Lymphadenopathy and HIV infection

Question 1

causes of lymphadenopathy

Answer 1

Proliferation of lymphocytes in response to a local infection
Proliferation of malignant cells that have metastasised to the node by lymphatic spread
Proliferation of malignant lymphocytes
Inflammation within nodes resulting from killing of lymphocytes infected by a virus

Question 2

Investigation of lympatdenopathy

Answer 2

Look for adjacent infection e.g. boils, cellulitis
look for adjacent cancer e.g. breast, lung, skin
Look at features of cells in lymph node
Look for evidence of infection that targets lymphoid cells

Question 3

common types of bacteria that infect lymph nodes

Answer 3

Staphylococcus aureus

Mycobacterium tuberculosis

Question 4

Common viruses that infect lymph nodes

Answer 4

EBV
Cytomegalovirus (CMV)
HIV

Question 5

common causes of illness with generalised lymphadenopathy

Answer 5

EBV –> glandular fever

CMV –> less severe glandular fever like illness

Question 6

Herpes viruses

Answer 6

DNA virus
Acute infection, followed by:
Latent infection (asymptotic) with reactivation
Chronic infection (asymptomatic)

Question 7

Acute EBV infection

Answer 7

glandular fever / infectious mononucleosis/ kissing disease
Minor illness when acquired as a child
More severe illness when acquired as adolescent / adult
virus transmitted in saliva
Incubation period of 4-6 weeks illness for 1-2 weeks (usually)
Fever, sore throat, cervical adenopathy, malaise, fatigue

Recovery but persistent salivary excretion of EBV

Question 8

Laboratory diagnosis of acute EBV infection

Answer 8

Lymphocytosis (>50% of WBC’s)
Atypical lymphocytes (>10% of lymphocytes)
Abnormal liver function tests
- mono spot test, detects hetrophile antibodies which bind to guniea pig, sheep and horse RBC’s but not to EBV

• Specific EBV serology: detects antibodies that bind to EBV and EBV antigens

Question 9

Laboratory diagnosis of acute CMV infection

Answer 9

Lymphocytosis (>50% of all WBC’s)
Atypical lymphocytes (>10% of all lymphocytes)
abnormal liver function tests
Detection of antibodies (IgM or IgG) to CMV
Detection of CMV in the blood

Question 10

Checklist for HIV infection

Answer 10

Epidimiologic risk for HIV infection
Recent (3-6 weeks previously) exposure
Glandular fever like illness
Persistant viraemia and virus in genital secretions
Presence of antibodies to HIV in the blood

Question 11

Cause of the rapid evolution of HIV during infection

Answer 11

continuous production of HIV (10^9 HIV/day)
Highly error prone copying of HIV RNA by reverse transcriptase
No “proof reading” for errors
Generation of a very wide range of mutant viruses everyday

Question 12

HIV pathogenesis

Answer 12

1. HIV infects T helper cell
2. New HIV is produced, these viruses differ from the infecting viruses
3. Cytotoxic lymphocytes kill those cells they recognise as infected
4. Some virus producing cells are not recognised as infected and produce more virus
5. Other cytotoxic lymphocyte clones recognise these infected cells and kill them
   There is continuous selection pressure exerted by the immune system selecting HIV that is less well recognised by cytotoxic lymphocytes

Question 13

Time course of untreated HIV infection

Answer 13

1. Infection
2. Level of HIV in tissues and blood rises
3. Cytotoxic T lymphocytes kill many HIV producing cells
4. Number of T helper lymphocytes in blood falls
5. Level of HIV in blood falls
6. Killing of infected lymphocytes causes a brief glandular fever like illness
7. B lymphocytes start producing antibodies the HIV
8. Level of HIV remains stable for many years
9. T helper lymphocyte number continues to fall
10. T helper lymphocyte depletion is severe
11. AIDS illness
12. Level of HIV in blood rises further

Question 14

Diagnosis of HIV infection

Answer 14

1. Detect antibodies to HIV in blood
   a) screening test = ELISA
   b) confirmatory test = western blot
2. Detect HIV genome in blood by PCR

Question 15

Describe ELISA

Answer 15

Enzyme linked immunosorbent assay

1. HIV antigen stuck to base of ELISA wells
2. Serum sample added - antibody in serum attaches to HIV antigen
3. anti human antibody with adherent enzyme added - attaches to serum antibody
4. reagent added - cleaved by enzyme on antihuman antibody - results in colour change

Question 16

Western blot test

Answer 16

1. HIV proteins separated (by molecular weight and charge) by gel electrophoresis
2. Proteins transferred from gel to a membrane
3. membrane strips incubated with serum from patients - antibodies in serum attach to separated HIV protein bands
4. Human antibodies stained with silver dye

Question 17

AIDS defining illnesses

Answer 17

Toxoplasmosis gondii = brain abscess 
candida albicans = osteophagitis 
mycobacterium tuberculosis 
Kaposi's sarcoma 
CNS lymphoma 
cytomegalovirus retinitis

Question 18

HIV replication cycle targets for drug treatment

Answer 18

reverse transcriptase e.g AZT, 3CT, tenofovir
Protease e.g. lopinavir, atazanavir
HIV binding e.g. maraviroc
DNA integration

Question 19

Nucleoside analogue reverse transcriptase inhibitors (NRTIS)

Answer 19

a) reverse transcriptase enzyme
b) complementary strand of DNA (white circles)
c) nucleotides added to the complimentary strand
d) single strand of HIV RNA
e) altered nucleotide e.g. AZT blocks elongation of complementary strand