Immuno CCOM 3 Flashcards
(146 cards)
1
Q
What do Leukotrience C and D do?
A
smooth muscle contraction
increased vasc. permeability
mucus secretion
Leukotriene B formation
2
Q
What does Leukotriene B do?
A
chemotactic for neutrophils
3
Q
Oxidation of arachidonic acid via cyclooxygenase yields what?
A
PGs
thromboxanes
4
Q
Oxidation of arachidonic acid via lipoxygenases yields what?
A
Leukotrienes C and D
5
Q
What do PGs and thromboxanes do?
A
vascular and smooth muscle tone
platelet aggregation
immune reactivity
6
Q
What does Platelet Activating Factor do?
A
platelet aggregation and secretion
neutrophil aggregation
degranulation
O radical release
7
Q
What does TNF-a do in allergy repsonses?
A
actiavtes endothelium extravasation
proinflammatory
8
Q
What are the 3 events characteristic of asthma?
A
- reversible obstruction (mucous)
- brochial hyperresponsiveness
- inflammation
9
Q
What are the 3 possible lethal outcomes of Type 1 hypersensitivity and why?
A
- asphyxiation - largyngeal edema
- suffocation - bronchiole constriction
- shock - overwhelming peripheral edema
10
Q
How do antihastamines work?
A
compete with histamine for H1 and H2 receptor sites on effector cells
Used prophylactically
11
Q
What does chromalyn sodium do?
A
stabilizes mast cell membranes and prevents degranulation prior to exposure of allergen
12
Q
What do corticosteroids do?
A
Prevents arachadonic acid pathways –> prevents late phase reactants
13
Q
Which cytokines stimulate eosinophil growth and differeentiation?
A
GM-CSF
IL-3
IL-5
14
Q
How does Omalizumab work?
A
humanized anti-IgE Ab
Inhibits binding of IgE to FceRI on mast cells and basophils
15
Q
How does Singulair work?
A
Leukotriene receptor antagonist
Blocks action of Leukotriene D4 on CysLT1 receptor
16
Q
What is the timing of initial and late phase repsonses in T1H?
A
initial: minutes
late phase: hours
17
Q
Describe the hyposensitization technique
A
injection of diluted allergen with increasing concentrations over months
18
Q
What are the theorized mechanisms for hyposensitization?
A
- blokcing Abs are formed (IgG) and will bind up and remove allergens before they reach IgE
- CD8 T-suppressor cells induced
- Switch from Th2 to Th1
19
Q
Describe desensitization (ie to antibiotics) and how does it work
A
- Administer allergen increasingly over hours
- Trigger sublethal doses of histamine release from mast cells, to deplete them of granules so larger therapeutic dose can be given
20
Q
What are some classic examples of T2H?
A
Transfusion reactions
Rh incompatibility
drug induced reactions
some autoimmunes
21
Q
Briefly describe T2H
A
Involved INSOLUBLE antigens( cells or tissue) and Abs of IgM or IgG.
22
Q
What mechanisms are involved in T2H?
A
- classical complement and lysis
- opsonic effects of Fc and C3b receptors
- occasionally ADCC
23
Q
What does the term ‘secretors’ mean?
A
A and B antigens are present in mucopolysaccharides in secreionts like salive and sweat
- about 80% of people
24
Q
Describe the dominance of the blood group alleles
A
A and B are dominant over O
A and B are codiminant to each other
25
How are isohemaglutanins believed to arise?
from colonization of gut in first couple years. They induce cross-reacting Abs against ABO blood antigens
-Evidenced by babies lacking anti-A or anti-B when theyre young
26
What type of Ig class are isohemaglutinins?
IgM
27
Briefly describe ADCC
Directly lysis of host cell via killer cells
28
On what other cells are Rh andtigens expressed?
none
29
What are the presentations of hemolytic disease in the newborn?
```
anemia
leukopenia and thrombocytopenia
hepatomegaly
splenomegaly
ascites and edema
petechia
```
30
What is the mechanism of RhoGam?
It binds to and removes fetal RBCs from the mother's immune system prior to initiating a response against Rh
31
What is a potential treatment if Rh sensitization occurs with a fetus?
intrauterine transfusion or exchange transfusion with O- blood
32
What can happen from a major injcompatibility in a blood transfusion?
If complement is activated, rapid lysis can occur causing anaphylaxis (not IgE mediated). Shock and death can happen
33
Briefly describe T3H
Allergic reactions involving deposition of immune complexes with activation complement. SOLUBLE antigens.
34
What is the Arthus recation>
localized deposition of insoluble IC
High IgG levels
subcu or intradermally or IM
Reaction 1-2 hours after injection
35
What are the cilnical manfestations of the Arthus reaction?
