Week 3 & 4 Flashcards
(124 cards)
1
Q
CD16+
A
NK cells
peak response 3-4 days; no immunologic memory
2
Q
congenital agranulocytosis
A
phagocytic deficiency
- complete absence of neutrophils
- ↓ production of G-CSF (acitvation of CTL)
3
Q
leukocyte adhesion deficiency
A
phagocytic deficiency
- leukocytes can’t extravasate/bad cell-cell interactions
- lack β chain common to integrins (or selectin)
4
Q
TH1
signal to activate, TF, what it secretes
A
signal: IL-12, IFNγ
TF: T-bet
secretes: IFNγ, IL-2
5
Q
sjogren’s syndrome
A
autoantibodies and autoreactive T cells to ribonucleoprotein Ags → lymphocyte infilitration in exocrine glands leading to dry eyes and mouth
6
Q
TLR4
A
recognizes LPS from gram negative bacteria
7
Q
chronic rejection of kidney
A
- glomerulitis: inflammation cells in capillary loop/accumulation of mesangial matrix
- interstitial fibrosis and tubular atrophy
8
Q
bare lymphocyte syndrome
A
combined immunity deficiency
- dec. expression MHC I or II
- all Ig decreased
- defect in transcription of MHC genes; fatal w/o transplant
9
Q
Belatacept
A
CTLA4:Fc fusion portein that binds to B7 to prevent the generation of signal 2 from CD28 to turn off T cell activation
10
Q
tumor infiltrating lymphocytes (TIL)
A
isolated from solic tumors and activated with high doses IL-2; consists of CTL
re-injection is beneficial
11
Q
cross presentation in cDCs
A
DCs take up viral Ags from outside the cell by phagocytosis of apoptotic cells (cells that die due to viral infection) and present on MHC I to CD8+
(normally foreign Ags are stim. MHC II and CD4+ but this way it stim. CTLs)
*important in acute transplant rejection
12
Q
SCID mice
A
mutation in DNA protein kinase and deletion of recombination activating enzymes
13
Q
CD40/CD40L
A
activates CD8+ CTLs to give help to B cells for Ab formation
14
Q
chronic rejection
A
months-year post tranplanatation due to repetitive complement mediated cell damage and then vasculopathy (capillaropathy) with tissue injury, fibrosis and loss of function of graft
15
Q
self-non self model of immunity
A
dendritic cells are activated thru triggering their PRR thru PAMPs that are essential for bacteria/not expressed by host
16
Q
chronic rejection of heart
A
characterized by cardiac allograft vasculopathy (CAV) due to arteriole thickening and interstitial fibrosis; immunosuppressive drugs can’t treat
17
Q
CCR5
A
cDCs express when they need to go to peripheral tissues and be resident there, then start upregulating CCR7
18
Q
what signals activate the innate immune system, and what are the receptors that are activated?
A
PAMPs and DAMPs activate the innate immune system
they stimulate PRRs on phagocytes (granulocytes, macrophages, dendritic cells)
19
Q
molecular mimicry
A
exposure of an Ag thatis very similar to self-Ag and induces immune response to infectious Ag and self Ag (ex. rheumatic fever in strep pyogenes)
20
Q
multiple sclerosis
A
autoreactive T cells to brain antigens to MBP and MOG → sclerotic plaques and myelin destruction
T cell pathogenic; TH1 and TH17
21
Q
GM-CSF
A
boosts Ag recognition phase: ↑ dendritic cells → CTL activation → tumor destruction
22
Q
cross-matching
A
done to ID preformed anti-HLA Abs (for hyperacute rejection)
calcularte the PRA panel reactive antibody profile using:
- complement dependent cytotoxicity (CDC) assays
- flow cytometric crossmatch
- solid-phase assays (SPAs)
23
Q
type I diabetes
A
autoreactive T cells to pancreatic islet cell Ags → destruction of β cells leading to non-production of insulin
T cell pathogenic
24
Q
myasthenia gravis
A
auto antibodies to Ach R on SkM (B cell pathogenic) leading to inhibition of SkM contraction and weakness
25
dose-response relationship
monotopic (unidirectional) response curve; ex. amount of smoking and lung cancer
26
strength of the association
stronger association is more likely to be causal; weaker association is more likely to be explained by undetected bias
