Immunodeficiency

Question 1

Describe immunodeficiency and what occurs during the process.

Answer 1

Immunodeficiency- Failure of the body’s defenses to get rid of pathogen.
This may occur as pathogens evade and subvert (escape) the immune system
Immunodeficiency diseases are mostly INHERITED Deficiencies caused by mutant alleles (genes encoding for immune system)

Question 2

Explain how some pathogens may decrease long-term immunity. What is one example of a bacterium that prevents long-term immunity?

Answer 2

Some species of pathogens evolve Numerous different strains which allow for antigen variability as strains differ in their antigenic macromolecule on outer surface
Ex; Streptococcus pneumonia (90 serotypes) has 90 different strains ( antigenic different capsular polysaccharide).
the genetic variation prevents humans from developing effective memory cells and long-term immunity.

Question 3

Describe the immune response that occurs when one is infected with streptococcus pneumoniae?

Answer 3

Streptococcus pneumoniae have many serotypes (differ in their capsular polysaccharides)
Process:
1. Person is infected with one serotype of s. pneumoniae
2. Antibody response will clear the infection
3. However, these antibodies from previous infection CANNOT prevent infection of second serotype of S. pneumoniae (different strain).
4. A new antibody must be produced for second infection to clear it

Question 4

What is antigenic Drift? Provide an example of a virus that undergoes this process

Answer 4

Antigenic Drift: Process by which point mutations in INFLUENZA virus genes causes alterations in structure of viral surface antigens-causing year to year antigens (lead to epidemics)
Virus- influenza and other viruses (retroviruses, coronaviruses) undergo antigenic drift

Question 5

Describe the steps of how antigenic drift is developed

Answer 5

1. During first encounter with influenza virus, person P develops antibodies against epitopes of viral hemagglutinin. V, neutralizing antibody will bind to hemagglutinin that prevents Virus V from infecting cells of person P
2. When infecting person Q, viurs V mutates to give Virus V* with altered hemagglutinin (differs from virus V)
3. Virus V* infects person P because antibody made against V does NOT neutralize V* (new strain)

Question 6

*What is antigenic shift?

Answer 6

Antigenic shift- process by which influenza viruses reassort their segmented genomes and change their surface antigens radically- shift
antigenic shifts usually the cause of influenza PANDEMICS.

Question 7

*differentiate between antigenic drift and antigenic shift

Answer 7

Epidemics occur with mutations in the virus and ANTIGENIC DRIFT
Pandemics occur with recombination of genes, antigenic SHIFT

Question 8

*What kind of viruses cause pandemics? Which Viruses are more error prone?

Answer 8

The Influenza strains that cause Pandemics are RECOMBINANT Viruses that derive some of their RNA genome from avian influenza virus and remainder from human influenza virus.
The viruses emerging from antigenic shift cause more severe disease and greater mortality than viruses emerging from genetic drift.
RNA Viruses are more error prone, likely to mutate- INFLUENZA, HIV

Question 9

What leads to generation of new viral strains that decrease immunity?

Answer 9

Mutation and recombination of viruses- lead to generation of new viral strains that avoid immunity.

Question 10

Describe how antigenic shifts occur with influenza virus.

Answer 10

process:

1. A pig is infected with human and avian strains of influenza virus (RNA genome sorted to make various recombinant viruses)
2. Recombination of avian and human RNA produces a virus that infects human cells and has new form of hemagglutinin (glycoprotein)
3. No humans have antibodies that recognize the new hemagglutinin: so the entire population is vulnerable to infection (leading to pandemic)

Question 11

*Describe the gene rearrangement that occurs with the bacteria in Africa? What are the features of this parasite and how does it affect humans?

Answer 11

Trypanosoma brucei : African Trypanosome (Protozoa) that changes their surface antigen by gene rearrangement. This protozoa is cause of sleeping sickness
The African trypanosome has Insect(mostly) and human hosts (insect bite transmits to trypanosome to human).
The genome encodes for 1000 genes encoding for *Variable Surface Glycoproteins (VSGs; glycoproteins with variants)
*For VSG gene to be expressed it has to be rearranged into an expression site. Gene conversion occurs when gene in the expression site is excised and replaced by a copy of different homologous gene
When a host (infected person) has primary immune response, it will make defense to DOMINANT VSG form NOT Minority VSG, so selection for minority will continue (as the minority VSG become dominant form)

Question 12

What is the gene conversion process?