Gross: local swelling, hemorrhage or necrosis at center of lesion from vessel blockage
Acute Inflammatory repsonse: neutrophils, thrombi w platelets,
36
What is the mechanism of local response in an Arthus reaction?
Ag-Ab complexes get too big
Fc regions bind Ig and activate complement
C5a and C3a increase permeability
C5a chemoattractant.
Neutrophils frustrated phagocytosis
Release protesases, collagenase, O- intermediates...
37
Briefly describ sserum sickness syndrom
a systemic reaction to Ag give intravenously
38
What is the time of onset for serum sickness?
sensitized: hours to 4 days (anamnestic)
| non-sensitized: 7-14 days (primary)
39
What is the relative Serum CH50 level during serum sickness? Why?
Reaches its lowest level because complement is being fixed and consumed quicker than it can be produced
40
When do T4H reaction soccur?
24-48 hours in a sensitized person
41
What is the key manifestation/distinction in T4H?
indurations - cutaneous or subcutaneous hardening
| they do not 'give'
42
What is an allograft and will there be rejection?
Donor and recipient are histoincompatible or nonhistocompatible
Graft rejection is expected
43
Why do you not need tissue typing for corneal transplants?
Cornea has immune privilege
44
What do you give before a peripheral blood transplant?
pretreatment with colony stimulating factors (CSFs)
45
What are the steps for am allogenic bone marrow transplant?
CSFs enrich donor HSCs
anti-mitotic drugs
irradiation (alblation)
46
What are first set rejection and second set rejection?
graft from histoincompatible (allograft or xenograft) leads to rejection after two weeks. Second graft from that donor rejected in one week
47
What would you witness for an athymic individual receiving a transp;lant>
No rejection of allografts or xenografts
48
When does a hyperacute rejection occur? What is it caused by?
Within a few hours
Preformed Abs to incompatible MHC or blood groups
NO cell mediated immunity
49
What is the mechanism of hyperacute rejection?
Binding of Abs induce complement cascade --> platelets--> thrombosis--> hemorrhage--> necrosis. Loss of function. Remove organ
50
When does acute rejection occur? What is it caused by>
within a few days. complete within 14 days.
| Caused by T cell mediated immunity from mismatch of HLAs. Also maybe Abs against graft
51
When does chronic rejectino occur? What is it caused by?
months to years
initial activation of CD4
Then macrophages, CD8, Abs, classical complement, ADCC...
52
During which type of allograft rejection will exhibit lymphoid proliferation and follicles?
Chronic rejection
53
How would immunosuppresive thearpy work in chronic transplant rejection?
It would be useless
| the damage has already taken place
54
What is Graft vs Host disease
donor lymphocytes attacking recipients tissues
55
What is the Graft-versus leukemia effect?
Some donor HSC preparations and T cells recognize minor histocompatibility or tumor specific antigens. These donor cells attack and kill leukemia cells
56
On which cells are HLA-1 expressed?
all nucleated cells
57
On which cells are HLA-2 expressed?
some HSCs (DCs)
thymocytes
Inducible in others via IFN-gamma
58
How many alleles of HLA does a normal human have?
12
59
What is the type of dominance in HLA genetics?
co-dominantly expressed (one haplotype inherited from each parent)
60
What is serotyping?
using Abs to determine differences bw HLA molecules
61
What is the key initiating event in acute allograft rejection?
The Recipient's CD4 cells recognize the donor's nonself HLA-2 on grafted tissue
(Passenger leukocytes from donor can also express HLA-2)
62
What is direct recognition?
Mere recognition of nonself HLA even without processed foreing peptide on HLA
63
What is indirect recognition?
The recipients APCs process donor antigens and present the to T cells
64
What are the most potent transplantation antigens?
HLA-2 molecules
| particularly HLA-DR
65
With which type of HLA molecule would you see the longest graph survival?
HLA-DR
66
What are the main mechanisms involved with graft rejection/HLA expression?
1) CD4 activation
2) recipient CD8 activation (IL-2)
3) Type 1 response (cytokines TH1)
67
What does IFN-gamma do in transplantation?
Activation of macrophages
| HLA-2 expression
68
What does TNF-B do in transplantation?
cytotoxic to graft cells
69
Which cytokines increase HLA-1 expression and result in cytolysis of transplanted cells?
IFN-gamma
IFN-alpha/beta
TNF-a
TNF-B
70
Which organ transplants are particularly dependent on HLA matching
Kidney and bone marrow allografts
71
When might you see graft rejection even if the donor adn recipient are an HLA match?
differences in minor histocompatibility antigens
72
Where are the polymorphic regions on HLA genes?
Class 2: Exon 2
| Class 1: Exons 2 and 3
73
What do corticosteroids do?
