Lecture 26: Lymphadenopathy and HIV infection Flashcards
What are the causes of lymphadenopathy?
- Proliferation of lymphocytes in response to a local infection
- Proliferation of malignant cells that have metastasized to the node by lymphatic spread
- Proliferation of malignant lymphocytes
- Inflammation within nodes resulting from killing of lymphocytes infected by a virus
How do you investigate lymphadenopathy?
- Look for adjacent infection (i.e boil, cellulitis)
- Look for adjacent cancer (i.e breast, lung, skin)
- Look for features of cell in lymph node
- Look for evidence of an infection that targets lymphoid cells
What test should you perform on a lymphadenopathy?
- Fine needle aspiration of cells from within lymph node and/or excision of lymph node.
- Cytology or histology - are malignant cells present?
What bacteria and virus’ cause infections of lymph nodes?
Bacterial
- S. aureus, mycobacterium TB, others
Viral
- EBV, CMV, HIV, others
Describe the time course of herpes virus infections:
Acute infection followed by:
Latent infection (asymp) with reactivation chronic infection (asymptomatic)
What are some herpes viruses?
HSV - Cold sores
Varicella zoster virus - Shingles
EBV - Glandular fever
CMV - Less severe glandular fever-like illness
= These two are common causes of illness with generalised lymphadenopathy
Describe how acute EBV infection causes common illness:
Glandular fever = infectious mononucleosis
Minor illness as child, more severe illness when adolescent/adult
Virus transmitted in saliva, incubation 4-6 weeks, illness 1-2 weeks usually.
Symptoms = Fever, sore throat, cervical adenopathy, malaise, fatigue
Recovery, but persistent salivary excretion of EBV
Describe how acute EBV can be diagnosed in the lab:
- Lymphocytosis, atypical lymphocytes, abnormal liver function tests.
- Monospot test: Detects heterophile AB which bind pig, horse, sheep RBC but not EBV i.e detects AB that would bind EBV
How is acute CMV diagnosed in lab?
- Lymphocytosis, atypical lymphyocytes, abnormal liver functions
- Detection of AB to CMV
- Detection of CMV in blood
Describe acute HIV infection:
- At risk group
- Recent exposure
- Glandular fever-like illness
- Persistent viraemia and virus in genital secretions
- Presence of antibodies to HIV in blood
Describe the rapid evolution of HIV during infection:
- Continuous production of HIV
- Highly error prone copying HIV RNA by reverse transcriptase
- No-proof reading of errors
- Generation of a very wide range of mutant viruses every day
= Consequently HIV infection can evade immune responses - Infected CD4 t cells are killed by cytotoxic CD8 cells
Describe the diagnosis of HIV infection:
- Detect AB to HIV in blood
a) Screening test = Elisa
b) Confirmatory test = western blot - Detect HIV genome in blood PCR
What is an ELISA?
Enzyme Linked Immunosorbent Assay
- HIV antigen stuck to base of ELISA wells
- Serum sample added - antibody in serum attaches to HIV antigen
- Anti-human antibody with adherant enzyme added - attaches to serum antibody
- Reagent added - cleaved by enzyme on anti-human antibody - results in colour change
Describe the western blot:
- HIV proteins separated by gel electrophoresis
- Proteins transferred from gel to a membrane
- Membrane strips incubated with serum from patients - antibodies in serum attach to separated HIV protein bands
- Human antibodies stained with silver dye
What are the AIDS defining illnesses?
Pneumonia Brain abscess (tox. gondii) Candida albicans Meningitis (Crytococcus neoformans) TB CNS lymphoma