Hypersensitivity Reactions Flashcards
(364 cards)
1
Q
type I hypersensitivity
A
immediate - following rexposure to antigen they are hypersensitive to the response is immediate, can detect within minutes
2
Q
type I hypersensitivity is mediated by Ig
A
E
3
Q
type II hypersensitivity are mediated by Ig
A
M or IgG
4
Q
type II hypersensitivity is result of
A
antibody eing generated against a cel surface antigen
5
Q
type III hypersensitivity is mediated by Ig
A
usuallyu IgG
6
Q
type III hypersensitivyt
A
formation of immune complexes b/c it is soluble antigen, deposition of antibody antigen complexes at particular sites in body that gives rise to symptoms
7
Q
Type IV hypsersensitivity is mediated by
A
t cells
8
Q
type IV hypersensitivity
A
delayed reaction, will take two or more days, mediated by T lymphocytes
9
Q
type IV hypersensitivity is similar to
A
type I response
10
Q
what t cell type is involved in DTH response
A
Th1
11
Q
inhaled antigens generally give rise to what hypersensitivity response
A
type I
12
Q
materal into circulation (injection, drugs, etc.) generally gies rise to what hypersensitivity response
A
I or III
13
Q
ingested materials generate what hypersensitivity response
A
type I
14
Q
result of allergins, especially chemicals and metal ions in contact with skin, like poison ivy or nickel generate what hypersensitivity response
A
type IV
15
Q
type I hypersensitivity response results form allergin rexposure binding to
A
IgE coated on surface of mast cells
16
Q
IgE response against alergin than what Th response is involved
A
Th2
17
Q
to get type I hypersensitivity response you need
A
IgE
18
Q
IgE is found in very low concentrations inserum, majority is foudn bound to
A
high affinity receptors Fcepsilon RI on mast cells
19
Q
once allergin is reintroduced into individual sensitized to the allergin, the allergin can crosslink
A
Fcepsilon receptors
20
Q
for alergin to cross link Fcepsilon receptors there has to be at least
A
two antibodies specific for that antigen bound to that mast cells
21
Q
type I response has two phases:
A
early stage and late stage
22
Q
Type II HRS is with antibody produced against
A
surface antigen
23
Q
once antibody binds to antigen in type II HRS
A
destruction of cell, drug induced hemolytic anemia
24
Q
type III HRS
A
antibody produced against soluble protein, antibody produced by B cell specific for foreign protein will form immune complexes that can be in walls of blood vessels, which will activate complement, so anything downstraem is initaited by activation of classical pathway of complement, including neutrophil of netrophil
25
what from complement recruits neutrophil
C5a
26
type IV HRS
not antibody mediated, response by Th1 cells, normal self proteins beingind to surface protein, so self peptide presented by DC or langerhans going to regional lymph node and it will be recognized as foreign by t cell and they will migrate back to site of exposure and activate macrophages to do classic cell mediated response
27
soluble anigen being recongized by IgE and mast cell activation and degranulation is
Type I HRS
28
most serious result of type I HRS
anaphylatic shock
29
mediated by IgG or IgM, directed against moleculs on surface of cell, that can result in destruction of cell
Type II HRS
30
what is IgM best at activating
complement
31
IgG directed aginst soluble antigen resulting in formation and deposition of immune complements to compelent activation and recruitment of phagocytes is
Type III HRS
32
serum sickness is result of
type III HRS
33
drug allergies usually result of
Type II HRS
34
cell mediated, Th1 and CTL component
Type IV HSR
35
antigen that gives rise to allergic response is called
allergen
36
allergic response is
an undesirable physical reaction, or a state of hypersensitivity. “Allergy” is generally synonymous with HSR I
37
most serious case of Type I HSR can result in
anaphylaxis
38
anaphylaxis is
is a serious, life-threatening allergic reaction. The most common anaphylactic reactions are to foods, insect stings, medications and latex.
Anaphylaxis can cause you to go into shock (blood pressure drops suddenly and airways narrow) and if untreated can be fatal.