Answer 12

Gene conversion process:

1. Initially, there are many inactive trypanosome VSG genes but only ONE site for expression
2. then inactive genes are copied into expression site by gene conversion(remove gene in express site, replace with another)
3. Many rounds of gene conversion occurs, allowing trypanosome to vary the VSG gene expressed)

Question 13

*Explain the trypanosome cycling that occurs with African protozoa (Trypanosoma brucei). What can this lead to in humans? What other parasites have similar effects?

Answer 13

There is Dramatic cycling (gene conversion)in the number of parasites in the individual. The cycle of antibody production (against dominant VSG) and then antigen clearance leads to INFLAMMATION, and NEUROLOGICAL DAMAGE eventually leading to coma
Salmonella Typhimurium and Neisseria gonorrhoeae are BACTERIA that also use GENE conversion to escape human immune responses.

Question 14

*What cells usually clear viruses? Explain the viruses that are difficult to clear? How does HSV affect human cells?

Answer 14

Viruses- cleared by cytotoxic CD8 T cells
Difficult to clear viruses when in Quiescent state (like HIV, Herpes simplex Virus (HSV) that remain in LATENCY (virus in resting state without producing more virus, replication or disease)
HSV (Herpes Simplex Virus; double stranded DNA virus) infects epithelial cells (causing Cold sore) and then spreads sensory neurons (trigeminal ganglion) . The immune response will clear the virus from epithelium , but virus will still persist in Latent state in NEURONS.
Factors like stress (sunlight, bacterial infection) can cause REACTIVATION of virus which allows travel down axons of sensory neuron and reinfect epithelium

Question 15

*Why are Neurons a good site for latent virus? What other viruses besides HSV (Herpes simplex virus) can cause reactivation of virus in the cell?

Answer 15

Neurons are good site for LATENT virus to hide because they express small numbers of MHC class I molecules (reduce the potential for presentation of viral peptides to CD8 T cells)
Herpesvirus Varicella-Zoster causes chicken pox(skin rash of red blisters) and after acute infection occurs, virus remains latent in ganglia and stress may lead to reactivation of virus called SHINGLES. Epstein-Barr Virus- herpes virus are also exposed to humans and have a latent state that decreases the number of MHC class I molecules as well.

Question 16

What occurs in the disease Epstein-Barr Virus?

Answer 16

Epstein- Barr Virus- herpesvirus to which most humans are exposed to.
In childhood EBV virus can cause mild cold like disease while in adulthood the virus can cause infectious mononucleosis (grandular fever) causing infection of acute memory B lymphocytes. the B lymphocytes will then be virus-infected and killed by cytotoxic CD8 T cells and infection is latent in small amount of cell. Epstein Bar nuclear antigen 1 (EBNA-1) will allow virus persist in human host and prevent peptides to present to MHC I (decrease MHC I class)

Question 17

*Which viruses all have a latent state and may lead to reactivation of the virus in cells?

Answer 17

Herpes simplex Virus, Varicella Zoster (chicken pox/shingles) and EBV (Epstein-Barr Virus)
all have LATENT state and stress can cause reactivation of virus, leading to reduction of MHC class I molecules

Question 18

Describe the bacteria that subvert the human immune response.

Answer 18

1. Myobacterium Tuberculosis- prevents the fusion of phagosome with lysosome in macrophages- FLOURISHES in the Vesicles
2. Toxoplasma gondii- encloses itself in an impenetrable membrane-enclosed vesicle that does NOT fuse with other vesicles- issues with antigen processing (prevent T. gondii peptides from binding to MHC)
3. Treponema pallidum (Syphilis)- coats itself with human proteins to evade antibody binding (also seen in helminth worm; Schistosoma)

Question 19

Why are viruses so powerful in human immune system? How can they avoid immune responses?

