Unit 5 Flashcards
(228 cards)
1
Q
Type A Blood Type Serology
A
Anti B
2
Q
Type B Blood Serology
A
Anti A
3
Q
Type AB Blood Serology
A
Anti A Anti B
4
Q
Type O Blood Serology
A
None
5
Q
Universal Donor
A
Type O
6
Q
Universal Recipient
A
Type AB
7
Q
Peripheral Tolerance
A
Either renders self-reactive lymphocytes nonresponsive or actively generates inhibiting lymphocytes
8
Q
Where does Peripheral Tolerance Occur
A
Outside Bone Marrow and Thymus
Secondary lymphoid organs
9
Q
Central Tolerance
A
Deletion of lymphocytes before they mature
Takes place in primary lymphoid organs
10
Q
Central Tolerance limits
A
The development of Autoreactive T and B Cells
Has a high affinity for self Ag and results in the induction of apoptosis in B and T Cells
11
Q
Which Cells go through receptor editing?
A
B Cells
A Second V gene segment is rearranged into the first rearrangement
12
Q
Peripheral Tolerance regulates
A
Autoreactive cells in the circulation
13
Q
Autoimmunity is caused by
A
The failure of tolerance processes
May be organ-specific or systemic
May involve antibodies, T Cells, immune complexes, or a combination of elements
14
Q
Hashimoto’s Thyroiditis
A
Autoantibodies and sensitized Th1 cells specific for thyroid Ag are present
15
Q
Hashimoto’s is most common in
A
Women
16
Q
In Hashimoto’s an antibody produced interferes with
A
Iodine Uptake
Decreases Thyroid Function leading to hypothyroidism
Goiter is a result
17
Q
Goiter
A
Visible enlargement of the Thyroid gland
18
Q
Type 1 Diabetes Mellitus
A
Autoimmune disease affecting 2 in 1000 children in the US
caused by autoimmune attack against insulin-producing beta calls in the pancreas
19
Q
In Type 1 DM, what occurs?
A
CTLS infiltrate the pancreas and activate macrophages
Cytokines are released and Auto Abs are produced
Complement activated
Eventual DTH response releases destructive enzymes
20
Q
Myasthenia Gravis
A
Autoimmine Disease
autoantibodies bind to acetylcholine recetors on motor plates of muscles are produced
Blocks the normal ACH binding, inducing complement–meidiated lysis of cells
21
Q
Result of Myasthenia gravis
A
A Progressive weakening of the skeletal muscles
22
Q
Treatments of Myasthenia Gravis
A
Increasing Acetylcholine Levels
Decreasing Antibody production
Removing the Antibodies
23
Q
Systemic Lupus Erythematosus (SLE)
A
More common in women (9:1)
Onset between 20 and 40 yrs of age
Frequent in african americans and hispanics
Auto Antibodies against DNA, histones, and other self structures produced
24
Q
How can SLE be detected
A
with indirect immunofluorescent staining
25
Symptoms of SLE
```
Fever
Weakness
Arthritis
Skin Rashes
Kidney Dysfunction
```
26
SLE is what type of Hypersensitivity?
Type III
27
Multiple Sclerosis (MS) Statistics
Occurs in women 2-3x more than in men
| More common in the northern hemisphere
28
MS
Autoreactive T Cells form inflammatory lesions along myelin sheaths around nerve fibers in the brain and spinal cord
Breakdown leads to a range of symptoms, from numbness to paralysis and loss of vision
29
Rheumatoid Arhtritis is diagnosed within what age range?
