biol 5500 exam 3 (starting with transplantation)

transplantation

requires histocompatibility at virtually every locus

alloreaction

immune responses directed at MHC that is different than self

transplantation

may require use of immunosuppressive drug regimens, broadly inhibiting response

rejection

e.g. a transplanted kidney is attacked by the recipient’s T cells

graft-versus-host disease

e.g. T cells from transplanted bone marrow attack the recipient’s tissues

rejection

when a recipient of a solid organ transplant, the recipients immune response is directed against the cells of the graft and can kill the grafted organ

graft-versus-host-disease

when a recipient’s immune system is destroyed and receives a new one, the donors mature T cells attack and reject the recipients healthy tissue

hyperacute

in this rejection, pre-existing antibodies against HLA or ABO bind vascular endothelium, start inflammatory response, occlude blood vessels, resulting in rapid death of graft

acute

in this rejection, effector T cells are responding to MHC differences between donor and recipient, takes days to develop, donor dendritic cell prime recipient T cells

Chronic

in this rejection, vessel walls of the graft are thickened, damage mediated by antibodies, T cells, granulocytes, and macrophages, takes months or years to develop

hyperacute

antibodies against ABO blood group antigens can mediate _______ rejection of transplanted organs

hyperacute rejection

this is an irreversible process that can be avoided by determining if recipient serum contains antibodies that will recognize donor cells

AB

this blood cell type has no antibodies but two antigens

O

this blood cell type has two antibodies but no antigens

anti-HLA

these antibodies can arise from pregnancy, blood transfusion, or previous transplants

syngeneic

matches donor MHC at every locus

allogeneic

does not match donor MHC at every locus

dendritic cells

in the case of a kidney rejection, these migrate to the spleen where they activate effector T cells, leading to destruction of the grafted kidney

direct allorecognition

MHC-driven reaction dominated by recognition of donor MHC by donor APC (dendritic cells)

Mixed Lymphocyte Reaction (MLR)

used by clinicians to determine the compatibility of donor/recipient before testing via transplantation

direct allorecognition

recipient CD4/8 T cells recognizing donor foreign MHC, directly stimulating a strong rejection response from T cells

indirect

CD4 T cells from the recipient recognize processed components of donor MHC, presented on recipient MHC

direct

this allorecognition leads to acute rejection

indirect

this allorecognition leads to chronic rejection

AB+

universal blood recipient

O-

universal blood donor

rh-

these blood types can only recieve rh- blood types

rh+

these blood types can recieve rh- or rh+ blood types, given the ABO antigen is compatible

syngeneic, antigen

in indirect allorecognition, the presenting MHC (recipient) is ______, while the peptide (donor) is the ______

minor histocompatibility antigens

even when a full MHC match is achieved, chronic rejection can still be mediated in response to differences in:

H-Y antigens

minor histocompatibility antigens derived from proteins encoded on the Y chromosome

hyperacute

the underlying mechanism of this type of rejection is due to pre-existing antibodies to different blood types

ENDED AT H-Y ANTIGEN DIFFERENCES AND IMMUNOSUPPRESSIVE DRUG TARGETS

STARTING TUMOR IMMUNITY FROM HERE

angiogenesis

important for tumor survival, in order to supply enough blood

metastasis

invasion of a tumor to other sites and tissues

neoplasm

synonymous with tumor

BRCA1/2

mutant forms of these tumor suppressor genes can increase risk of breast/ovarian cancer by 5x

proto-oncogenes

genes whos products positively regulate cell division

oncogenes

mutated versions of proto-oncogenes that contribute to malignant transformation

tumor suppressor genes

encode proteins that prevent unwanted proliferation of mutant cells

p53

over half of human tumors have a mutation in this tumor suppressor gene

cancer

papillomavirus, hep b, EBV, HTLV-1, HIV-1, and HHV-8 can all cause:

leukemia

cancer of immune system cells

lymphoma

cancer of the immune system involving solid lymphoid tumors

myeloma

cancer of the immune system involving bone marrow

tumor specific

antigens present on tumor cells but not normal cells:

tumor associated

antigens present on tumors, but also normal cells at lower levels

tumor specific antigens (TSAs)

variants p53, ras, b-catenin, MART2, ME1, KIAA0205, triosephosphate isomerase, and BCR-ABL fusion protein can all be:

Tumor associated antigens (TAAs)

possibly include Her2-Neu, MUC-1

Tumor associated antigens (TAAs)

expression of these are restricted to gametogenic tissues and cancer

Tumor associated antigens (TAAs)

often mapped to chromosome X

Tumor associated antigens (TAAs)

immunogenic in cancer patients, expression may be associated with tumor progression and metastasis

immunogenic

chemical or raditation-induced tumors as well as virally-induced tumors are generally _________ because of the generation of the altered self

immunogenic

many spontaneous tumors may not be very _________

IL10, TGFbeta, PGE2

these secreted immunosuppressive factors all decrease the potency of anti-tumor effector cells,

FasL, TRAIL, IDO (Idoleamine 2 3-dioxygenase)

These factors promote apoptotic destruction of T cells

CTLA4/B7, PD1/PDL1

these two pairs of factors are associated with negative costimulation to down-regulate MHC

NK cells, macrophages, dendritic cells

three factors of innate immunity against tumors

CD4 CD8

two main factors of adaptive immunity against tumors

IFN gamma, TNF alpha

expressed by NK cells to inhibit tumor growth

NK

tumors can express ligands that activate ______-mediated killing

MHC

tumor cells that lack ____ molecules are sensitive to NK-mediated killing

cytokines

instructs t cell differentiation

MHC/peptide, costimulation

induce T cell activation

costimulation

CD80/CD86 do this

TH1

responses driven by this cell primarily protect agaiinst intracellular pathogens and tumors

TH1

these cells support the CD8 T cell response (proliferation via IL-2)

TH1

activated phagocytes that kill pathogen via respiratory burst and dispose of cells that were killed by infection

TH1

recruit NK cells to kill infected cells (often virus infection downregulates MHC class 1)

IFN gamma

signature cytokine product of TH1

IL12

major inducing cytokine of TH1 cells

macrophages

IFN-gamma acts on these to activate both MHC classes, increasing microbicidal activity

B cell

IFN-gamma acts on these to stimulate isotype switching and differentiation

IFN-gamma

this acts on naive CD4+ t cells to develop TH1 effector cells

APCs

IFN-gamma acts on these to increase MHC expression

TH2

responses driven by this cell primarily provides protection against multicellular parasites and mediate hypersensitivity responses

B cells

TH2 cells provide proliferative signals to:

TH2

This cell drives B cell isotype switching to IgG1 and IgE

TH2

this cell is often associated with allergy due to IgE production and mast cell recruitment

IL4

major cytokine product of TH2

IL4

major inducing cytokine of TH2

IL4

this cytokine acts on b cells to promote activation and growth, and produce IgG1 and IgE, MHC class 2 induction

IL4

cytokine that acts on T cells to promote growth and survival

IL4

cytokine that inhibits macrophage production

IL4

cytokine that promotes development and expansion of TH2 cells

TH1

tuberculoid M. leprae infections stimulate a ___-type CD4+ T cell response

TH2

lepromatous M. leprae infections stimulate a ___-type CD4+ T cell response

TH2

this T helper cell inhibits macrophage activation, therefore inabling macrophages from killing intracellular bacteria

TH1 TH2

these T helper cell subsets antagonize each other

TH17

recently discovered CD4 subset which is pro-inflammatory

TH17

this cell mainly protects against extracellular bacteria by recruiting neutrophils

TH17

T helper cell often associated with immune disorders

IL17

major cytokine product of TH17

TH17

TGF-beta and IL6 are the major inducing cytokines of:

TGF-beta, IL6

major inducing cytokines of TH17

TH17

these TH cells appear early in infection, before TH1 or TH2

TGF-beta, IL6

to become a TH17 cell a naive CD4 t cell must be exposed to BOTH:

Treg

if a naive CD4 T cell is exposed to ONLY TGF-beta, it will become this:

IL23

important for maintenance of the TH17 phenotype

IL17

cytokine that activates endothelial cells, which then recruit neutrophils via IL6