Secondary Immunodeficiencies

Question 1

how does aging alter Thymic development of T cells?

Answer 1

decreased thymic output of T cells

Question 2

how does aging alter homeostasis and function of old T cells in periphery (spleen and lymph node)

Answer 2

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

Question 3

how does aging alter T cells in the tissues (skin, gut, lung)

Answer 3

1. decreased immune protection 2. decreased proliferation

Question 4

how does aging alter T cell development in the bone marrow?

Answer 4

1. decreased common lymphoid progenitor output 2. decreased ability to self renew 3. increased DNA damage

Question 5

what are 3 secondary immunodeficiencies that are related to nutrition?

Answer 5

1. associated with malnutrition
2. associated with zinc deficiency
3. associated with vitamin deficiencies

Question 6

how does malnutrition cause secondary immunodeficiency?

Answer 6

severe protein-calorie malnutrition associated with depression of cell mediated immunity (T cell anergy, low T cell counts, reduced mitogen stimulation)

Question 7

how does one acquire a zinc deficiency?

Answer 7

low meat consumption, high fiber diet, chronic diarrhea, chronic kidney insufficiencies, weight loss, bulimia, alcoholism, diabetes, psoriasis, hemodialysis

Question 8

what does vitamin D3 deficiency result in?

Answer 8

higher frequency of inflammatory diseases and lower numbers of natural Treg cells

Question 9

deficiency in which vitamins reduce cell-mediated immunity?

Answer 9

vitamin A, folic acid, pyridoxine

Question 10

what are the results of burn associated immunodeficiencies?

Answer 10

1. depressed neutrophil function
2. macrophage activation
3. depressed cell-mediated immunity

Question 11

why do burn victims have depressed neutrophil function?

Answer 11

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)

Question 12

macrophages harvested from burn patients are in a state of activation. what do they produce?

Answer 12

large amounts of IL-1, TNFalpha, IL-6, TGFbeta, prostaglanding E2 (PGE2)

Question 13

why are burn patients at increased risk of sepsis?

Answer 13

endotoxins can promote cytokine production of IL-1, IL-6, TGFbeta, and PGE2

Question 14

why do burn victims have depressed cell mediated immunity?

Answer 14

1. reduced production of IL-2 upon mitogenic stimulation
2. PGE2 released by macrophages/monocytes increase intracellular cAMP in T cells, preventing proliferation
3. TGFbeta levels elevated 1 week post injury which is immunosuppressive

Question 15

why are patients immunodeficient after surgery?

Answer 15

transient depression of mitogenic responses of peripheral blood mononuclear cells, cutaneous hypersensitivity, and Ig production

Question 16

why does surgery exactly make a pt immunodeficient?

Answer 16

1. transient lymphopenia postop (decreased B and T cells)
2. release of PGE2 by phagocytes decrease T cell mitogenic response
3. blood loss means decreased IL-2 from T cells, decreased MHCII expression, and decreased Ig production
4. transfusion reaction?
5. anesthesia and painkillers decrease phagocyte and NK functions

Question 17

when is normalization of immune reactivity restored after surgery?

Answer 17

10 days for T cell mitogenic responses and 30 days for Ig

Question 18

what does PGE2 do?

Answer 18

decreases T cell mitogenic response

Question 19

what does blood loss during surgery lead to?

Answer 19

decreased IL-2 by T cells, decreased MHCII expression on APC, and decreased Ig production

Question 20

how does a splenectomy affect secondary immunodeficiency

Answer 20

they are weakly responsive to bacteria expressing polysaccharide capsules, so they are prone to septicemia

Question 21

what bacteria commonly cause sepsis in splenectomized patients?

Answer 21

strep pnuemo (50%), H influenziae, and neisseria meningitidis

Question 22

how does a thymectomy affect secondary immunodeficiencies?

Answer 22

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

Question 23

what does chronic alcoholism result in (secondary immunodeficiency)

Answer 23

depressed cell mediated and humoral immune responses (zinc deficiency?)

Question 24

do cannabinoids have impact on immune system?

Answer 24

unclear

Question 25

do opiates have impact on immune response?

Answer 25

cocaine can impair T cell reactivity but at very high levels

Question 26

how do bacterial infections affect the immune system?

Answer 26

1. mycobacterium infections are shown to induce state of anergy in T cells.
2. staph superantigens stimulate nonspecific T cells to cause disease (generalized immunosuppression - d/t Treg activation)

Question 27

which parasitic infections are associated with a generalized state of immunosuppression?

Answer 27

1. trypanosoma cruzi - reduced IL-2 receptor expression on T cells
2. toxoplasma
3. schistosoma
4. leishmania
5. plasmodium

Question 28

how does the measles virus affect the immune system?

Answer 28

1. measles virus can produce transient state of immune anergy and lymphopenia
2. DC cells have impaired IL-12 production

Question 29

how do viruses impact the immune system?

Answer 29

do not impose generalized immunosuppression, but more localized immunosuppression for persistence of infection

Question 30

how does HIV impact the immune system?

Answer 30

depletes CD4 T cells and produces viral proteins for immune evasion that decrease MHC I expression