Acquired Immunodeficiencies

Question 1

Hallmark of diabetes immunodeficiency

Answer 1

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.

Question 2

Increased risk of which infections w/ diabetes? (7)

Answer 2

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)

Question 3

Why does pregnancy cause immunodeficiency?

Answer 3

• Progesterone inhibits lymphocyte proliferation
• Uromodulin – pregnancy-specific serum factor which inhibits B cells
• Both B and T cells are inhibited

Question 4

Increased risk of which infections w/ pregnancy? (9)

Answer 4

• 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.

Question 5

Which 3 infections are more likely to disseminate w/ pregnancy?

Answer 5

Chlamydia, GC, TB

Question 6

Where is Listeria found?

Answer 6

• Found in foods like cantaloupe, cottage cheese, cold meats.
• Colorado is hotbed for Listeria
• May infect the baby through the placenta.

Question 7

Protein / Calorie Malnutrition
What type of immunodeficiency?
Low levels of what? (6)
Increased risk of which types of infection?

Answer 7

• 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.

Question 8

Immunodeficiency w/ aging

Answer 8

• 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

Question 9

3 things that increase risk of infection w/ trauma / critical illness

Answer 9

• 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.

Question 10

Stress
Immune dysregulation
Increased risk of what? (3)

Answer 10

• Reduced NK cell activity, depressed lymphocyte mitogen response, release of endogenous glucocorticoids
• Increased susceptibility to respiratory tract infection, reactivation of herpes, cancer

Question 11

3 reasons liver disease may cause immunosuppression

Answer 11

• 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.

Question 12

2 most common infectious complications of cirrhosis

Answer 12

Sepsis and bacterial peritonitis

Question 13

3 specific / unusual infections that occur w/ liver disease

Answer 13

Cryptococcus, Candida (usually a line infection), and Vibrio vulnificus (salt water; causes deep purple-colored rash after cut)

Question 14

Why does protein loss cause immunodeficiency?

What causes protein loss? (7)

Answer 14

• Leads to hypogammaglobulinemia.

* May be caused by nephrotic syndrome, IBD, Celiac, massive lymphedema, peritoneal dialysis, burns, or dermatitis

Question 15

Immunodeficiency from malignant heme problems
B cell problems
T cell problems
What does Hodgkin increase risk of?

Answer 15

• 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).

Question 16

6 viruses that cause immunodeficiency

Answer 16

HIV, CMV, EBV, measles, VZV, HTLV

Question 17

How does measles cause immunodeficiency?

Answer 17

• 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

Question 18

How does HTLV-1 cause immunodeficiency?

What does it stand for?

Answer 18

• 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.

Question 19

Risk of CMV infection

Answer 19

CMV infection in transplant pxs increases risk for opportunistic infections (PJP / aspergillosis) and increases risk of transplant rejection

Question 20

What 2 types of bacteria can cause immunosuppression?

Answer 20

Superantigens (Staph / Strep) and mycobacteria

Question 21

How do superantigens cause immunodeficiency?

Answer 21

• 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”.

Question 22

How does mycobacteria cause immunodeficiency?

Answer 22

• 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.

Question 23

How do parasites cause immunosuppression?

Answer 23

Release immunosuppressive factors that inhibit macrophages and induce suppressor T cells.

Question 24

What 2 infections increase risk for Burkitt’s lymphoma?

Answer 24

Malaria + EBV

Transformation of B cells

Question 25

How is rheumatology related to immunodeficiency?

4 associated autoimmune diseases

Answer 25

• 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.

Question 26

What do TNF inhibitors increase risk of?

Answer 26

TNF inhibitors (often used for RA) place a person at risk for granulomatous infections, such as TB and fungal infections

Question 27

How does renal dysfunction cause immunodeficiency?

What 2 infections should you keep an eye out for in pxs w/ kidney disease?

Answer 27

• 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.

Question 28

5 Iatrogenic forms of immunodeficiency

Answer 28

• 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.