DA Exam 4 Lecture 4: Biologics-Biological Response Modifiers - Shaw Dawg

what are substances that modify immune responses

biological response modifiers (BRM)

T/F: BRMs can be endogenous and exogenous

t

T/F: BRMs only reaction can be an enhancement of immune response

F: can enhance or suppress

how can BRMs enhance an immune response

by arousing the bodys response to an infection

how can BRMs suppress an immune response

keep the response from becoming excessive

T/F: BRMs serve as immunomodulators in immunotherapy

t

BRMs are useful in treating what 2 things

cancer and autoimmune disease

what are 2 examples of autoimmune diseases

arthritis and dermatitis

T/F: most BRMs are not biopharmaceuticals

F: they are

what are 4 examples of biopharmaceuticals

1. monoclonal antibodies

2. interleukin 2

3. interferons

4. colony-stimulating factors (CSF, GM-CSF, G-CSF)

immunotherapy uses BRMs to enhance/suppress the immune system to increase the bodys natural defense mechanisms against cancer

enhance

BRMs for rheumatoid arthritis aim to do what

reduce inflammation

what are the adverse effects of BRMs

nausea and vomiting

diarrhea

loss of appetite

fever and chills

muscle aches

weakness

skin rash

increased tendency to bleed

swelling

Granulocyte colony-stimulating factor (G-CSF)

stimulates the formation of granulocytes from myeloblast cells

what type of G-CSF is produced in E. Coli

amgen (filgrastim)

amgen is produced by what 2 things

fibroblasts and monocytes

how does Amgen act upon cells

stimulates neutrophil development and differentiation

how many clinical studies are G-CSF being used in

250

Granulocyte-macrophage colony-stimulating factor (GM-CSF)

acts on the one marrow to increase production of WBCs

what type of GM-CSF is produced by Immunex

LEUKINE Sargramostim

GM-CSF are produced by what 2 things

macrophages and T cells

how does GM-CSF affect cells

stimulating growth and differentiation of myelomonocytic lineage

GM-CSF stimulates growth and differentiation of what

myelomonocytic lineage

how many clinical studies are GM-CSF being used in

86

T/F: we need cytokines to stimulate proliferation of T and B cells for a cell immune response

t

which interleukin is produced by T cells, and some B cells

interleukin 2

which interleukin is also called T cell growth factor

interleukin 2

which interleukin deals with T cell proliferation

interleukin 2

how many clinical studies are interleukin 2 being used in

96

which interleukin is produced by macrophages and B cells

interleukin 12

what cells does interleukin 12 activate

NK cells and CD4 T cell differentiation to TH1-like cells

interleukin 12 activates NK cells and CD4 T cell differentiation to what type of cells

TH1-like cells

how many clinical studies is interleukin 12 being used in

20

what is produced by T cells and NK cells and acts on activation of macrophages

interferon-gamma

interferon-gamma acts on activation of

macrophages

how many clinical studies is interferon-gamma being used in

11

T/F: interleukin 2, interleukin 12, and interferon gamma attack viruses

t

how are interleukin 2, interleukin 12, and interferon gamma produced

recombinant technology

what is CD4 T cells involved in

HIV

what type of cells kill invading organisms

NK

T/F: phagocytosis kills bacteria

t

what is described as cytokines with potent anti-viral activity

interferons

what produces interferons

host cells in response to viral infections

IGNy is produced by

T-lymphocytes and NK cells

what are the 3 major classes of interferons

alpha, beta, gamma

T/F: clinically used interferons are recombinant non-glycosylated proteins

t

what is the approximate size of the non-glycosylated proteins used for interferons

19.5 Kd

what do IFNs bind to

their specific receptors

what pathway do IFNs activate

JAK-STAT signaling pathway

what in the JAK-STAT pathway causes the sense of the activation

series of proteins phosphorylated and therefore passes a signal

what type of proteins are IFNs

enzymes that inhibit viral replication, destroy single-stranded RNA or DNA or inhibit protein synthesis in the presence of double-stranded RNA

