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Pharmacology II > Immunopharmacology - Immune Diseases > Flashcards

Immunopharmacology - Immune Diseases Flashcards

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1
Q

5 roles of the immune system? what are their implications?

A
  1. Defense against infections (vaccines)
  2. Defense against tumors (cancer)
  3. Clearance of dead cells and tissue repair (deficient:secondary infections, excessive:fibrosis/organ dysfunction)
  4. Injure cells and induce inflammation (allergic reactions/inflammatory diseases)
  5. Recognizes/responds to tissue grafts and new proteins (transplantations and gene therapy)
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2
Q

Two types of immunity? which one is always present? which one is more potent?

A

Innate : always present

Adaptive : more potent

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3
Q

Cells involved in innate immunity? (4)

A

Phagocytes
Dendritic cells
Complement
NK cells

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4
Q

Cells involved in adaptive immunity? (2)

A 
B lymphocytes
T lymphocytes (effector T cells)
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5
Q

3 types of cells of the immune system?

A

Lymphocytes
Antigen-presenting cells (APCs)
Effector cells

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6
Q

Role of lymphocytes?

A

Mediates adaptive immune response, only cells with specific receptors for antigens

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7
Q

Role of APCs? 4 cells?

A

capture, concentrate, display antigens for lymphocyte recognition
Dendritic cells, macrophages, B cells, follicular dendritic cells

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8
Q

Role of effector cells? 3 cells?

A

Eliminate microbes

Lymphocytes, Granulocytes, Macrophages

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9
Q

Which cells make antibodies?

A

B cells

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10
Q

How are B cells activated? (2)

A

Antigen must bind to sites

Stimulation by Helper T cells

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11
Q

3 types of T cells?

A

Helper T cells
Cytolytic T cells
T-regulatory cells (Tregs)

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12
Q

What do Helper T cells produce?

A

CD4, helps bind to class II MHC complexes on antigen presenting cells

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13
Q

What do Cytolytic T cells produce?

A

CD8 protein, binds transplanted tissue, infected cells, cancer cells

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14
Q

Role of Tregs?

A

Suppress activation of immune system to help maintain homeostasis

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15
Q

Development of B and T cells in Generative lymphoid organs (3) and Peripheral lymphoid organs?

A 
Generative lymphoid organs : 
-B lymphocyte and T lymphocyte lineage produced by bone marrow stem cell
-B transported to Bone marrow
-T transported to thymus
Peripheral:
-Mature B circulates in blood
-Mature T circulates in blood and lymph
-Both transported to Lymph nodes, Spleen and Mucosal and cutaneous lymphoid tissues
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16
Q

Two types of adaptive immunity?

A

Humoral

Cell-mediated

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17
Q

Humoral immunity:

Which lymphocyte acts on microbe? Overall function?

A

B lymphocyte

Blocks infections and eliminates extracellular microbes

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18
Q

Cell-mediated immunity:

Two lymphocytes? Which type of microbes do they each respond to and what is their function?

A

Helper T lymphocyte:
Responds to phagocytosed microbes in macrophages, activates macrophages and kills microbes

Cytotoxic T lymphocyte:
Responds to Intracellular microbes, kills infected cells and eliminates reservoirs of infection

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19
Q

4 steps of the immune response?

A
  1. Antigen recognition and presentation
  2. IL-1 production
  3. IL-2 and other cytokine expression
  4. Lymphocyte proliferation and differentiation
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20
Q

What are immunomodulators: two types of immunomodulators?

A

Agents that will modulate the immune system

Immunosuppressants and immunostimulant

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21
Q

3 immunostimulatory cytokines?

A

Interleukins
Colony stimulating factors
Interferon

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22
Q

2 types of colony stimulating factors? what are their roles?

A

G-CSF
GM-CSF
Stimulates division and proliferation of various stem cell types

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23
Q 
3 types of interferons? 
Which disease are they involved in?
Are they all:
viral or antiviral?
proliferative or antiproliferative?
Which one induces MHC II on top of MHC I?
A 
alpha (anticancer)
beta (relapsing MS)
gamma (chronic granulomatous disease)
-Antiviral
-Antiproliferative
-Gamma
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24
Q

2 other types of stimulants?