Answer 19

Viruses- have the greatest ability to evade human immune system- replication and life cycle depend on metabolic and biosynthetic processes of human cells- They can evade the immune system by:
capture of cellular genes encoding for cytokines or their receptors; synthesis of proteins that prevent complement fixation or antibody processing and presentation to CD8 T-cells.

Question 20

What are the viral strategies that different viruses use ? What are common viruses involved?

Answer 20

Viral Strategies:
1. Inhibition of humoral immunity
2. Inhibition of Inflammatory response
3. Blocking of antigen processing and presentation
4. immunosuppression of host
Examples of viruses:
Herpes simplex, Cytomegalovirus, Vaccinia, Epstein-Barr virus

Question 21

Explain the CMV (Cytomegalovirus ) subversive effect on immune response

Answer 21

Cytomegalovirus (CMV; largest of human herpesvirus) has 10 proteins that work together to DIMINISH MHC I from stimulating NK-cells and CD8-T cells.
158 million people are infected with CMV, and have few initial symptoms, but the virus remains LATENT(no symptoms)
CMV can be life threatening in IMMUNOCOMPROMISED Individuals.
treatment for CMV: ganciclovyir

Question 22

what is a bacterial superantigen and how does it function? what are two kinds of examples that use superantigens?

Answer 22

Bacterial superantigen- small bacterial toxin that can cross link MHC II on APC (Antigen-presenting cell) with TCR (T-cell receptor) on CD4 T- cell. This will create a NON-SPECIFIC activation of CD4-T cells that (comprise 2-20% of body's CD4 T cells) and Excessive production of IL-2, IFN-gamma, and TNF-alpha. 
(IL-2, IFN-gamma, and TNF-alpha interfere Confuse innate immune response)
Streptococcus Aureus  (S. Aureus) and Streptococcus Pyogenes are bacteria that secrete the superantigen toxins.

Question 23

Explain how S. Aureus works as a superantigen and other components produced. What is SSLP7?

Answer 23

S. Aureus has SSLPs (staphylococcal super antigen-like proteins)
The SSLP7 prevents MONOMERIC IgA from delivering bacteria to phagocytes
and it also contains binding sites for FC region of Ig A and C5 complement protein (prevent complement-mediated killing of bacteria)- pathogen wins

Question 24

Differentiate between when the host wins vs when the pathogen wins

Answer 24

Host wins- when there is NO SUPERANTIGEN, and Ig A binds bacterium (with Fab arms) and engages FcalphRI of a neutrophil or macrophage. This allows for phagocyte to activate and destroy bacterium bound to Fc receptor.
Pathogen Wins- Presence of superantigen
SSLP7 has binding sites for Fc region of Ig A and complement protein C5. SSLP7 binds to C5 and Ig A and protect bacteria from being killed.

Question 25

What do superantigens have in common?

Answer 25

Superantigens have in common:

binding sites that allow superantigen to cross link MHC II on APC with antigen receptor on CD4 T cell

Question 26

Explain the mechanism of the superantigen

Answer 26

Process:

1. Bacterial superantigen binds to MHC class II on antigen presenting cells
2. Then a second site on superantigen will bind to VBeta domain of CD4 T-cell receptor.
3. At third site, superantigen binds to co-stimulator CD28 (CD28 and B7 interaction not affected)

Question 27

Differentiate between primary and secondary immunodeficiency Diseases

Answer 27

Primary- INHERITED defects- Enhanced susceptibility to infection or autoimmunity (genes ?)
Secondary- due to ENVIRONMENTAL factors (immunosuppressive drugs)

Question 28

Differentiate between dominant, recessive and X-linked immunodeficiency diseases

Answer 28

Dominant- disease is seen in children- only ONE ALLELE required
Recessive- disease required TWO alleles- can be CARRIER
X-linked- Recessive defects in genes on X-chromosome (disease seen more in MALES)
Dominant deflect- disease seen EQUALLY between Males and Females.

Question 29

What cellular structures make IFN-gamma cells and what is its function. Also differentiate between the IFN-gamma and IFN-R1 levels in healthy individuals vs recessive and dominant genotypes.

