Acquired Immunodeficiencies Flashcards
Hallmark of diabetes immunodeficiency
Neutrophil dysfunction. “Bogged down” by high sugar. Poor circulation also decreases delivery.
Type 1 DM is autoimmune, so immune dysregulation is worse than type 2.
Increased risk of which infections w/ diabetes? (7)
Increased risk of pneumonia, influenza, UTI’s, skin infections, Candida (superficial and deep), rhinopulmonary zygomycosis (mucormycosis; especially in pxs w/ ketoacidosis; may see black necrosis on palate), malignant otitis media (Pseudomonas)
Why does pregnancy cause immunodeficiency?
- Progesterone inhibits lymphocyte proliferation
- Uromodulin – pregnancy-specific serum factor which inhibits B cells
- Both B and T cells are inhibited
Increased risk of which infections w/ pregnancy? (9)
- Hepatitis A / B
- Hepatitis E (mortality can approach 20%)
- Influenza – more severe in pregnancy. Tx w/ Tamiflu (Oseltamivir).
- Herpesviruses
- Chlamydia / GC
- Listeria
- Campylobacter – may cause miscarriage.
- Tuberculosis
- UTI
- Malaria – very high mortality. Pregnant women should not travel to endemic areas.
Which 3 infections are more likely to disseminate w/ pregnancy?
Chlamydia, GC, TB
Where is Listeria found?
- Found in foods like cantaloupe, cottage cheese, cold meats.
- Colorado is hotbed for Listeria
- May infect the baby through the placenta.
Protein / Calorie Malnutrition
What type of immunodeficiency?
Low levels of what? (6)
Increased risk of which types of infection?
- Impaired cellular and humoral immunity. Low levels of leptin.
- Low levels of zinc, iron, folate, pyridoxine, and Vit A are especially important.
- 10x increased mortality from pneumonia. 30x increased mortality for gastroentertitis.
Immunodeficiency w/ aging
- Natural decrease called “immune senescence”
- Decrease in size of thymus
- Decrease in suppressor cell function –> increase in auto reactivity.
- Increased risk of latent-virus infection
3 things that increase risk of infection w/ trauma / critical illness
- Trauma / critical illness → Massive release of cytokines causes immune depression
- Massive protein loss and disruption of physical barriers increases risk of infection, especially in burn pxs.
Stress
Immune dysregulation
Increased risk of what? (3)
- Reduced NK cell activity, depressed lymphocyte mitogen response, release of endogenous glucocorticoids
- Increased susceptibility to respiratory tract infection, reactivation of herpes, cancer
3 reasons liver disease may cause immunosuppression
- Shunting of portal blood reduces ability of hepatic Kupffer cells to clear opsonized organisms
- Cirrhotic pxs often have hypocomplementemia
- Reduced hepatic metabolism of endogenous glucocorticoids. Immunosuppressive and may cause gynecomastia.
2 most common infectious complications of cirrhosis
Sepsis and bacterial peritonitis
3 specific / unusual infections that occur w/ liver disease
Cryptococcus, Candida (usually a line infection), and Vibrio vulnificus (salt water; causes deep purple-colored rash after cut)
Why does protein loss cause immunodeficiency?
What causes protein loss? (7)
- Leads to hypogammaglobulinemia.
* May be caused by nephrotic syndrome, IBD, Celiac, massive lymphedema, peritoneal dialysis, burns, or dermatitis
Immunodeficiency from malignant heme problems
B cell problems
T cell problems
What does Hodgkin increase risk of?
- Advanced cancer of almost any type impairs cell-mediated and humoral responses.
- B cell deficiencies occur in multiple myeloma, Waldenstrom’s macroglobulinemia (IgM), CLL, and well-differentiated lymphomas.
- T cell deficiencies occur w/ Hodgkin’s disease and advanced solid tumors
- Hodgkin’s Lymphoma increases the risk of shingles, especially in young people (this should be a sign; also a clue for HIV).
6 viruses that cause immunodeficiency
HIV, CMV, EBV, measles, VZV, HTLV
How does measles cause immunodeficiency?
- Very significant immune suppression, possibly w/ fatal superinfection
- T cell lymphopenia w/ depletion of T-dependent areas of LN’s and spleen
- Cutaneous anergy – T cells do not react
- Diminished Ab production
How does HTLV-1 cause immunodeficiency?
What does it stand for?
- Human T lymphocyte virus
- Retrovirus w/ tropism for transforming CD4 cells. Causes adult T cell leukemia / lymphoma (ATL). Aggressive. Pxs have severe immune defects and opportunistic infections.
Risk of CMV infection
CMV infection in transplant pxs increases risk for opportunistic infections (PJP / aspergillosis) and increases risk of transplant rejection
What 2 types of bacteria can cause immunosuppression?
Superantigens (Staph / Strep) and mycobacteria
How do superantigens cause immunodeficiency?
- Superantigens associated w/ toxin-producing staph and strep. May simultaneously bind MHC class II antigens and non-antigen binding region of T cell receptor → massive stimulation of T cells → inflammatory cytokines → vasodilation similar to septic shock → organ failure.
- After hyperactivation, these T cells become anergic and cannot be activated anymore. Think of them as being “exhausted”.
How does mycobacteria cause immunodeficiency?
- Mycobacteria inhibit ability of infected cell to kill invader. Also prevents coordination of immune response.
- May lead to increased risk of secondary infection.
- May cause false negative of PPD for TB. IFg release assay is better.
How do parasites cause immunosuppression?
Release immunosuppressive factors that inhibit macrophages and induce suppressor T cells.
What 2 infections increase risk for Burkitt’s lymphoma?
Malaria + EBV
Transformation of B cells
How is rheumatology related to immunodeficiency?
4 associated autoimmune diseases
- Immune dysregulation can lead to auto-immunity and increase risk of infection
- Examples – RA, SLE, IBD, granulomatosis w/ polyangiitis (GPA; Wegener’s granulomatosis) all cause immunosuppression, even w/o drugs used to treat these.
What do TNF inhibitors increase risk of?
TNF inhibitors (often used for RA) place a person at risk for granulomatous infections, such as TB and fungal infections
How does renal dysfunction cause immunodeficiency?
What 2 infections should you keep an eye out for in pxs w/ kidney disease?
- Dialysis and uremia reduce T cell function, Ab production, and neutrophil function.
- Protein loss in nephrotic syndrome and peritoneal dialysis may cause hypogammaglobulinemia.
- Look for disseminated histoplasmosis and TB in pxs w/ renal disease.
5 Iatrogenic forms of immunodeficiency
- Glucocorticoids
- Signal transduction inhibitors – cyclosporine, tacrolimus, sirolimus
- Purine synthesis inhibitors – azathioprine and mycophenolate mofetil
- Abs – TNF inhibitors increase risk of granulomatous infections
- Radiation / Toxins – damage hematopoietic cells.
