Week 3 Flashcards
1
Q
arthus reaction
A
type III IgG mediated hypersensitivity; occurs at skin ; can occur if too many boosters are given; reaction against antigen antibody complex
2
Q
reaction against penecillin
A
type II IgG mediated hypersensitivity
3
Q
serum sickness
A
type III IgG mediated hypersensitivity; IgG neutralizes ag, forming Ag-ab complexes; get IgG and C3 deposits due to excessive cross linking
4
Q
hapten
A
an antigen with a single epitope; needs a carrier to be immunogenic
5
Q
urticaria and serum sickness
A
urticaria is associated with complement activation because C3a and C5a are anaphylacticin (stimulates anaphylaxis)
6
Q
vasculitis and serum sickness
A
vasculitis occurs because the antigen antibody complexes deposit in small blood vessels, which causes hemorrhaging or damage to these vessels resulting in purpuric lesions
7
Q
genetic component to celiac
A
HLA DQ8 and DQ 2 genes
8
Q
celiac immune mech
A
type IV hypersensitivity reaction but its actually technically not an autoimmune disease because the antigen is exogenous
9
Q
what is the enzyme with abnormal activity in celiac disease?
A
tissue transflutaminase
10
Q
what is the mechanism of presentation of gluten “antigen”
A
MHC II / CD4+
11
Q
Fc eRI
A
high affinity Fc receptor present on mast cells; the Fc of IgE will bind here and cause mast cell to release Il4 which increases the secretion of IgE by the plasma cell
12
Q
where are the key areas that are affected by mast cell degranulation
A
GI
eyes, nose, airways
blood vessels
13
Q
impact of mast cell on GI
A
causes increased fluid secretion, incr peristalsis; expulsion!!! (diarrhea or vomiting)
14
Q
impact of mast cells on eyes nose and airways
A
decreased diameter and increased mucus secretion; congestion, swelling and mucus secretion in nose
15
Q
impact of mast cells on vessels
A
incr blood flow, incr permeability
can lead to hypotension and anaphylactic shock
16
Q
what enzymes do mast cells have and what do they do
A
remodel connective tissue matrix; cathepsin, chemise, tryptase
17
Q
omalizumab
A
anti-IgE antibody
18
Q
Th1
A
IFN gamma , make macrophages angry
19
Q
hyper acute response
A
within minutes due to pre-existing recipient antibodies reacting to donor antigen; type II hypersensitivity and activate complement
20
Q
what causes GVHD
A
alloreactive effector T cells from the donor that attacks normal tissue;
21
Q
what kind of hypersensitivity rxn is hyper acute rejection?
A
type II
22
Q
what kind of hypersensitivity rxn is acute rejection
A
type IV
23
Q
what kind of hypersensitivity reaction is chronic rejection
A
type II and type IV
24
Q
clinical manifestation of GVHD
A
rash and diarrhea
25
effector fxns of macrophages (5)
```
phagocytosis
opsinizaiton (binding constant aspect of antibodies)
antimicrobial
secretion of factors (TNFalpha, Il6)
Antigen processing and presentation
```
26
shape of dendritic cell in tissue
expanded
27
shape of dendritic cell in circulation
round
28
shape of dendritic cell when presenting antigen
extend thin processes
29
how do dendritic cells enter lymph node?
through afferent lymphatic vessels to the outer cortex
30
CD141+ cells
conventional dendritic cells found in blood and secondary lymphoid organs
produce lots of IL12
do cross presentation
31
CD123+ cells
plasmacytoid dendritic cells (the major producer of type I interferons, alpha beta)
32
class I cytokine receptors
IL246 12 , JAK, STAT
33
class II cytokine receptors
IFN alpha beta and gamma
34
what should you associate IFN gamma with
TH1, activation of macrophages
35
CCR5
tells dendritic cell to go to periphery and be resident there
36
CCR7
after DC has encountered antigen, this chemokine tells it to go to the draining lymph node
37
as the DC goes to the lymph node with antigen, what does it do to mature?
up regulated MHC I and MHC II, up regulate costimulatory molecules, up regulate adhesion molecules , acquire the ability to produce pro-inflammatory cytokines
38
what do cDCs express in the resting states
MHC II in INTRACELLULAR stores
little to no costimulatory molecules
39
upon maturation, what do cDCs express?