40-60
30
Common Rheumatoid Arthritis population
More frequent in women, aged 40-60
31
Rheumatoid Arthritis symptoms
Chronic inflammation in joints
32
Rheumatoid Arthritis cause
Rheumatoid factors are produced
Auto-Antibodies reactive with determinants in the Fc region of IgG
Form immune complexes and activate complement cascades
33
Treatments for Rheumatoid Arthritis
Non-specific anti-inflammatory drugs and corticosteroids
| More specific anti-Cytokine autobodies have also been introduced
34
Environmental factors favoring susceptibility to autoimmune disease
Diet differences leading to gut microbe changes
| Different geographic areas have different endemic diseases
35
HLA-B27
90x more likely to develop ankylosing spondylitis
36
Ankylosing Spondylitis
An Autoimmune disease which causes inflammation in vertebral joints
37
Aire and Fox P3 genes result in
Particular immunodeficiencies that affect central and peripheral tolerance
38
Autoreactive Th1 cells and their effects on Multiple Sclerosis
Th1 cells secrete IFN-gamma and assist in the development of MS
39
IL-17 levels and their effects on Rheumatoid Arthritis
Elevated IL-17 levels in RA and psoriasis, indicating a role for Th17 cells in those autoimmune diseases
40
Broad-Spectrum therapies for autoimmunity
Early methods reduce symptoms
Strong Anti-Inflammatory drugs that inhibit lymphocyte proliferation or kill the cells
Organ removal
41
Side effects of Broad-Spectrum therapies for autoimmunity
General Toxicity
Predisposes individuals to uncontrolled infections
Can promote development of cancer by removing anti-tumor T and NK cells
42
If a disease is caused by immune complexes, targeting
B cells can be effective
| Monoclonal Ab against CD20 can be used in RA Cases
43
TCell Targeting Therapies in Autoimmunities
Used more often because the cells are usually directly pathogenic or provide help to B Cells
44
Drugs that block TNF alpha are used to
Treat RA, Psoriasis, and Crohn's disease
45
IL-1, IL6, and IL-15 receptor antagonist is used against
RA
46
Statins
Lower serum levels of C-Reactive protein, an indicator of inflammation and reduce pro-inflammatory cytokine levels
47
Compounds that block Chemokine or adhesion molecule signals
Prevent movement of lymphocytes to areas of inflammation
| FTY720, an analog of S1P
48
Abatacept (Orencia)
Approved for RA Treatment for use by formation if an extracellular domain of CTLA-4 and human IgG1 constant region
Binds to T cell region, tricking them into an arrangement that inhibits stimulation
49
Holy Grail of Antigen-Specific Immunotherapy
Stimulate tolerance to the Auto-Antigen, restoring balance
50
Autograft
Self Tissue graded to another self area (Skin, blood vessels)
51
Isograft
Transplant between genetically identical individual (Twins)
52
Allograft
Tissue transferred between genetically different members of the same species (Majority of transplants)
53
Xenograft
Tissue transferred between different species
54
First-Set rejection in transplants
12-14 days, but memory o the anti-graft response is generated
55
Second-Set rejection
Occurs faster, within only 5-6 days
56
T-Cells' role in transplants
CD4+ cells seem to be more involved than CD8+ cells, but both facilitate rejection
57
Tissues that are antigenically similar are typically
Histocompatible
58
The Loci most likely to lead to transplant rejection
MHC genes
| MHC differences found in heterozygous outbred human populations
59
Siblings have what percentage of a chance of MHC identity
25%
60
Parent to child grafts have what percentage of match, and why?
50%
| because one MHC haplotype is always the same
61
Blood Group antigen differences
Cause the most intense graft rejections
| First items to be matched between donor and recipient
62
MHC compatibility in transplants
After Blood Group
Second to be matched
Siblings/Parents first choices
63
Molecular assays are used to
Provide a fast method of MHC screening to assess match quality
64
Anti-rejection drugs allow
Organ transplants between completely mismatched people
65
CD4+ and CD8+ cells in the sensitization stage of graft rejection
```
recognize alloantigens expressed on foreign graft cells
T Cells proliferate
Direct Presentation
Indirect Presentation
Memory T Cells generated
```
66
Direct Presentation in Transplants
Recognize donor cells w/ MHC presentation (Direct presentation)
67
Indirect Presentation in transplants
Recognize peptides from donor MHC (indirect presentation)
68
Hyperacute rejection
pre-existing antibodies
Occurs before grafted tissue ever revascularizes
Ab binds to graft cells, activate complement
Complete rejection in as few as 24 hours
69
Acute rejection
Mediated by T-Cell responses
Response within 7-10 days after transplant
Induce massive infiltration of lymphocytes and macrophages
70
Chronic Rejection
Develops months or years after acute rejections have subsided
Humoral and CMI responses
Anti-rejection meds help, but are not perfect
71
1-Year Kidney Graft Survival Rates
97%
72
10-Year Kidney graft Survival Rates
60%
73
Total lymphoid irradiation to eliminate lymphocytes
Often used in bone marrow transplants or to treat GVHD
| Wipes out recipient's immune cells, donor stem cells engraft and form a new immune system
74
Azathioprine
A mitotic inhibitor that diminishes B and T cell proliferation
Dramatically increases survival rates of allografts
75
Cyclophosphamide
inserts into DNA Helix, disrupting it
| More effective than Azathioprine
76
Belatacept
Soluble CTLA-4 fusion proteins can induce T-Cell Anergy
77
Ideal immunosuppressants
would be antigen-specific
78
Monoclonal AB can achieve
Antigen-Specific immunosuppression
79
OKT3
A Monoclonal Antibody to C3, depletes T Cells prior to transplants
80
Cell Cycle Inhibitors
Methotrexate
| Azathioprine
81
FK506, Cyclosporin
Calcineurin pathway blockers
82
Ant CTLA, CD40L
Block Costimulatory molecules
83
Immunologically privileged sites
Allografts in such areas less likely to experience rejection
84
Which transplants are most successful and why?