Answer 29

IFN-gamma activates macrophages
NK-cells (innate), TH1-CD4 T cells and CD8 T cells make IFN-gamma cells.
In healthy individuals: you have a lot of IFN-gamma that bind to IFN-gammaR1 (receptor) on cell surface
Patients with RECESSIVE allele (two recessive IFN-gammaR1 alleles)- have NO IFN-gammaR1 on surface
patients with DOMINANT allele : dominant IFN-gammaR1 allele, and on wildtype allele (partial IFN-gammaR1 chain)

Question 30

What occurs if during antibody deficiency? How does this affect’s ones susceptibility to infection?

Answer 30

Antibody deficiency will lead to POOR clearing of extracellular bacteria
one will be susceptible to ENCAPSUALATED bacteria (S. aureus, s, pneumoniae, P.aeruginosa) often evades innate immunity- and must be cleared by Specific antibody and complement.

Question 31

Describe what occurs in the disease XLA (X-linked Agammglobulinemia. Also discuss how this disease can be treated with antibiotics and better treatment options.

Answer 31

X-Linked agammaglobulinemia (XLA)- inherited immune disorder that occurs when there’s a DEFECT in Bruton’s tyrosine Kinaase (BTK)- which is required for B-cell activation and pre-B cell development and differentiation
XLA can be treated with antibiotics- successive treatments can lead to TISSUE DAMAGE (excessive release of proteases from bacteria and phagocytes)- and affect airways; cause bronchiectasis (, thickening of bronchi walls from infection/inflammation) \
disease seen almost exclusively in Males
Treatment: Monthly injections of Immunoglobulin- form ANTIBODIES against common pathogens (passive immunity). This is seen as better treatment

Question 32

Compare and contrast the X-linked (Bruton’s) vs autosomal (Non-Bruton’s) form of agammaglobulinemia. Include what lab findings can be seen and signs of disease

Answer 32

X-linked aggamaglobulinemia- X-linked RECESSIVE disorder.
 X-linked (Brution's) agammaglobulinemia is characterized by ABSENCE of Mature B cells and all IMMUNOGLOBULINS.  It results in Defect in BTK (tyrosine kinase gene) on sex X chromosome (recessive pattern), which prevents B cell maturation. 
XLA presents with recurrent bacterial infections 6 months of age, when maternal IgG is no longer present.  This disease exclusively seen in MALES
Lab findings : absence of mature B cells and Decreased Immunoglobulins of ALL classes.
Autosomal Aggammaglobulinemia (NON-Bruton)- can be caused by Mutations in large number of genes (usually autosomal recessive), but there have been reports of autosomal dominant mutations in families.

Question 33

What is the main affect of phagocytosis defects? what diseases are associated with this?

Answer 33

Phagocytosis defects- ENHANCED susceptibility to bacterial infection
Syndromes associated- Leukocyte adhesion deficiency (LAD), Chronic granulomatous disease (CGD), and Chediak-Higashi syndrome (CHS)

Question 34

Describe what occurs in Leukocyte Adhesion deficiency (LAD-1) and how it affect phagocytic function. Explain symptoms or signs that occurs.

Answer 34

Leukocyte adhesion deficiency (LAD-1) is an AUTOSOMAL Recessive immunodeficiency causing phagocytic dysfunction. It is caused by defect in LFA-1 INTEGRIN PROTEIN on phagocytes that prevents their adherence migration out of blood vessels (phagocytes unable to stick to LFA-1 and hence migrate out of blood).
LDA-1 will have signs of recurrent bacterial infections, absent pus formation, poor wound healing, and delayed separation of umbilical cord. NEUTROPHILIA- will be observed on peripheral blood smear due to inability of phagocytes to exit circulation.
(Neutrophilia) -higher number of neutrophils in blood

Question 35

Describe what occurs in Chediak-Higashi syndrome and clinical findings that are present.

Answer 35

Chediak-Higashi Syndrome- characterized by recurrent staphylococci/streptococci infections, partial albinism, and peripheral neuropathy (ex: nystagmus). CHS is caused by defect in LYST gene.
CHS- AUTOSOMAL RECESSIVE immunodeficiency which causes phagocyte dysfunction. It is caused by a defect in Lysosomal Trafficking regulator (LYST) gene, which leads to MICROTUBULE Dysfunction in Phagocytes.
patients present 3 P’s: Pyogenic infections (strep/staph), Partial albinism, and Peripheral neuropathy (damage to peripheral nerves). Giant GRANULES will often be observed in Neutrophils on a peripheral blood smear.

