Exam 3 - Objectives

Question 1

List the major differences between mucosal immunity and systemic immunity (in the skin, for example)

Answer 1

Mucosal:
Many active immune cells present
No inflammation - inflammation can be a sign of an autoimmune disease

Systemic:
Not many immune cells present
Inflammation can occur - helps to bring immune cells to the infection

Question 2

Describe the basic structure and chemical features of mucin that allow it to protect mucosal tissue

Answer 2

Huge glycoproteins composed of subunits disulfide-bonded together

Has sialic acid as a glycan (sugar)

Polyanionic surface that can bind positively-charged defensins, antimicrobial peptides, and secretory IgA

Have N-terminal globular domains -allows them to disulfide bond together.

Question 3

Describe the organization of Peyer’s patches, being sure to identify abundant cell types within them and the function of the M cells

Answer 3

Peyer’s patches are found only in the small intestine.
They vary in size and contain between 5 and 200 lymphoid follicles with germinal centers, interspersed with T cell areas that also include dendritic cells.
M cells within the Peyer’s patch brings in antigen from the gut.
There are efferent lymphatics that take the antigens taken in to the mesenteric lymph nodes.
Peyer’s patch release CCL21 and CCL19 that bind to CCR7 expressed on naive T and B cells causing them to leave the lymph vessel and enter secondary lymphoid tissue.

Question 4

Associate intraepithelial lymphocytes (IEL) with the gut, and describe what their characteristics are and how abundant they are

Answer 4

IEL are dispersed in the epithelial layer of the gut. They are a type of CD8+ cytotoxic T cells that are activated by antigen and loaded with granules. There is a mix of alpha beta and gamma delta TCR with limited specificity. They express CCR9 and alphaE:beta7 integrin that allows them to bind to E-cadherins of the intestinal epithelial cells. There is one IEL for every 7-10 epithelial cells.

Question 5

Identify chemokine and intgrin receptors expressed differentially on IEL, lamina propria lymphocytes, and skin lymphocytes that are responsible for these cells homing to the correct body site

Answer 5

IEL’s express the chemokine receptor CCR9 and alphaE:beta7 integrin that allows them to bind to E-cadherins of the intestinal epithelial cells.
Lamina propria lymphocytes (B and T cells) press CCR9 and alpha4:beta7 inegrin that binds to MAdCAM-1 mucosal addressin.
Skin homing lymphocytes express CCR4 and alpha4beta1 integrin

Question 6

List the four known cytokines that cause plasma cells located in the gut to isotype switch to IgA production

Answer 6

TGF-beta drives isotype-switching to IgA (Treg and TFH).
TGF-beta cooperates with BAFF and IL-10 which are produced by dendritic cells scattered throughout the lamina propria (IgA1).
APRIL, a proliferation-inducing ligand, produced by colon epithelial cells (IgA2) and dendritic cells.

Question 7

Identify the two main functions of dimeric IgA in the mucosa

Answer 7

Neutralization and transport of toxins

Question 8

Describe how the immune system seems to compensate for a lack of IgA in “selective IgA deficiency”

Answer 8

Imune system compensates by over-producing IgM and exporting IgM across mucosa (J-chain via poly-Ig receptor)

Question 9

Describe how Th2 responses in mucosal tissues are specifically effective at ridding the body of helminth infections, including the specific functions of Th2 cytokines Il-4, Il-5, and Il-13

Answer 9

Naive CD4 T cells activated during helminth infection differentiate to become Th1 or Th2 effector cells.
Th2 cells produce IL-13, which increases production of epithelial cells in the infected tissue - increase number of goblet cells produces more mucus and the increase in enterocytes increases their rate of turnover in the epithelium.
Th2 cells produce IL-5 which recruits eosinophils to the infected tissue and activates them - activated eosinophils acquire granules containing MBP and parasite-specific IgE bound to FceRI - this degranulation kills helminths.
Th2 cells produce IL-9 which recruits mast cells to the infected tissue. Mast cells bind parasite-specific Ige - degranulation causes muscle spasms and diarrhea that expels helminths.