T/F: IFNs inhibit viral replication

t

T/F: IFNs build single-stranded RNA or DNA

F: destroy

T/F: IFN inhibit protein synthesis in the absence of double-stranded RNA

F: presence of double-stranded RNA

T/F: IFNs can modulate immune response

t

what happens once a virus enters the body

- it enters the cell/nucleus then reproduced inside the cell

IFNs decrease/increase host resistance to viral infection

increase

how is rheumatoid arthritis treated

by targeting cytokines that contribute to the disease process

how can BRMs reduce symptoms of rheumatoid arthritis

by neutralizing or eliminating targeted cytokines, it decreases inflammation

what does hyperactive immune cells produce

combat cytokines

what medication possess the biological activities of human native interleukin 2

Proleukin (aldesleukin)

T/F: proleukin stimulates the immune system

t

what 4 ways does Proleukin work

1. enhances lymphocyte mitogenesis and stimulation of long-term growth of human interleukin 2 dependent cell lines

2. enhances lymphocyte cytotoxicity

3. induces killer cell activity

4. induces interferon-gamma production

Proleukin enhances lymphocyte mitogenesis and stimulation of what cells

long term growth human interleukin 2 dependent cell lines

T/F: Proleukin enhances lymphocyte cytotoxicity

t

what type of killer cells does Proleukin induce

lymphokine activated (LAK)

natural killer (NK)

T/F: Proleukin suppresses interferon gamma production

F: induces

in what 3 ways does proleukin induce interferon-gamma production

1. produces multiple immunological effects in a dose dependent manner

2. activation of cellular immunity with profound lymphocytosis, eosinophilia, and thrombocytopenia

3. production of cytokines including tumor necrosis factor, IL-1, and gamma interferon

T/F: proleukins produce multiple immunological effects in a dose dependent manner

t

T/F: proleukins activate cellular immunity with profound _____, ______, and _____

lymphocytosis, eosinophilia, and thrombocytopenia

lymphocytosis is dealing with

WBC

eosinophilia is dealing with

RBC

thrombocytopenia is dealing with

plasma

Abciximab is previously known as

c7E3 Fab

what is Abciximab

a glycoprotein IIb/IIIa receptor antagonist manufactured by Jassen Biologics BV

T/F: abc is a global immune antibody

t

what is Abciximab trade name

ReoPro

when is ReoPro most used

platelet aggregation inhibitor used during and after coronary artery procedures

when using ReoPro before and after coronary artery procedures what does it do

prevents platelets from sticking together and causing thrombus within the artery

T/F: ReoPro is a glycoprotein IIb/IIIa inhibitor

t

T/F: abciximab has a short plasma half life

t- due to strong affinity for its receptor on the platelets

in practice how soon does platelet aggregation gradually return to normal

96-120 hours after discontinuation of the drug

what is abciximab made from

the Fab fragments of an immunoglobulin

what of abciximab targets the glycoprotein IIb/IIIa receptor on the platelet membrane

Fab fragments

what is Anakinra used for

rheumatoid arthritis- a second line treatment to manage symptoms after treatment with a disease modifying antirheumatic drug (DMARD) has failed

what type of drug needs to fail before a patient can try Anakinra

DMARD

Anakinra is a recombinant and slightly modified version of what receptor antagonist protein

human interleukin I

how is Anakinra administered

SQ injection

T/F: Anakinra can be used in infants and adults

t

what is an off label use of Anakinra

Schnitzler's syndrome

T/F: Anakinra is safe for pregnancy

eh- not tested in pregnant women, but passed in animal studies

what types of patients should not use Anakinra

- active infections

- latent tuberculosis

- low white blood cells counts

- taking TNF inhibitors

what is the trade name of Etanercept

Enbrel

what is Enbrel used for

treatment in autoimmune diseases by interfering with tumor necrosis factor (TNF)

what 5 things does Enbrel have the FDA approval to treat

1. rheumatoid arthritis

2. juvenile rheumatoid arthritis

3. psoriatic arthritis

4. plaque psoriasis

5. ankylosing spondylitis

what is the mater regulator of the inflammatory response in many organ systems

TNF-alpha

what are autoimmune diseases caused by

overactive immune response

what type of protein is Etanercept? what is it produced by?

fusion protein produced by recombinant DNA

what is the role of Etanercept

fuses the TNF receptor to the constant end of the IgGI antibody

Etanercept fuses the TNF receptor to the ________ of the IgGI antibody

constant end