Secondary Immunodeficiencies Flashcards
how does aging alter Thymic development of T cells?
decreased thymic output of T cells
how does aging alter homeostasis and function of old T cells in periphery (spleen and lymph node)
in the spleen and lymph nodes, there is: 1. decreased naive T cell pool, because of this, there is a relative increase in memory T cells (bc decreased naive). 2. increased release of TGFbeta and IL-6. 3. decreased DC maturation and Ag presentation 4. increased inflammatory cytokines 5. failure to get armed
how does aging alter T cells in the tissues (skin, gut, lung)
- decreased immune protection 2. decreased proliferation
how does aging alter T cell development in the bone marrow?
- decreased common lymphoid progenitor output 2. decreased ability to self renew 3. increased DNA damage
what are 3 secondary immunodeficiencies that are related to nutrition?
- associated with malnutrition
- associated with zinc deficiency
- associated with vitamin deficiencies
how does malnutrition cause secondary immunodeficiency?
severe protein-calorie malnutrition associated with depression of cell mediated immunity (T cell anergy, low T cell counts, reduced mitogen stimulation)
how does one acquire a zinc deficiency?
low meat consumption, high fiber diet, chronic diarrhea, chronic kidney insufficiencies, weight loss, bulimia, alcoholism, diabetes, psoriasis, hemodialysis
what does vitamin D3 deficiency result in?
higher frequency of inflammatory diseases and lower numbers of natural Treg cells
deficiency in which vitamins reduce cell-mediated immunity?
vitamin A, folic acid, pyridoxine
what are the results of burn associated immunodeficiencies?
- depressed neutrophil function
- macrophage activation
- depressed cell-mediated immunity
why do burn victims have depressed neutrophil function?
exaggerated complement activation triggered by proteases released in injured tissues causes large amounts of C5a that can disturb proper neutrophil chemotaxis and promote MASSIVE GRANULOCYTE ACTIVATION
also burn blister fluids block opsonization (low levels of complement and Ig)
macrophages harvested from burn patients are in a state of activation. what do they produce?
large amounts of IL-1, TNFalpha, IL-6, TGFbeta, prostaglanding E2 (PGE2)
why are burn patients at increased risk of sepsis?
endotoxins can promote cytokine production of IL-1, IL-6, TGFbeta, and PGE2
why do burn victims have depressed cell mediated immunity?
- reduced production of IL-2 upon mitogenic stimulation
- PGE2 released by macrophages/monocytes increase intracellular cAMP in T cells, preventing proliferation
- TGFbeta levels elevated 1 week post injury which is immunosuppressive
why are patients immunodeficient after surgery?
transient depression of mitogenic responses of peripheral blood mononuclear cells, cutaneous hypersensitivity, and Ig production
why does surgery exactly make a pt immunodeficient?
- transient lymphopenia postop (decreased B and T cells)
- release of PGE2 by phagocytes decrease T cell mitogenic response
- blood loss means decreased IL-2 from T cells, decreased MHCII expression, and decreased Ig production
- transfusion reaction?
- anesthesia and painkillers decrease phagocyte and NK functions
when is normalization of immune reactivity restored after surgery?
10 days for T cell mitogenic responses and 30 days for Ig
what does PGE2 do?
decreases T cell mitogenic response
what does blood loss during surgery lead to?
decreased IL-2 by T cells, decreased MHCII expression on APC, and decreased Ig production
how does a splenectomy affect secondary immunodeficiency
they are weakly responsive to bacteria expressing polysaccharide capsules, so they are prone to septicemia
what bacteria commonly cause sepsis in splenectomized patients?
strep pnuemo (50%), H influenziae, and neisseria meningitidis
how does a thymectomy affect secondary immunodeficiencies?
thymectomy after birth seems to have few if any effects on the development of the immune system. because most of the T cells are generated before birth, then after, spleen takes over in making them
what does chronic alcoholism result in (secondary immunodeficiency)
depressed cell mediated and humoral immune responses (zinc deficiency?)
do cannabinoids have impact on immune system?
unclear
do opiates have impact on immune response?
cocaine can impair T cell reactivity but at very high levels
how do bacterial infections affect the immune system?
- mycobacterium infections are shown to induce state of anergy in T cells.
- staph superantigens stimulate nonspecific T cells to cause disease (generalized immunosuppression - d/t Treg activation)
which parasitic infections are associated with a generalized state of immunosuppression?
- trypanosoma cruzi - reduced IL-2 receptor expression on T cells
- toxoplasma
- schistosoma
- leishmania
- plasmodium
how does the measles virus affect the immune system?
- measles virus can produce transient state of immune anergy and lymphopenia
- DC cells have impaired IL-12 production
how do viruses impact the immune system?
do not impose generalized immunosuppression, but more localized immunosuppression for persistence of infection
how does HIV impact the immune system?
depletes CD4 T cells and produces viral proteins for immune evasion that decrease MHC I expression
