Block E Lecture 4: Immunodeficiency

Question 1

What is a primary immunodeficiency?

Answer 1

An inherited genetic defect in the immune system
(Slide 3)

Question 2

What is a secondary immunodeficiency?

Answer 2

Loss of immune function due to exposure from an external agent
(Slide 3)

Question 3

What is an example of secondary (acquired) immunodeficiency?

Answer 3

Acquired immunodeficiency syndrome (AIDS)
(Slide 4)

Question 4

What does AIDS result from?

Answer 4

Infection with the Human Immunodeficiency Virus (HIV)
(Slide 4)

Question 5

What is HIV?

Answer 5

A retrovirus that establishes a chronic infection that slowly progresses to AIDS
(Slide 4)

Question 6

What cell is a major source of HIV replication?

Answer 6

Activated CD4 T cells
(Slide 6)

Question 7

Does HIV kill off cells it infects?

Answer 7

Yes
(Slide 6)

Question 8

What does HIV killing off activated CD4 T cells result in?

Answer 8

A severe immunodeficiency
(Slide 6)

Question 9

Other than activated CD4 T cells, what other cells can HIV infect?

Answer 9

Other cells expressing CD4, such as macrophages, dendritic cells and brain microglial cells
(Slide 6)

Question 10

What is the first step of HIV infecting an activated CD4+ T cell

Answer 10

The virus particle binds to CD4 and then CXCR4 or CCR5 chemokine co-receptors
(Slide 8)

Question 11

What happens after the HIV virus particle binds to CD4 and then either CXCR4 or CCR5?

Answer 11

The viral envelop fuses with the cell membrane allowing a nucleocapsid containing viral genome and enzymes to enter the cell
(Slide 8)

Question 12

What happens after the HIV viral envelop fuses with the cell membrane allowing a nucleocapsid containing viral genome and enzymes to enter the cell?

Answer 12

The viral genome and enzymes are released following removal of core proteins
(Slide 8)

Question 13

What happens after the viral genome of HIV is released following removal of core proteins?

Answer 13

Viral reverse transcriptase catalyses the reverse transcription of ssRNA forming RNA-cDNA hybrids
(Slide 8)

Question 14

What happens after reverse transcription forms RNA-cDNA hybrids of the HIV genome?

Answer 14

The original RNA template is partially degraded by ribonuclease H, and then a second DNA strand is synthesised to yield HIV double-stranded DNA
(Slide 8)

Question 15

What happens after double-stranded HIV DNA is created?

Answer 15

The viral double stranded DNA is translocated to the nucleus and is integrated into the host chromosomal DNA by the viral integrase enzyme
(Slide 8)

Question 16

What is a provirus?

Answer 16

A form of virus integrated into the genetic material of a host cell
(Slide 9)

Question 17

What is the first step of the activation of the provirus of HIV?

Answer 17

Transcription factors stimulate transcription of proviral DNA into genomic ssRNA and after processing, into several mRNAs
(Slide 9)

Question 18

What happens in the activation of the provirus of HIV after the proviral DNA is transcribed into mRNA?

Answer 18

The viral RNA is exported to the cytoplasm
(Slide 9)

Question 19

What happens in the activation of the provirus of HIV after the viral RNA is exported to the cytoplasm?

Answer 19

Host-cell ribosomes catalyse the synthesis of viral precursor proteins which are then cleaved into viral proteins by a viral protease
(Slide 9)

Question 20

What happens in the activation of the provirus of HIV after viral proteins are created by host-cell ribosomes?

Answer 20

HIV ssRNA and proteins assemble beneath the host-cell and gp41 and gp120 are inserted into the host-cell membrane
(Slide 9)

Question 21

What happens in the activation of the provirus of HIV after gp41 and gp120 are inserted into the host membrane?

Answer 21

The membrane buds out, forming the viral envelope
(Slide 9)

Question 22

What happens in the activation of the provirus of HIV after the host cell’s membrane forms the viral envelope?

Answer 22

Release viral particles complete maturation and remaining precursor proteins are cleaved by viral protease present in viral particles
(Slide 9)

Question 23

Does HIV have a lipid bilayer?

Answer 23

Yes
(Slide 10)

Question 24

How many copies of an RNA genome does HIV have?

Answer 24

2
(Slide 10)

Question 25

How many structural and regulatory genes does HIV’s RNA genome contan?

Answer 25

3 structural and 6 regulatory genes
(Slide 10)

Question 26

What do the structural and regulatory genes in HIV’s RNA genome encode?

Answer 26

The proteins necessary for the infection and replication of the host cells
(Slide 10)

Question 27

What do HIV variants do?

Answer 27

They bind different chemokine receptors
(Slide 12)

Question 28

What grants resistance to the HIV infection?

Answer 28

A genetic deficiency of the co-receptor CCR5
(Slide 12)

Question 29

How can dendritic cells transfer HIV to CD4 T cells?

Answer 29

Intraepithelial dendritic cells bind HIV using DC-sign, which internalises HIV into early endosomes.
The dendritic cells that have migrated to the lymph nodes then transfer HIV to CD4 T cells
(Slide 13)

Question 30

What are the 3 phases of HIV infection?

Answer 30

Acute phase
Asymptomatic phase
AIDS
(Slide 14)

Question 31

How long after infection are anti-HIV antibodies detected?

Answer 31

Within 2 months
(Slide 14)

Question 32

How long can the asymptomatic phase of HIV last?

Answer 32

Years
(Slide 14)

Question 33

What is the viral set point?

Answer 33

The immune response acts to control the virus
(Slide 14)

Question 34

What happens in the acute phase of HIV progression?

Answer 34

The amount of viral copies in the blood rapidly increases and starts to reduce CD4 T cell numbers quickly
(Slide 14)

Question 35

What does the viral set point do to HIV?

Answer 35

It significantly reduces the number of viral copies of HIV in the blood - but doesn’t eliminate it completely, this starts the asymptomatic phase
(Slide 14)

Question 36

What occurs during the asymptomatic phase of HIV progression?

Answer 36

CD4 T cell levels continue to lower but slowly this time, asymptomatic as CD4 T cells are still at a high enough level for the body to function.
Number of viral copies in the blood start to slowly increase, correlating with the slow fall of CD4 T cell levels
(Slide 14)

Question 37

When does HIV move into the AIDS phase of HIV progression?

Answer 37

When CD4 T cell levels fall to the point that the body’s immune system cannot function properly
(Slide 14)

Question 38

What occurs after HIV has moved into the AIDS phase of HIV progression?

Answer 38

CD4 T cell levels start to rapidly fall to the point they almost hit 0, while viral copies in the blood start to rapidly increase, the host eventually dies due to not being able to fend of opportunistic infections
(Slide 14)

Question 39

What 2 things do drugs that block HIV replication lead to?

Answer 39

A rapid decrease in titer (concentration) of infectious virus cells and an increase in CD4 T cells
(Slide 16)

Question 40

What does anti-retroviral therapy (ART) focus on?

Answer 40

Inhibiting HIV replication and disease progression
(Slide 16)

Question 41

How can HIV become resistant to drugs?

Answer 41

As during the course of infection HIV can accumulate many mutations, which can generate variants of enzymes and other viral proteins that render the virus resistant to drugs
(Slide 17)

Question 42

What method is used to try and counteract HIV/AIDS becoming resistant to drugs?

Answer 42

Different combinations of drugs are taken
(Slide 17)

Question 43

Does a vaccine for HIV exist?

Answer 43

No
(Slide 17)