27
dendritic cell cycle
live in resting state in peropheral tissues → activated and go thru afferent lymphatic vessel to node and present Ag → T cells clonally expand → T cells leave lymph node for site of inflammation
28
graft vs. host disease
life threatening complication of HSCT whereit attacks normal tissue (skin, intestine, liver, lung) and reconstitutes thymocytes/hematopoetic cells. caused by infused donor T cells including CD4+ and CD8+; assoc. with ↓ risk of leukemic relapse
minor histocompatability also contributes - caused by HY antigens in M but not F (if sister is receiving from brother, T cells specific for self antigens are on brothers cells but not same HLA as sister). most miHLAs are presented by **MHC I**
29
tumor specific antigen (TSA)
not expressed on normal cells and are unique to tumor cells:
1. mutation in gene that is in normal cells (K-ras)
2. protein in tumor cells but not normal cells (viral protein)
3. unusual mRNA splicing/post-translational modification
4. hybrid/chimeric protein from chromosomal translocation
1. makes new epitope
2. CML/phila chromosome (9:22) Bcr/Abl is oncoprotein
30
CAR T therapy
T cell collection for B cell lymphoma → express CD19 sepecific Ig linked to CD3 → put back in patient
31
TLR5
binds flagellated bacteria
32
Treg
signal to activate, TF, what it secretes
signal to activate: TGFβ
TF: foxp3
secretes: TGFβ, IL-10
33
cDC vs pDC markers
cDC: express MHC I and II (MHC II is expressed intracellular until triggerred by PRR), also upregulate ICAM1, LFA1 and B7 (CD80/86)
pDC: IFNα and β, express TLR7 and TLR9 to sense viral nucleic acids. make 1000x more IFNs than any other blood cell type
34
immune system activation (normal and when rejecting a graft) 3 steps:
1. **Ag + MHC recognition**
1. MHC I has 3 domains and peptide binding is between α1 and α2 - present to CD8+
2. MHC II is α and β chain - present to CD4+ processed in endocytic compartment
2. costimulatory molecules
3. pro-inflammatory cytokines
35
x-linked bruton's agammaglobulinemia
humoral immunity deficiency
* lack of mature B cells
* all Ig classes ↓
* due to defect in bruton's tyrosine kinase for B cell development
36
humoral immunity deficiencies
* recurrent infections
* lack of long term protection/antiviral immunity
* delay of onset due to passive transfer of maternal IgG
* tx with passive admin of normal Igs
37
lymphokine associated killers LAK
obtained from acitvation of peripheral blood mononuclear cells of cancer patients with high **IL-2**
consists of NK cells; reinjection is beneficial but activity per cell isn't as good as TIL
38
acute rejection:
how long does it take
2 weeks to 3 months due to requiring time to activate and clonally expand B and T cells; 2nd reaction is due to memory T cells
39
peripheral tolerance
unresponsiveness induced in mature lymphocytes that have recognized their Ag → lack of signal 3 (cytokines) → anergy
tolerogenic APC tolerizes CD4+ cells; failuret o activate Th leads to B cell energy and lack of CTL
40
monogenic autoimmuntiy
immunity assoc. with one gene
* AIRE - APS-1
* CTLA4 - graves, TID
* FOXP3 - IPEX
* FAS - ALPS
* C1q - SLE
41
minor histocompatability ex.
HY in mice is encoded on Y chromosome/only expressed in males so females reject it; different in humans because we are so polymorphic
42
atacxia-telangiectasia
immunodeficiencies assoc. with other defects
* abnormal walk, vascular malformations
* ↓ IgA and IgE, IgM normal, IgG normal/decreased, T cells ↓
* malignancy prone
* ATM gene mutation (protein in DNA repair)
43
TH2
signal to activate, TF, what it secretes
signal: IL-4
TF: GATA3
secretes: IL-4, IL-5
44
main target of hyperacute rejection
vascular endothelium
(in kidneys leads to dec. RA perfusion secondary to vascular spasm, microvascular injury/intravascular coagulation)
45
selective IgA deficiency
humoral immunity deficiency
* most common immunodef.
