these cells on their surface, the virus won’t be able to get in and cause disease. |
|
|
Term
| CXCR4 (co-receptor) is present in which stage and cells do they infect? |
|
Definition
| CXCR4 are present in late stage disease and only infect T cells (T tropic) since they are the only ones that express a high level of CXCR4 |
|
|
Term
| CCR5 (co-receptor) is present in which stage and what cells do they infect? |
|
Definition
| CCR5 is found in early infection and infect macrophages (M tropic) |
|
|
Term
Which co-receptor is syncytium inducing and non-syncytium inducing
(synctium-when cells fuse together to form large cells with many nuclei? |
|
Definition
CXCR4-syncytium inducing
CCR5- non-syncytium inducing |
|
|
Term
| The natural ligand SDF-1 is for which chemokine receptor? |
|
Definition
|
|
Term
| The natural ligands MIP-1alpa, MIP-1beta , & RANTES are for which chemokine receptor? |
|
Definition
|
|
Term
| What mutation results in patients to not get infected with HIV or Cholera? |
|
Definition
| delta32 deletion in CCR5 homozygotes |
|
|
Term
What kind of HIV infection is it when when you have the reverse transcription step and the viral DNA formed, but it has not integrated yet?
Do those cells dies off quickly? |
|
Definition
Pre-integration latency
Yes- Due to lability of unintegrated DNA, this pool is dependent on continual de novo (new) infection |
|
|
Term
What type of HIV infection is it when there is an integrated provirus with low or absent transcription of viral genes?
Can you treat HIV during this stage? |
|
Definition
Integrated latency
No- only cells expressing proteins can be killed by immune system (likely the major reason for eradication failure) |
|
|
Term
| How can HIV gain a resistance to drugs/so difficult to treat? |
|
Definition
| Reverse transcriptase causes at least 1 mutation during each replication = a lot of different sequence variants in a single person |
|
|
Term
Is there a (direct or inverse) relation of "viral fitness" in vivo growth rate and drug resistant phenotype for HIV?
What is the recipe for resistance? |
|
Definition
inverse
Partial drug mediated inhibition of growth |
|
|
Term
| What are the sign and symptoms of primary HIV infection? |
|
Definition
kind of like the flu
but only about 1/2 the people infected have clinical syndrome at all |
|
|
Term
What do you measure to diagnose HIV?
What tests must be done? |
|
Definition
measure HIV antibodies
ELISA test first, then Western Blot (assures true positive result and not just a cross-reactive antibody) |
|
|
Term
| What appears in the plasma first in an HIV infection? (viral RNA or antibodies?) |
|
Definition
| viral RNA (important for blood blanks to use because there are several weeks where the blood is infectious but no antibodies) |
|
|
Term
| Can the assay test used to measure viral RNA be used to diagnose HIV? |
|
Definition
|
|
Term
| What must you do if you get stuck by an HIV infected needle? |
|
Definition
Immediately report to HIV response team or ER
Take post-exposure prophylactic (ART), an antiviral drug, for a month immediately after (Time is critical!) |
|
|
Term
| What test may be used to detect early HIV infection, to monitor HIV therapy and HIV progression, and to screen blood for HIV. |
|
Definition
| p24 protein testing (less sensitive than antibody testing) |
|
|
Term
| What test may be used to decide when to start therapy and to monitor therapy and HIV progression and degree of viremia. |
|
Definition
| Viral load testing (measuring the RNA) |
|
|
Term
| What test may be used to when to start therapy and to monitor therapy, HIV progression, and the status of the immune system (disease progression). |
|
Definition
| CD4 testing (primary target of HIV) |
|
|
Term
In HIV, if CD4 count is low and the viral load is high, what is that indicative of?