Question 10

Define primary immunity and secondary immunity

Answer 10

Primary immune response is the adaptive immune response that follows a first exposure to antigen. This can be slow, but it leads to the generation of memory cells with high specificity to the antigen for future attacks.

Secondary immune response is the adaptive response that occurs the second time a antigen is encountered. This response is quicker because it causes reactivation of memory cells. B and T cells are involved.

Question 11

Describe the timeline of an adaptive immune response, including the amounts of effector T cells and antibody. Also be able to include the relative timing of first infections, aborted infections, and secondary infections

Answer 11

1 to 2 weeks after first infection, effector T cells and antibody are made. This was able to terminate the first infection. Effector T cells were soon inactive, but antibody remained to protect against further exposure (aborted infections). After about a year, antibody has decreased and an infection could occur again. If a second exposure occurs, the response will be much quicker as the memory cells will quickly respond and produce antibody.

Question 12

Explain three ways that memory is maintained (antibody, T memory, B memory cells) and the cytokines needed for each

Answer 12

Antibody is maintained by plasma cells in bone marrow nursed by stromal cells secreting IL-6.

Memory CD4+ and CD8+ T lymphocytes rely on IL-7 and IL-15 for maintenance.

Memory B cells have isotype-switched high-affinity BCR and express CD27 which distinguishes them from naive and effector B cells.

These cells/molecules will recognize the specific antigen that they were created for quickly and be able to get rid of it before it causes a huge infection.

Question 13

Explain how pre-existing antibody prevents naive B cell activation

Answer 13

In a primary response, antigen will activate a B cell and it will become an antibody-producing plasma cell creating low-affinity IgM antibodies.
In a secondary response, the antigen receptor and the inhibitory Fc receptor FcgRIIIB1 on a naive B cell can be cross-linked by a pathogen coated in IgG that delivers a negative signal that prevents the activation of the cell.
Memory B cells do not express the Fc inhibitory molecule, so they will become activated and make IgG.

Question 14

Explain “original antigenic sin”

Answer 14

An occurrence in which the body will only respond to the original antigens of a pathogen, and has no response mechanism (sinning) to antigens that are rapidly changing. The memory response is to a mutated version of the antigen that no longer exists within the environment due to the pathogen rapidly changing.

Question 15

Describe how RhoGAM protects agains hemolytic disease of the fetus and newborn

Answer 15

When the father is RhD+ and the mother is RhD-, the baby can be born with hemolytic disease.

In a first pregnancy, RhD+ erythrocytes can cross the placenta and stimulate the mother’s immune system to create anti-RhD antibodies. These will cause little harm to the fetus as they will be IgM and can’t cross the placenta.

In a secondary pregnancy, IgG antibody can be created and transported across the placenta by FcRn and can cause disease in the fetus.

If the mother had not begun created the IgG antibody in the secondary pregnancy, she could get infusions of RhoGAM. This coats fetal erythrocytes with IgG and prevents the mother from making her own that will attack the erythrocytes.

Question 16

Identify the 4 general requirements necessary for a “good” antigen (an antigen that will be immunogenic)

Answer 16

1. Must have a high molecular weight (at least 100,000 daltons)
2. Should have high molecular complexity (like proteins of 20 or more amino acids)
3. Foreignness = taxonomically distant from the host
4. Inflammatory: inducing inflammation by possessing TLR ligand or some other sort of ligand that a pattern recognition receptor in our body induces or also by inducing cell stress that would give a danger signal to our immune system

Question 17

Identify 4 mechanisms that may be responsible for the ability of adjuvants to enhance the immune response to vaccination

Answer 17

1. Complex with the antigen to increase its size
2. Trap the antigen in material that allows it to be relatively indigestible
3. Lipid emulsion - antigen slowly leaks out (causes adaptive immune response rather than innate)
4. Hyper-activate the innate immune cells (like macrophages that will initiate inflammation that will cause adaptive immune cells to be activated)