* respiratory and GI infections
* (can't treat with Igs because not enough for lack of secretory IgA)
46
acute rejection of heart: cell mediated vs humoral
**cell mediated**: maybe reversible with subtle enlargement/ECG changes and ↓ EF, interstitial infiltrate
**humoral**: high death rate, no infilitrate, due to endothelial swelling - can see Igs on surface thru immunofluoresence
47
hashimoto's thyroiditis
autoantibodies and autoreactive T cells to thyroid Ags → hypothyroidism thru destruction of tissue
Th1 mediated; causes DTH
48
antibody mediated rejection AMR
tx?
activation of B cells to produce Abs (seen in indirect recognition of allo-Ag). due to:
1. undetected preformed memory response
2. newly acute primary response
3. fixing complement onto BVs (deposits on capillary endothelium)
tx: rituximab, Ab that binds CD20, GCs, IV IG
49
selective IgG subclass deficiency
humoral immunity deficiency
* decrease in IgG2 or IgG3 (but total IgG levels normal)
* asymptomatic
50
5 susceptible genes leading to autoimmune disease
1. HLA alleles
2. genes in clearance of apoptocic cells
3. genes in TCR BCR signaling
4. genes in negative regulation of lymphocyte activation
5. genes in lymphocyte apoptosis
51
TH17
signal to activate, TF, what it secretes
signal to activate: TGFβ and IL-6
TF: RORγT
secretes: IL-6, IL-17
52
migratory DCs
CD14+ dendritic cells secrete IL-12 which activates Tfh leading to plasma cells and long lived memory B cells
ex. langerhans cells of epidermis and interstitial DCs of dermis; sample Ag in peripheral tissues and then migrate to Lymph nodes where they present to CD4+ and Tfh
good at cross presentation to CD8+ to present to MHC I
53
acute rejection in kidney
capillaritis; inflammation in peritubular capillaries and complement deposition C4d in peritubular capillaries and glomerulus
54
x-linked hyper-IgM syndrome
humoral immunity deficiency
* dec. IgA and IgG, increased IgM
* mutation in CD40L; can't interact for B cell activation
* inhibition of B cell response to T dependent Ags
55
TH1 secretes what which does what
IL-2 which interacts with IL-2 R on naive CTL to boost/make more CTL to kill tumor cells
(dont forget Th1 is CD4 so it interacts with MHC II, and CTL is CD8 so it interacts with MHC I)
56
digeorge syndrome
cellular immunity deficiency
* lack thymus, parathyroid glands
* CVD and facial abnormalities
* T cell count and functions ↓ but increase w/ age (ectopic thymus)
* microdeletions on chromosome 22
* humoral immunity also affected
57
PD-1
binds SHP1-2 phosphatases and reduces signaling of TCR → dec. T cell prolif, survival and IL-2 production
58
plasmacytoid DCs
CD123 BDCA-2+
secrete type I IFNs "interfere" with viral replication; mostly make IFNα
59
chronic granulomatous disease
phagocytic deficiency
* x-linked, most common
* defect in **cytochrome b** needed for peroxide production
* bacteria get injested but aren't killed / get transported to organs
* **tx: give recombinant IFNγ**
60
SLE
autoantibodies and autoreactive T cells against DNA, chromatin proteins, and ribonucleoprotein antigens → glomerulonephritis, vasculitis, rash
B cell pathogenic, type III hypersensitivity (proliferative glomerulitis and vasculitis) but disease if disordered immunity
61
direct vs. indirect recognition of allo-Ag
**direct:** APCs from graft mgrate out and go to draining lymph node, get recognized by host T cells (CD4 help CD8 become CTL) thru recognition of donor MHC and foreign peptide
**indirect:** host APCs get to graft, aquire donor specific Ags and go to lymph nodes/present to T cells which recognize self MHC and donor Ag; **cross presentation** important where dendritic cells present on MHC I to CD8 - important in graft rejection after donor DCs die in 1st days post transplantation. Self MHC CD4 cells secrete IL-2, IL-4, IL-5 (eosinophilic infiltration), IFNγ (act. macrophages) to facilitate **DTH** (macrophage activation) and **activation of B cells to produce antibodies (AMR antibody mediated rejection)**
62
multistep process of tumor formation:
loss of APC → hyperproliferative epithelium
DNA hypomethylation → early adenoma (benign)
activation of K-ras → intermediate adenoma
loss of DCC → late adenoma
loss of p53 → carcinoma → metastatis
63
TLR2,4,6
recognize products of oxidative stress (oxidized LDLs/phospholopids) and molecules released by dying cells like HMGB1
64
CD45-44
maintain engaged the APC-Tcell interaction
65
acute rejection in liver
reversible cell mediated rejection
diagnostic triad: portal inflammatory infiltrate, bile duct damage, endothelitis - lymphocytes, eosinophils
use Banff grading for liver rejection
66
adaptive t regs
1. **deletional tolerance (recessive) -** self reative T cells deleted in thymus; can be activatd in perophery
2. **regulatory tolerance (dominant)/infectious tolerance** - T cells specific for self Ag become Treg; regulatory DCs make TGF β and IL-10; require TGFβ and IL-2 to survive and express CD25
67
hyperacute rejection
what type of hypersensitivity is it?
