Tumor Immunology Hypersensitivity Flashcards
(183 cards)
1
Q
What is a tumor
A
An abnormal growth resulting from uncontrolled proliferation with no physiologic funtion
2
Q
other name for a tumor
A
Neoplasm (new growth)
3
Q
What is Cancer
A
Malginant tumor
4
Q
Difference between Benign and Malignant Tumors
A
Slow growth: Rapid Growth
Well-defined capsul: Not encapsulated
Not invasive: invasive
Well differentiated: pooly differentiated (anaplasia)
Low Mitotic index: High Mitotic index
Does not metastasize: Can spread distantly (metastasis)
5
Q
what is cancer a predominantly a disease of
A
Aging
6
Q
How does Cancer proliferate
A
Clonal
7
Q
why does cancer spread so rapidly
A
as a mutation it is benifical to the cell to grow fast, so it has a selective advantage ocer its neighbored (increased groth or decreased apoptosis)
8
Q
What needs to occur to have Full blown cancer
A
4-7 mutations in a step wise accumulation of alterations occuring in specific genes
9
Q
What are Carcinogens
A
Agents that can cause genetic mutation or alterations of gene expression that can lead to the development of cancer
10
Q
Examples of Carcinogens
A
Chemical (Alcohol, asbestos, benezene, tobacco, aluminum)
Radioactive (plutonium-239, radon-222, iodine-131)
Pathogens (Epstein-Barr Virus, H. pylori, Hep B and C, HPV)
11
Q
What do Cancer-Causing Mutations affect
A
Activation of growth-promotion pathways
Block antigrowth signals
Prevent apoptosis
Turn on telomerase and new blood vessel growth
Allow tissue invasion and distant metastasis
12
Q
What are tumor associated antigens
A
Normal proteins that are expressed in abnormally high levels, in an abnromal location, or during an abnormal stage of cellular development
13
Q
What are tumor specific Antigens
A
Macromolecuels (PR or carbs) that are unique to the tumor
14
Q
What suppresses many developing malignancies
A
An efficient immune system
15
Q
Defects in the immune system increase the risk of what type of cnacer
A
Viral assocaited
16
Q
What is antitumor immunity
A
Innate and adaptive responses that can contribute to tumor destrucution and elimiation
17
Q
Can Tumors evade the immune system
A
Yes
18
Q
What is Protumor immunity
A
Evidence that some immune responses can perpetuate tumor development (Chronic inflammation)
19
Q
Innate cells invovled in Antitumor Immunity
A
MAcrophages (M1)
Neutrophils (N1)
Dendritic Cells
NK cells
20
Q
What can innate antitumor cells recognize
A
DAMPS that may be upregulated during tumor growth
21
Q
How do DAMPS forom tumors contribute to inflammation
A
Via IFN gamma, IL-12, TNF-alpha, ROIs, and RNIs
22
Q
How are NK cells activated to a tumor
A
IFN gamma
23
Q
What are Nateral Killer Cells biolgoically
A
Lymphoid cells that contain perforin and grnzymes
24
Q
what do NK cells recognize
A
MHC I but are not ag specific
25
What is the ROll of NK cells in fighting off tumors
Important for removing virally-infected and tumor
| cells
26
How to NK cells kill
Antibody binds antigen on the surface of target cells
Fc Receptors on NK cell recognizes bound antibody
Cross linking of Fc Receptors signals the NK cells to kill the target
Target cell dies by apoptosis
27
What drives the Th1 response to tumors
IFNgamma and IL-12
28
what lymphocytes are invovle in adaptive antitumor immunity
Cytotoxic T lymphocytes (CTLs)
29
What must be broken for a T cell to be invovled in ANtitumor immunity
A break in central tolerance in order for a T cell to be involved
30
Cells in Protumor Immunity
```
MAcrophages (M2)
Dendritic CElls
Regulatory T cells
Th2 cells
Myeloid-derived suppressors cells
```
31
Roll of Macrophages (M2) in protmor Immunity
PRomote Angiogenesis and invasiveness
32
Roll or Dendritic cells in Protumor Immunity
Suppress T cell functions
33
Problem with inflammation relation with cancer
an important factor in the development of cancer
34
what does Active inflammation do for cancer
Predisposes a person to cancer by stimulating a wound-healing reponse that includes proliferation and new blood vessel growth
35
Susceptible organs to get cancer from inflammation
GI tract, Pancrease
Thyroid gland
PRostate, urinary bladder
Pleura, skin
36
Anti-tumorigenic effect of Dendritic cell
Release Cytotoxic Cytokines
| Antigen presentation to T cells
37
PRo-tumorigenic roll of Dendtriic Cells
Suppress T cell function
| Promote tumor growth and progression
38