Question 18

Identify the types of vaccines that are currently in use to immunize individuals against viral infections and bacterial infections

Answer 18

Virus:
Killed/inactivated virus
Live-attenuated virus
Subunit vaccine

Bacteria:
Live-attenuated bacterial vaccines
Subunit (toxoid and purified capsular polysaccharide from different bacterial organisms)
Combination vaccine

Question 19

Describe the process of creating/inducing live-attenuated viral vaccines

Answer 19

1. The pathogenic virus is isolated from a patient and grown in human cultured cells
2. The cultured virus is used to infect monkey cells
3. The virus acquires a variety of mutations that allows it to grow well in monkey cells
4. The virus is not longer grows well in human cells (it is attenuated) and can be used as a vaccine

Question 20

In general, identify how 𝛄δ T cells, NK cells and NKT differ from classic αβ T cells in their antigen recognition

Answer 20

ab T cells recognize peptide in MHC class I or II and use Cd1a,b, and c. 
gd T cells recognize a variety of antigens without classical class I or II. Use class-1 like, but can recognize without presentation. 
NK cells activating or inhibitory ligands. Lack of MHC class I will cause them to kill. 
NKT cells can recognize class-1 like molecules such as CD1d. These present lipids.

Question 21

Specifically identify the antigen that V𝛄9:Vδ2 T cells bind, where these T cell populations are located in the body, and what their general effects function is once activated

Answer 21

V𝛄9:Vδ2 T cells: dominants adult human blood 𝛄δ T cells.
Contain the same V gene segments and variable D and J gene segments
Respond to a range of pathogens
Antigen recognized is NOT peptides, but phosphoantigen
Most (80%) can’t enter secondary lymphoid tissues and instead home to inflamed/infected site by using CCR5
Act as cytotoxic T cells to kill infected cells

Highly activated:
Capable of antigen presentation
Begin expressing MHC class II, B7, and CD40L
Increase MHC class I expression
Gain CCR7 expression to allow migration to lymph nodes and there present antigen to alpha beta T cells

Question 22

Identify the CD protein expressed on the surface of all human NK cells

Answer 22

Mononuclear cells that lack CD3, but express CD16 and CD56 on their cell surface
Some will lack CD16, but all will have CD56

Question 23

Compare and contrast NK and Tc target cell recognition and killing mechanisms

Answer 23

NK and Tc cells kill in a similar manner.

NK cells use inhibitory and activating receptors to find target infected cells or tumor cells that need to be killed. They lack CD3 and TCR proteins. They are an innate immune cell. They detect the loss of MHC class I on the infected cell. Can kill by signaling through activating receptors that detect stress ligands. All NK cells express NKG2D and CD56.

Question 24

Describe the “ligand” for NK cell receptors (in general) and how the signals through these receptors are interpreted by the NK cell

Answer 24

HLA-E inhibitory ligand whose presence depends upon HLA-A,B, and C. 
"Self-MHC class I"

Question 25

Identify the specific ligand for the NKG2D receptor, whether it is an activating or inhibitory receptor, and what the NK cell will do if it encounters this ligand

Answer 25

NKG2D is an activating receptor. It gets a signal from MIC stress receptors expressed on the target cell. NK cells also need another signal such as 2B4 getting a signal from CD48 from the target cell. Once the NK cell is activated, it will release its cytolytic granules on the target cells surface and induce apoptosis,

Question 26

Describe how HLA-E is involved in preventing NK cell killing of healthy self cells

Answer 26

HLA-E is invariant; it can only be expressed on the cell surface and fold properly if it is containing nonamer peptides derived from the leader sequence of HLA-A, HLA-B, and HLA-C HLA-E on the target cell will signal CD94:NKG2A on the NK cell to say that it is healthy and not to kill it Lack of HLA-E targets a cell for killing (no inhibitory signal will occur)