MHC II in PLASMA MEM
ICAM
LFA1
CD80/CD86 (B7.1 and .2)
40
how do dendritic cells present to CD8 cells if not infected themselves?
cross presentation
or transfer of antigen from an infected dendritic cell to a non infected dendritic cell
41
which DC is main producer of IFN alpha
plasmacytoid DC
42
which DC is main producer of IFN beta
conventiona myeloid l DC
43
what kind of cell expresses CD28
CD28 is constitutively expressed on T cells
44
what does triggering of CD28 induce?
T cell proliferation
IL2 production
T cell survival
(NFKB!)
very important but not ~absoluteyl necessary for survival~ b/c in absence, have weakened but not totally wiped out t cell activation
45
what other molecule in addition to CD28 is imp for NFKB pathway
PKC theta
46
ICOS
especially important for germinal center T cells --> T follicular helper cells that help B cells
47
what kind of cells express PD-1
activated T and B cells, macrophages
when bound to ligand, decrease downstream signaling of T cells and reduce T cell proliferation, survival and Il2 production
48
immune checkpoint blockade
prevents the induction of tolerance of T cells, or inhibition of activation by DCs of T cells
this means DCs can activate T cells
49
immune checkpoint
CTLA-4 and PD-1
both are inhibitory to T cell proliferation, survival and Il2 production
50
what kinds of cells can produce IL4
Ancillary mast cells
basophils
T cells
51
what induces Tregs to become Tregs
TGF beta
52
why are TFH so great at helping B cells make antibodies
because they have the right costimulatory molecule (ICOS)
| and the right chemotactic to get to the germinal center (CXCR5)
53
AIRE
allows expression of peripheral tissue antigens to be presented in the thymus; induces tolerance to the endocrine organs (pancreas, thyroid...)
without it, get APS = autoimmune polyglandular syndrome
54
addisons disease
adrenal insufficiency, clinical manifestation of AIRE impairment aka APS
55
clinical manifestations of ALPS
hypothyroidism, hypoparathyroidism, diabetes, addisons disease (adrenal insufficiency)
56
tolerogenic conditions
induce tolerance
therefore --> induce apoptosis or anergy
therefore--> signal 1 without signal 2 (apoptosis)
OR signal 1,2 without 3 (anergy)
57
what kinds of cells induce tolerance
resting DCs (low costimulatory molecules)
absence of adjuvant (APCs not activated)
presentation of cells that are not APCs (no costimulatory molecules)
58
signal 1
MHC:peptide
59
signal 2
costimulatory molecule (like CD80/86:CD28)
60
signal 3
pro inflammatory cytokines
61
In the absence of T cell help B cells are ____
anergized
62
what signals do B cells require to activate?
antigen:BCR
| T cell co-stimulation (CD40L:CD40 )
63
what can absence of Tregs lead to?
IBD and hemolytic anemia
64
EAE
experimental autoimmune encephalitis; experimental model of MS
65
what is oral tolerance mediated by?
TGF beta producing T regs
66
how is the tolerogenic process sustained?
Tregs induce tolerogenic DCs
67
does RA involve antibodies or T cells
auto reactive T cells
68
does diabetes involve antibodies or T cells
auto reactive T cells
69
does MS involve antibodies or T cells
auto reactive T cells
70
does SLE involve antibodies or T cells
both
71
does hashimotos involve antibodies or T cells
both
72
does graves involve antibodies or T cells
antibodies
73
does Sjogrens involve antibodies or T cells
both --> against ribonucleoprotein
74
genetic susceptibility to autoimmunity
GENES FOR
1) HLA
2) clearance of apoptotic cells (self presented without anti-inflame signals)
3) TCR/BCR signaling
4) neg regulation (ex: CTLA4)
5) Lymphocyte apoptosis (no Fas, no killing of bad stuff)
75
what do infections have to do with autoimmunity?
they can be the trigger or ADJUVANT
76
molecular mimicry
exposure to antigen that is super close to self-ag that initially the immune response is against the antigen but then it becomes against self (ex: Rheumatic fever )
77
APS
AIRE defect
78
ALPS
Fas defect; lympho-proliferative disorder in which failure of inducing apoptosis in T and B cells leads to accumulation of auto-reactive and abnormally activated lymphocytes.