Question 36

Describe what occurs in Chronic granulomatous disease (CGD) and clinical findings that are present. What does a normal NADPH oxidase do? What are examples of Catalase positive organism What are the forms of treatment for CGD?

Answer 36

Chronic granulomatous disease (CGD)- characterized by a DEFICIENCY of Neutrophil NADPH Oxidase. Patients with CGD have Neutrophils that are Dysfunctional, and have Increased Susceptibility to Infection by Catalase-producing organisms.
Normally NADPH oxidase generates reaction oxygen species (ROS) in the neutrophil which are converted into antibacterial HYDROGEN PEROXIDE.
Individuals with CGD and whose neutrophils cannot produce their own Hydrogen peroxide, are HIGHLY Susceptible to bacteria that break down Hydrogen peroxide (catalase-positive organisms)
Ex of catalase positive organisms: S. aureus, E. coli, PSEUDOMONAS, Aspergillus.
TREATMENT for CGD: 1) lifelong regimens of antibiotics and antifungals to prevent infections
2) Interferon gamma-treatment (immune booster)
3) hematopoietic stem cell transplant (make neutrophils

Question 37

What facilitates the effector functions that antibodies recruit to clear pathogens? Describe what occurs if there is a deficiency in C1-C4 or deficiency in C4 or C5-C9?

Answer 37

All the effector functions that are Antibodies recruit to clear pathogens are facilitated by COMPLEMENT Activation.
C1-C4- Classical pathway is required for elimination of immune complexes - CR1 binds C4b and C3b attached to complex and transported by erythrocytes.
If there is a DEFICIENCY in C1-C4 (C1, C2, C4), there will be an accumulation of immune complexes in blood and deposition of immune complex in tissue, leading affecting phagocyte activity and causing inflammation and tissue damage.

Question 38

What occurs if there is a deficiency in C3 or C5-C9?

Answer 38

C3: opsonin that promotes the efficient elimination of bacteria by phagocytes. Hence if there is a deficiency of C3: have Susceptibility to ENCAPSULATED Bacteria

C5-C9- Terminal complement components of membrane attack complex. If there is a deficiency of C5-C9: Susceptibility to Neisseria infections.

Question 39

Describe what occurs in Hereditary Angioedema and clinical findings present and treatment options. What occurs with C1INH replacement therapy?

Answer 39

Hereditary Angioedema: due to Deficiency in C1 Esterase INHIBITOR (C1INH) which leads to unchecked activation of complement components leading to decreased C2 and C4 protein. in turn, BRADYKININ is Inflammatory mediator that causes Capillary leakage and resulting Swelling. The condition is AUTOSOMAL DOMINANT
The disease may affect eyelids, lips, tongue, genitals, hands, and feet. there is LOCALIZED EDEMA, PUFFY skin, and SWELLING (severe cases, airway obstruction)
Treatment: DANAZOL (synthetic androgen and partial agonist at the androgen receptor that plays a role in treatment by promoting C4 synthesis and INCREASE in C1INH.
Replacement Therapy with C1-INH significantly SHORTENS time to onset symptom relief in hereditary angioedema attacks.

Question 40

Briefly describe the mechanism/pathway of hereditary angioedema.

Answer 40

Hereditary angioedema:
1.C1r (bait protein) and C1INH present
2. C1r cleaves C1INH and forms covalently bonded intermediate
3. This causes conformational change that stabilizes intermediate and disables C1r.
once C1INH is inhibited, it promotes bradykinin (leading to increase inflammation, swelling)

Question 41

Explain the effects of t-cell development and function defects?

Answer 41

T cell development and function defects:

• usually have Depressive effect on immune system
• those with T-cell defect are more susceptible to persistent and recurrent infections with Broader range of pathogens than patients with B cell deficiencies.
• deficiency in T-cell dependent antibody response and cell-mediated immune response leads to SCID (sever combined immune deficiency)
• Infants- with underdeveloped thymus contains a few lymphocytes.