39
anaphylaxis if atal if
untreated
40
atopy definition
similar to allergy, but this refers to genetic predisposiiton to generate allergic response
41
central feature of Type I HSR
IgE
42
sensitization phase is (of Type I HSR)
initial part where you will produce IgE from the first contact with allergen
43
allergens that gives rise to type I HSR are usually
small soluble polypeptides delivered at low doses
44
common inhaled allergens
pollens, dander from animals, mold spores, house dust mite
45
common ingested materials that act as allergens
food, orally administered drugs
46
two major components to deveopment of type I HSR
genetic factors
| enviornmental factors
47
hygiene hypothesis
exposure to bacteria as a child generates a Th1 response, if not you will generate a Th2 response and could be more susceptible to develop allergies
48
what is the enviornemnt part of type I HSR
thought to be about hygeiene and whether you have been exposed to bacteria at a young age
49
with a high genetic susceptibilitybackground and in hygenic enviornment you will develop:
atopic or allergy
50
if you are raised in less hygienic enviornemnt (exposed to micro-organisms) and genetic susceptibility is lower, you will not generate
atopic or allergic response
51
MHC II is associated with the development of
type I HSR
52
why is MHC II associated w/ type I HSR
need to isotypte sitch so need t cell help and CD4 cell help
53
TLR and their polymorphisms are associated w/ developmen tof
Type I HSR
54
polymorphisms associated with overproduction of ceratin
cytokines, leading to heightened response
55
to enhacne presentation to allergins for type I HSR are what genes
MHC class II genes & TCR alpha locus (pg 14)
56
type I hypersensitivity push you toward
Th2 response
57
increased expression iof IL _ are associated with increase type I HSR
IL-4
58
describe hygiene hypothesis
lack of exposure to microbes as a child, can be overuse of antibiotics and over-clean enviornmen
you want Th1 response, so following allergen exposure they will not have hypersensitivity. if enviornment is more sterile, you will generate more Th2 resopnses, following allergen exposure will generate Th2 response and Type I hypersensitivity
59
features of Th2 response are mediators important for dealing with
helminth parasites
60
Th2 response, what components?
Th2 cells
IL: 3, 4, 5, 9, 10, 13
IgE
61
wherever you are likely to be exposed to parasitic infections you are less lieklyk to have
allergy
62
majority of IgE is found hwere
surface of mast cells, not in circulation, also basophils
63
for most Fc receptors the antibody has to be bound to antigen, but the exception is
IgE
64
IgE will bind to high affinity of epsiolon receptor in absense of
antigen
65
if allergen gets into blood stream it can cause
anaphylaxis
66
site of allergen exposre in IgE mediated allergic reactions
inhalation
| defect in skin barrier
67
essential antibody in Type I HSR is
IgE
68
IgE bound to Fc epsiolon recptors on mast cells are crosslinked which causes release from
mediators from granules that gives rise to type I HSR
69
IgE has extra
constant domain: 4
70
how many constant domains does IgE have
4
71
IgE normally has very ___ concentratoin in serum
low
72
Fc portion binds to what on mast cells
Fc epsion receptor, very tightly
73
granules released from mast cells contain
histamine, some TNF alpha, leukotrienes
74
release of mediators by mast cells cause what of Type I HSR
early or immediate phase of type I HSR
75
what enzymes are released from mast cells
enzyme: tryptase and chymase
76
what toxic mediator is released in mast cells
histamine & heparin
77
what cytokines are released from mast cells
TNF alpha
78
what does TNF alpha do
pomotes inflammation
79
what response does TNF alpha contribute to in Type I HSR
late stag
80
what lipid mediator are rleased from mast cells
prostaglandins, leukotrines, platelet activating factor
81
essential first step of Type I HSR is activation of
Th2 cells by allergen presented by antigen presented cells which will promote IgE
82
what is sensitization phase of Type I HSR
Allergen activated Th2 cells promote IgE production by production of IL-4 and IL-13
83
in sensitization phase the pt will not have ____
symptoms
84
eotaxin is
chemoattractant for eosinophils
85
Th2 cells secrete what cytokines
IL-5 and eotaxin to recruit eosinophils to site of reaction
86
cyokines produced in Type I is what phase
late phase
87
what do eosinophils release
enzymes and toxic protein & lipid mediators
88
what cytokine is needed to differentaite from Th0 to Th2
IL-4
89
IL-4 induceses expression of TF
GATA3
90
sensitization of Type I HSR involves class switching to
IgE
91
following rexposure of allergin in Type I HSR