Question 27

Describe the role of fetal HLA-E and HLA-G in creating the maternal blood supply to a developing placenta, and the immune cell involved in this process

Answer 27

Fetal extravillous trophoblast cells invade maternal tissue in order to develop placental blow supply. They do not express classical MHC class I, they express low levels of HLA-C, and high levels of HLA-E, HLA-F, and HLA-G which interact with the NK cells from the mother. HLA-E and HLA-G inhibit the NK cells from the mother from attacking the developing trophoblast and then the placenta and the developing fetus. Soluble HLA-G activates NK cells to secrete cytokines and vascular growth factors to create the blood supply for the placenta.

Question 28

Compare and contrast αβ and 𝛄δ T cells in regard to expression of CD3, CD4, and CD8, type of antigen and antigen-presenting molecule each TCR binds to, the amount of TCR diversity, their abundance in blood/lymph circulation, and their overall functions

Answer 28

1

Question 29

Identify what kind of antigen is presented by CD1a, CD1b, and CD1c molecules and what cell they present this unique antigen to

Answer 29

These are considered "class-1 like" and associated with B2-microglobulin. They present lipid antigen. Expressed on dendritic cells, activated macrophages, and double positive cortical thymocytes of developing T cells. The lipid sits in a hydrophobic channel with the hydrophilic head group sticking out for TCR recognition.

Question 30

Identify the class-I like molecule that presents antigen to NKT cells, where NKT cells are located in the body, and what they do in response to antigen presentation that can influence a subsequent adaptive immune response

Answer 30

CD1d is the class-1 like molecule that presents antigen to NKT cells. CD1d is expressed on epithelial cells present within the intestine, liver, pancreas, uterus, thymus, and tonsils. NKT cells recognize lipid antigens and respond rapidly to infection, but do not generate memory because they are not classical T cells. NKT cells develop in the thymus and when mature are distributed throughout the tissues. They make up less than 1% T cells in the blood and do not recirculate like classic T cells do.

Question 31

Define the acronym SCID. List the currently known mutations that can lead to SCID, and the consequences of SCID in regards to infectious disease susceptibility (e.d. is SCID associated with bacterial infections, fungal infections, viral infections, or all of the above?)

Answer 31

SCID = severe combined immune deficiency Absence of both B and T lymphocyte function General susceptibility to all infectious agents. Recurrent infections begin appearing when a child is only a couple months old when the mother's passive IgG becomes depleted. Genetic cause is sometimes X-linked

Question 32

Describe the basis of DiGeorge Syndrome and the immune cell population that is defective as a result. Explain why DiGeorge Syndrome can have variable levels of severity associated with it

Answer 32

Causes variable decrease in T lymphocytes (both CD4+ and CD8+) due to thymic chromosomal aboration Loss of a portion of chromosome 22 Depending on how much information is lost in the chromosome depends on how much the thymus will develop Symptoms: immune deficient, mental retardation, cardiac abnormalities, and abnormal facial development

Question 33

Identify what two primary immune deficiencies lead to selective susceptibility to viral infections, and for each, whether the patent is susceptible to all virus infections or just certain types of viruses

Answer 33

MHC class I deficiency: Lacks of CD8+ T lymphocytes Susceptible to all viral infections NK Susceptible to only herpes infections

Question 34

Explain why MHC class II deficiency causes infectious disease susceptibility similar to SCID

