Acquired Immunodeficiency

Question 1

Acquired Immunodeficiency

Answer 1

Defects in the immune system not arising from genetic abnormalities, but from infections, nutritional deficencies, other medical conditions or treatments, or external stimuli

Question 2

Etiologies of acquire immune deficiency

Answer 2

1. Disorders of biochemical hoemostasis (diabetes, dialysis/uremia, cirrhosis) 2. Disorders of protein loss (nephrotic syndrome, dialysis, protein losing enteropathies) 3. trauma/burns 4. environmental exposures (radiation, chemical) 5. splenectomy/hyposplenism 6. life events (pregnancy, stress) 7. Infections (in addition to HIV)

Question 3

Disorders of biochemical homeostasis

Answer 3

Disorders leading to chronic imbalance in hormones, nutrients, and toxic metabolic waste products in body fluids; may have significant effects on the function of one or more components of the immune system (ex. DM, dialysis and uremia, cirrhosis)

Question 4

Diabetes Mellitus (biochemical homeostasis)

Answer 4

Leads to decreased neutrophil function (directly related to the level of hyperglycemia/high blood glucose); Poor peripheral circulation increases risk of skin ulceration (higher risk of infected lesion, decreased delivery of neutrophils to sites; usual infectious complications of DM include disseminated candidiasis/yeast and other fungi

Question 5

Dialysis and uremia (biochemical homeostasis)

Answer 5

Hemodialysis-reduced T-cell function and Ig production, compromised neutrophil and dendritic function

CAPD: Chronic ambulatory peritoneal dialysis-no significant systemic immune defects, but changes in peritoneum, peritoneal neutrophil function depressed due to removal of opsonic factors (immunoglobulin and complement) with the dialysate. Presence of a foreign body increases risk of infection

Question 6

Cirrhosis (biochemical homeostasis)

Answer 6

liver dysfunction- greater risk of bacterial sepsis and peritonitis; etiology higher endogenous glucocorticoids and low complement levels (complement made in liver)

Question 7

Disorders of Protein loss

Answer 7

Nephrotic syndrome (loss through kidneys/urine), protien losing eneropathies (loss through GI tract/stool), severe dermatitis, peritoneal dialysis (in this category too), any disease process with increased protein loss can lead to hypogammaglulinemia, often present as low IgG and IgA, sometimes near normal IgM, antibody levels present in low titer (patient may not have increased susceptibility to infection)

Question 8

Nephrotic syndrome (protein loss)

Answer 8

Significant protein loss leading to low IgGs as well as depressed cellular immunity due to loss of vitamin D and other serum factors

Question 9

Treatment with nephrotic syndrome

Answer 9

immunosuppressive drugs, glucocorticoids

Question 10

Infectious complications of nephrotic syndrome

Answer 10

recurrent respiratory tract infections, UTIs, pritonitis, and sepsis particularly with ENCAPSULATED BACTERIA such as streptococcus pneumonia. Varicella problematici n patients requiring immunosuppression

Question 11

Peritoneal dialysis (protein loss)

Answer 11

Can have protein loss if on peritoneal dialysis for chronic renal disease leading to low Ig.

Question 12

Protein losing enteropathies (protein loss)

Answer 12

Include inflammatory bowel disease, celiac disease, intestinal lymphangiectasia. All through GI tract

Question 13

Trauma

Answer 13

Impact on immune system varies with degree of injury etc. Mechanism initiating cascade of immune effects is massive release of INFLAMMATORY CYTOKINES (IL-1, TNF) due to widespread activation of monocytes and macrophages by products of cellular necrosis

Question 14

Burns (trauma)

Answer 14

Greater immune suppression than mechanical trauma, even when the extent of injury is similar. In addition to defects seen in non-burn trauma, burns disrupt a relatively large area of nonspecific defense (skin)=increased loss of fluids/proteins, by various mechanism increased risk of infection

Question 15

Environmental exposures

Answer 15

Ionizing radiation, UV radiation, tooxic chemicals

Question 16

Ionizing radiation (Environmental exposures)

Answer 16

x-rays, gamma rays=damages DNA leading to impaired cell division (somatic mutations may be expressed-> Impaired immune function, may induce apoptosis in susceptible lymphocytes, may impair function of cellular proteins that regulate cell division (p53 tumor suppressor gene) leading to malignant cell growth.