get crosslinking, degranulation, early phase
92
following eposure to antigen (Type I HSR) you generate a primary response which is the
sensitization stage
93
in sensitization stage there will not be any
symptoms
94
what is elicitation stage of Type I HSR
secondary response
95
what happens in eliciatation stage of Type I HSR
symptoms
96
allergen sensitization is very similar to
parasite Ag sensitization
97
what cytokines are needed to swith to IgE
IL4 and IL13
98
rexposure of allergin with Type I HSR is what phase
elicitation
99
immediate phase of Type I HSR happens within
minutes
100
late phase of Type I HSR happens in what time
up to 24 hours after exposure
101
why does late phase take so much longer in Type I HSR
recruitment of inflammatory cells and recruitment of cytokines
102
immediate response being so quickly is due to release of
release of histamine, serotonin, heparin, tryptase
103
what is wheal
fluid filled itchy bump - edema
104
what is flare
redness - erythema
105
what are second wave mediators, in late response (Type I HSR)
prostaglandins, leukotrienes, heparin, cytokines (pg 33)
106
inhaled allergins give rise to
hay fever
107
seasonal rhinoconjuctivitis is
hay fever
108
what is the response to hay fever
edema of conjunctiva and nasal mucosa, sneezing
109
food allergins most commonly give rise to what symptoms
vomitting and diarrhea, can be more serious: systemic anaphylaxis
110
wheal and flare rxn symptoms:
hives
111
actute uticaria is
hives on skin
112
systemic anaphylaxis, route of entry of allergin is
intravenous
113
what is respnse of systemic anaphylaxis
systemic mass cell degranulation, drop in blood pressure, can be fatal, collapse of blood vessels, most serious form of type I hypersensitivity
114
most serious response of type I HSR
systemic anaphylaxis
115
inhaled allergins, if not confined to upper respiratory tract, that can go to bronchi, etc (like cat dander) can give rise to
allergic asthma
116
effects of mast cell degranulation depends on
where and how antigen is encountered
117
where can antigen be encounteredfor mast cell degranulation
GI tract
eyes, nasal, airways,
blood vessels
118
route of encounter with allergin determins what of type I HSR
symptoms
119
most serious form of type I HSR response
intravenous in injection of high dose of allergin
120
allergin via injection and high does,e, what happens
fluid moving from circulation into tissues, collapse of blood vessels
121
inhalation f allergin at low does gives rise to
hay fever, asthma
122
subcutaneous low dose response with Type I HSR
local release of histamine, wheal and flare rxn
123
ingestion of allergin at low dose, symptoms type I HSR
vomiting, diarrhea, if in circulation more systemic affects like anaphylactic shock
124
inhaled allergins is due to what kind of antigen inhaled
solublw
125
soluble inhaled antigen activates
protein
MHC II
CD4 T cells
126
what t cell response necessary for type I HSR
type 2
| Th2
127
inhaled antigen results in production of what binding to mast cells
```
B cells
Th2
IL-4, IL-13
IgE
Mast cells
```
128
important features of inhaled allergens:
low dose
| proteins, because that's what t cells can recognize & need to be able to bind to MHC II
129
low dose promotes differentation of Th0 to
Th2
130
high dose promotes diferentiation of Th0 to
Th1
131
main features of type I response in respiratory tract in upper tract
allergic rhinitis
132
main features of type I response in respirtatory lower tract
bronchial asthma
133
allergic asthma is more serious b/c it ca be associated with
difficulty breathing
134
chronic ashtma can be caused from bronchial asthma due to
eosinophils, toxic to host cells
135
allergens associated w/ respiratory type I HSR:
pollen, dust mites, fungal hyphae, spores, animal dander
136
large particles for respiratory type I HSR are limited to
upper airways
137
large particles for respiratory type I HSR are associated with what response
hay fever
138
smaller particles inhaled allergens for typw I HSR respiratory can be associated with
asthma
139
IL-4 and IL-13 promote
IgE production
140
IL5 activates
recruits activated eosinophils
141
allergin cross links receptors on surface of mast cells whch causes
degranulation of mast cells
142
after degranulation of mast cells what will be released
cytokines and eosinophils
| IL-5 will activate eosinophils
143
allergic asthma is example of what kind of asthma
extrinsic asthma
144
intrinsic asthma caused by
unknown, thought to be stress, exercise, cold temperatures, drug induced (aspirin)
145
look at chart
pg 41
146
hives are example of what response from type I HSR
wheal and flare response
147
dermatitis is a form of
eczema
148
atopic urticaria is
hives
149