Answer 34

``` Loss of transcriptional regulators of MHC class II leads to an absence of CD4+ T cells due to a lack of positive selection in the thymus Susceptible to all infectious agents because CD4+ cells are necessary for activating cytotoxic T cells to kill Technically not SCID because B cells are there, they just can't function properly ```

Question 35

Compare and contrast X-linked agammaglobulinemia and X-linked Hyper-IgM syndrome,, specifically listing whether B cells are present in circulation, and whether IgG, IgA, and IgM are absent or produced as reduced, normal, or excessive levels, and the type of infection susceptibly associated with the diseases

Answer 35

X-linked agammaglobulinemia: Absence of B lymphocytes du rot Btk deficiency (Pre-B cells die in bone marrow - never released) Seen in males Can make no Ig Selective susceptibility to pyogenic extracellular bacterial infections X-linked hyper-IgM syndrome: Lack of isotyoe switching because of CD40-L deficiency B lymphocytes are there but not effective because interaction with T lymphocytes is not occurring because of the lack of CD40L B cells can only make T-independent IgM - no memory response created Can only make IgM Selective susceptibility to extracellular bacterial infections because IgM is not generally allowed into interstitial tissues

Question 36

Identify why complement deficiencies are associated with increased susceptibility to extracellular pyogenic bacterial infections (be sure to define pyogenic)

Answer 36

pyogenic = pus causing. | Complement deficiencies would cause bacteria to not be opsonized so not phagocytosis would occur.

Question 37

Identify whether deficiencies of early components of the classical complement pathway, the alternative complement pathway, or the lectin complement pathway can cause a risk for systemic lupus autoimmunity, and why this risk develops

Answer 37

Classical pathway. The way remove immune complexes from the blood using C1q. Immune complexes will start participate out - not able to clear them. Make too much antibody.

Question 38

For the primary phagocyte deficiencies (CGD, Chediak-Higashi syndrome, G6PD or Myeloperoxidase deficiency, and LAD), identify the type of infectious disease susceptibility seen in patients, and whether the infections respond to antibiotic treatment or not, and why some do not respond to antibiotics

Answer 38

Chronic granulomatous disease (CGD): Lack a subunit of NADPH oxidase and can't activate granule proteases Patients do not have effective respiratory burst Can't kill the pathogen they ingest, causes macrophages to fuse together and form a granuloma Can treat with antibiotics because the cells are able to leave the bloodstream because inflammation will occur. Chediak-Higashi syndrome: Endosomes and lysosomes will not fuse together Can develop granulomas Can be treated with antibiotics G6PD or Myeloperoxidase enzyme deficiency: Defective respiratory burst - impairs killing of ingested bacteria or fungi Mores susceptible to fungal infections Can be treated with antibiotics Leukocyte adhesion deficiency (LAD): Loss of CD18 Leads to defective neutrophil and macrophage migration into infected tissue and an inability to phagocytose opsonized pathogens Respond poorly to antibiotics because the cells are not able to leave the bloodstream

Question 39

Identify the infectious disease susceptibility that results from defects in the IL-12 or IFN-𝛄 receptors, and the immunological basis for this susceptibility

Answer 39

See a defect in cell-mediated immunity to particularly resistant or resilient organisms. Leads to tuberculosis from M. avian and M. bovine vaccine. Defects in innate and adaptive immunity. IL-12 that is secreted from macrophages can't activate NK cells since its deficient. IFN-𝛄 from NK can't activate macrophage production of inflammatory cytokines.

Question 40

List 2 routine laboratory tests that can be performed using patient blood samples (serum or cells) which are useful in evaluating possible primary immune defects in humoral immunity

Answer 40

First test would be a CBC with WBC differential. This will tell you if the innate and adaptive cell components are present. Can quantify the B cells using CD19 or CD20 surface marker by flow-cytometry. If B cells are there, can look for their activity state by looking for IgA, IgD, IgM, and IgD Can quantify the amount of total soluble IgG, IgM, and IgA present in patient serum.

Question 41

Describe the steps of a complement activation enzyme (CAE or CH50) immunoassay (specifically identifying what is coated onto the assay EIA plastic plate wells, the patient sample used, the detection reagent used, and how results are reported) and what pathway of complement is being assayed

