Immunodeficiency and HIV

Question 1

What are the 4 main components of the immune system?

What happens if one of these is compromised?

Answer 1

T cells, B cells, phagocytes, complement

The immune defence will be severely compromised if one or more components is absent or deficient.

Question 2

What is immunodeficiency restricted to?

What indicates it?

Answer 2

Usually restricted to part of the immune system leading to increased susceptibility.

Occurrence of a repeated or unusual infection indicates it.

Question 3

What is the definition of immunodeficiency?

Answer 3

A disease that is the result of loss of function (or defective function) of a component of the immune system. It can be due to the absence of that component.

Question 4

What are the two types of immunodeficency?

Answer 4

1. Primary = genetically determined

2. Secondary = acquires, caused by a disease of immunosuppressive treatment

Question 5

Give the main causes of primary immunodeficiency?

Answer 5

Genetic:

• Autosomal
• X-linked chromosome
• Gene deletions/rearrangements

Biochemical or Metabolic:

• Adenosine deaminase deficiency
• Purine nucleoside phosphorylase deficiency
• Lack of development in immune cells

Question 6

Primary immunodeficiency:

Give the 4 main defects that can occur in complement and explain what they can cause

Answer 6

Classical pathway deficiencies e.g. c1qrs, C3 or C4:

• Leads to immune complex disease when the antigen-antibody complex cannot be removed from the pathogen.
• Susceptibility to encapsulated organisms

C3 deficiency:
- Opsonisation becomes defective so less removal by phagocytosis

Alternative pathway deficiencies

• Low C3b levels
• Do not get immune complex disease because there are no antibodies. You need antibodies to get the immune complex disease which you do not have in the alternative pathway

MAC complex deficiency:

• Inability to lyse bacterial cells
• Recurrent infections occur
• Antibody immunity is not affected

Question 7

Primary Immunodeficiency:

What are the two ways that phagocytosis can become deficient?

Answer 7

1. Congenital abnormalities = direct problem with phagocytosis due to differentiation, chemoattraction and intracellular killing
2. Secondary extrinsic defects results from antibody/complement deficiencies i.e. defect in opsonisation

Question 8

Primary Immunodeficiency:

What are the 3 ways that phagocytosis can become deficient?

Answer 8

1. Stem cell differentiation
   - too few neutrophils
   - leukocyte adhesion disease (lack of cd18 required for the neutrophils to get recruited)
2. Phagocytosis
   - lack of fusion of phagosome with lysosomes
3. Defective intracellular killing
   - deficient in NADPH system required for oxygen radicals
   - lack of oxygen radicals means increased bacterial and fungal infections

Question 9

Primary Immunodeficiency:

What are the 3 ways that the humoral B cells can be deficient?

Answer 9

1. Few or no mature B cells
   - blockage in the maturation
   - normal T cells
2. Common variable immunodeficiency
   - IgG or IgA deficiency
   - Either B cells do not undergo differentiation or T cell signalling is defective
3. B cells do not switch antibody classed from IgM
   - little or no IgG in circulation

Question 10

Primary Immunodeficiency:

What are the 3 defects in T cells?

Answer 10

1. Lack of developed thymus
   - Lack of T cells and abnormal B cell immunity
2. Stem cell defect or death of developing T cell
   - SCID (severe combined deficiency syndrome)
   - Defect in gamma chain so no T cell development
3. MHC 2 deficiency
   - No mature CD8 T cells
   - apc function low, no antibodies produced
   - death by 5 years old due to bacterial and viral function
   - bone marrow transplant needed

Question 11

What are the clinical signs of immunodeficiency?

Answer 11

• Chronic infection
• Recurrent infection
• Unusual microbial agents
• Incomplete response to treatment
• Skin lesion
• Diarrhoea
• Recurrent abscesses
• Autoimmunity

Question 12

What can cause secondary immunodeficency?

Answer 12

• Therapeutic drugs
• Infection
• Metabolic disorders
• Chronic infections
• Malnutrition
• Burns/trauma

Question 13

What causes AIDS?

Explain the structure of this virus

Answer 13

HIV

Virus is enveloped, has spikes with gp120 which is the outer part of the protein, on the inside is gp41 and together they are gp160. Has a central core containing the RNA. It as 3 main parts; integrase, protege and a reverse transcriptase to help replicate in the cell.
HIV has only 9 genes but can overcome a whole immune system.

Question 14

What happens when HIV comes in contact with the epithelial cell?

Answer 14

HIV binds to epithelial cell but doesn’t make new virus.
Few molecules on surface of epithelial cells which the HIV binds to and anchor it.

Capture of HIV by dendritic cell (langerhan cell). It binds to HIV and takes it in to the submucosa.

Question 15

When the dendritic cell takes HIV to the thymus,

what happens and what receptors are involved?

Answer 15

T cell/macrophage molecules are bound by gp120 in the HIV envelope.

They two main receptors and CD4 and then co-receptors which are CCR5 for marcophage and CXCR4 for T helper cell.

(HIV targets the CD4 T cells and kills them so they can’t protect.

On macrophages you have CCR5 receptor and CXCR4 is on the T helper cell)

Question 16

What happens once HIV has bound to CD4?

Answer 16

Viral envelope fuses with the T cell membrane and releases the gene content.
Reverse transcriptase then converts the HIV RNA into cDNA and this DNA will integrate into the genome.

An infection comes along and this activates the HIV DNA as it has similar promotor regions to the human genome. HIV is made.

The enveloped protein is made and accumulates on the inside of the T cell membrane and it buds out.

Most of the HIV is human membrane as it buds from the host cell so hides it from the immune system. Has a single protein sticking out

Question 17

What happens to CD4 cells when HIV is present?

Answer 17

They all die off (viral DNA inserted and explodes out the T cell). It affects the mucosal T cells the most.

Question 18

When does AIDS occur?

Answer 18

When the CD4 cell level becomes 0.

Question 19

What are typical signs of HIV?

Answer 19

Fever
Weight loss
Mouth sores
Liver enlargement 
Skin rash
Vomiting
Headaches