A

Thymic hormones

Adjuvants of bacterial origin

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25
4 major classes of immunosuppressants?
Corticosteroids Calcineurin inhibitors Antiproliferative/Antimetabolic agents Biologic (Ab)
26
3 examples of corticosteroids? | It decreases inflammation caused by what? (4)
Prednisone, Dexamethasone, Cortisol | Cytokines, NO, Prostaglandins, Leukotrienes
27
3 examples of NSAIDS?
Aspirin Ibuprofen Acetaminophen
28
3 drugs that reduce production of IL-2 from T cells
Cyclosporin A Tacrolimus Rapamycin
29
3 Anti-TNFa biologicals?
Infliximab Etanercept Adalimumab
30
4 treatments of auto-immune disease?
Corticosteroids NSAIDS Drugs that reduce IL-2 production Anti-TNFa biologicals
31
Difference in potency between dexamethasone vs. prednisone and cortisol?
20-30x more potent that cortisol | 4-5x more potent than prednisone
32
MOA of corticosteroids? (2)
Transactivation : activates expression of anti-inflammatory genes Transrepression : decreases expression of pro-inflammatory genes
33
MOA of tacromilus?
binds to FK506-binding protein forms FK506-FKBP complex binds to and blocks CaN FK506-FKBP-CaN complex inhibits activation of NF-ATc, preventing entrance into nucleus
34
MOA of cyclosporin?
CsA binds to immunophilin, cyclophylin (CpN CsA-CpN binds to and blocks CaN function Failure of CaN to dephosphorylate NF-ATc, inhibiting it's transport into the nucleus
35
Anti-TNFa biologicals only bind human TNF-a with high...? (3)
Specificity Affinity Avidity
36
What is the main disease treated by immunosuppressants? What are two general mechanisms of this disease?
Autoimmune diseases 1. Failure of auto-antibodies and T cells to recognize own cells 2. Auto-antibodies and T cells launch attack against own cells
37
3 ways autoimmune diseases can develop?
1. Spontaneous 2. MHC associated genetic predispositions 3. Infectious agents
38
MOA of autoimmune disease induction? (6)
1. Infectious agent causes disease 2. Recovery from disease (T cell and Ab response) 3. A portion of a protein from infectious agents mimics a self protein 4. Due to MHC composition, some T cells specific for infectious agent protein also cross-react with self protein 5. T cell becomes pathogenic, responds to self antigen, recruits other immune cells 6. Tissue destruction
39
How is the classification of autoimmune diseases separated? Three classes?
Effector mechanism | Type II, Type III, Type IV
40
Type II autoimmune disease is a _______ mediated disease
antibody
41
Example of a type II autoimmune disease?
Graves disease
42
Graves disease happens in the ______ and it makes antibodies for which receptor? This leads to what disorder? These antibodies act as _____
Thyroid Thyroid-stimulating hormone receptor (TSHR) Hyperthyroidism Agonists
43
Is it possible to transmit Graves Disease to fetus? | How can this be cured
Yes, antibodies can cross the placenta | Plasmapheresis removes maternal anti-TSHR Abs and cures the disease
44
Type III autoimmune diseases are ______-_____ diseases
Immune-complex
45
4 processes that immune complexes can be subject to?
Complement deposition Opsonization Phagocytosis Processing by proteases
46
Immune complexes in which autoimmune diseases? (5)
``` Lupus erythematosus Cryoglobulinemia Rheumatoid Arthritis Scleroderma Sjogren's syndrome ```
47
Type IV autoimmune diseases are mediated by which cells?
T cells
48
4 examples of Type IV autoimmune diseases?
Diabetes mellitus Rheumatoid arthritis MS Celiac disease
49
Antigen and consequence of Insulin-dependent diabetes mellitus?
Pancreatic Beta-cell antigen | Beta-cell destruction
50
Antigen and consequence of Rheumatoid Arthritis?
Unknown synovial joint antigen | Joint inflammation and destruction
