Core Immunology - Infections and Immunocompromised (15) Flashcards
Immunocompromised
Disruption of specific defence of an organ/system (humoral/cellular)
Humoral immunity
Antibody led
Cellular immunity
T/B cells
Innate defences
- Skin
- Interferons, complement, lysozyme, acute phase proteins
- Mucous membranes
- Normal commensal flora in gut
How are mucous membranes an innate defence?
Tears, urine flow, phagocytes
Example in the lungs
Cystic fibrosis - goblet cells, much-ciliary escalator
Classification of immunodeficiencies
- Congenital/Primary
- Acquired/Secondary
What is 2nd line of defence?
Neutrophil
What is a qualitative defect of neutrophils?
Lose ability to kill/chemotaxis
What is a quantitative defect of neutrophils?
Less present
Qualitative chemotaxis neutrophil defect
Rare, congenital, inadequate signalling/abnormality in receptors/NE movement
Qualitative killing power neutrophil defect
Inherited, NE fail to mount respiratory burst in phagocytosis, deficient in NADPH oxidase - H2O2 not formed, at risk of staph aureus (Chronic Granulomatous Disease)
Cause of quantitative defects (Neutropenic)
Cancer treatment, bone marrow malignancy, aplastic anaemia caused by drugs
Quantitative defect complications
Over half develop infection - highly lethal (50% pseudomonal infections will die in 24hrs if not treated)
Neutropenic bacterial infections
Gram neg bacilli (E.coli), Gram positive cocci (S.aureus), normal flora (coagulase neg staph)
Neutropenic fungal infections
Candida, Aspergillus
Treatment of neutropenic infections
Gentamicin and antipseudomonal penicllin (cabanpenem then antifungals)
GCSF
Granulocyte stimulating factors - gets immune system working again
Congenital T cell deficiencies
Rare
Acquired T cell deficiencies
- Drugs (ciclosporin after transplantation/steroids)
- Viruses (HIV)
T cell deficiency opportunistic pathogens - bacterial
Listeria monocytogenes (food),
Mycobacteria – MTB, MAI
T cell deficiency opportunistic pathogens - viral
Leukaemia and transplant - HSV, CMV, VZV
T cell deficiency opportunistic pathogens - fungal
Candida, cryptococcus
T cell deficiency protozoan - Cryptosporidium parvum (sporozoa)
Occysts spread by cattle/humans, faecal-oral, recover after 3 weeks (T deficient longer)
T cell deficiency protozoan - Toxoplasma gondii (sporozoa)
Cats/humans infected by contact with cat faeces/transplanted heart with bradyzoites present, lesion in brain/neurological signs (immunocompetent asymptomatic)
T cell deficiency protozoan - Strongyloides sterocoralis (Nematode)
Larvae penetrate skin and migrate, normally asymptomatic/rash, immunocompromised huge invasion of tissues/gram -ve septicaemia as larvae move, suspect in tropical countries/old, picked up on feet - dormant
Hypogammaglobulinaemia
Antibody problems, encapsulated bacteria (S.pneumoniae in resp tract/Giardia lambila/cryptosproidium in GIT)
Congenital Hypogammaglobulinaemia
Rare
Acquired Hypogammaglobulinaemia from
Multiple myeloma, chronic lymphocytic leukaemia, burns
Compliment deficiency
Hereditary and rare, encapsulated bacteria, need complement to help kill organisms, earlier defect in pathway greater number of organisms may infect
Complement deficiency illnesses
Neisseria meningitidis and S.pneumoniae lysis not achieved by MAC/opsonisation (50-60% patient 1 epsiode of disease)
Spleen
Source of complement and antibody producing B-cells, removes opsonised bacteria from blood
Causes of splenectomy
Traumatic, surgical, functional (sickle cell anaemia)
Infections in splenectomy patients
Strep penumoniae, H. influenza type B, N. meningitis, malaria (high mortality - prophylactic penicillin)
Biologics
Antibodies/other peptides, inhibit inflammatory cytokine signals (TNF/T-cell activation/deplete B-cells)
Biologics used for
RA
Biologics increased risk of
TB, Herpes zoster, Legionella pneumophila, Listeria monocytogenes
Organ transplant e.g.
Liver in HCV/paracetamol OD, stem cells in haematological malignancy
Anti-rejection treatment
Suppresses cytoxotic and NK cells