Eye/Cornea transplants
| because there is little immune response in privleged site, like eyes
85
Inducing Transplant Tolerance theory
Generation of mixed hematopoietic chimerism prior to transplantation
Cells get used to each other and generate tolerance to the graft before it actually takes place
86
Type I Hypersensitivities
Allergy
| Atopic individuals produce IgE against common environmental Ags
87
Type II Hypersensitivity
Cell Lysis
88
Incorrect Blood group Transfusion will result in
Antibodies will quickly attach tot he donor blood cells and trigger complement proteins
Degraded RBC components can build to toxic levels
89
Hemolytic Disease
An example of Type II hypersensitivity
Develops when maternal IgG Ab specific to expressed RhD allele crosses the placenta
Destroys fetal RBCs, activating complement
Can be fatal, but treated with intrauterine blood exchange transfusion
90
Hemolytic disease can be alleviated by
Exposure to UV Light
91
Rhogam
Anti-Rh Antibodies given to the mother
92
Hemolytic Anemia
Can be drug induced
Adsorb nonspecifically to proteins on RBC membranes
May stimulate Ab production
93
What drug can induce all 4 types of hypersensitivity reactions
Penicillin
94
Type 3 Hypersensitivity
Immune Complex-mediated hypersensitivity
If immune complexes aren't cleared correctly, they deposit in the tissues
Trigger inflammatory mediators and vasoactive mediators
Proteases released cause damage
Clots may form
95
Symptoms of Type 3 Hypersensitivity
```
Fever
RashesJoint Pain
Lymph Node enlargement
Protein in the urine
Vasculitis
Glomerulonephritis
Arthritis
```
96
If an Autoantigen is involved in the immune complex-mediated reaction
Antigen can't completely go away, symptoms persist
97
Athus Reaction
Localized type 3 rxn
| Inflammatory rxn induced by injection of an Ag in an individual with high levels of circulation Ab specific to it
98
How soon after injection does an Arthus rxn occur
4-10 hours post-injection
99
DTH (Delayed Type-4 Hypersensitivity)
Cell-Mediated
Initiated by T-Cells
Requires a delay for rxn to develop
Recruitment of macrophages at inflammation site
100
Most common types of Delayed type-4 hypersensitivity (DTH)
Poison Ivy
Contact Dermatitis
Herpes Simplex Virus
Tuberculosis
101
DAMPS (Damage-associated molecular patterns)
```
Self Ag released by certain conditions associated with damage
-Tumors
-Autoimmune Diseases
-Atherosclerosis and Heart Disease
-Obesity
All capable of long-term inflammation
```
102
Visceral Adipocytes are secretors of
Pro-inflammatory Cytokines
TNF-Alpha
IL-6
103
TNF-Alpha and IL-6 induce what in insulin resistance?