51
Antigens (2) and consequences (2) of MS?
Myelin basic protein, proteolipid protein | Brain degeneration, paralysis
52
Antigen and consequences (2) of Celiac disease?
Gluten modified by tissue transglutaminase Malabsorption of nutrients Atrophy of intestinal villi
53
4 T-cell mediated effects in type IV autoimmune diseases?
1. T cell cytotoxicity via CD8+ cytotoxic T lymphocytes 2. Self-destruction of tissue cells induced cytokines 3. Recruitment and activation of macrophages leading to bystander tissue destruction 4. Induction of target tissue apoptosis by the T cell membrane protein FasL
54
In rheumatoid arthritis, _____antigens cause non-specific activation of T-cells resulting in what? (2)
Superantigens Polyclonal T cell activation Massive cytokine release
55
In rheumatoid arthritis, the immune complex precipitates on synovial lining, what is the MOA? (6)
1. Complement deposits 2. Macrophages infiltrate synovium and become activated 3. CD4 and CD8 lymphocytes infiltrate synovium 4. Th1 cytokine secretion predominates 5. Infiltration of B cells 6. Acute inflammation occurs with destruction of cartilage and bone
56
Psoriasis is a Type IV autoimmune disease that causes activation of T cells where?
in skin cells
57
Topical medications of psoriasis? (7)
``` Corticosteroids Vitamin D analogue creams Topical retinoids Moisturizers Topical immunosuppressants Coal tar Anthralin ```
58
Example of a vitamin D analogue to treat psoriasis? It acts mainly on which receptor? Vitamin D3 inhibits production of ___ and ____ Blocks transcription of ______ and _______ Inhibits activity of which cells? (2)
``` Calcipotriene (Dovonex) Vitamin D receptor (VDR) IL-2 and IL-6 IFN-gamma and GM-CSF Cytotoxic T cells and natural killer cells ```
59
Vitamin D3 inhibits proliferation of which cells?
Keratinocytes
60
Which biological agent interferes with lymphocyte activation?
Alefacept
61
Which biological agent blocks TNFa and TNFB binding to receptor?
Etanercept
62
Which two biological agents and monoclonal antibodies that block TNFa binding to receptor?
Infliximab | Adalimumab
63
Three types of organ donors? Explain
Syngeneic : between genetically identical individuals Allogeneic : from one individual to another of the same species Xenogeneic : between individuals of different species
64
3 Types of Host vs. Graft organ rejection?
Hyperacute Acute Chronic
65
Onset of hyperacute organ rejection? | Mechanism?
Immediate Abs against donor tissue, caused by accidental ABO blood type incompatibility. Presents while still in surgery with thrombosis and occlusion of graft vessels
66
Onset of acute organ rejection? Mechanism?
Weeks to months T-Cell mediated response against foreign MHC. Inflammation and Leukocyte infiltration of graft vessels
67
Onset of chronic organ rejection? Mechanism?
Months to years T-cell mediated process from foreign MHC looking like self-MHC carrying an antigen. Results in intimal thickening and fibrosis of graft vessels
68
Mechanism of "Graft vs. Host" organ rejection?
Donor T-cells in graft proliferate and attack recipient's tissue. Commonly in bone marrow transplants. Presents with diarrhea, rash and jaundice
69
Prior to transplants, patients receive which immunosuppressive regimen? (4)
Antithymocyte Globulin, Muromonab-CD3, Daclizumab or Basiliximab
70
Muromonab-CD3 blocks what?
blocks killing by cytotoxic human T cells
71
Basiliximab is what type of immunoglobulin? Role? | Similar drug? Where does this one bind?
IgG1 Binds to CD25, the IL-2 receptor alpha chain on lymphocytes -IL-2 antagonist, blocks IL-2 from binding to lymphocytes Daclizumab : binds to alpha subunit of IL-2

Pharmacology II (21 decks)

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