Bacterial infections in the immunocompromised Flashcards by Alice Scholfield

What characteristics of skin make it an effective barrier to pathogens?

low pH
Antimicrobial peptides
Cell sloughing

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What type of epithelium is there in the resp tract

Ciliated epithelium

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How is the urinary tract adapted to protect against pathogens

Urethral sphincter
One way flow
Antimicrobial peptides

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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

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How does the innate immune system kill?

Phagocytosis and intra-cellular killing

- Release of extracellular substances

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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

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In the innate immune system complement, what does C1q bind to to recognise pathogens?

Antibody-antigen complex

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What does mannose binding lectin bind to

Repeating sugars

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What is the main role of the complement system

Adjunct in the defence against extracellular pathogens

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What is opsonisation

Process where microbes are chemically modified and become ‘stuck’ to phagocytes and NK cells

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What complement receptor is involved in opsonisation

C3b

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What phagocyte complement receptor is involved in chemotaxis

C3a

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Which aspect of the innate immune system is an essential component in response to Neissreia species

C5-9

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What cells are involved in recognition within humoral immunity

B cell receptors recognises extracellular antigens

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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

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Where are the receptors on the antibody for phagocytes

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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)

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Which antibody fights off multicellular helminths

IgE

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How do cell mediated immunity recognise pathogens

T cell receptors recognise intracellular antigens presented in MHC molecules

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What cells express MHC-1 molecules? What about MHC-2?

1- all cells

2- antigen presenting cells

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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

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What antigens to MHC-2 molecules present? And to what cells?

Antigens from within vesicles, such as phagocytosed bacteria
Presents to CD4+ cells

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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