If the CD4 count and the viral load are both low, what is that indicative of? |
|
Definition
death is close
the disease is at a standstill, and there is still a chance to recover (better to suppress viral load and stop disease progression, even if it means that you have very little CD4) |
|
|
Term
| What is thought to cause resistance against HIV antiretroviral drugs? |
|
Definition
| thought to be caused by patients not taking their drugs correctly (partially taking drugs is worse than not taking them at all bc low level of viral replication in the presence of drugs is bad) |
|
|
Term
| What concept states that any human bodily fluids could be contaminated with infectious agents transmitted by parenteral exposure |
|
Definition
| Concept of Universal precautions |
|
|
Term
| List the 3 phases of HIV disease |
|
Definition
Acute infection syndrome ("flu-like", high viral load resolves)
Clinical "Latent" Disease (progressive viral load and loss of CD4 T cells)
End Stage Disease (AIDS) |
|
|
Term
| What phase of HIV infection is it when the person has "flu-like" clinical illness and a high viral load that resolves coincident with development of effective CD8 T cell response |
|
Definition
|
|
Term
| What phase of HIV infection is it when people infected have widely variable viral load (gradually goes up) correlated with rate of disease progression (loss of CD4 T cells) and lymphadenopathy and constitutional symptoms |
|
Definition
| Clinical "Latent" Disease - people can feel healthy but be infectious (propels epidemic) |
|
|
Term
| What phase of HIV infection is it when CD4 T cells < 200; often increase in viral load and the development of opportunistic infections (not enough T cells to mediate immunity) |
|
Definition
|
|
Term
| How many CD4 T cells are there in an AIDS patient? |
|
Definition
|
|
Term
| How long (months) will a person be in the End Stage Disease if left untreated? |
|
Definition
|
|
Term
What are some infectious diseases that are characteristic of end stage HIV because it is almost never seen elsewhere?
What neoplasma effects endothelial cells (causes tumor growth)?
What is common because there is hyperplasia of the immune response over a long period of time, which sets the stage for mutations in the B cells. |
|
Definition
protozoa, Cryptosporidiosism, cytomegalovirus, blindness, etc..
Kaposi sarcoma
Lymphomas |
|
|
Term
| What was used to better understand viral dynamics? |
|
Definition
| highly active anti-retroviral therapy (HAART) |
|
|
Term
| When you start antiretroviral drugs, the ______ falls exponentially and the rate of the initial fall is usually ______ (independent or dependent) of how high the viral load was at the beginning) |
|
Definition
|
|
Term
When using HAART, what does the rate of fall represent?
Why can HIV stay in steady state? |
|
Definition
the elimination of the infected cells (infected cells have a short half-life (~1 day)
the virus infects 1 cell for every infected cell destroyed |
|
|
Term
In HAART induction,
what rapidly falls?
what rapidly increases (what is the primary mechanism of this)? |
|
Definition
Rapid fall in viral RNA in plasma (1st phase very rapid-t1/2=1 day, 2nd phase slower)
Rapid Increase in CD4 T cells in Blood (Redistribution of lymphocytes from inflammed tissue and into blood is primary mechanism) |
|
|
Term
| Why is it that HIV infection can not be eradicated? |
|
Definition
Concept of Reservoir- residual viable virus during HAART
-Latently infected CD4 T cells (small proportion of CD4 T cells but can ignite infection when antiretroviral drugs stop)
-Sequestered Anatomic site - CNS, ?others
-Persistent rounds of de novo infection
-Intermittent Non-adherence |
|
|
Term
| During HIV treatment, are viruses going through reverse transcription? Are T cells being infected? |
|
Definition
| no virus is not going through the reverse transcription step and T cells are not being infected = slow evolution of quasi-species |
|
|
Term
What is the goal of pharmacological HIV management?
How do they do this? |
|
Definition
Pharmacological suppression of viral Replication
Multiple drugs available – low replication --> low mutations (low resistance)
Monitoring status – viral load and CD4 count (if viral load goes up during therapy=resistance, need to switch drugs) |
|
|
Term
| If a patient has RECURRENT SINOPULMONARY (respiratory) and GI infections/diarrhea, what immunodeficiency disease would you expect them to have? |
|
Definition
| B cell-antibody deficiency (more severe sinopulmonary=more severe immunodeficiency) |
|
|
Term
| What is milder form of immunodeficiency that may escape diagnosis until later in life and may not be suitable for transplantation even though they're having infection but it's not so severe? |
|
Definition
| Combine immunodeficiencies |
|
|
Term
| When a patient suffers from OPPORTUNISTIC infections beginning early in infancy (thrush, diarrhea, failure to thrive), what immunodeficiency would you expect them to have? |
|
Definition
| T cell and Severe Combined Immunodeficiency (milder form=Combined Immunodeficiency) |
|
|
Term
| If a patient suffers from deep tissue infections (cellulitis, abscesses, osteomyelitis) and mucositis/gingivitis, what immunodeficiency would you expect them to have? |
|
Definition
Phagocyte deficiency
Mucositis and gingivitis are very common in people who have neutropenia or functional defects in their neutrophils |
|
|
Term
| If a patient had infections primarily with encapsulated organisms and NEISSERIA, what type of immunodeficiency would you expect them to have? |
|
Definition
Complement deficiencies
the terminal complement defects in C5,6,7,8,9 |
|
|
Term
| What are some of the causes for "Pure" T Cell Deficiencies |
|
Definition
-DiGeorge/Velocardiofacial syndrome (aka Chromosome 22q11 deletion syndrome)
-T cell receptor deficiencies/CD4 complex defect
-Zap 70 deficiency (cytoplasmic tyrosine kinase essential for T cell receptor signaling --> severe T cell deficiency) |
|
|
Term
What are the 3 most common diseases of DiGeorge/Velocardiofacial Syndrome (a multi system, dominant disorder)?