Answer 41

CAE immunoassay is EIA that detects C9 bound to IgM-coated micrometer wells. CH50 liposomal lysis assay replaced traditional hemolytic titration assay. Measures the classical complement pathway ability to lyse antibody-sensitized membranes.

Question 42

Explain the flow cytometry technique, including the reagents that are used, the patient sample utilized, and how that label is detected. List what information can be collected on each cell analyzed, and how that information is interpreted

Answer 42

A cell mixture is labeled with fluorescent-tagged monoclonal antibodies specific for cell marker of interest (sample is whole blood). Cells are suspended in saline and run through a flow cytometer. This separates the cells into a single-cell stream and activates the fluorochrome labels with a laser light. It will deter the fluorescent emission with detectors.

Question 43

Identify whether AIDS (Acquired Immunodeficiency syndrome) due to HIV infection is a primary or secondary immunodeficiency

Answer 43

Secondary

Question 44

Identify whether HIV-1 or HIV-2 is more common in the U.S.

Answer 44

HIV-1 is the principle cause of AIDS in most countries. HIV-2 is endemic in West Africa, widely seen in Asia, and occurs in small but significant numbers in all countries (including the US). HIV-1 causes more aggressive disease than HIV-2.

Question 45

State whether the number of people infected with HIV worldwide has leveled off, declined, or is still increasing

Answer 45

Still increasing

Question 46

Identify the function of gp120 and gp41 in the interaction with host cell membranes and eventual infection of host cells

Answer 46

HIV gp120 proteins forms knobs that protrude from the viral envelope and bind CD4 and a chemokine receptor. gp120 and gp41 are virally encoded envelope glycoproteins that form the viral spike. gp120 binds tightly to human CD4 and that allows gp41 to be released which will allow the fusion of the plasma membrane and then allow the RNA to be released into the host cell.

Question 47

Explain the difference between macrophage-tropic and lymphocyte-tropic HIV strains, and how they can change over time during HIV infection of an individual

Answer 47

Macrophage-tropic HIV strains generally initiate infection at mucosal sites of entry by binding to CCR5, and preferentially infect macrophages and dendritic cells as well as CD4+ T cells. Lymphocyte-tropic HIV strains preferentially bind CXCR4 and preferentially infect CD4+ T lymphocytes (later in infection, hastens progression to AIDS)

Question 48

Explain the function and importance of “reverse transcriptase” and integrase” HIV enzymes in creating a permanent stable infection of a host cell

Answer 48

Reverse transcriptase converts the viral RNA into cDNA Integrase splices it into the host DNA - the virus is now part of our DNA and is permanent.

Question 49

Explain when the Acute HIV syndrome occurs following exposure to HIV and identify the symptoms of this syndrome. Is the infected individual infectious to others at this time? Do all patients develop these symptoms?

Answer 49

Acute HIV syndrome occurs at around 4-8 weeks. Flu like symptoms occur within this syndrome. This individual is highly infectious to others at the time. Not all patients develop these symptoms.

Question 50

Explain why CD4+ T cell numbers temporarily plummet during the end of the acute infection stage of HIV, and then rebound at least partially

Answer 50

They plummet because T cells kill all the CD4 cells. B cells are making antibodies that neutralize gp120 that binds to CD4. After the immune system gets ramped up, CD4 T cell count rises

Question 51

Define the acronym HAART and explain why HAART drug treatment is used in fighting HIV infection instead of single drug therapy

Answer 51

HAART = highly active antiretroviral therapy. Single drug therapy will combat one mechanism of action, whereas HAART is a combination drug therapy of 1 drug from 2 or 3 classes with different mechanisms of action.

Question 52

List the characteristics of HIV that make it very difficult to create an effective vaccine against HIV

Answer 52

Hight mutation rate Must target both CD8+ T cell response and mucosal antibody response HIV remains latent as provirus integrated into host genome and can reactivate at a later date.

Question 53

Identify the two main analyses that can be measured in serological tests for infectious disease

Answer 53

Pathogen antigen and host antibody