```
Inhibit gene expression
down regulate adhesion receptors
inhibit phagocytosis
inhibit HLA expression
Often given with antimetabolites
```
74
What do Antimetabolites do?
Inhibit lymphocyte proliferation
purine antagonists
DNA alkylating agents
methotraxate
75
What are some examples of antimetabolites?
azathioprine-purine antagonist
| cyclophosphamide- DNA alkylating agent
76
What are some blockin agents for immunosuppression?
monoclonal Abs against CD3 and against IL-2R (CD25)
77
What does cyclosporine do?
Interferes with gene transcription in T cells - inhibits cytokine production
More effective when given before transplant
78
Which drugs are similar to cyclosporine?
FK 506 (Tacrolimus) and rapamicin
79
Which is the most critical antigen to match in transplantation?
the ABO blood group
80
What happens if a person previously exposed to a tumor is introduced to a new tumor of the same type?
Anamnestic response
81
Which cell is particularly important for tumor cell surveilance?
NK cell
82
What is the immune seurveillance theory?
Mechanisms resopnseible for allograft rejection have evolved primarily as a means to defend against spontaneously arising neoplams
83
In what situations are Abs good at attacking tumors? When are they not?
good: single cell tumors or metastases
bad: large or encapulated fibrous ones where Abs cant access
84
Which Ig classes can lyse tumor cells?
IgG and IgM
85
When can tumor cells be phagocytosed?
When they are opsonized by IgG
86
Which Ig is usually used in ADCC? How does ADCC work?
Ig
K cell uses its Fc receptor to bind IgG
Apoptosis ensues
87
What is the most important end line defense against tumors?
CD8 - HLA1 mediated killing
88
What are lymphokine activated natural killer cells?
mostly NK cells from blood of cancer patients.
Grown in IL-2 and then transfused back
Allows immune system to escalate in vitro before in vivo
89
What are Tumor Infiltratin Lymphocytes?
NK cells and some T cells from tumors.
| Cultured in IL-2 and tranfused back with more IL-2
90
What is the role of CD4 cytoines in tumors?
activate macrophages
induce CD8 activity
upregulate HLA-1 on tumor cells
upregulate HLA-2 on APCs
91
What does IFN-gamma do in tumor?
attracts and activates macrophages
prevents emigration of macrophages
Upregulates HLA-1 and HLA-2
92
What does immunologically privileged mean? Ex?
Cells of the immune system do not have access to certain compartments
ex: eye, brain, gonads, outer skin
93
How do activated macrophages destroy tumor cells?
TNF-a
| lysosomal enzymes
94
How do tumor cells employ active immune suppression?
Production of soluble factors:
PGs
IL-10
TGF-B
95
What are some of the effects of TGF-B when tumors secrete it?
inhibits Th1 response
decrease NK cell activity
inhbit antigen uptake
dampens CD4 and CD8 function
96
Describe the antigenicity of a tumor cell that survives surveillance?
Usually the least antigenic because it can avoid the immune system
97
What are blocking factors used by tumor cells?
- Coat themselves in polysaccharides
- Secreted Ags bind up Ab in circulation
- Blocking Abs coat tumor cells to avoid CD8 recognition/killing
98
What is Rituximab?
Anti-CD20 to target B cells in B cell lymphomas
99
What is Her2/neu?
targets tumor cells in breast and ovarian cancers
100
What is Cetruximab?
anti-EGFR against colorectal and head/neck cancers
101
What is Zevalin?
murine Ab that targets CD20 on small tumors
| Releases MoAb toxin
102
What is trastuzumab/Herceptin?
-anti-ErbB-2 that attaches to cancer cell and targets it
-also tells that cancer cell to stop growing and proliferating
Depletes target cells w opsonization, complement, ADCC
receptor blockers
103
What is Tositumomab? What is used to treat?
anti-CD20 conjugated to Iodine 131
| Treats non-Hodgkin lymphoma
104
Which cells are involved in tolerance?
B and T cells
105
What are the two mechanisms for Central B cell tolerance?
Clonal anergy for soluble antigens
| Clonal deletion for insoluble
106
Describe peripheral B cell tolerance
Escaped B cells receive constant low level stimulation of the BCR in absence of any other secondary signals --> anergic
-Also they are barred from lymphoid follicle in nodes, so ithey dont get survival signals
107
What type of peptides are the ones presented on MHC in the thymus?
Self-peptides
108
Where does central T cell toelrance occur?
thymus
109
Primary stimulation of T cells without secondary stimulation leads to what?
functional inactivation - clonal anergy
| They can never be activated even if they encounter antigen
110
What happens when CD28 and B7 dont associate
Since CD28-B7 signal stabilizes IL-2 mRNA, there is a lack of IL-2 production --> anergy
111
Repeated stimulation of activated T cells reults in what?