What are some common cranial facial dimorphisms? |
|
Definition
Conotruncal cardiac malformation (heart disease)
Hypoparathyroidism (variable)
Always have some degree of Thymic hypoplasia leading to variable immunodeficiency (no thymus=no T cells)
Cleft palate and micrognathia (small lower jaw) |
|
|
Term
| What gene is deleted in DiGeorge/Velocardiofacial syndrome? |
|
Definition
|
|
Term
In DiGeorge syndrome, what are cardiac abnormalities?
Do you always have cardiac abnormalities? |
|
Definition
Interrupted aortic arch
Truncus arteriosus
Tetrology of Fallot
No- disease may escape detection without a severe cardiac malformation |
|
|
Term
What technique is used to diagnose DiGeorge syndrome?
Can you treat DiGeorge syndrome patient that doesn't have any T cells with a bone marrow transplant? |
|
Definition
FISH- fluorescence in situ hybridization and CGH array (
No- T cells can't mature without thymus |
|
|
Term
If a baby had symptoms of
Failure to thrive
Onset of infections in the neonatal period (even with maternal antibodies)
Opportunistic infections
Chronic or recurrent thrush
Chronic rashes
Chronic or recurrent diarrhea
Lacking lymphoid tissue (no T cells)
What immunodeficiency would you expect them to have? |
|
Definition
| Severe combined immunodeficiency |
|
|
Term
In Severe combined immunodeficiency, what treatment is required in order for a person to survive beyond the age of 1 or 2?
Is the treatment difficult? Why? |
|
Definition
-Bone marrow transplant, preferably from a histocompatible sibling (only treatment)
-Gene therapy
No- because T cell's don't function (pure T cell deficiency or combined T and B cell deficiency) |
|
|
Term
If a person's lab report comes back with low immunoglobulins (hypogammaglobulinemia), absence of antibody responses to immunizations, absent mitogen (protein binds to carbs on cells) responses to T cells, Low or absent T cells, Often low or absent B cells
What immunodeficiency does this person have? |
|
Definition
| Severe combined immunodeficiency |
|
|
Term
| Should you focus on the lymphocyte or neutrophil count when trying to diagnose severe combined immunodeficiency? |
|
Definition
|
|
Term
| Should you give an infant with severe combined immunodeficiency a vaccine? |
|
Definition
| NO- attenuated vaccine can kill baby |
|
|
Term
| In X-linked Severe Combine Immunodeficiency, there is a ___ deficiency. |
|
Definition
| gamma(c) deficiency-signaling molecule for cytokine receptors |
|
|
Term
| What kind of immunodeficiency is deficiency of antibodies and usually have respiratory infections beginning 8-10 months old (ear infections, sinus infections, and finally pneumonia) |
|
Definition
| B cell immunodeficiencies |
|
|
Term
| Bruton’s (X-linked) Agammaglobulinemia (Bruton’s tyrosine kinase (btk) deficiency) is what type of immunodeficiency? |
|
Definition
|
|
Term
| How would you treat a B cell Immunodeficiency? |
|
Definition
| immunoglobulin replacement |
|
|
Term
A patient has chronic/recurrent respiratory infections and diarrhea (esp due to Giardia) that did not develop until after infancy and progressively got worse with age. You check their immunoglobulins and they're low (panhypogammaglobulinemia), but then you check their B and T cells and they have normal numbers.