Question 54

Describe the testing algorithm that should be followed for diagnosis of HIV infection in a high risk adult. Interpret possible HIV screening and confirmatory test results using the CDC testing algorithm for HIV diagnosis. For example, if the screening test is negative, the interpretation would be that the patient does not have HIV infection

Answer 54

Screen: HIV-1/HIV-2 antibody and antigen combination assay. Detects patient Ab to HIV-1 or HIV-2 or circulating antigen HIV-1. Any of these will cause a positive test result. Confirmatory: HIV-1/HIV-2 differentiation immunoassay. Works with antibody only. Will determine if positive for HIV-1 and/or HIV-2. Can also be negative for both. If negative for both, then do nucleic acid test to look for HIV RNA.

Question 55

Explain the EIA treating for detection of either patient antibody, or antigen in patient serum

Answer 55

Take solid antigen (HIV viral antigen) and place it in the well and wash out excess. Add patient serum (antibodies) that will stick to the viral antigen, wash away excess. Add an anti-human anti globulin conjugate that reacts against the heavy chain of the antibody. An enzyme is attached to the anti-human conjugate which seeks out its conjugate antigen (the human antibody) and sticks, forming a "sandwich" complex. Wash away. Add a clear substrate specific to the enzyme. If the Ab-Ag complex formed, you will get a color change reaction. If there is no color change, there were no antibodies in the patient serum, therefore the conjugate had nothing to stick to. The less color you see, the fewer number of the complexes that formed and caused a color change. This is used as a semi-qualitivative measures of how much antibody is there.

Question 56

List the drawbacks of the early generation EIA tests for HIV diagnosis, and how the “fourth generation” EIA test has limited these

Answer 56

Fourth generation decreases the window period of a false negative to 14-21 days instead of 45. Now can detect both HIV1 and HIV2 using recombinant proteins in a sandwich EIA format. It can detect p24 antigen from HIV-1. Still many false positives in low risk populations due to history of multiple pregnancies, auto-antibodies, severe liver disease, recent vaccinations, certain malignancies, repeated freezing/thawing of specimen. Earlier generation tests couldn't detect HIV-2 infections or patient antibody to HIV-2

Question 57

Identify the confirmatory tests available for HIV diagnosis in adults (assuming the screening test is positive)

Answer 57

HIV1/HIV-2 antibody differentiation immunoassay.

Question 58

Identify the preferred methodology for detecting HIV infections in newborn infants, and why the usual screening test for HIV cannot be used to diagnose HIV infections in infants

Answer 58

Can't test baby's serum because of mother's passive IgG antibody can result in false positive in children up to 18 months. Baby's IgM antibody to HIV lacks specificity and is not adequate for testing. Best method for babies is viral nucleic acid when baby is >1 month old. This is qualitative PCR for HIV cDNA provirus in baby's mononuclear cells.

Question 59

Correlate an increase or decrease in HIV viral load to the success of drug therapy in the patient. Identify specifically what “HIV viral load” is measuring and the patient sample used

Answer 59

Viral load testing is quantitive HIV viral RNA. Successful drug therapy results in drop in viral load level. Drug resistance results in increased viral load.

Question 60

Identify the laboratory test used in monitoring patient progression from HIV+ to AIDS

Answer 60

Monitored by CD4 T cell counts and HIV RNA vial load with repeat testing every 3-6 months

Question 61

Define antigen.

Answer 61

Antigen is a substance that reacts with antibody (BCR) or T lymphocytes and their TCR

Question 62

Define immunogen.

Answer 62

Immunogen implies that the antigen evokes a protective adaptive immune response and usually this equates with the fact that there is some component in the immune system that causes inflammation by activating a pattern recognition receptor, the most well-known as the TLRs

Question 63

Define hapten

Answer 63

Small molecules (even a chemical side chain) that can become immunogenic when complexed to larger molecules (like proteins), even though by themselves are not immunogenic Responsible for latex allergies, drug allergies, and poison ivy

Question 64

Define adjuvant

Answer 64