prevention?
why are xenografts so immunogenic?
within hours due to Abs from previous exposure to Allo-Ag (multiple pregnancies, blood transfusions) or ABO mismatch
activates complement → thrombosis and hemorrhage and neutrophil invasion
**type II hypersensitivity** (Ags present on cell surgcae leads to complement activation)
prevent with plasmapheresis and IVIG
xenografts so immunogenic because CD59 and DAF are less effective at complement inhibition
68
what 2 signals do B cells need to activate?
1. binding of Ag to BCR
2. CD40/CD40L on CD4+ Tfh cells → B cell proliferation, isotype switch and Ab production
\*anergy without this
69
rapamycin
blocks response of T cells to IL-2
downstream of IL-2 is mTOR that leads to AKT activation for cell survival and proliferation
70
TLRs 3, 7, 8, 9
recognize nucleic acids after their shuttled to endosomal compartments of APCs via endocytosis and phagocytosis
TLR3: dsRNA
TLR7,8: ssRNA
TLR9: CPGs that come from viruses
71
rheumatoid arthritis
rheumatoid factor
autoreactive T cells to antigens of joint synovium
CD4+ fells make TNFα and IL-6 which activates fibroblast like synoviocute cells to make MMPs (cartilage damage) and RANKL (bone erosion)
**rheumatoid factor:** an auto-Ab (IgM) that recognizes Fc portion of IgG
autoantibodies to citrullinated peptides (Arg → cit by PAD peptidyl arginine deaminase) which are presented to CD4 cells, trigger complement
72
Tfh
signal to activate, TF, what it secretes
signal to activate: IL-6
TF: Bcl6
secretes: IL-21, ICOS
73
specificity of the association
an invalid criterion - smoking has multiple effects
74
resident DC
in lymphoid tissue; acquire and present Ags within lymphoid organs
75
wiskott-aldrick syndrome
immunodeficiencies assoc. with other defects
* thrombocytopenia, eczema, bacterial infections
* IgM ↓, IgA and IgE ↑, IgG normal
* defective response to bacterial polysaccharides
* x-linked defect in WASP gene that encodes protein for signal transduction/cytoskeleton of T cells
76
central tolerance
eliminating autoreactive T and B cells during development in central lymphoid organs, thymus and BM where self-Ags are expressed for induction of tolerance
1. apoptosis (deletion in b and t cells)
2. anergy (b cells)
3. changes in B cell receptors / RAG reactivation
4. development of Treg
77
Danger model of immunity
dendritic cells are activated by endogenous stress signals thru DAMPs recognized by PRRs
78
2 things that label cell and self/don't kill by NK cell
```
class I MHC
AR ligand (AR is on NK cell)
```
if MHC I downregulated, in virus/cancer cell, NK cell will kill
79
heteroconjugate of anti-CD3 and anti-TSA/TAA
facilitates T cell immune repsonse to tumor cells by bringing T cells and cancer cells close together
80
common variable immunodeficiency
humoral immunity deficiency
* B cells don't mature into plasma cells
* ↓ in Ab producing plasma cells
* ↓ all Ig classes
* recurrent infections
81
CCR7
allows DCs to move to the draining lymph node through lymph and end up in T cell area to present to T cells, also upregulates MHC expression I and II
82
ICOS
on surface of germinal T cells for Tfh/CD4+ required to help B cells; without it mice can't Ab isotype switch. ICOS-L is expressed by activated APCs
83
antimicrobial activity of macrophages
1. O2 dependent: ROS, H2O2, and NO
2. O2 independent: lysozyme, defensins
84
Goodpasture's syndrome
auto-Abs against basement membrane type IV collagen of glomerulus → glomerulonephritis
85
immunological tolerance
unresponsiveness to an Ag due to previous encounter of specific lymphocytes with their Ag in conditions that inhibit their activation
required for life. failure = autoimmune disease
86