What is this disease and what could be the cause? |
|
Definition
Common variable immunodeficiency
B Cell receptor and signaling deficiencies (B cells don't receive sufficient activation to make plasma cells); has selective IgA deficiency and IgG subclass deficiency that progressed |
|
|
Term
Can people with Selective IgA deficiency be relatively healthy?
Why? |
|
Definition
They can be healthy
Because IgG can replace the function of IgA to certain extent when mucosal becomes leaky due to inflammation and IgG comes in. (more problems with viral infections and allergies) |
|
|
Term
| People with IgA deficiency frequently coexists with _________ deficiency, especially ________ |
|
Definition
IgG subclass
IgG2 and IgG4 |
|
|
Term
| In 2/3 of patients with Common Variable Immunodeficiency, there is a linkage to _______ Region of ____ complex |
|
Definition
|
|
Term
| What are the 4 genes identified to Common Variable Immunodeficiency? |
|
Definition
| Four genes identified: ICOS (B7h), BAFF-R, CD19, and TACI (co-stimulatory molecules on T and B cells) |
|
|
Term
| If a person gets chronic/recurrent upper respiratory infections, especially sinusitis and tendency to develop respiratory and gastrointestinal allergies and autoimmunity, you would expect them to have what kind of deficiency? |
|
Definition
| IgG Subclass and IgA Deficiencies |
|
|
Term
If a patient had eczema, thrombocytopenia (low platelets in blood), immunodeficiency, what would you expect them to have?
Is it easy to determine this condition early?
Is transplant required? |
|
Definition
Wiskott-Aldrich Syndrome
Easy to determine because patient always have low platelets
Almost always goes to transplant |
|
|
Term
If a patient sas a DNA repair disorder (can't fix breaks in DNA), isotype switch defect, they can't recombine their T and B cells receptors effectively, and are very susceptible to ionizing radiation (no x-rays) what would you expect them to have?
Can you fix them with a bone marrow transplant? |
|
Definition
|
|
Term
What condition is it when the CD40 ligand and NEMO have a combined defect in which their T and B cells can get together to switch out of the IgM mode, T cell dysfunction, and frequent opportunistic infections because they can't make antibodies well?
Will these patients need a transplant? |
|
Definition
|
|
Term
| What disorder would you expect a patient to have if they get overwhelming mono or are left with an immunodeficiency (hypogammaglobulinemia) after they get this viral infection, and lymphoma? |
|
Definition
| X-linked Lymphoproliferative Disorder |
|
|
Term
| What disorder is it when patients have impressive oral thrush and cutaneous infections (nail infections with fungi, etc.) and autoimmunity? |
|
Definition
| Chronic Mucocutaneous Candidiasis |
|
|
Term
| What syndrome is it when there is a markedly elevated IgE with bacterial & fungal infections ? |
|
Definition
|
|
Term
| If a patient has coarse facies, joint hypermobility, retention of primary dentition, tend to have fractures, what syndrome do they have? |
|
Definition
|
|
Term
| Hyper-IgE syndrome has a dominant negative mutation in what signaling molecule that is essential for different cytokine receptors? |
|
Definition
|
|
Term
| In Hyper-IgE syndrome, patients have high levels of ___ and ___ but normal levels _____ and _____. They do NOT have _____ cells. They get invasive infections with _____ and _____. |
|
Definition
| High levels of IgE and peripheral eosinophilia (in the blood) normal levels immunoglobulins and antibody responses Absent TH17 cells Invasive infections with extracellular bacteria and fungi |
|
|
Term
| What is the essential signal modulator of a central signal transduction complex for leukocytes called NF-kappa B (if NF-kappa B doesn’t get activated well, nothing works well. These patients have a partial defect in the function of NF-kappa B because complete deficiency is lethal) |
|
Definition
|
|
Term
| If a patient has Hypohidrotic ectodermal dysplasia and infections (abnormal development of structures including the skin, hair, nails, teeth, and sweat glands=heat intolerance), hypotrichosis (reduced hair), and hypodontia/anodontia with conical incisors, and opportunistic infections like myobacteria, what deficiency does this person have? |
|