Anti-Tumorigeneic role of T cells
Directly lyse cancer cells
| Release cytotoxic cytokines
39
Pro-tumorigenic roll of T cells
Release tumor promoting cytokines
40
Anti-tumorigenic Roll of Treg
Restor homeostasis to reduce chronic inflammaion
41
Pro-tumorigenic roll of Treg
Suppresses anticancer immune responses
| Stimulate inflammatory cytokine producion
42
Anti-tumorigenic roll of macrophages
RElease cytotociv cytokines
| Antigen presentation to T cells
43
PRo-tumorigenic roll of MAcrophages
PRomote Angiogeneisis, tumor proliferation, chemotaxis, invasiveness, and metastis
44
Anti-tumorigenic roll of Myeloid derviced suppressor cells (MDSC)
Limited
45
Pro-tumorigenic Roll of MDSC
Suppress T cell function
| REcruit immunosuppressive immune cells
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Anti-tumorigenic roll of NK cells
Relase Cytotociv cytokines
| Directly Cytotocix to Cancer cells
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Pro-tumorigenic roll of NK cells
Limited
48
Conventional Cancer treatmetns
Surgery
Chemo
Radiation
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When is surgery not good for cancer treatment
NOt good for diffuse cancers
50
Problem with Chemo to treat cancer
Non-specific
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How does Chemo fight cancer
TArgets rapidly growing cels, but can also damages normal cels too such as immune cells, GI and Hair
52
Benifit of Ratiation over Chemo
More target than Chemo
53
How does Radiation Work to fight cancer
Radioactive substances generate ROIs that can severely damage tumor DNA causign the cells to die
54
Why is Monoclonal Ab good to fight cancer
Advantageous due to specificity, but first need to find a specific target
55
what must be found to use Monoclonal Ab
Tumor specific or tumor-associated antigens
56
What is HErceptin (trastubzumab) used to treat
Breast cancer treatment for patients with tuomrs that overexpres HER2
57
What is HErceptin (trastuzumab)
A monoclonal Ab that binds to HER
58
How does Herceptin work
PRomotes NK cell mediated ADCC
| INterferes with HER2-directed Signa that promote tumor growth
59
How to do adoptive T cell transfer therapy
Remove T cells from patient
--Isolate T cells taht recognize cancer or T cell can be genetrically engineered to recognize cancer cells
Clonally expand cancer-specific T cells
Infuse PAtient with Cancer specific T cells
60
Types of Adoptive T cell transfer therapies
TIL (Tumor Infiltrating Lymphocytes)
TCR (T cell receptor)
CAR (Chimeric Antigen Receptor)
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What type of Adoptive T cell transfer is the most advances
CAR T cell therapy
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What is the main side effect of CAR T-cell therapy
Cytokine relase syndrome in which a patient feels flu symptoms for 5-7 days
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What is CAR T-cell therapy approved for
PEdiatric Acute lymphoblastic Leukemia (ALL) and for adult with advanced lymphoma
64
3 main causes of hypersensitivies
Reaction to Sself (autoimmunity)
Reaction against Micrboes
Reaction against Envirnomental Antigens
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Other name for Type persensitivityI HY
Allergy, Atopy, immediate hypersensitivity
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when does Type I hypersensitivity occur
within minute after reexposure to antigen/allergen
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What is The Type I Hypersensitivity response
Rapid IgE and Mast cell mediated vascular and smooth muscle reaction that is often followed by inflammation
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What determines what reactions may affect due to type I hypersensitivity
depending on the route of allergen entry
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Commonness of Tyep I hypersensitivity
Most common disorder of the immune system of about 20% of the population
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Typr I hypersesnsitivity General sequence of envents
1. Initial exposure to antigen and production of IgE antibodies
2. Binding of IgE ab to Fc receptors on mast cells
3. Cross-linking of bound IgE upon reexposure to allergen
4. Release of mast cell mediators
71
What is Sensitization
Intial exposute to antigen and production of IgE antibodies in Type I Hypersensitivty