cytokine escape strategy of tumor cells
they secrete TGFβ (inhibits Th1 cells) and IL-10 (inhibits macrophages)
87
CTLA-4
inhibits T cell activation by:
1. stimulating phosphatases SHP-1 tht inhibit TCR
2. competes with CD28 for binding (and is 20x more avid)
Abs to block CTLA4 in tumor treatment to get the T cells to attack tumor
88
CD28
costimulatory molecule in Ig superfamily that binds CD80/86 (B7) which induces T cell proliferation and NFAT regulated IL-2 production and T cell survival, enhances NFKB translocation to nucleus which activates pro-survival genes (Bcl-xl)
89
graves disease
autoantibodies to TSH R → hyperthyroidism
90
tissue typing
PCR to determine HLA of donor and recipient to see how different their haplotypes are (DNA test) - T cells from recipient are incubated with donor cells and cytotoxicity is measured
91
tumor associated antigen (TAA)
not unique to tumor cells - expressed in low levels in normal cells/fetal cells:
1. c-myc: constitutive overexpression → HER2 breast cancer
1. Burkitt's lymphoma
2. α fetoprotein AFP and carcinoembryonic ag CEA: on fetal cells
1. AFP high in liver cancer
2. CEA high in pancreatic and colorectal cancer
92
SCID
combined immunodeficiency
* fatal unless tx with BM transplant
* lack B and T cells; all Ig low
* causes:
* x-linked coding for γ chain of IL-2 family (IL-2, IL-4, IL-7, IL-11, IL-15)
* mutated JAK3 kinase (autosomal recessive)
* defect in RAG1 or RAG2 - lack of rearrangement of TCR/Ig
* adenosine deaminase ADA or purine nucleoside phosphorylase PNP deficiency - ADA is toxic metabolites for B and T cells, PNP is mostly B cells
93
AIRE
autoimmune regulatory - allows ectopic expression in thymic medulla of peripheral tissues specific Ags so that they can be presented in the thymus and induce negative selection of thymocytes autoreactive for them
disorder = APS-1 where immune system attacks/destroys endocrine glands → hypothyroidism, hypoparathyroidism, addison's disease, diabetes
94
sources of hematopoetic stem cells
1. BM HSC: from iliac crest
2. PB HSC: recruit HSC from bone marrow into peripheral blood once treated with G-CSF and GM-CSF, the extract Abs with CD34
3. umbilical cord blood: from placenta - have fewer alloreactive T cells
4. spleen - but not lymph node
95
temporality
exposure to factor must precede outcome - hard to demonstrate in diseases with long latent periods (london fog, food-bore illnesses)
96
allo-antigen
molecules recognized as different by the immune system of members of the same species; MHC (series of genes clustered into a haplotype) are most important/cause alloreactivity
97
3 types of APCs
dendritic cells, macrophages, B cells (but B cells only present one specific Ag because they don't phagocytose)
98
corticosteroids:
1. mechanism of action
2. indications
3. adverse effects
1. reduce size of lymph nodes/spleen and interfere with cell cycle of activated lymhoid cells; indirectly induce T cell death; suppress Ab/PG/leukotriene formation
1. **block monocyte production of cytokines like IL-1 for T cell maturation**
2. autoimmune, allergies, bronchial asthma, transplant
3. weight gain, psychoses, glucose intolerance, HTN, cataracts, skin fragility, bone dissolution, infection, cushingoid reactions (moon face, weight gain, facial hair, acne, buffalo hump, weird skin)
99
cyclosporine A
1. mechanism of action
2. indications
1. selective inh. T cell activation - inh. IL-2; binds cyclophilin (FKBP) and inihibts calcineurin → NFAT not activated to nucleus → no IL-2 made
2. inhibition of transplant reactions
100
tacrolimus (FK506)
macrolide antibiotic from strep tsukubaenis
(like CsA) binds to FKBP and inhibits calcineurin → ↓ IL-2; blocks activation of T cells