Question 42

What are major conditions related to with SCID

Answer 42

Conditions related to SCID (severe combined immuno deficiency):

1. Adenosine deaminase deficiency
2. X-linked SCID
3. Complete DiGeorge Syndrome
4. Wiskott-Aldrich Syndrome (WAS)

Question 43

Describe what occurs in SCID (severe combine immunodeficiency) and clinical findings present. What are main causes of SCID? also compare and contrast SCID due to X-linked vs autosomal recessive

Answer 43

SCID (severe combined immunodeficiency) - a deficiency in T cells that impairs both cell-mediated immunity (directly mediated by T-cells) and Humoral immunity (deficiency in T cells= helper cell impaired too)
The most COMMON cause of SCID- X-LINKED DEFECT leading to an IMPAIRED Common Gamma chain on cytokine receptors.
Another cause of SCID: Cellular Absence of Adenosine deaminase (ADA) or Purine nuceloside phosphorylase (PNP); this disease is AUTOSOMAL Recessive
Both ADA and PNP impairments lead to a deficiency of T-cells and hence decrease in both cell-mediated and humoral immunity
In SCID that is X-linked- you will have mainly ABSENCE of T cells
-IN SCID that is AUTOSOMAL Recessive Variant, you will have absence of B, T, an NK cells.

Question 44

Explain what occurs in DiGeorge Syndrome and clinical findings of the disease.

Answer 44

DiGeorge Syndrome- a Genetic abnormality caused SPONTANEOUS DELETION of a portion of chromosome 22. Because of this deletion, there is NOT proper formation of the THYMUS (among other organs/structures). The affected part of chromosome includes dozens of genes related to development of several systems in the body. Hence when this part of chromosome is Missing, related organs and systems d not develop normally. This results in Decreased/Absent T cell-mediated immune responses

Question 45

What are different forms of treatment for DiGeorge Syndrome?

Answer 45

Forms of treatment for DiGeorge Syndrome:

1. Antibiotic medications to treat infections
2. Calcium supplementation to treat low Calcium levels
3. Ear tubes or hearing aids to improve hearing
4. Occupational therapy to improve developmental and behavioral issues
5. Physical therapy to improve mobility and movement
6. Replacement of missing hormones such as parathyroid hormone, growth hormone, or thyroid hormone
7. Surgery to repair a heart defect, cleft palate or nasal speech.

Question 46

What kind of disorder is Wiskott-Aldrich syndrome and what are the clinical findings present? Discuss how this affects immunoglobulin levels an WASP gene present.

Answer 46

Wiskott-Aldrich Syndrome- X-linked recessive disorder that often presents EARLY in childhood in MALES with Recurrent bacterial infections, Eczema, purpura, epistaxis, and splenomegaly.
in most cases IgM levels are LOW, and IgE and IgA level are ELEVATED. The mutated gene (WASp) has been identified on the short arm of X-chromosome
WASp gene- is expressed solely on hematopoietic stem cells. The protein itself plays an important role in relaying extracellular signals to actin cytoskeleton of the cell. Mutations play a role in regulating the expression of the WASp gene, with more severe mutations resulting in more severe phenotype disease

before treatment (18 months)- child has bruises on face, legs or arms. 
Can be treated with HSCT (hematopoietic stem cell transplant) that repairs the defects after 36 months (clears bruises on child's arm)

Question 47

What is Hyper-Ig M syndrome and what are the clinical findings and treatment? What occurs as a consequence of CD40 ligand deficiency? What type of treatment is used for those with HIGM and why?

Answer 47

Hyper IgM syndrome- immunoglobulin (Ig) deficiency characterized by normal or elevated serum IgM levels and DECREASED Levels of absence of other serum Igs. This results in susceptibility to bacterial infections.
As a consequence of CD40 ligand, the T-lymphocytes in patients with X-linked Hyper IgM (XHIGM), are UNABLE to instruct B-lymphocytes to SWITCH their production of Igs from IgM to IgG, Ig A, and IgE.
The most common form of HIGM syndrome-results from Defect or deficiency of protein found on surface of activated- T lymphocytes
Treatment: Since patients with all forms of HIGM syndrome have severe Ig G deficiency, they require Immunoglobulin replacement therapy.

