Card Set Information
What pathogens are normally found in the neutropenic patient
Neutrophil count less than 0.5x10
, or less than 1x10
Fever develops in almost all patients
S.Aureus, enterococci, E.coli and especially fungi
Define chronic granulomatous disease
An X-linked inherited cause of innate deficiency
Defect in NADPH oxidase = reduced O2 radical production in macrophages
Causes recurrent gram +ve and fungal infections
What is the significance of lymphopenia?
It affects humoral immunity as well as adaptive
Leads to infection by most types of pathogen
Why does a splenectomy cause immunodeficiency?
Splenic macrophages eliminate non-opsonised microbeds, including encapsulated organisms
Site of primary Ig response
All phagocytic cells impaired
When did HIV arise in the human population?
What is the wordwide and national epidemiology of HIV?
Small IVDU population, mainly found in london
MSMs largest population in UK
Heterosexual disease in other counties, especially africa
Outline common presentations of HIV infection
Oral hairy leukoplakia (EBV infection)
List some characteristics of AIDS?
CD4:lymphocyte ratio >0.15
Polycystic pneumonia (P.jirovecii)
Outline the genome of HIV virus and its replication in cells
Integrated into T4 host lymphocyte chromsome, causing latent infection and incurability. Also infects macrophages and dentritic cells
What processes can HIV antivirals inhibit?
Entry into cell via CCR5 receptor
Envelope fusion with membrane via GP41
Reverse transcription via reverse transcriptase
Chromosome entry via integrases
Replication via nucleotides
What characteristics of HIV make it difficult to treat?
Most enzymes used for replication are cellular not viral
Reverse transcriptase has a high mutability; inhibits treatments
What is HAART?
Highly active anti-retroviral therapy
A regimen of 3 or more drugs used to treat HIV
What problems imitate HIV drug resistance?
Insufficient drug dosage
Weak antiviral regimen
Drug interactions reducing half life
Pregnancy (changes metabolism)
What resistance tests for HIV are available?
: Virus grown in changing concentrations of drugs. Expensive and lengthy
: Multiple RT-PCR primes used to sequence protease, RT, integrase or envelope genes
Give examples of immunosuppresants
What is the mechanism of action of azathioprine? What are its adverse affects?
Prevents DNA synthesis, especially in lymphocytes, causing apoptosis
What is the mechanism of action of glycophenolate mofetil? What are its indications?
Inhibits purine biosynthesis and so lymphocyte proliferation (other cells can scavenge purines)
Transplantation and vasculitis
What is the mechanism of action of methotrexate?
Inhibit folate synthesis to prevent thymine/purine synthesis
Define a biologic therapy
A medication tailored specifically to target an immune or genetic mediator of a disease
Give examples of some biologic therapies
What is the mechanism of action of rituximab?
Regulates immunosuppression by inducing B cell apoptosis via CD20 binding
What is the mechanism of action of cyclosporine?
Inhibits calceneurin pathway, preventing calcium metabolism and influx into nucleus
Prevents IL-2 transcription (lymphocyte chemokines)