what is basic for skin test to diagnose type I HSR
atopic uticaria (wheal and flare)
150
usually atopic urticaria will resolve and not leave a
mark/trace
151
usually atopic urticaria will resolve itself, if not can give
steroids
152
in chronic form of atopic dermatitis what happens to epidermis
it thickens
153
Atopic dematitis (eczema) is the epidermal equivalent of
chronic asthma
154
what allergens give rise to Atopic dematitis
a lot unknown, can be food, inhalant
155
a person who has type I response to an allergen will often have multiple
responses to different alelrgens
156
what is lichenification
thickening of skin b/c of scratching
157
biopsy of skin with atopic dermattitis, wil find
activated CD4+ memory Th ceols and elevated serum IgE
158
for majority of time with not severe food allergies the symptoms happen
in GI tract
159
most food allergies are what kind of HSR
type I HSR
160
most common food allergens
nuts (especially peanuts), shellfish, eggs, cow’s milk and soy proteins, (gluten not Type I HSR).
161
response against gluten is what kind of HSR
type IV HSR - triggers celiac disease
162
what is sytemic anaphylaxis
Bronchial and tracheal constriction, complete vasodilation.
Shock, multi-organ system failure and death are possible outcomes
163
penicillin acts as a
hapten
164
penicillin (hapten) in itself will not enduce
immune response
165
how does penicillin induce type I HSR resopnse
Penicillin modifies self protein and presented by macrophages
T cell helps activated B cell to switch to IgE
Mast cells are armed with IgE
Armed mast cells degranulate
166
site of exposure determines
what symptoms you get
167
tryptase is enzyme released
upon degranulation of mast cells
168
elevated serum tryptase is indication of recent
anaphylactic rxn
169
when is peak of serum tryptase
30-70 min following antigen exposure
170
individuals w/ serious allergies are advised to carry EPI pen b/c EPI will
counteract drop of blood pressure during systemic anaphylaxis
171
how you diagnose if someone has a type I HSR
skin test to detect if pt has wheal and flare rxn -they will generate hive if they are allergic
172
what is only test that will determine if someone is allergic to something
wheal and flare rxn test
173
IgE can tell you if somebody has response but
other people can have high levels of IgE and not have allergy
174
basis of wheel and flare response
increase in vascular permeability alowing seapage of fluid and proteins into tissue
175
positive control of wheel and flare response
histamine
176
what is wheal
raised patch of skin in the center
177
what is the flare
red flush around the outside of response on skin
178
wheal and flare response aginst someone who has type IV response what would happen
you would get similar looking response as with the type I but it would take two hours to happen
179
individuals with type I hypersensitive responses are often allergic to multiple
allergins
180
can test if indiviaul has IgE against allergin, what does this tell you
it can indicate if they have allergy, but is not definitive b/c you can have IgE and not be allergic
181
what test is used to do IgE test
RAST
182
RAST STANDS FOR
RADIOALLERGOSORBENT TEST
183
describe RAST
allergin coated onto disk, add serum from pt, if they have antibodies specific for allergin the antibodyies will bidn to allergin immobilized on disk, so have disk with allergin and allergin specific antibody. you aren't interested in IgG, you want to detect IGE specific for allergin. use radiolabeled anti-human IgE antibody, if you add it to disk and disk have IgE antiallergin added to it it will bind and you can detect by putting the disk into counter
184
what is often used instead of rast
ELISA
185
ELISA, DESCRIBE
wells coated w/ allergin, then add pts serum, so fi pt has IgE specific it will bind to allergin on wells, then detect if IgE has bound to allergin, so have another layer that is commercially antibody that will bind to human IgE with enzyme attached, then add substrate and if it is bound then you will either get color change or fluorescence
186
what is the best way to treat type I HSR
avoid allergen
187
how do you block mediators for type I HSR
block mediators - Antihistamines, leukotriene inhibition, corticosteroid inhibition of NF-kappaB
188
NF kappa B is required for production of
pro-inflammatory cytokines
189
desensitization as treatment for type I HSR
injection into skin of minute quantities of allergen and then gradually increase over two year period, can convert response into IgG response
190
prevent IgE mediated degranulation as treatment for type I HSR, describe
binds to Fc portion of Ige and prevents IgE from binding to mast cell
191
describe monoclonal antibody as a treatment for Type I HSR