Question 48

What is HIV? What does it stand for? How do you distinguish it from Aids?

Answer 48

HIV- Human Immunodeficiency Virus- virus that can attack the body’s immune system.
AIDS- (Acquired Immune Deficiency Syndrome)- that occurs once HIV has destroyed immune system and you have a Massive REDUCTION in CD4-T cells and SEVERE infection from pathogens that rarely cause trouble in healthy individuals (OPPORTUNISITC infections).
There are two types of HIV Virues: HIV-1 (came from Chimpanzee; more common) and HIV-1 (came from Monkey, less transmittable).
over the years AIDS cases have decreased (due to effective treatment)

Question 49

Describe what a retrovirus is. What is an integrase?

Answer 49

Retrovirus- RNA Virus
-It uses RNA genome to direct synthesis of DNA intermediate (cDNA by Reverse Transcriptase)
Integrase- INTEGRATES cDNA into Host genome (LTRs; long terminal repeats)- provirus
-It recruits human proteins to replicate
provirus-virus genome integrated in DNA of host cell

Question 50

Differentiate between endogenous retroviruses and exogenous retroviruses?

Answer 50

Endogenous retroviruses- retrovirus-like sequences that are PERMANENTLY part of the human genome
Exogenous retrovirus- when RNA or DNA virus are transmitted from one organism to another. ex: HIV

Question 51

What is the most extensively studied infectious disease?

Answer 51

HIV

Question 52

What type of virus is HIV?

Answer 52

A exogenous retrovirus.

Question 53

What genes are located on LTR (long terminal repeats) ?

Answer 53

Genes located on LTRs:

gag, pol, env, tat, rev, vif, vpr, vpu, nef

Question 54

elaborate on the process of retroviruses incorporating RNA genome into DNA

Answer 54

Retrovirus mechanism:

1. Virion binds to CD4 and co-receptor on T cell
2. Viral envelope fuses with cell membrane and viral genome enters the cell
3. Reverse transcriptase copies viral RNA genome into double stranded CDNA
4. Viral cDNA enters nucleus and integrates into host DNA (provirus)
5. T-cell activation induces some transcription of provirus
6. RNA transcripts are spliced to allow the synthesis of the early protein
7. RNA transcripts are spliced to allow synthesis of the early proteins Tat and Rev.
8. Tat amplifies transcription of Viral RNA. Rev increases transport of RNA to cytoplasm
9. Gag, pol, and Env are made and assembled with viral RNA into virions which bud from the cell.

Question 55

What other functions does the virion HIV have? Differentiate between CCR5 and CXCR4?

Answer 55

HIV infects macrophages, CD4-T cells, and dendritic cells- express CD4 and CCR5

• CCR5- MACROPHAGE trophic (receptor allows entry of M-tropic HIV 1 strains)
• CXCR4- LYMPHOCYTE tropic
• this is a receptor that allows entry of T-tropic HIV strains

Question 56

Describe the timeline of HIV-specific immune response.

Answer 56

HIV-specific Immune response:
Initially, when you have flu-like disease (2-6 weeks_ you will have high number of CD4 T cells and towards the end of period your CD4 T cells drop.
Then during 2-6 weeks, seroconversion occurs: you get a small increase of CD4 T cells, and antibodies are forming in blood due to exposure to virus.
In the period of 10 years: Asymptomatic phase (no symptoms show) and gradual decline of CD4T cells
During symptomatic phase: you have decrease in CD4 T cells.
AIDS- when there is significant decline in CD4 T Cells, causing death.

Question 57

Describe the current trend of hemophilia patients an rate of becoming infected with HIV. What is hemophilia?