Can cause T cell to undergo apoptosis - clonal deltion
112
Is B or T cell tolerance quicker?
T cell toelrance is quicker
113
What are the main mechanisms of Peripheral T cell tolerance?
lack of CD28-B7 signal
Fas-FasL expressed
pro-apoptotic proteins
114
How can you distinguis Tregs?
They express FoxP3, a transcription repressor
115
What are the mechanisms of Treg cells?
Inhibitory cytokines:
Th1-Th2 couterregulation
TGF-B: anitinflammatory that suppresses T cell proliferation
Cell lysis also used
116
How do Breg cells work?
The produce IL-10 that negatively regulate the activation of Th1 CD4 cells and CD8 cells. This dampens autoreactivity
117
Which diseases demonstrate low levels of IL-10?
Multiple slerosis
| SLE
118
Describe immune responsiveness with regards to age?
the very young and old are immunosuppressed
| AI diseases occur commonly after puberty
119
What is one of the main causes of Ai diseases?
malnutrition
120
How does stress influence the immune resonse?
heat schock proteins are upregulated by stressed cells
Increased Ag presentation
gamma/delta T cells recognize this
121
What dosage levels of an antigen induce toelrance?
very high or very low doses over long periods of time
122
What is sympathetic ophthalmia?
When a perforated ocular injury allows access of immune molecules to immune privileged site and autoimmune response generated
123
What is Ag sequesteration?
self molecules are hidden from the immune system in immunoprivileged sites
124
What anatomical locations demonstrate Ag sequesteration?
lens of eye
synovial chondrocytes
spermatozoal antigens
125
How does immunogenicity relate to tolerance?
Weak immunogens (less complex and soluble) readily induce tolerance
126
What are some examples of molecular mimicry?
Strp pharyngitis-rheumatic fever
Camp. jejuni - Guillan barre
Klebsiella - AS
127
What are the histological changes in Celiac Disease?
villus atrophy
T cell infiltration
(T cell mediated)
128
What is Celiac Disease associated with?
Abs against tissue transglutaminase
HLA-DQ2 (or HLA-DQ8)
IgA deficiency
129
How does gender influence autoimmunity?
Women are more likely
| Estrogen receptors on immune cells may play a role
130
Describe Myasthenia Gravis
Abs produced against ACh receptors at neuromuscular junctions. Severe muscle weakness. HLA-DR3
131
What is lazy leukocyte syndrome?
Defefct in neutrophil response to chemotactic factors or a deficiency in production of C3a and C5a
132
What is the defect in Chronic Granulomatous Disease?
X linked recessive
cytochrome b and NADPH oxidase defects
(G6PD and myeloperoxidase defect can also cause this)
133
What is the defect in Chediak Higashi Syndrome.
mutation in LYST generesulting in defect in lysozome generation and function. Neutrophils and CTL are defective.
134
What is Bruton's X linked agammaglobulinemia?
recurrent infection from bacteria that produce antiphagocytic capsules
normal pre B cell level but low mature B cell level
Defect in BTK gene (BCR signaling)
135
What is X linked hyper-IgM syndrome?
high IgM levels. Rest are low
CD40L mutation
autoAbs for neutro, RBCs
pyogenic infections
136
What are the general physiologic effects of anaphylaxis?
periphery: vasodilation and smooth mm relaxation
| bronchoconstriction in lungs and GI
137
Which cell types play a significant role in asthma?
gamma/delta TCR
| eosinophils
138
What are the three main groups that T1H mechanisms are grouped in?
Sensitization
Activation
Effector
139
Which organs stimulate a stronger IgE response when presented with an allergen?
respiratory
GI
skin
140
Which age groups are predisposed to immediate hpyersensitvity and asthma? Why?
very young and very old (rare)
| probably related to thymus development - peaks in size at puberty
141
What are some common polymorphisms for allergies?
IL-13
IL-4R
CD14
HLA
142
What is the difference bw FceRI and FceRII?
FceRI: high affinity - mast cells/ basophils
FceRII: low affinity- platelets, lymphs, mono, eosins
143
How does the mast cell slow down degranulation during T1H?
influx of Ca increases cAMP and cGMP. This signaling slows down degranulation
144
What are the clinical manifestations of histamine release?
increased vasc perm.
edema
pruritis
increased exocrine secretions
145
What are the preformed mediators that are released from a mast cell?
Histamine
Eosinophil activating factor
Proteases/Hydrolases
Heparin
146
What are the newly synthesized mediators that are released from a mast cell?
```
Arachidonic acid
Leukotrienes B, C, D
PGs, thromboxanes
Platelet Activating Factor
IL4, IL13, TNFa, GM-CSF
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