79
key examples of monogenic autoimmunity
Defect in:
```
AIRE (APS)
Fas (ALPS)
FOXp3 (Tregs --> IPEX)
CTLA4 (graves, type 1 diabetes)
C1q (SLE)
```
80
two key mechanisms of autoimmunity
auto-antibodies
| auto reactive T cells
81
anti-chromatin antibodies
diagnostic for lupus
82
anti-nucleolar
diagnostic for scleroderma
83
what are some methods to detect autoantibodies?
ELISA or immunofluorescence
84
Ab-Dependent Cell-mediated Cytotoxicity (ADCC)
NK cells, neutrophils, eosinophils, macrophages and monocytes can kill opsonized cells using several mechanisms:
1) release of cytolytic granules containing perforin and granzymes like the CTLs
2) or other lytic enzymes like the neutrophils
3) or through the production of pro-apoptotic cytokines like the TNFa secreted by macrophages.
85
ADCC is a classic example of
adaptive immune system assisting the innate cells in clearing pathogens.
86
Goodpastures
AutoAbs deposit along the glomerular basement membrane; the autoantibodies are against the basement membrane collagen Type IV of the glomeruli in the kidney => glomerulonephritis
87
what pathology is due to stimulating autoantibodies
graves
88
what autoimmune pathology is due to direct cell damage
goodpastures
89
clinical manifestation of graves
hyperthyroidism
90
what autoimmune pathology is due to blocking autoantibodies
myasthenia gravis
91
myasthenia gravis
auto-antibodies bind Ach receptors on the skeletal muscle --> blocks binding of natural ligand acetylcholine and the transmission of the nervous signals;
also induces internalization and degradation of the receptors
92
clinical manifestation of myasthenia gravis
inhibition of skeletal muscle contraction and weakness.
93
4 ways that autoantibodies are pathogenic
1) direct cell damage (good pastures)
2) stimulating autoantibodies (graves --> hyperthyroidism0
3) blocking autoantibodies (myasthenia gravis --> muscle weakness)
4) immune complex (SLE which is type III hypersensitivity)
94
what kind of hypersensitivity is lupus
type 3
95
T cell help is required for
IgG autoantibody production
96
insulitis
destruction of islets of langerhans by CTLs, infiltration by CD4, DC and macrophages
97
what kind of T cell in hashimotos?
Th1
98
what gender is hashimotos more common in?
women
99
are their autoantibodies in hashimotos?
yes, it is an autoimmune disease involving both B and T cells; the auto-antibodies are against thyroid things like thyroid peroxidase and thyroglobulin
100
muscle weakness, ataxia, blindness and limb paralysis
MS
101
what are the antigens in MS
myelin basic protein, MOG (myelin oligodendrocyte glycoprotein)
auto-reactive T cells kill these and destroy myelin sheath
102
what stimulates innate immune cells in the beginning of RA
TLR
103
fibroblast-like synoviocyte
activated by TNF alpha and IL6; produce matrix metalloproteases and express RANK-L thereby activating osteoclasts
104
rheumatoid factor
IgM antibody to the Fc part of IgG
105
peptidyl arginine deaminase
PAD; inducible enzyme in RA that causes argnini to be changed to citrulline (removes charge); autoantibodies to citrulinnated peptides are found in 90% RA patients
106
ACPA
anti-citrillunated peptides autoantibodies
107
imp examples of citrulinated self peptides
citrullinated epitopes on fibrinogen, vimentin, fibronectin, collagen, enolase, and histones.
can induce NETosis!