Answer 57

HIV infection usually leads to AIDS
Hemophilia- inherited disease in which the blood clots poorly. Hence this disease is treated with intravenous blood transfusions of clotting factors purified by donors of blood. This led to donors also being infected with HIV (through contamination)
however, HIV+ hemophiliacs born before 1943 began to have increasing percentage of people develop AIDS.
Over the years, the HIV+ Hemophiliacs born after 1943 began to decrease rate of having AIDS. Also those that were HIV- with hemophiliac were compared having higher rates of patients NOT develop AIDS
rate of progression of HIV- infected patients to aids increases as you age since the ability of forming new T cells decreases, due to thymic involution.

Question 58

Discuss the benefit of CCR5 deficiency and the how it affects incidence of HIV infection. How did CCR5 deficiency help a patient with AML (Acute myelogenous leukemia)

Answer 58

CCR5 deficiency- people who have cells that do NOT express CCR5 (co-receptor for M-tropic HIV entry) will be able to RESIST infection from HIV.
Caucasian people- 10% heterozygous for deletion variant (mutated allele for CCR5 gene) and 1% for homozygous for the deletion variant.
Only those that are homozygous for deletion variant (CCR5-delta32) are RESISTANT to HIV infection
Patient with AML (Acute Myelogenous leukemia) - needed a hematopoietic stem cell transplant and the bone marrow donor happen to have CCR5 deletion mutant (made them resistant to HIV). After transplant, the patient was able to have immune system composed of hematopoietic cells with no CCR5 receptor, hence HIV in patient had no cells to infect and virus died out. This provided A CURE for patient (transplant from donor cured patient’s HIV infection).

Question 59

Discuss the course of immune response to HIV. What occurs with reverse transcriptase? What is a good target for drugs?

Answer 59

People with HIV infection will develop immune response, but these responses do not eliminate virus.
Retroviruses like HIV have HIGH mutation rates due to reverse transcriptase having no proofreading mechanism and thus enzyme makes errors. Hence, this causes VIRAL VARIANTS to form.
Reverse transcriptase- Good Drug target- as when you inhibit reverse transcriptase, you prevent further infection of human healthy cells.
Also mutation causes re. What is HAAsistance to drugs- which is effective during pregnancy (in order to prevent mothers from transferring HIV to their babies.

Question 60

Elaborate on the time period of gaining an immune response to HIV

Answer 60

In early phase of HIV infection (4-8 weeks), the HIV virus will reach high levels
Within 2-12 years, the production of HIV-specific antibodies( to HIV core protein; or to HIV envelope)and cytotoxic T cells, virus will be CONTROLLED, but NOT Eliminated.
Once, CD4 T cells are being destroyed, that surpasses the renewal of cells, level of virus increases

Question 61

Explain the role of combination therapy. What is HAART used for?

Answer 61

Combination therapy- composed of several antiviral drugs was a method of destroying population viral load and avoiding disease progression. It was a way for destroying populations of viruses before they accumulate mutations to resist drugs.
HAART- Highly active anti-retroviral therapy- began in 1997 aka combination therapy.
Data showed that using active anti-retroviral therapy reduced blood-borne HIV levels to undetectable levels

Question 62

Discuss the process of how antiviral drugs can clear the virus from blood.

Answer 62

Process of anti-retroviral drugs rapidly clearing virus from blood and increasing CD4 t cells.

1. Productive infection of CD4 T cells accounts for more than 99% of virus in plasma (maintain HIV levels)
2. This occurs since infected cells are SHORT-LIVED, So HIV must continually infect new cells
3. If virus production is blocked by a drug, the virus is rapidly cleared from the blood.
4. CD4 T cell numbers will rapidly increase and replace those lost by infection. Hence increase in CD4 t cells.

Question 63

which infections are classified as Opportunistic infections? What does that indicate? What are Latent viruses

Answer 63

Opportunistic infections-infections that occur more often in people with weakened immune systems (than healthy immune system).
Example of opportunistic infections: Parasites, bacteria, Fungi, and Viruses
Latent Viruses- Herpes simplex, Cytomegalovirus, Varicella-zoster

Question 64

What is the important role of Broadly neutralizing antibodies?

Answer 64

Broadly neutralizing antibodies bind to four conserved epitopes of glycoprotein that form VIRAL SPIKE.
The antibodies bind tightly to this spike in order to prevent HIV Virus from infecting human cells and causing disease