Acquired Immunodeficiency Flashcards
Acquired Immunodeficiency
Defects in the immune system not arising from genetic abnormalities, but from infections, nutritional deficencies, other medical conditions or treatments, or external stimuli
Etiologies of acquire immune deficiency
- 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)
Disorders of biochemical homeostasis
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)
Diabetes Mellitus (biochemical homeostasis)
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
Dialysis and uremia (biochemical homeostasis)
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
Cirrhosis (biochemical homeostasis)
liver dysfunction- greater risk of bacterial sepsis and peritonitis; etiology higher endogenous glucocorticoids and low complement levels (complement made in liver)
Disorders of Protein loss
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)
Nephrotic syndrome (protein loss)
Significant protein loss leading to low IgGs as well as depressed cellular immunity due to loss of vitamin D and other serum factors
Treatment with nephrotic syndrome
immunosuppressive drugs, glucocorticoids
Infectious complications of nephrotic syndrome
recurrent respiratory tract infections, UTIs, pritonitis, and sepsis particularly with ENCAPSULATED BACTERIA such as streptococcus pneumonia. Varicella problematici n patients requiring immunosuppression
Peritoneal dialysis (protein loss)
Can have protein loss if on peritoneal dialysis for chronic renal disease leading to low Ig.
Protein losing enteropathies (protein loss)
Include inflammatory bowel disease, celiac disease, intestinal lymphangiectasia. All through GI tract
Trauma
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
Burns (trauma)
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
Environmental exposures
Ionizing radiation, UV radiation, tooxic chemicals
Ionizing radiation (Environmental exposures)
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)
Ionizing radiation leading to dose-dependent decline in peripheral blood lymphocyte counts leads to
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
UV Radiation
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
Splenectomy/hyposplenism etiology
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)
Splenctomy/hyposplenism risks
Risk of sepsis with encapsulated organisms. Can be fatal, children>adults, management=immunization prior to splenectomy if possible) plus consideration of abx prophylaxis
Normal life stages and events (pregnancy) characteristics
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
Normal life stages and events (Stress)
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
Infections (Non-HIV)
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)
Measles (infections)
Significant morbidity and mortality world wide. Much of M&M due to SIGNIFICANT IMMUNE DEPRESSION which leads to SUPERINFECTION
Most frequent complications of measles
pneumonia, gastroenteritis, otitis media, ginivostomatitis, and other URIs
Super fections often with common respiratory viruses, staphylococcus aurea or strep pneumonia
***Immune alterations induced by measles
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
Herpes viruses
Infections can cause transient depression of cell-mediated immunity; especially noted with CMV. Herpes persistence has also been implicated in immunosenescence
Parasites (malaria)
IMMUNE SUPPRESION from protozoan infection is more pronounced than any other class of microbe (excluding HIV)
***Malaria leads to
Decreased cell-mediated immunity with subsequent increased susceptibility to infections by other microbes, delayed graft rejection, and higher rate of carious malignancies
Malaria mechanism
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
Superantigens
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