IgE binding to mast cells is blocked
192
when desensitization works you get production of what
IgG and IgG
193
how does desensitization work
IgG will be made and it will bind to allergen so that IgE doesn't get a chance to
194
draw chart of type I hypersensitivty rxns
pg 65
195
what is tie frame of Type I HSR following re-exposure
minutes, it is immediate
196
what is the immunologic mechanism? (Abs, or T cells? INnate cells? cytokines?) type I HSR
IgE is the ab
Th2
innate: mast cells, eosinophiles, basophils
cytokines: IL-4 & 13, IL-5, eotaxin
197
the immune response elicited in type I HSR is usually directed to which pathogens?
parasitic infections
198
name the two stages of type I HSR
early and late (sensitization & elicitation)
199
describe the immediate and late phase responses in type I HSR
immediate: degranulation products of mast cell (eesp histamine)
late phase: leukotrienes and prostaglandins and cytokines, and cells attracted like eosinophils
200
name some allergens for type I HSR
cat dander, ragweed
201
what feature do allergens ahre? type I HSR
proteins - they have to be able to be recognized by t cells
202
type II HSR mediated by
IgM or IgG
203
type III HSR mediated by
IgG - directed against soluble antigen
204
in type II IgM or IgG is directed against
cell surface antigen
205
type III HSR is directed against
soluble protein
206
when antibody binds to antigen (ike type II and III HSR) what can happen
ctivation of complement
207
IgG binding to cell surface antigen can do what
opsinize that cell and target it for phagocytosis
208
two main type sof type II HSR
cytotoxic & non-cytotoxic
209
cytotoxic type II HSR lead to
death/destruction of cell
210
non-cytotoxic type II HSR lead to
degranulation of mast cells
211
example of non-cytotoxic type II HSR
graves & myesthenia gravis
212
type II HSR, what is common cause
drugs, like penecillin
213
differences b/w type II and I HSR (4)
isotype of Ig, type II is never IgE and type I is only IgE
antigen recognized in type I is soluble, antibodies in type II recognize cell surface or extracellular matrix
antibody binding to self protein leads to classical complement activation in type II (so can result in opsonization, phagocytosis, MAC, phagocytosis)
214
what are particuaily prone to lysis by complement
RBC
215
frustrated phagocytosis:
neutrophil releases its stuff directly into tissue
216
following binding of antibody in type II HSR what happens
recruit inflammatory cells
opsonize or activate complement
interfere w/ cellular functions
217
complememt will recruit and call over what cells
neutrophils and macrophages
218
c3b will do what to cells
opsonize
219
how is tissue injured in type II HSR
complement recruites leukocytes & macrophages
opsonization
hormone receptor signaling (pg 72)
220
describe complement activation of tissue injurty in type II HSR
neutrophils recruited and activated, they will engulf or destroy cell or relase their ROS and degrative enzymes into tissue and cause tissue injury
221
describe opsonization & phagocytosis in type II HSR in regards to tissue injury
C3b binds due to complement activation leads to phagocytosis
222
myasthenia gravis
blocks binding of ACh to receptor, antibody is antagnositc antibody
223
graves' disease
pg 74 notecard
224
hemolytic disease of the newborn is caused by
IgG directed against fetus antigen, attacks RBC of fetus and fetus can be still born
225
describe hemolytic disease of newborn
IgG directed against fetus antigen, attacks RBC of fetus and fetus can be still born
226
describe transfusion/transplantation reaction
Natural antibodies to ABO blood group antigens cause hemolysis of non-matched donor RBCs (or hyperacute rejection of a donor transplant)
227
blood group antibodies are all
IgM
228
HDNB stands for
Hemolytic Disease of the Newborn
229
when does HDNB occur
RhD negative mother and RhD positive fetus
230
consequence of HDNB and blood mixing
mother is immunized against RhD antigen
231
what is sensitization phase of HDNB
mixing of mom and baby blood and mom develops antibodies against RhD
232
what happens with second pregnancy for mom who was sensitized to RhD positive if she has a second RhD positive baby
it would attack baby blood
233
what is treatment for HDNB
prevent antibody forming against IgG (RhD positive)
234
what is Rhogam
antibody to protect against HDNB
235
when is other treated with Rhogam
28 weeks, 36 weeks, at birth
236
what does rhogam do
prevents b cell activation and memory cell formation by blocking Rh antigen from activating maternal b cells
it is specific for b cells that would bind the RhD
it prevents activation of RhD positive by signaling through the negative co-receptor on b cells
237
would IgM anti-Rh work?
