Bacterial infections in the immunocompromised Flashcards
What characteristics of skin make it an effective barrier to pathogens?
low pH
Antimicrobial peptides
Cell sloughing
What type of epithelium is there in the resp tract
Ciliated epithelium
How is the urinary tract adapted to protect against pathogens
- Urethral sphincter
- One way flow
- Antimicrobial peptides
How does the innate immune system recognise pathogens
Pathogen Recognition Receptors such as TLR, C type lectins etc recognise PAMPS
They also express receptors for complement and antibodies
How does the innate immune system kill?
- Phagocytosis and intra-cellular killing
- Release of extracellular substances
Describe the 5 stages of phagocytosis
1- Chemotaxis of phagocyte to microbes 2- Adherence 3- Ingestion of microbes by phagocytes 4- Killing of micobes by enzymes and other chemicals 5- Elimination
In the innate immune system complement, what does C1q bind to to recognise pathogens?
Antibody-antigen complex
What does mannose binding lectin bind to
Repeating sugars
What is the main role of the complement system
Adjunct in the defence against extracellular pathogens
What is opsonisation
Process where microbes are chemically modified and become ‘stuck’ to phagocytes and NK cells
What complement receptor is involved in opsonisation
C3b
What phagocyte complement receptor is involved in chemotaxis
C3a
Which aspect of the innate immune system is an essential component in response to Neissreia species
C5-9
What cells are involved in recognition within humoral immunity
B cell receptors recognises extracellular antigens
What are the 3 main actions of the antibodies produced in humoral immunity?
1- Neutralisation- antibodies block the binding of pathogens/ toxins to cells
2- Complement activation: C1q binds to Ab-Ab complexes
3- Antibody dependent cytotoxicity
Where are the receptors on the antibody for phagocytes
Fc
What are the main roles of humoral immunity
- Preventation of entry of intracellular pathogen (virus, bacteria) into cells
- Enhanced killing of extracellular pathogens (bacteria and fungi, paracites)
Which antibody fights off multicellular helminths
IgE
How do cell mediated immunity recognise pathogens
T cell receptors recognise intracellular antigens presented in MHC molecules
What cells express MHC-1 molecules? What about MHC-2?
1- all cells
2- antigen presenting cells
What antigens do MHC-1 molecules present? And to what cells?
- MHC-1 molecules present antigens from within the cell cytosol (viruses)
- Presents to CD8+ cytotoxic T cells
What antigens to MHC-2 molecules present? And to what cells?
- Antigens from within vesicles, such as phagocytosed bacteria
- Presents to CD4+ cells
What is the action of CD8+ cytotoxic T- cells
Kill cells expressing antigens by perforating the cell membrane and inducing apoptosis
What is the action of CD4+ T helper cells
Mediates the release of TH1, 2 and 17
What is the action of Th1
- Stimulate antigen presenting cells to kill intra-cellular pathogens
What is the action of Th2
- Stimulate B cells to make antibodies
What is the action of Th17
-Stimulating epithelial cells to produce antimicrobial peptides
Which particular pahogens in Th1 involved in?
TB
Salmonella
Leishmania
Toxoplasma
Define a commensal organism
A micro-organism that derives benefit from another organism without causing damage
What is an oppurtunistic pathogen?
Pathogen that is generally only able to cause disease in the setting of a weakened immune system
What is primary immunodeficiency
Immune defect the patient is born with, often due to genetic mutation
How can skin be broken, thus leading to worse immunity
Surgery, cannula, burns, trauma
Which organisms often infect the patient via broken skin
- Skin flora
- Perineal flora
- Environmental, usually by innoculation
How can mucosa be damaged leading to a deficiency immunity
Chemotherapy- leads to mucositis
Broad spectrum abx- leads to altered flora
How can the resp barrier be damaged
Intubation
Which organisms often infect the patient via damaged resp tract
Gram negative organisms
Candida
Name two primary diseases related to phagocyte deficiency or number
- Chronic granulomatous disease
- Defects in neutrophil migration and granule release
Name 3 secondary causes of innate immune defects
- Disease related (AML, aplastic anaemia, diabetes)
- Chemotherapy associated neutropenia
- Impaired neutrophil function- eg corticosteroids
Which antibiotics can be used in the prophylaxis of innate immune defects relating to phagoctes
Quinolones
What is a primary cause of an immune defect affecting the complement system
Defect in function/ number of complement components
Name 2 secondary causes of complement defects
- Eculizumab: a monoclonal abx for C5 (used for acute rejection)
- Autoantibodies in myeloma
A defective membrane attack complex is associated with significantly increased risk of….
Neisseria Meningitidis infectoin (meningococcal meningitis & sepsis)
Name 5 primary immunodeficiencies associated with impared humoral immune response
SCID CVID IgA deficiency HLA Hyper IgM
Name a disease, a surgical procedure, and 2 medications which result in impaired B-cell number/ function?
CLL
Splenectomy
Corticosteroids, rituximab
What is the main risk of humoral immune defects
Extracellular pathogens (bacteria) that have evolved ways of evading phagocytosis and complement
Name 3 encapsulated organisms
- Streptococcus pneumoniae
- Haemophilus influenza
- Neisseria meningitis
Which organisms commonly invade in IgA deficiency
GI pathogens- protozoa (Giardia & Cryptosporidium)
Which organisms commonly invade in IgG deficiency
Encapsulated organisms
Recurrent sino-pulmonary infection
Which type of organisms commonly invade post splenectomy
Encapsulated organisms
Which organisms invade post splenectomy causing a more severe infection
- Capnocytophaga Canimorsus
- Babesiosis
- Malaria
What diseases can cause defects in cell mediated immunity (Seconday cause)
HIV
Malignancy
Name some treatment related causes of cell mediated immunity defects
Anti- rejection medication Steroids anti- TNF Stem cell transplant Radiotherapy
Impact of defects in cell mediated immune defects?
Intracellular
What does HIV target mainly, and what does it have a ‘knock on effect’ on
CD4 cells
Knock on effects to CD8_ and Th2
What aspect of the immune system does Anti-TNF therapy target
Cell mediated immune defects
What does anti-TNF have the biggest impact upon
Macrophage responses to intracellular pathogens
What features of a patient may lead you to suspect that they are immunocompromised?
- Failure to thrive
- IV abx user
- > 4 ear infections in 1/12
- > 2 or more pneumonias in 1/12
- Frequent deep skin/ organ abscesse
- Thrush or cutaneous fungal infection for >6 months
- Two or more deep seated injections, including septicaemia (blood poisoning) within three years