INCREASED SUSECPTIBILITY TO INFECTION ALSO DUE TO DAMAGED LOCAL BARRIERS (I.e. areas with high rates of cell division (gut>skin)

Question 17

Ionizing radiation leading to dose-dependent decline in peripheral blood lymphocyte counts leads to

Answer 17

B-cells>T-cells, Tissue (nodes, speen) affected, impacts lymphocyte homing and recirculation, T-cell numbers recover more rapidly than B-cells, primary antibody responses diminished, Most functions of mature, long lived phagocytic cells (relatively radiation resistant

Question 18

UV Radiation

Answer 18

ultraviolet B radiation exposure is the major determinant of risk for skin cancer; chronic sun exposure leads to diminished function of all skin resident immune cells

Question 19

Splenectomy/hyposplenism etiology

Answer 19

Congential aspelnia; trauma or s/p splenectomy; atrophy/non-functional spleen (sickle cell disease/functional asplenia (autoimmune disease, severe celiac disease, inflammatory bowel disease, chronic graft vs. host disease, untreated HIV infection)

Question 20

Splenctomy/hyposplenism risks

Answer 20

Risk of sepsis with encapsulated organisms. Can be fatal, children>adults, management=immunization prior to splenectomy if possible) plus consideration of abx prophylaxis

Question 21

Normal life stages and events (pregnancy) characteristics

Answer 21

Higher incidence of infections dependent upon cellular immunity for their control (Hep A and B, influenza, herpes virus, chlamydia, listeria, camplobacter, tuberculosis, and severe fungal, protozoan and helminthic infections.

Depressed cellular immunity during pregnancy: “survival benefit” by reducing the likelihood of maternal rejection of the fetus which contains potent alloantigenic stimuli derived from the father

Question 22

Normal life stages and events (Stress)

Answer 22

Major life stresses (school, etc.) associated with higher rates of URIs, reactivation of herpesvirus infections, and increased incidence of cancer.

DIMINISHED CELLULAR IMMUNE FUNCTION decribed in post-traumatic stress disorder; REDUCED NTK cell activity, and depressed LYMPHOCYTE MITOGEN RESPONSES in stressed individuals

Question 23

Infections (Non-HIV)

Answer 23

HIV major etiology of acquired immune deficiency in world today, but other infections impact host immmunity to a lesser extent (measlea, herpes, parasitic infections, bacterial infections)

Question 24

Measles (infections)

Answer 24

Significant morbidity and mortality world wide. Much of M&M due to SIGNIFICANT IMMUNE DEPRESSION which leads to SUPERINFECTION

Question 25

Most frequent complications of measles

Answer 25

pneumonia, gastroenteritis, otitis media, ginivostomatitis, and other URIs

Super fections often with common respiratory viruses, staphylococcus aurea or strep pneumonia

Question 26

***Immune alterations induced by measles

Answer 26

T-cell lymphoneia with deltion of T-dependent areas of lymph nodes and spleen; dimihsed in vitro T-cell proliferation with mitogens or alloantigens; diminished antibody production; Effectrs by direct infection of T-cell and dendritic cells by measels virus=impaired antigen present/accessory function in T-cell activation

Question 27

Herpes viruses

Answer 27

Infections can cause transient depression of cell-mediated immunity; especially noted with CMV. Herpes persistence has also been implicated in immunosenescence

Question 28

Parasites (malaria)

Answer 28

IMMUNE SUPPRESION from protozoan infection is more pronounced than any other class of microbe (excluding HIV)

Question 29

***Malaria leads to

Answer 29

Decreased cell-mediated immunity with subsequent increased susceptibility to infections by other microbes, delayed graft rejection, and higher rate of carious malignancies

Question 30

Malaria mechanism

Answer 30

Plays a role in EBV-associated Burkitt’s lymphoma in africa. The parasite inhibits the ability of Cytotoxic t cells to maintain EBV transformed B cells under control leading to lymphomas

Question 31

Superantigens

Answer 31

staphylococci and streptococci; Lead to significant immune stimulation, but T-cells eventually decrease in number and exhibit decreased activity. Neutrophil function, specifically opsonophagocytosis, is decreased