no, because the constant region of IgM is not gamma, it's mu, so IgM cannot bind to gama receptor
238
review pg 81
81
239
notecard
pg 82
240
type A recipient, type B donor, what antibody
anti-B antibody that will attack the transfused RBC from donor
241
penicillin rxn b/c penecillin can bind to
glycoproteins on our cells, generates antibody against the protein, leading to hemolytic anemia
242
how does penecillin act as hapten
it can modify proteins to create foreign epitopes, which leads to destruction of the RBC either by phagocytosis or ADCC, the drug modified penecillin protein is presented to Th2 leading to production by B cell of high affinity isotype switched
243
myasthenia gravis
autoantibody against Ach
244
graves disease
autoantibody against thyroid stimulating hormone
245
certain compounds that can give rise to all 4 HSR
like penecillin, hapten
246
how do you determien what HSR it is with something like penecillint hat can give rise to all 4 HSR
timing & symptoms
247
Type III HSR are
immune complex diseases
248
Type III HSR, where will immune complex deposit
skin, joints, blood, kidney
249
antigen component of Type III HSR immuen complex is
poorly catabolized antigen
250
antibody most commonly involved in Type III HSR
IgG
251
just like type I HSR the antigen recognized by antibody for Type III HSR
soluble
252
immune complex deposited where in blood in Type III HSR
vessel walls
253
why do immune complexes deposit in blood vessels in Type III HSR
FC gamma dnc omplement receptors
254
when complement is generated in response to Type III HSR what happens
C3a and c5a, which will attract neutrophils, damage to endothelial cells: tissue factor, coagulation cascade, so occlusion of blood vessels
255
how do you distinguish Type III HSR from type II?
type II: antibody binds to anitgen of surface of cel or ECM, so specific damage
type III: deposition can occur throughout body, not due to specific interaction b/ antibody and immune complex, so bystander destruction
256
what do type II and III HSR have in common
never IgE
257
Type III HSR result from
immune complex that are poorly handeled/poorly eliminated
258
why are Type III HSR poorly eliminated
their size - they are usually small circulating immune complexes
259
3 main types of immune complexes depnging on ratio of
antigen to immunogen (?)