72
What occuring in Sensitization
```
Antigen presention to Th2 cell or Tfh cell
Antigen bound B cell and Il-4 and CD40L causes class switching to IgE
```
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Release of Mediators from mast cells in Type I Hypersensitivity leads to what
A biphasic Response
74
What are the Immediate Effects of Type I hypersensitivity
Dilation of Bloodvessel, increased vascular permeability, and smooth muscle contraction (the immediate reaction)
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what is the Late response of Type I hyper sensitivity
Inflammation (late phase reaction)
76
What must bind to create Type I hypersensitivity
ANtigen-specific IgE
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The Immeidate REsponse of MAst Cell Degranulation
```
Vasoactive amines (Histamines and sesroton) and Proteases
Synthesis and secretion of lipid mediators (prostaglandins and leukotrienes)
```
78
what happens in the Late Phase reaction for MASt cell Degranulation
Synthesis and secretion of Cytokines (TNFalpha, IL-4, Il-5, GM-CSF) and Chemokines (MIP-1alpha)
Infiltration of eosinophils, monocytes, and nuetrophils
79
What do Eosinophils that come in response to mast cell degranulation do
Release granules containing reactive oxygen species, prostaglandins and Leukotrienes
80
Roll of Histamine and lipid mediates in Type I hypersensitivty
Vascular/smooth muscle response (immediate reactions)
81
Roll of Cytokines in Type I hypersensitivty
Inflammation (late phase reaction)
82
How common is Asthma
22 million americas, 6 millions
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how often does Asthma ,kill
80% of deaths occur in low to low mid income countries
84
What does Asthma tend to do to someone
PRoduce extra mucus and breathing becomes hard
85
What are the most common signs of ASthma
Coughing
Wheezing
Shortness of breath
86
Triggers for Asthma
Airborne allergnes (pollen, animal dander, mold, corckroaches and dust mites)
Respiratory infections, such as common cold
Physical activity (exercise induced asthma)
Col air
Air pollutants and irritants such as smoke
87
Why does Asthma make it hard to breath
Muscles of the broncial tunes tighten and thicken
| Air passages become inflammed and mucus filled making the air difficult to move
88
How is Asthma treated
Inhaled corticosteroids
Inhalaed long acting beta2 agonist
Leukotriene inhibitors
Cromolyn
89
What is the most effective long-term control mediation for asthma
Inhaled Corticosteroids
90
what is a inhaled corticosteroids
Flovent
91
How do Inhaled long actiing beta2 agonist fight asthma
Act on beta-adrenergic receptors to cause bronchodilation
92
why use inhaled long-acting beta2 agonists
As a rescue medication
93
What is an inhlaed long-acting beta2 agonist
Albuterol
94
How do Leukotriene inhibitors work
Hlep block the chain reaction that increases inflammation in your airways
95
example of Leukotreien inhibitors
Singulair
96
what is Cromolyn
Inhaled medication to help prevent mast cell degranulation
97
what drives an anaphylaxis response
Driven by systemic release of vasoactive amines and lipid mediators from mast cells
98
What does Anaphylaxis cause
Life-threatening drop in BP accompanied by severe bronchoconstriction
99
how to treat anaphylaxis
Epinephrine (vasocontrictor and bronchodilators) and antihistamine
100
THe most severe form of immeidate hypersensitivty
Anaphylaxis
101
what leads to different immeidate hypersensitivty syndromes
Mediators produced in different amounts and in different tissues
102
What is Type II hypersensitivty
Antibody Dependent Cytotoxicty
103
what occures in Type II hypersensitivty
Antibodies produced by the immune response that bind to antigens on own cell srufaces
104
What Antibodies tend to be involved in Type II Hypersensitivty
IgG and IgM isotypes
105
Binding of IgG and IgM isotypes to their own Cell surface due to Type II Hypersensitivty results in what
Activate Complement result inmembrane attack complex formation, ultimately to destruction of cells, inflammation, or intereference with normal cellular functoin
106
Target antigen of Autoimmune Hemolytic anemia
Erythrocyte membrane proteins
107
Target antigen of Graves' Disease
Thyroid-stimulating hormone (TSH) receptor
108
Target antigen of Myasthenia gravis
Acetylcholine (ACH) receptor
109