Signaling cascades that inhibit the ability of insulin recepts to function
104
HIV infects
CD4+ and macrophages
| CD4 is the co-receptor
105
Non-infectors in HIV
Mutation in the co-receptor (Delta Mutation)
| HIV cannot enter the cell, resulting in no infection
106
Primary Immunodeficiency
Occurs as a result of genetic defects or infection prior to birth
107
Secondary immunodeficiency
Occur after birth, after infection, or after immunization
108
Therapeutic agents inhibiting retrovirus replication
HIV Life Cycle Targets
- Chemokine Receptor Antagonists (Entry)
- Fusion Inhibition (Entry)
- Reverse transcriptase inhibition
- Integrase Inhibition
- Protease Inhibition
109
Ways pathogens evade host defenses
Antigenic Variation
Latency
Avoidance of Killing
Immunosuppression
110
Antigenic Variation
Varying Surface Antigens
Ex. Streptococcus pneumoniae
Encapsulates
~84 Serotypes known
111
Influenza Virus Antigenic Variation
Vaccine changes every year because antigen surface changes
| Antigenic variation caused by antigenic drift and shift
112
Antigenic Drift
Results from point mutations to surface hemagglutinin and neuraminidase
113
Antigenic Shif
Results from re-assortment fo an RNA Genome
114
How many Serotypes for Rhinovirus have?
100+
115
Xoflusa
Prevents viral replication inside the cell
116
Tamiflu, Relenza
Neuraminidase inhibitors which inhibit the infection of new cells
Reduce symptoms and time of infection in influenza
117
Antigenic Sin
Once an effective response is produced, a new one will not be made until the old one is no longer effective at all.
118
African Sleeping Sickness
Caused by two trypanosome species
Transmitted by tsetse fly bites
Differentiates and divides every 6 hrs in blood
119
Latency
Disease symptoms are not present, but infection has occurred
| Asymptomatic
120
Common latent infections
Chickenpox-> Shingles
Herpes Simplex
HIV
Epstein-Barr Virus
121
How latency keeps infection
Without replication, no viral peptides are produced and immune system is not stimulated
122
Bottom Line Strategy of Latency
Lay Low
123
Herpes Zoster Virus
Causes Chickenpox, becomes latent, and then can reactivate as shingles
124
HSV
causes Cold sores, herpes Encephalitis
125
Treponemes
Escape by coating themselves in host proteins
| Causes Syphilis
126
Toxoplasma gondii
Escape by Creating its own vacuole
127
Listeria Moocytogenes
Escapes the lysosome and phagosome
128
Mycobacterium tuberculosis
Escapes by inhibition of lysosomal fusion
129
immunosuppression in leprosy
Humoral or cellular suppression
| Activates humoral instead of CMI response
130
Immunosuppression in HIV
Mediates Depletion of CD4 T Cells
131
Heptatis C
Overcomes interferon antiviral effects by blocking and inhibiting PKR
132
HSV
```
Inhibits TAP activity, shutting down MHC class 1 presentation on CD8 Cells
-Adenovirus and Cytomegalovirus use similar strategies
```
133
Measles and HIV
infect MHC Class II expression and presentation to Helper T Cells
134
Other ways viruses evade host defenses
Code for anti-Complement proteins
| Constantly change their surface Ag
135
Leading Causes of Death
```
Heart Disease
Cancer
Chronic Lower Respiratory Disease
Stroke
Unintentional Injuries
Alzheimers
Diabetes
```
136
Cancer
Cells that have lost control of the cell cycle will produce a tumor or neoplasm
137
Benign Tumor
UNable to invade healthy surrounding tissue, incapable of indefinite growth
138
Malignant tumor
Becomes progressively more invasive
| May Metastasize- invade other distant tissue
139
Carcinoma
Epithelial Cancer
140
Leukemias, Lymphomas
Blood, Lymphatic System
141
Myeloma
Muscle
142
Sarcoma
Bone, Muscle
143
DNA Alteration can induce
Malignant transformation
144
Malignant transformation can be induced by
```
Chemical Substances (Formaldehyde, DDT)
Physical Agents (asbestos)
Ionizing Radiation (all)
Certain infectious agents ( H. pylori, Schistosoma)
```
145
Proto-Oncogenes
Found in normal Cells
| May lead to cancer if altered to lose control of expression
146
Alterations of proto-oncogenes
Transformin viruses
Exposure to Carcinogens
Genetic Predispositions
147
Proto-Oncogenes enhance survival when
their control mechanisms fail
148
Tumor-suppressor Genes