260
in antigen excess will only form
small immune complexes
261
small immune complexes at beginning of response will not activate
complement
262
zone of equivalents:
ratio of antibody to antigen is roughly the same
263
what happens when ratio of antibody to antigen is roughly the same
large complexes that are efficienty removed
264
antibody excess stage in ratio of antibody to antigen is roughly the same
medium sized immune complexes that are efficiently removed from circulation
265
how are immune complexes normally removed from body
RBC have CR1 receptor
| so RBC ahdn off the complexes to splenic macrophages and cooper cells
266
CR1 is receptor for
C3b
267
CR1 on RBC & WBC
RBC have much less receptor on their surface, but b/c there are so many RBC compared to WBC theya re most important for delivering immune complexes to liver and spleen for their removal
268
once immune complexes in liver and spleen the phagocytes have
CR1 & FC gamma receptors
269
how do phagocytes bind and take the immune complexes from RBC
they have much higher affinity
270
review pg 94
94
271
small immune complexes do not efficiently bind to
RBC
272
class places small immune complexes accumulate
small blood vessel
renal glomerulus
skin and joints
273
when level of immune complexes exceed disposal mechanisms, then
IC can deposit
274
what are the most systemic autoimmune disease
immune complex disease
275
IC stands for
immune complex
276
IC deposit in cell wall which attracts
neutrophils, IL-8, tissue factor, C3bR and (pg 96)
277
characteristics of ratio of antibody to antigen is roughly the same
directed against self or foreign soluble antigens
caused by deposition of antigen/antibody complexes (immune complexes) in tisue and blood vessels
tissue damage by neutrophils and possible generation fo MAC and complement mediated lysis
clotting cascade and so ischemic damage to tissues and scarring
278
arthus reaction
localized inflammatory response
279
intravenous delivery of high doses of antigen can give rise to (Type III HSR)
serum sickness
280
subcutanous route of Type III HSR can give irse to
arthus reaction
281
inhaled route of Type III HSR can give rise to
farmer's lung
282
farmer's lung
deposition of IC in alveoli
283
faermer's lung has same mechanism as
arthus reaction
284
serum sickness:
any soluble protein, antigen usually Immunoglobulin from passive immunization
285
antibody generated against streptococcal will form
small complees wnad deposit in kidney
286
Post-streptococcal glomerulonephritis can be caused by
streptococcal antigens
287
staining pattern of glomerunoephrits
lumpy/bumpy
288
if serum sickness is a response against what foreign antigen what happens
antigen will be removed
289
if intravenous injection is anti-venom (passive immunization), draw out serum sickness graph
pg 101
290
associated w/ inflammation you will have
fever
291
post-streptococcal glomerulonephritis want to see if there are
IC deposited
292
stain biopsy with antibody against IgG to see if pt has IC deposited following streptococcal
will see granular or lump-bumpy pattern (pg 103)
293
arthus rxn is
localized visualized resposne
294
what test can you do to see if pt has Type III HSRs
arthus rxn test - skin test
295
what is timing for Type III HSRs for skin test (or any repsonse)
hours
296
describe arthus rxn for Type III HSRs
local injection w/ antigen
local immune complexes form, c5a binds which attracts neutrophilsdegranulation of mast cells due to binding of FcgammaR
mast cells activated them formation of lesion that looks like what it does in type I HSR, it just takes longer than with type I
essentially wheal and flare response, timing is very different from type I
297
minimum timing for Type III HSRs rxn
2 hours
298
tetanus booster can give rise to what response
Type III HSRs
299
inhaled allergens from spores can give rise to arthus rxn at what site
alveoli
300
chronic farmer's lung is what type of HSR
IV
301
cwhat cells required for Type IV HSR
th1 cells
302
Th1 clls activate
CD8 cytotoxic t cells
303
how long does Type IV HSR take
48-72 hours, so about 2 days after antigen exposure
304
what cytokine important for activating macrophage
IFN gamma
305
Type IV HSR symptoms
```
contact dermititis (poison ivy, nickel)
most common form of transplant rejection
```
306
type Type IV HSR are inappropriate manifestation of
normal Th1 response against intracellular bacterial and fungal infection
307
delayed-type hypersensitivity response describe
redness, swelling, induration, cellular infiltrate, so it is hard bump
308
what is antigen in delayed type hypersensitivity
protein
309
what is antigen for contact hypersensitivity
haptens
310
what are examples of antigens for contact hypersensitivity Type IV HSR
nickel, poison ivy
311
describe Type IV HSR tiem course
antigen injected into subcutanous tissue