A substance administered with (physically mixed with) an antigen to enhance its immunogenicity By itself, the antigen might be ignored, but if it is mixed with the adjuvant, it now becomes an immunogen Examples: aluminum hydroxide, aluminum phosphate, or potassium aluminum sulfate

Question 65

Define vaccination

Answer 65

Any deliberate immunization intended to induce immunity against disease

Question 66

Define herd immunity

Answer 66

The ability to prevent epidemics of dangerous infections when the vast majority of the population (>95%) are immune by vaccination. Individuals who are not immune or cannot be vaccinated are protected because the organism cannot spread in the highly immune population See outbreaks of disease when immunity reaches 85%

Question 67

Pros and cons of live attenuated virus vaccine

Answer 67

Pro: induces both cytotoxic T cells which can rapidly go out and kill cells infected by the virus and it also induces neutralizing antibody to protect against further infections More potent than killed vaccines because it replicates in the human cell and mimic real diseases Cons: can cause disease in individuals who have cell-mediated immune deficiency that either could be induced by drugs from treatment for cancer for instance, or that might have an underling immunodeficiency we did not know about Can revert back to pathogenic strain and then cause disease

Question 68

Pros and cons of killed/inactivated viral vaccines

Answer 68

Pro: safe for those who might have underlying immunodeficiency Con: manufacture large amounts of live virus in the manufacturing facility that is dangerous to the workers Activates neutralizing antibody but does not activate cytotoxic T cells

Question 69

Pros and cons of subunit viral vaccines

Answer 69

Pros: induces neutralizing antibody Can be produced without live virus - protects manufacture personnel Con: only effective in 85% of the population

Question 70

Pros and cons of live-attenuated bacterial vaccines

Answer 70

Pros: induces a very strong cell-mediated immunity and neutralizing antibody at the same time Cons: can be dangerous and cause disease in someone with an underlying immune deficiency

Question 71

Pros and cons of bacterial subunit toxoid vaccines

Answer 71

Toxoids are inactivated forms of bacterial toxins Goal: induce high titer of neutralizing antibody in the individual Cons: Toxoids by itself does not induce T cell help or protective antibody, so it must be combined with another vaccine (whole killed bacteria) to be effective

Question 72

Pros and cons of bacterial subunit purified capsular polysaccharide vaccines

Answer 72

Bacteria can coat themselves with polysaccharide that inhibits the innate immune complement from binding to it. Goal: Create opsonizing antibody that can allow for phagocytic disposal of these extracellular bacteria Con: Only induces protective T-independent antibody responses in healthy adults

Question 73

Identify where V𝛄4:Vδ5 T cells cells bind, where these T cell populations are located in the body, and what their general effects function is once activated

Answer 73

Respond to tumor cells and cells with CMV infection Interacts with conserved epitope of ligand expressed on tumor cells and CMV-infected cells = EPCR (Endothelial protein C receptor) Phosphoantigen is in groove of EPCR - helps it fold properly in the ER and be transported to the cell surface where it provides the activating signal to kill CMV= cytomegalovirus (herpes that infects myeloid lineage cells: monocytes and macrophages)

Question 74

Identify where V𝛄:Vδ1 T cells bind, where these T cell populations are located in the body, and what their general effects function is once activated

Answer 74

Abundant in the fetus and neonate In adulthood, these cells move from the blood and become confined to mucosa and spleen Kill damaged or infected gut epithelial cells, leading to eventual repair of injured mucosa by removing damaged cells and allowing new cells to replace them Target lipid antigens that are presented in MHC class-1-like molecules called CD1d

Question 75

Define serology

Answer 75

Study of non-cellular components in the blood

Question 76

Define window period

Answer 76

Time between potential exposure to HIV infection and the point when the test will give an accurate result. During the window period a person can be infected with HIV and infections but have a negative HIV test.

Question 77

Define false positive:

Answer 77

A test result that indicates a person does not have a disease or condition when the person actually does have it

Question 78

Define false positive

Answer 78

A test result that indicates a person has a disease or condition when the person actually does not have it.