Acquired Immunodeficiency Flashcards
t/f secondary immunodeficiency is more common than primary
true
conditions associated with secondary immunodeficiency
- immunosuppressive therapy
- microbial infection
- malignancy
- disorders of biochemical homeostasis
- autoimmune disease
- trauma
- environmental exposure
- others
excess amounts of infectious agents / their toxins can cause ___
active immune system -> nonresponsive state
infection of the bone marrow by viral and bacterial organisms can lead to ___
neutropenia or pancytopenia
immunopathogenesis of hiv
- begins with binding of hiv gp120 to cd4 and ccr5 of target cells
- infected cells migrate to lymph nodes
- initial replication and infection of nearby cd4 t cells in lymph nodes
acute phase of hiv
- galt is depleted
- loss of cd4 t cells
- high viremia and immune activation
- 1-6 wks after infection
- nonspecific symptoms
asymptomatic phase of hiv
- clinical latency
- degree of control is determined by levels of cytokines and viral load
symptomatic phase of hiv
- production of anti-hiv cd4 and cd8, and neutralizing anti-hiv antibodies
- immune response evaded by virus
- fever, weight loss, diarrhea, lymphadenopathy, infections
aids phase of hiv
- peripheral cd4 t cell <200 cells/ml
- infections that define aids
- persistent viremia, progressive disease if not treated
- death
hallmark of hiv
within 1st weeks of infection = massive loss of t cells in the galt and progressive loss of cd4 in peripheral blood
mechanisms of hiv to evade humoral immune system
- neutralizing antibody response becomes ineffective once virus mutates
- coats itself with sugars (glycan shield) to prevent antibody binding
- point mutations, insertions, deletions
effect of inflammation on tregs
- tregs: suppress virus-specific cell mediated immune responses
- loss of th17 = loss of galt
- loss of galt = translocation of microbial products into peripheral circulation
inflammation = expansion of tregs, less th17
stages of hiv infection
- viral transmission
- acute hiv infection
- chronic hiv infection: asymptomatic, aids <200 cd4, advanced hiv <50 cd4
distinguishing features of hiv-2
- same natural history as hiv-1
- lower levels of plasma virus
- slower declines in cd4
- longer asymptomatic period
recommended laboratory hiv testing
- sensitive elisa to detect hiv protein p24
- confirmatory: specific western blot or hiv dna pcr
only other viral agent implicated in significant global immunosuppression
measles
- leads to severe and sometimes fatal superinfection
important independent risk factor for severe measles or death from measles
malnutrition
most frequent infectious complications of measles
- pneumonia
- gastroenteritis
- otitis media
- gigivostomatitis
- laryngotracheobronchitis
causes of immune alterations in measles
- direct infection of t cells
- infection of dendritic cells = impaired antigen presenting function and t cell activation
superantigens from bacterial infections bind to ___
mhc class II antigens and non-antigen binding region of tcrv = stimulate large numbers of t cells
how do bacterial infections cause secondary immunodeficiency
- many stimulated t cells -> many inflammatory cytokines -> septic shock
effects of mycobacterial lipids
- inhibit dendritic cell devt and production of cytokines
- macrophages: inhibited tnf-a production
- myeloid cells: produce cytokines
- t cells: inhibited responses and secretion
effects of tb
- cd4 lymphopenia
- lowered cd4/cd8 ratio
- b cell lymphocytosis
- cd8 lymphocytosis
- clinical and radiographic features of more advanced diseases
effects of parasite infestation
- diminished vaccine responsiveness
- susceptibility to infection by other microbes
- delayed graft rejection
- higher rate of various malignancies
- less prone to develop allergy or autoimmune disease
possible mechanisms for causing immune dysfunction (parasites)
read!!
effects of ebv and cmv
- lower cd4, higher cd8 (inverted cd4/cd8 ratio)
- t cells respond poorly to antigens + depressed function
- affects b and t cells = broad based transient immune deficiency
- cd4/cd8 ratios return to normal in 4-6 wks
____ underlies much of predisposition to bacterial and fungal infections in patients with diabetes
neutrophil dysfunction
characteristic infections in dm
- disseminated candidiasis
- mucormycosis
- malignant otitis due to pseudomonas
- burkholderia pseudomallei
host specific factors that predispose diabetics to infection
- hyperglycemia-related impairment of immune response
- vascular insufficiency
- sensory peripheral neuropathy
- autonomic neuropathy
- increased skin and mucosal colonization
impaired immune functions in diabetics due to hyperglycemia
- neutrophil chemotaxis and adherence to vascular endothelium
- phagocytosis
- intracellular bactericidal activity
- opsonization
- cell mediated immunity
major pathway for glycemic damage in diabetics
methylglyoxal glycation
effects of vascular insufficiency in diabetics
- local tissue ischemia
- impaired local inflammatory response
- impaired absorption of antibiotics
effect of autonomic neuropathy in diabetics
urinary retention and stasis = uti
organism-specific factors that predispose diabetics to infection
- glucose inducible proteins promote adhesion of candida
- ketone reductases let rhizopus thrive (mucormycosis)
effects of hemodialysis
- reduced t cell function
- diminished antibody production
- compromised neutrophil and dendritic function
- low expression and/or function of igg fc receptors
examples of immune hyporesponsiveness
- esrd = high levels of il2 receptor = diminished response to il2
- uremic pts = suppress mitogenic response of t cells
- chronic peritoneal dialysis = bacterial peritonitis*
possible mechanisms of immunodeficiency in malnutrition
- low adipocytes = low leptin
- low leptin = reduced t cell response
- weakened barrier mucosa, intestinal malabsorption
- micronutrient deficiencies
effects of malnutrition on immune function
- decreased lymphocyte numbers
- absent dth
- decreased phagocytic activity
- low serum antibody levels
- increased infections
dramatic feature of protein-energy malnutrition
lymphoid atrophy
immune defects in protein-energy malnutrition
read
t/f antibodies in malnutrition are elevated, but they have impaired quality and affinity
true
hematopoietic tumors
read
examples of bacteria that asplenic patients can get
encapsulated bacteria
- s penumoniae
- n meningitidis
- h influenzae
immunizations for patients on elective splenectomy
anti-pneumococcal, anti-hemophilus influenzae, anti-meningococcal at least 2 wks before surgery
defects i the complement system in sle
read
most common quantitative disorder in sle
t cell lymphopenia
disorders of protein loss
read
inflammatory response in trauma
- loss of epithelial barriers
- vasodilation and increased vascular permeability
- cellular activation and increased adhesion toe dnothelia
- neuroendocrine stress response
mechanism of inflammatory response in trauma
systemic inflammatory response syndrome
- activation of monocytes and macrophages (il1, tnf)
effects of burns
- depressed cd4 %
- reduced t cell helper activity (reduced il2)
- depressed neutrophil function
causes of immunodeficiency in newborns
- secondary lymph organs not mature
- no memory cells
- innate immunity*
causes of immunodeficiency in aging
- decreased ability to clear infections
- decline in hematopoietic tissue in marrow
- defects in dna
t/f depressed cellular immunity during pregnancy is assumed to have a survival benefit
true
effects of stress
- increased rates of rti
- reactivation of herpes virus
- increased cancer
- reduced nk cell activity
- depressed lymphocyte mitogen responses
other environmental conditions that can cause immunosuppression
- confinement, isolation, sleep-cycle alterations
- acute sleep deprivation
- prolonged bedrest
- chronic hypoxia
adverse consequence of medical intervention
read