Autoimmune hemolytics anemia mechanism of disease
Opsonization and phagocytosis of erythrocytes, complement-mediated lysis
110
GRaves' disease mech of disease
Antibody-mediated stimuation of TSH receptors
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Myasthenia gravis mechanism of Disease
Antibody inhibits ACH binding to receptor leading to downregulation of receptors
112
Clinicopathologic manifestations of autoimmune hemolytic anema
Hemolysis, anemia
113
Clinicopatholgoic manifestations of Graves' disease
Hyperthyroidism
114
Myasthenia gravis Clinicopathologic manifestations
Muscle weakness
| Paralyiss
115
How does Hemolytic disease of the NEwborn work
1st baby has RBC's with Rh antigen
mom has Rh-specific B cell that creates Anti-Gh IgM and Memory cells to fight it
2nd pregnancy not has IgG and antiRh ab crosses placenta and attacks fetal RBS's leading to erythroblastosis fetalis
116
Roll of Rhogam in fighting Hemolytic disease in the newborn
Prevents B cell activation and memory cell formation
117
How to treat Autoimmaves Diseaseune hemolytic anemia
Corticosteroids or blood transfusion
118
How to treat Hemolytic disease of the newborn
Rhogam injections (anti-Rh ab)
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How to treat Graves Disease
Radioactive Iodine, anti-thyroid drugs, or thyroid removal
120
How to treat Myasthenia Gravis
Cholinesterase inhibitors and corticosteroids
121
What is Type III hypersensitivty
Immune complex-Mediated
122
a grouping of antigens bound to their specific antibodies
Immune complex
123
where do Ag-Ab complex clump and deposit
In blood vessels or tissues attracting an acute inflammatory reaction
124
what type of Immune complexes tend to be cleared by phagocytes
LArger immune complexes
125
Where do small immune complexes tend to deposite
In blood vessels or tissues
126
What do Small immune complexes act on
Ligate Fc receptors on leukocytes, leading to activation and tissue damage
127
What kinds of Antigens can Cause Type III Hypersensitivity
Exogenous and endogenous antigens
128
when does Type III hypersensitivty occur
within hours (3-10h) after exposure to antigen
129
where do Type III hypersensitivity immune complexes tend to accumulate
at sites where antigen is localized
| Sites of turbulence (vessel branches) or high pressure (kidney glomeruli and synovium)
130
Because Type III Hypersensitivity locolize at sites of Turbulence and high pressure how does the disease manifest
Vaculitis, arthritis, or nephritis
131
Diseases Caused by type III hypersensitivity
Systemic Lupus erythematosus
Post-streptococcal glomerulonephritis
Serum Sickness
132
Antigen involved with Systemic Lupus Erythematosus
DNA
Nucleoproteins
others
133
Antigens involved with Postr-streptococcal glomerulonephritis
Streptococcal cell wall antigens
134
Antigens invovled with SErum sickness
Various proteins
135
Clinical manifestation of Systemic lupus erythematosus
Nephritis, arthritis Vasculitis
136
Clincial manifestation of Post-streptococcal glomerulonephritis
Nephritis
137
Clinical manifestations of Serum sickness
Arthritis
Vasculitis
Nephritis
138
Mechanisms of Type III Hypersensitivity
Mast cell activation
Macrophages release TNF_apha and IL-1 that induce the inflammatory cascade
Complement activation (C3a, C4a, and C5a)
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what does Complement activation of Type III Hypersensitivity do
Stimulate mast cels to release more histamine, serotonin, and chemotactic factors
Attracts monocytes, neutrophils, and other leukocytes
140
Cells bearing Fc receptors for IgG (or IgM) and IgE may be crucial for what type of hypersensitivty
Antibody complex mediated hypersensitivity
141
Causes of Serum SIckness
Antivenom (serum from horses immunized with snake venoms_
Anti-lymphocyte globulin
Antibiotics
Steptokinase (a bacterial enzyme)
142
What is Antivenom
A source of Neutralizing antibodies to treat people with poisonous snake bites
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What is anti-lymphocyte globulin
Animmunosuppressive agent used for transplant recipients
144
what is streptokinase used as
A thrombolytic agent used to treat heart attack patients
145
How to treat serum sickness
Avoid drugs, antihistamines,corticosteroids
146
Treating Lupus
NSAIDS, Corticosteroids, immunosuppressive agents
147
What kind of Recation is Type IV hypersensitivity
