The Immunocompromised Host Lecture 25 PDF

The Immunocompromised Host Lecture 25 Glenn Patriquin MD  Objectives To review the basics of the innate and adaptive immune system To develop an overview of immune system deficiencies that can lead to infectious diseases Classic features of inflammation:...

The Immunocompromised Host Lecture 25 Glenn Patriquin MD  Objectives To review the basics of the innate and adaptive immune system To develop an overview of immune system deficiencies that can lead to infectious diseases Classic features of inflammation: 1. Rubor (redness) 2. Calor (heat) 2. Tumor (swelling) 3. Dolor (pain)  Why is this important? A patient’s immune status (by deficiencies, past infection, vaccine, etc…) will often completely change the way you think about their clinical presentation Such as … (just for interest)  Why is this important? “Hello, Infectious Diseases?” “I have a post-kidney transplant patient who has Pseudomonas aeruginosa in their urine – you think three days of ciprofloxacin ought to do it?” [anti- rejection drugs] “This healthy 30 year old non-smoker has a non-resolving patchy pneumonia in spite of 4 weeks of antibiotics!” [HIV/AIDS] “This 16 month old has been admitted to hospital 4 times with pneumonia in the past 11 months!” [primary immunodeficiency] “Dog bite in a 56y man who had lymphoma 20 years ago – his bite wound looks ok – I’m going to just keep an eye on it.” [asplenia]  Outline Innate and adaptive immunity – Non-specific defenses – Trained immune system Examples of immunodeficiencies and their related infectious conditions – Primary – Secondary Non-specific Specific Barriers Innate immunity – secretions Macrophage (big eater) Induces cell death of infected or malignant host cells  Do not memorize complement pathways! Complement Just for your understanding – not to memorize! Non-specific Specific  The trained immune system Antibody- mediated (humoral) immunity Cell-mediated immunity Just for your understanding – not to memorize! Review…  Outline Innate and adaptive immunity – Non-specific defenses – Trained immune system Examples of immunodeficiencies and their related infectious conditions – Primary – Secondary Immunodeficiency States  Genetic Deficiencies of components of the immune system result in “gaps” in the defenses. Complement deficiencies: – May occur as a result of lack of any of the complement components. – Causes failure of the cascade. – Loss of early components result in increased Staphylococcal, and Streptococcal infections – Loss of late components results in increased Neisseria infections.  Genetic (cont’d) Defects in Phagocytic Cell Function – These predispose to bacterial infections. – Inability to kill organisms that have been ingested is typical of Chronic Granulomatous Disease. A group of genetic disorders characterized by the inability to form superoxide (O2-) needed to kill organisms in WBC Staphylococci and other catalase- producing organisms tend to cause infections.  Genetic (cont’d) Lymphocyte Function – There is a variety of syndromes where there is deficiency in lymphocytes including Subacute Combined Immune Deficiency (SCID) Genetic defects may result in failure of development of B cells, T cells or NK lymphocytes. Results in a non functional immune system Severity may vary depending on the defect caused by the genes affected – These patients will present with fungal and viral infections, as the maternal immunity transferred at birth wears off. – Live vaccines may cause severe disease  Genetic (cont’d) B Cell deficiencies – Tend to get bacterial infections. T cell deficiencies – Tend to get infection with viruses, especially herpes family, intracellular bacteria, and fungi.  Primary Immunodeficiency Diseases Know these  Secondary/acquired Chemotherapy – Many of these agents affect lymphocytes particularly. – They act by interfering with cell division and, therefore, inhibit regeneration of cells that have a rapid turn over e.g. PMN (neutrophils). – After treatment with these agents, often the numbers of PMN (and other blood cells) will drop and may remain depressed for 1-4 weeks depending on the therapy, during which time there is a greatly increased risk of infection and death (due to neutropenia).  Secondary/acquired (cont’d) Corticosteroids (e.g.prednisone, dexamethasone) – Damp down inflammation by many mechanisms including PMN are unable to migrate to the site of infection Reduced macrophage migration and antigen presentation (also dendritic cells) Reduction in T lymphocytes – decrease antibody responses. Results in increased viral, bacterial and fungal infection  Secondary/acquired (cont’d)  Post Transplant  Commonly used agents include cyclosporinA, tacrolimus and serolimus which inhibit cytokine production and T lymphocyte function.  The result is immunosuppression with a predisposition to infections of T cell deficiency.  Secondary/acquired (cont’d) Splenectomy – Removal of the spleen may be required because of trauma or as part of treatment for malignancies, or other conditions. Rarely, it may be congenitally absent. – The spleen is the main site of production of opsonizing antibody (important for bacteria with capsules). – It removes circulating microorganisms, immune complexes, and old blood cells.  Secondary/acquired (cont’d) Splenectomy (cont’d) – Removal increases the risk of life threatening infection with encapsulated organisms including Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, and also Salmonella and other less common bacteria. – These infections can progress very rapidly from health to death in