Allow cancer cell survival when they fail
149
Apoptosis Gene problems
Lead to abnormal cell survival
150
Genes associated with cancer control
cell proliferation and survival
151
HPV is the leading cause of
Cervical Cancer
152
Avian Leukosis Virus
Integrates into C-myc gene and transforms B Cells into lymphomas
153
Pro-Apoptotic genes act as
Tumor Suppressors
154
Anti-Apoptotic Genes
Act like oncogenes
155
BCL2 Genes
Important in the survival of selected B and T Cells during Maturation
EBV similar
156
Failure of Pro-Apoptotic genes or Overactivity of anti-Apoptotic genes can lead to
Encouraging neoplastic transformation of cells
157
Neplastic Cells
Altered Self Antigens
158
Four Groups of Neoplasms recognized by T Cells
ag Encoded by genes exclusively expressed by tumors
Ag encoded by variant forms altered by mutation
Ag normally expressed at certain developmental stages
Ag Overexpressed in certain tumors
159
TSA(Tumor-Specific Antigens)
Unique to tumor cells
May result from mutations in tumor cells that generate altered proteins (New Ag)
HPV E6, E7
160
TAA (Tumor Associated Antigens)
Normal Cellular proteins with unique Expression patterns
| TAAs not unique to the cancer itself
161
AFP (Alpha-fetoprotein)
Milligram levels in fetuses drop after birth
162
Carcinoembryonic Antigen (CEA)
Found in GI/Liver cells in 2-6 mo old fetuses
163
EGF- Epiderma Growth Factor
100x higher in some tumors
164
Melanotransferrin (p97)
Fibroblast
Gowth-Factor like activities
Before Birth, regulates cell divison
165
Innate Hinhibitors of Cancer
NK Cells-Target Neoplasmic Cells
Perforin Deficiency
Activated Macrophages
Eosinophils
166
Activated Macrophages
Bind to AB-Coated tumor cells and secrete TNF-Alpha
167
Mutations resulting in loss of NK Cells also result in
Increase in certain cancer types
168
Mutations in perforin deficiency
Can result in increases in certain cancer types
169
TNF Alpha
A astrong anti-tumor cytokine
170
Lack of T Cells leads to
An increase in Cancer
171
Tumor0Infiltrating lymphocytes
T Cells
NKT Cells
NK Cells
172
B-cells Generate
```
Anti0tumorr AB against tumor-Specific aG
Promotes tumor-cell recognition and lysis
May Block CTL access to tumor AG
Opsonization
Ab-dependent
```
173
IFN-Y (interferon Gamma ) Role in cancer immunity
Activates Macrophages make TNF Alpha
174
All interferon types
Enhance tumor-Cell removal activities of immune Cells
175
IL-12
Encourages FCs to activate Strong TH1 and CTL responses
| Deficiencies result in more papillomas
176
Therapies for Cancer Treatment
```
Surgery
Radiation
Chemotherapy
Bone Marrow Transplant
-GVHD is an issue
```
177
Vaccines in cancer
HBC vaccine preventshepatocellular carcinoma
| HPV vaccin reduces cervical Cancers
178
Active therapy
Extract T Cells from individual with cancer
Activate T Cells w Tumor they have
Reintroduce activated T Cells into patient
-Tedious, Costly
179
Methotrexate, Abitrexate, fluoracil, adrucil, mercaptourine, purinethol
Prevents DNA Replication
| Chemotherapy
180
daunorubicin (Cerubidine)
| Doxorubicin (Adriamycin)
Directly damage the DNA in the nucleus of the cell
181
Mitotic Spindle Inhibitors
Effects the synthesis or breakdown of the mitotic spindles
Vincristine (Oncovin)
Paclitaxel (Taxol)
182
Rhogam
Binds to Rh- RBCs, activates complement , lyses fetal RBCs that cross into mother's body
183
Heptatosplenomegaly
Enlarged Liver and Spleen from RBC Digestion
184
sERUM sICKNESS
a sYSTEMIC REACTION LIKE A SNAKE BITE
185
Central Tolerance
Deletion of lymphocytes before they mature
| Primay lymphoid organ
186
Peripheral Tolderance
Occurs in secondary lymphoid organs
| Renders self-reactive lymphocytes nonresponsive or actively generates inhibiting lymphocytes
187
Privleged Sites
Sites which do not have a full immune response
188
Example of prvlegd Sites
Eye, Brain, CNS, Sex organs, Placenta
189
First organ to be transplanted
Eye
190
Chronic presentation f privleged cells results in
Increased inflammatory reaction
Goes into Anergy (Immune System)
Antigenic Fatigue
191
NTreg cells
Specialize in regulatory responses against self antigen to inhibit autoimmune rxn
192
ITreg Cells
Controll reactions to benign antigens ant mucosal surfaces.