Cell Mediated
148
How does Type IV Hypersensitivity occure
Mediated by antigen-specific T cells which induce macrophage infiltration iin a sensitized individual
149
What initiates Type IV Hypersensitivity
Haptens
Ag presented by APC's activates Th cells
Th Cells secrete cytokines with activate macrophages
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what are haptens
Small molecules that must become bound to a larger carrier molecule in order to Illicit and immune or inflammatory responce
151
How are Th Cells activated in Type IV Hypersensitivty
Ag presented by APC's
152
What is Type IV hypersensitivity also called
Delayed-type hypersensitivity (DTH) since the action takes 2-3 days to develop
153
What antibodies mediated Type IV Hypersensitivity
Not antibodies (Mostly Th cells)
154
what cells are important effector cells in the DTH response
Macrophages, CD8 T cells, and NK cells
155
what do Activated CD8 cells do in Type IV hypersensitivity
Destroy target cells on contact
156
How does CD* cells destroy target cells on contact
2 phases:
Sensitization
Elicitation
157
when does Sensitiziation ocur
During the first exposure to Ag
158
How long does Sensitization take to develop
Take 10-14 days
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what happens during Sensitization during Type IV hypersensitivity
Angitegn presenting cells take up AG and present to T cells
| Formation of CD4+ memory T cells specific for the Ag
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When does Elicitation for type IV Hypersensitivity occurs
during reexposure to Ag
161
when does Elicitation develop for type IV exposure
within 24-48 hour
162
what happens in elicitation for type IV hypersensitivty
LC Ag presentaion to memory T cells at site of Ag entry
T cells release IGNgamma and Pro-inflammatory cytokines
Cytokines recruit macrophage, CTL, NK, and other efector cells
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Types of Type IV Hypersensitivity
```
Tuburculin type hypersensitivity
Contact Dermatitis
Chronic Asthma
Gluten-sensitive Enteropathy
GRaft regjection
```
164
How does one get Tuburculin type Hypersensitivity
Injected into the skin
165
what mediates Tuburculin type Hypersensitivity
Th1 cells
166
How does one get Contact Dermatitis
Absorbed by the skin
167
what mediates Contact Dermatitis
Th1 Cells and/or CTL's
168
How does one get Chronic Asthma
Inhaled
169
what mediates Chronic Asthma
Th2 cells
170
how does one get Gluten-sensitive enteropathy
Injgest
171
What mediates Gluten-sensitive enteropathy
poorly understood but evidence suggest that Th1 and Th2 are involed
172
what mediates Graft rejections
T cells
173
HOw to test if previously exposed.infected with Mycobacterium tuberculosis
Tuberculin Test (Mantoux PPD test)
174
how is the Tuberculin test done
Small amounts of Tuberculin are injected intradermally
24-72 hours a local T cell mediated inflammatory reactions evolves in individuals previously with Mycobacterium tuberculosis
175
what mediates response in the Tuberculin Test
TH1 cells and infiltrating macrophages and other inflammatory mediators causing visible swelling and redness
176
what type of hypersensitivity is Poison ivy
Contact dermatitis (type IV)
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what are the response parts of poison ivy
Sensitization period and elicitation of allergic response on subsequent interactions
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Common allergens associated with contact dermatitis
```
Poison oak, poison sumac, plants
Nickel and other metals
MEdication (antibiotics especially topical, topical anesthetics plus more)
Rubber and latex
Cosmetics
Fabric and clothing
Detergents
SOlvents
Adhesives
Fragrances and perfumes
Other chem
```
179
Therapeutic strategies for Type IV hypersensitivity for TB test injections
Usually self limiting
180
trerapeutic strategy for contact hypersensitivity due to type IV
Limit exposure
Corticosteroids
Antihistamines
181
Therapeutic stratogy for CHronic Asthma due to type IV hypersensitivity
Corticosteroids, bronchodilators, Cromolyn
182
Therapeutic stratogy for Crohn's disease
Corticosteroids
Immunosuppressants
Biologics
183
How to remember what type of sensitivity is What
```
I: Allergy
II: antiBody
III: immune complex
IV: Delayed (DTH)
ABCD
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