Definition
|
|
Term
| In NEMO deficiency, there is increased serum ____ and low ____ and/or ____ |
|
Definition
| Increased serum IgM and low IgA and/or IgG |
|
|
Term
| What disorder is caused by defective NK and cytotoxic T cell (CD8+ T cell) killing (produces too much) leading to infiltration of the liver, spleen, bone marrow, and central nervous system by activated T cells and macrophages |
|
Definition
| Familial Hemophagocytic Lymphohistiocytosis (FHL) |
|
|
Term
| What are the defective genes in Familial Hemophagocytic Lymphohistiocytosis (FHL)? |
|
Definition
perforin (PRF1) (up to 50%)
Munc13-4 (UNC13D) (20-30%)
syntaxin 11 (STX11) (10-20%) |
|
|
Term
| What are the therapies used for Familial Hemophagocytic Lymphohistiocytosis (FHL)? |
|
Definition
Immunosuppression with prednisone or cyclosporine
Bone marrow transplant (only effective treatment for severe type) |
|
|
Term
| If a patient has overwhelming infection with intracellular pathogens, esp. atypical mycobacteria, that spreads throughout the body, what pathway defect would you expect them to have? |
|
Definition
| IL-12/IFNgamma Pathway Defects |
|
|
Term
What phagocyte deficiency is generally in little boys because gp91-phox is on the X chromosome and there is a defect in WBCs to make hydrogen peroxide
Do some of these patients get transplants? |
|
Definition
Chronic granulomatous disease
Yes-the severe cases |
|
|
Term
What phagocyte deficiency is it when WBCs go past the area of inflammation and get trapped in the blood (can't make pus)?
Can these individuals receive transplant? |
|
Definition
Leukocyte adhesion defects (LAD I and II); beta-integrins CD11/CD18 absent
Yes-lethal within the 1st decade of life without bone marrow transplant |
|
|
Term
| What are the different types of phagocyte deficiencies? |
|
Definition
Chronic granulomatous disease (WBCs can't make H2O2)
Leukocyte adhesion defects
Granule defects
Chronic or cyclic neutropenia (low neutrophil count) (neutrophil elastase-enzyme helps degrade extracellular matrix that is important for remodeling after infections) |
|
|
Term
In Chronic Granulomatous Disease, do catalase (- or +) organisms cause severe tissue infections?
What are the organisms that cause it? |
|
Definition
| Severe tissue infections with catalase positive organisms, esp. Staph aureus, Serratia marcescens, mycobacteria, and fungi such as Aspergillus |
|
|
Term
What is the old fashioned test used to detect the presence of hydrogen peroxide to diagnose chronic granulomatous disease?
What is the more recent test? |
|
Definition
Nitroblue tetrazolium (NBT) test (makes black specks on cells if H2O2 present)
more recently, flow cytometric tests using fluorescent dyes such as dihydrorhodamine (DHR) (fluoresces red when H202 present) |
|
|
Term
| In the Nitroblue tetrazolium test, if the father is does not carry the chronic granulomatous disease, but the son does, how would you expect the tests to look on the father, mother, and son? |
|
Definition
| Father- all neutrophils covered with blue-black dots Mother- only some neutrophils stained black. Many of women’s cells are not using the functional X chromosome and are not producing any hydrogen peroxide. Son- unable to make any hydrogen peroxide (none covered) |
|
|
Term
| If a baby develops omphalitis (infection around the umbilical cord), what deficiency do they have? Is there pus? |
|
Definition
| LAD I (need neutrophils to heal) No pus, just inflammation |
|
|
Term
| What are the 3 arms that Complement divides into? |
|
Definition
Classical
Alternative
Late components |
|
|
Term
| What defect of complement has a strong tendency for people to get recurrent Neisseria infections (epidemic bacterial meningitis)? |
|
Definition
| Late defects in the classical pathways |
|
|
Term
| The classical pathway is activated through__________. There’s a strong tendency for people with defects in this area to have problems with __________. |
|
Definition
immune complexes
autoimmunity |
|
|
Term
Complement Deficiencies:
Rule I: In any inherited deficiency of a component of the classical pathway, total hemolytic activity (_____) will be close to zero
Rule II: In any inherited deficiency of a component of the alternate pathway, total hemolytic activity (_____) will be close to zero |
|
Definition
|
|