| Involved in regulating the immune response to fetal alloantigens and may influence pregnancy outcomes
193
Regulatory CD4+ Cells work via
Contact dependednt and independent mechanisms
| Dependent occr ass Treg express high levels f CTLA4 inhibitory molecules
194
Independendt Cd4+ Clel Regulation
Rely on secretion of IL10, TGFB, IL35 into surrounding area, sutting down nearly cells' responses
195
How does Hashimoto's affect TSH
Increases TSH Secretion
196
How Does Hashioto's afect T3 and T34 levels
Decreases T3 and T4 Levels
197
How does Graves disease affect TSH Levels
Decrease TSH Secretion
198
How Does Grave's Disease Affect T3 adn T4 Levels
Increase T3 and T4 Levels
199
In Diabetes Mellitus Type 1, how are T Cells affected
Tc binds to beta cells, destroyin g them, no insulin produced, recruit macrophages
200
Hyperglycemia
Excess sugars in the blood
201
Hypoglycemia
Deficiency of sugar in th e blood
202
What t Symptom is characeristic of SLE/ Lupsu
Butterfly Rash
203
Apoptosis
Programmed Cell Death
204
Necrosis Leads to
Inflammation, Leak Contents, Produce Antinuclear Antibodies, Cause Type I Hypersensitivity
205
First AB Produced in a repsonse
IGM
206
Second Antibody Produced
IgG
207
Graft Versus Host Diseases GVDH
A condition that occurs when donor bone marrow or stem cells attack the recipient.
208
How to prevent GVHD
Wash the organ During Transplant
| Give donor immunosuppressants to the reaction is less likely to occur
209
Mixed Heamtopoietic Chemerism
Encapsulate donor pacreatic cells and the recipient's immune system will get used to the donor cels
210
What type of transplant is a fetus considered to be
AN Alograft
211
Polyclonal Anitobidies
Prduced fro immunized animals
| Consists f complex mistures of different Abs by amy diferent B Cell Clones
212
Monoclonal Abs
Homogenous Abs repartations produced in the lab. COnsists of a single type of Ag-Binding Site
B Cell Calcer Specidic
213
There are approximately how many Antibodiy therapies?
500
214
Plasma Cells make how many Abs per day?
10^8
215
Orthoclone Muromonab
CD3 Immunospurressant inHigh Rates fo Failure
| Frorm another species, evoked immune response organt transplants, suppresses t Cell Acivation
216
CMI Immunodeficiency
Cancer Rates increase
| Pneumonia
217
Complement Immunodeficiency
Sepsis
218
Phacocytic Immonodeficiency
sKIN aBCESSES, sTAPH INFECTIONS
219
SCID
Severe Combined Immuneofeficiency
| Defective T Cells
220
SCID Treatment
Gene Therapy
221
Bare Lymphocyte Syndrome
No Functional MHC II or MHC I
222
MHCI deficiency Leads to
Viral infections, Cancer
223
MHCII Deficiency Leads to
Bacterial and Fungal infections
224
DiGeorge Symdrome
Deletions of Regions on Chromosome 22, including TBX, affects development of facial features and the thymus. Lack Immune Repsonse
225
Di George's Treatment
Thymic Transplant or passive IG Ab Teatments
226
wiskott Aldrich Syndrome
```
WAS, X-Linked
Defect in ASP gene for cytoskepeltal Protein expressed in hematopoietic Cells
Manifests w Eczema and thrombocytopenia
Impaired Humoran and CMI immunity
High Sschetibility to bacteria
```
227
Characteristic of Wiskott Aldrich Syndrom
Increased IGe and IFA
228
Long-Term Treatment of WAS
Hematopoietic Stem Cell Xfer