108
4 tx options for autoimmunity
1) replacement therapy
2) general immunosuppression
3) targeted immunosuppression
4) re-establish normal tolerance (still experimental)
109
histocompatibility
the property of a tissue to be accepted and not rejected by the immune system
110
chronic rejection
vasculitis
111
hyperacute
antibody mediated
112
mandatory step to prevent hyperacute rejection
testing ABO in donor and recipient
113
what kind of hypersensitivity is the hyperacutre rejection
type 2
114
cross matching
screen recipients serum for antibodies against HLA
115
what assays are used for cross matching
complement dependent cytotoxicity (CDC)
flow cytometric crossmatch
Luminex (solid-phase assay)
116
PRA = panel reactive antibody
allows estimation of the percentage of the population against which a candidate has pre-formed anti-HLA antibodies
part of cross matching a transplant candidate
117
how do you desensitize recepient to a xenograft?
plasmapheresis and administration of intravenous immunoglobulins
118
molecular test to detect the DNA sequence of the HLA alleles
PCR
119
Mixed Leukocyte Reaction (MLR)
determines the strength of the response of the host/recipient T cells against donor cells in vitro. (takes 5 days)
120
what does anti-CD3 block?
signal 1
121
cross presentation
phenomenon of dendritic cells presenting on MHC Class I to CD8+ T cells Ags acquired from other cells (usually cells that went into apoptosis)
122
what activates apc in transplant?
danger signals introduced by surgeon and trauma
123
survival of mature dendritic cells and why its important
3-4 days; this is why direct recognition in transplant happens early and indirect recognition is more important later
124
AMR
antibody mediated rejection; can be preformed or CD4+ T cells that participate in indirect recognition can activate B cells to produce antibodies against the graft
125
T cells in presence of ___ and ___ can help B cells make antibodies
Il2 and Il4
126
TSA
tumor specific antigen; a "new" or "mutated self" expressed on tumor cells (Bcr:Abl)
127
TAA
tumor associated antigen; a protein that is expressed on normal cells in low amounts or on fetal cells that becomes upreg or expressed on tumor cells
128
Burkitt's lymphomas
translocated c-myc gene (c-myc is example of TAA that can get unregulated in cancer cells)
129
NK cell surface profile
CD3- CD4- CD8- CD16+
130
CTL surface profile
CD3+ CD4- CD8+ CD16-
131
how do NK cells recognize tumor?
they do not recognize TSA or TAA, instead they note the lack of MHC; they are not specific in their response; they are part of innate immunity, first line of defense, no memory
132
How do CTL cells recognize tumor?
acquired immunity, delayed but SPECIFIC response; they get sensitized, create memory and have a clonotypic antigen receptor; respond to TSA or TAA
133
what can have decreased MHC?
virus infected cell or tumor cell; this is very important because this causes NK cell to kill it but also prevents the foreign antigen from being presented to T cell
134
in what diseases are all Ig classes low
bare lymphocyte, bruton's x linked agammaglobulinemia , common variable hypogammaglobulinemia
135
Wiskott Aldritch
IgM low, IgG normal, IgE and IgA ElevAted
136
Ataxia talengensia
IgM normal, IgG normal or low, IgA and IgE decreAsEd
137
radioallergosorbent assay = RAST
laboratory procedure that is designed to measure specific antibodies against given antigens (allergens). Usually looks at IgE specific for common allergens
138
skin test
Test for allergies; Skin test is viewed as better for the correlation of allergies.
139
mast cell degranulation is assoc with what kind of T cell response
TH2
140
chronic ashthma is assoc with what kind of T cell response
TH2
141
Derp1
cleaves occludin; primes TH2 response
142
most allergens are proteins and many function as ___ which break intercellular junctions and allow the penetration of the allergens to the mucosal surface
proteases
143
SPINK5 gene
codes for LEKT1 which usually inhibits serine peptidase
| mutated in netherton syndrome
144
clinical manifestations of Netherton syndrome
erythroderma (generalized skin erythema, pruritus, scaling of the skin, shivering, fatigue and fever)
atopic eczema
hair abnormality
145
Netherton syndrome
mutation in SPINK5 gene causes LEKT1 inhibition of serine processes to be released ("inhibition of inhibition") therefore serine peptidase destroy lots