more potent than CsA
indicated in trasplants
101
rapamycin (sirolimus)
macrolide Ab like FK506
binds FKBP and inhibits IL-2R
reduced toxicity than CsA/FK506 but better in combination therapy
102
thalidomide
useful in skin manifestations of lupus
103
mycophenolate mofitil
inhibits de novo pathway of purine/pyrimidine synthesis
104
azathioprine
1. mechanism of action
2. uses
1. antimetabolite - interferes with NA metabolism. absorbed in GI and metabolized to **mercaptourine**; deactivated by **xanthine oxidase** before excretion
2. combined with prednisone in transplants, glomerulonephritis/lupus, RA
105
cyclophosphamide
alkylating agent - most potent immunosuppressive drug. converted to active in liver which can cross like DNA and inhibit RNA synthesis → destroys proliferating lymphoid cells and alkylates resting cells
use very large single dose
\*NOT SELECTIVE
106
methotrexate
folate antimetabolite; prophylaxis for GvHD/severe RA
major AE is infection/GI
107
type I hypersensitivity treatment
IgE mediated releases assoc. with ↓ cAMP; treat by giving cAMP (catecholamines, corticosteroids, theophylline), chromolyn sodium prevents mast cell degranulation, antihistamines
108
Rh incompatability is what type of hypersensitvity
type II
109
formula of secretory IgA
(IgA)2JSC
heavier than serum IgA
110
where can u find M cells
above peyer's patches
111
where does immune activity in gastric mucosa occur?
in the lamina propria
112
production/transcytosis/secretion of IgA
plasma cell produces dimeric IgA in **lamina propria** → bind to **poly-Ig receptor** → receptor mediated endocytosis/transport to apical surface → receptor cleaved but SC stays on dimer
113
5 functions of sIgA
1. inhibition of microbial attachment @ mucosa
2. neutralization of viruses/toxins @ mucosa
3. containment of normal microbes in gut
4. inh. absorption of undigested foreign Ags
5. (colostrum) passively protects infant GI tract
114
why do IgA deficient patients survive?
compensation by IgM and IgG
115
IgA1 vs IgA2
**IgA1:** predominates in blood - many bacteria have IgA1 protease to invade - influenza, gonorrhea, meningitis, strep
**IgA2:** missing 13AA in hinge region; predominates in SI and vagina
116
do peyers patches have afferent lymphatics?
NO!!!! M cells are pinocytotic and sample environment of GI tract
Ag is taken in by M cell, presented by DC which activates T cells
117
where are inductive sites for production of IgA committed (switched) B cells?
peyers patches and ILFs (scattered isolated lymphoid follicles) and mesenteric lymph nodes
118
how do B cells get to GI tract?
B cells have integrin α4β7 and chemokine receptor CCR9
gut epithelial cells have CCR9 ligand CCL25
capillary HEV express MadCAM1 which binds integrin α4β7
119
whats the major switch factor for IgA
TGFβ
is T cell dependent/requires CD40; TFH drives IgA production once switching has occureed; IL-5 and IL-6 promot differentiation
120
T-dependent sIgA response
B2 cells in peyers patch; co-stimulatory signals signals from DCs and Th2; drive switch from IgM to IgA; make lots of IgG
in secondary lymphoid organs
121
T-independent sIgA response
B1 cells; occurs in ILFs; main response to commensal bacteria in gut
makes lots of IgM
in peritoneal and pleural cavitites
APRIL in B1 cell development
122
IELs
located between epithelial cells, CD8+ with γdelta - contribute to host defense (cytotoxicity) and immunosuppressions and tolerance (makes TGFβ and IL-10)
123
what type of T cells are in the LP and mesenteric lymph nodes?
CD4+ that help B cells by making IL-5 and IL-6
Tregs - mediate tolerance
124
TGFβ paradox
both an immunosuppressive cytokine by Tregs and a switch factor for IgA synthesis