Th1 effector cell recognizes antigen and releases cytokines, they act on vascular endothelium
recruitment of phagocytes
312
what causes swelling in Type IV HSR
infiltration of t cells
313
Th1 cells release
chemokines: CXCL2 especially
| IFN gamma
314
CXCL2 recruits
monocytes
315
IFN gamma activates
macrophage and promotes differentiation from monocytes into macrophages
316
IFN gamma induces expession of adhesion molecules on
vascular endothelial cells
317
LT stands for
lymphotoxin
318
TNF beta new name
lymphotoxin
319
TNF alpha and LT can induce
local tissue destruction
320
local Th1 cells secrete
GM-CSF
321
GM-CSF promote
production of monocytes by bone marrow
322
persistnet stimulation of Type IV HSR can give rise to
granuloma & contact hypersensitivity
323
test for Type IV HSR
put some on skin to see if there is rxn
324
tuberculin response
ejection of TB into skin to see if there is response (TB test)
325
Tdth is same as
Th1
326
tuberculin rxn is an example of what response
Type IV HSR
327
sensitization phase in Type IV HSR
generation of type of response that will ultimately give rise to symptoms
328
what is generated during sensitaation phase of Type IV HSR
Th1 from Th0 cells
329
what is signal to make Th1 from Th0
IL-12 & IFN gamma
330
what is lineage specific TF from Th1
Tbet
331
elicitation phase of Type IV HSR happens following
rexposure
332
are there symptoms in sensitzation phase of Type IV HSR
no
333
are there symptoms in elicitation phase of Type IV HSR
yes
334
what cytokines are involved in elicitation phase of Type IV HSR
IFN-gamma, TNF-beta, IL-2, IL-3 and GM-CSF
335
what chemokines are involved in elicitation phase of type IV HSR
IL-8, MCAF and MIF
336
MIF stands for
macrophage inhibition factor
337
how do we keep macrophages in area we want
MIF
338
describe elicitation phase of Type IV HSR
Macrophages are activated by IFNgamma & TNFbeta. They migrate to the site following a trail of IL-8 and MCAF, stop when they get there under the influence of MIF, and are activated to secrete their own cytokines by MCAF & CD40/CD40L interaction.
339
MCAF stands for
Macrophage Chemotactic and Activating Factor
340
what usually gives rise to contact dermatitis
nickel, rubber, poison ivy
341
how does contact dermatitis from type IV present
lymphocytes, later macrophages,edema of epidermis
342
sensitization phase of contact dermitisis for type IV, list all the steps
```
hapten introduction into epidermis
hapten-carrier complex
taken up by APC in epidermis - langerhans cell (LC)
migrate to lymph node
to paracortex
present antigen to naive CD4 T cell
CD4 T cell differentiate into Th1 cells
```
343
elicitation phase of contact hypersensitivity type IV HSR list steps
antigen specific CD4 Th1 cell
they migrate to epidermis
macrophages migrate to epidermis
macrophages migrate to epidermis
344
following second exposure to contact allergin ( like poison ivy) what happens
IFN gamma activates macrophages
MIF keeps macrophages to stay in tissue
IL-8 and MCAF also released
damage caused by release of enzymes from macrophages once they are activated
345
what enzymes to macrophaegs release that cause tissue damage
hydrolases & oxidases
346
besides contact hypersensitivty type IV HSR can cause
granuloma
347
response against intracellular bacteria that are difficult to control
granuloma
348
time frame for generation f granuloma
3-4 weeks
349
appearance of formation of granuloma
hadening of skin or lung
350
what will you see on histological magnification of granuloma
lots of macrophages, some t cells
| cells that arise from macrophages: epithelioid cells, giant cells, fibrosis
351
type s of antigens that give rise to granuloma
persistent infections that we cannot resolve
352
what are clinical examples that would give rise to ganuloma
tuberculosis, sarcoidosis, leprosy, schistosomiasis
353
steps in formation of granuloma (for example with TB)
pathogen picked up by M cells and brought o lamina propria
dendritic cells take it
DC to go lymph node
DC present to naive CD4 T cell in paracortex
clonal selection & clonal proliferation
activate macrophages
macrophages proliferate & fuse at center
at very center of macrophages are the ones that contain live TB
354
skin test to test for type IV HSR
TB test - inject into skin
355
what is the skin TB test called
PPD
356
clinical appearance of rxn to TB test (PPD)
localized swelling
357
PPD stands for
purified protein derivitive
358
what are the majority of the cells that respond to TB
macrophages - less than 5% will be TB specific t cells
359
review pg 130
130
360
what is time frame of type IV HSR
2-3 days
361
type IV immune mechanism is normally the immune response to what?
intracellular pathogens - viruses, bacteria, protosoan, fungi
362
another name for TDTH?
Th1
363
review slide 131
131
364
review slide 132
132
