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
Describe the timecourse of HIV infection:
CD4 cells begin to deplete weeks following infection and then stabilise. They then slowly deplete until around 5 years when infection becomes critical and other illness start. If treatment sourced this starts to increase CD4 count.
B cells produce antibodies
CD8 T cells kill infected CD4 cells/.
