HC18: Immune deficiencies and infection risk

Components of host defense

There are 6 components of host defense:

• Immunoglobulins
• T-cells
• Complement system
• Granulocytes
• Macrophages
• NK-cells

Impaired barrier function

There are many causes of an impaired barrier function:

• Literally
  • Wounds
  • Insect bites
  • Penetration of the skin by catheters
  • Skin/mucosal toxicity by cytostatic drugs
• Functionally
  • Urinary catheter, incomplete emptying of the bladder
  • Lack of gastric acid
  • Lack of tears
    • M. Sjörgen, an auto-immune disease
  • Disturbance of normal airway cleaning
    • Intubation, abnormal mucus, ciliary function, coughing, COPD
• Impaired colonization resistance
  • All protecting bacteria are removed
    • Can be caused by antibiotics

Microorganisms:

Various microorganisms can cause an impaired barrier function:

• Literal: the microorganisms that already are on the skin or mucosal membranes
  • Primary pathogens
    • Staphylococcus aureus → skin or nose
      • The most common cause of wound and catheter infection
    • Streptococcus pyogenes → skin or throat
  • Commensal opportunistic pathogens
    • Staphylococcus epidermidis → bowel
      • Cannot cause wound infections, but can cause catheter infections
    • Escherichia coli → bowel
    • Bacteroides fragilis → bowel
    • Clostridium sp. → bowel
    • Streptococcal sp. → throat or vagina
    • Candida albicans → throat or vagina
• Functional
  • Urinary catheter, incomplete emptying of the bladder → escherichia coli
  • Lack of gastric acid → salmonella species, vibrio cholera
  • Lack of tears → haemophilus influenzae, streptococcus pneumoniae
  • Disturbance of normal airway cleaning → streptococcus pneumoniae

Candida infection:

If all protecting bacteria are removed due to impaired colonization resistance, the candida will remain, multiply and cause local diseases, for example thrush ("spruw"). This can be caused by using antibiotics. It also is very common among HIV-patients.

Clostridium difficile:

Clostridium difficile is a gram-positive, anaerobic, rod-shaped bacteria that also survives in cases of impaired colonial resistance. It cannot be wiped out by antibiotics and isn't carried by everyone. When it starts to multiply, it causes pseudomembranous enterocolitis. A pseudomembrane consists of mucus and numerous granulocytes. This can cause the whole bowel to become necrotic.

A solution for such an infection is fecal microbiotica transplantation:

1. A healthy person donates their feces
2. The feces are washed and made into a fluid
3. The feces are transmitted to the bowel via a catheter
4. New and healthy microbiota are infused

This works in 80-90% of the cases.

Complement deficiency

Causes of complement deficiency are mainly genetic:

• Classical pathway
• Alternative pathway
• MB lectin pathway
• Terminal pathway (MAC)

One pathway can comprise for the falling out of the other. However, one is very essential to function correctly:

• Terminal pathway → forms the membrane attack complex (MAC)
  • This can cause MAC Neisseria meningitis and Neisseria gonorrhoea infections

Hypogammaglobulinemia

In case of hypogammaglobulinemia, there is an immunoglobulin deficiency. Causes are:

• Congenital
  • X-linked a-gammaglobulinemia
    • The B-cells are lacking
  • As part of SCID
• Acquired
  • Common variable immunodeficiency (CVID)
    • A gathering term for lack of immunoglobulins
      • Immunoglobulins disappear somewhere in life
      • Unknown causes
  • B-cell malignancies
    • Chronic lymphatic leukemia
    • Myeloma (M. Kahler)

Microorganisms:

Primary pathogens of hypogammaglobulinemia are:

• Capsulated bacteria → give infections very often
  • Streptococcus pneumoniae
  • Neisseria meningiditis
  • Haemophilus influenzae
• Campylobacter
  • Unknown reasons
• Persistent Giardia lamblia
  • A parasite
  • Hard to clear
• Persistent enterovirus infections
  • Can give chronic meningeal encephalitis

Hypogammaglobulinemia should be considered if infections are frequent, persistent, or have a combination of these pathogens.

Spleen disorder

In case of a spleen disorder, there is a deficiency of the entire humoral immune system. Causes or spleen disorder are:

• Asplenia: not having a spleen
  • Congenital
  • Surgical removal
• Functional asplenia
  • Chronic hemolysis syndromes
  • Infarction
  • Other

Microorganisms:

The function of the spleen is to remove things from the blood stream that shouldn't be there. Spleen disorders are often asymptomatic. Various microorganisms can be involved:

• Severe sepsis caused by capsulated bacteria → opsonized bacteria can't be removed
  • Streptococcus pneumoniae
  • Neisseria meningiditis
  • Haemophilus influenzae
• Severe plasmodium infections
  • For example severe malaria

Phagocyte disorder

In case of a phagocyte disorder, there is a deficiency of granulocytes. Causes are:

• Granulocytopenia
  • Cytostatic drugs
  • Immune medicated
    • Drug allergy
    • Auto-immune mediated
      • Antibodies against granulocytes are made
• Granulocyte dysfunction
  • Chronic Granulomatous Disease
  • Chronic glucocorticosteroids

Microorganisms:

Many microorganisms may be involved:

• Same as those associated with defects in the barrier function
  • Staphylococcus aureus → colonization of the nose
    • A primary pathogen
  • Streptococcus pyogenes → colonization of the throat
    • A primary pathogen
  • Staphylococcus epidermidis → commensal skin
  • Escherichia coli → commensal bowel
  • Clostridium sp. → commensal bowel
  • Candida albicans → commensal throat, vagina
• In addition
  • a-hemolytic streptococci → commensals mouth
  • Aspergillus fumigatus → ubiquitous in the environment

Symptoms:

Symptoms of granulocytopenia are:

• Necrotizing gingivitis (necrotic gums)
• Neutropenic enterocolitis (typhlitis)
  • Infection of the caecum
• Aspergillus pneumonia
  • A fungal infection
  • Patients usually cough up sputum
  • Aspergillus resides deep in the throat, in contrast to candida
  • Hyphae are all over the place

Granulocytopenia is acquired via air, where spores are transmitted.

Impaired cellular immunity

In case of impaired cellular immunity, there are problems with the T-cells. This can be:

• Congenital
  • SCID (severe combined immunodeficiency)
  • Other rare diseases
• Acquired
  • HIV infection → decrease of CD4 T-cells
  • Chemotherapy → decrease of all cell counts
  • Use of immunosuppressive drugs → decrease in T-cell function and/or cell counts

Microorganisms:

Various microorganisms can be involved, which nearly all are primary pathogens:

•  Intracellular bacteria
  • Salmonella species
  • Legionella pneumophila
  • Mycobacterium tuberculosis
• Herpes viruses
  • CMV, EBV, HSV, VZV
• Toxoplasma gondii
  • A protozoa which becomes an intracellular microorganism
• Strongyloides stercoralis
  • A hyperinfection
• Pneumocystis jirovecii
  • Common as the first manifestation of HIV infection
  • The only non-primary pathogens