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PMCOL 200 Final > Immunopharmacology > Flashcards

Immunopharmacology Flashcards

1
Q

What are the three applications of Immunosuppressive drugs

A
  1. Rejection: Prevent host from rejecting foreign tissue
  2. GVHD: Prevent Graft-Versus-Host Disease, Prevent lymphocytes in foreign tissue from attacking host body
  3. Auto-immune: Prevent host rejecting itself
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2
Q

Name some auto immune diseases

A

Lupus, Rheumatoid arthritis, Psoriasis, Ulcerative colitis, Idiopathic Thrombocytopenic purpura

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3
Q

What does GVHD affect

A

Liver, Skin, Mucosa, Gut

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4
Q

Rheumatoid arthritis

A

Auto immune disease affecting primarily the joints

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5
Q

Lupus

A

Multi organ auto-immune disease
Noticeable by rash on cheek
Many tissues are affected

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6
Q

Ulcerative colitis

A

T-cell infiltration and cause ulceration in the colon

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7
Q

Psoriasis

A

Auto-immune disease leading to scaly patches of skin (butterfly rash)

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8
Q

What are the phases of adaptive immunity
What are the sub phases

A

Induction Phase
Antigen-Presentation
Clonal Expansion and Maturation

Effector Phase

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9
Q

What happens in the antigen presentation step

A

Antigen presentation cells internalize foreign cells, will present antigens and activate T helper cells

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10
Q

What happens in the clonal expansion and maturation step

A

T-helper cells differentiate and mature

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11
Q

What is the role of Th1

A

T-helper cells that attack toxic cells

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12
Q

What is the role of Th2

A

T-helper cells that are the precursor to B cells

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13
Q

What is the Induction Phase

A

Recognition and presentation of foreign antigens
Activation and proliferation of naive Th0-cells into Th1 and Th2

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14
Q

What is the Effector Phase

A

Cell-mediated T-cell responses
Th1 activate macrophages that kill infected/foreign cells
Th2 cause antibody-mediated responses leading to the activation of B cells

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15
Q

Describe T-cell receptor pathway (Calcineurin)

A

T-cell receptor is activated
Creates Ca2+ signal
Activates calcineurin (a phosphatase)
NFAT is dephosphorylated by calcineurin
Dephosphorylated NFAT migrates to the nucleus
Expression of IL-2
IL-2 is used to activate and proliferate T-Cells

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16
Q

What happens if Calcineurin is inhibited

A

IL-2 gene transcription is suppressed meaning the activation and proliferation of T-cells is inhibited

17
Q

Cyclosporine

A

Binds to cyclophilin forming a complex inhibiting calcineurin

Prevents NFAT from being dephosphorylated and prevents NFAT mediated gene transcription of IL-2
Inhibits T-cell maturation and proliferation

18
Q

Tacrolimus

A

Binds to FKBP and forms a complex to inhibit calcineurin

Prevents NFAT from being dephosphorylated and prevents NFAT mediated gene transcription of IL-2
Inhibits T-cell maturation and proliferation

19
Q

What is the mTOR pathway

A

mammalian Target of Rapamycin
Responsible for promoting cell growth/division

20
Q

Rapamycin

A

Binds to FKBP and forms a complex to inhibit mTOR

Suppresses cell responses to IL-2 receptor activation and blocks its downstream signals
Causes less cell growth and division

21
Q

IL-2 receptor

A

Activation of receptor causes T cell maturation and proliferation

22
Q

What are Cytotoxic Agents

A

Directly attack DNA to suppress tumour growth

23
Q

What are Proliferation Signal Inhibitors

A

Inhibits mTOR to interfere with IL-2 pathway
Less T-cell maturation and proliferation

24
Q

What are Calcineurin Inhibitors

A

Inhibits calcineurin (Phosphatase) to prevent the dephosphorylation of NFAT

Without NFAT there is less expression of IL-2 that is needed for T-cell maturation and proliferation

25
Q

Cyclophosphamide

A

Interferes with DNA replication by cross linking neighboring bases

Useful in rapidly dividing cells
Used to treat cancer
Used to treat rapidly dividing immune cells

26
Q

Azathioprine

A

Metabolized to 6-mercaptopurine
A fraudulent nucleotide
Inhibits synthesis of nucleotides, interferes with cell division, and can prevent DNA replication

Effective against rapidly dividing cells during clonal expansion
6-MP can be incorporated into DNA and prevent replication

27
Q

What is an antibody’s structure

A

2 Heavy Chains
2 Light Chains

2 regions
Fab region
Fc region

28
Q

What is the Fab region of an antibody

A

Determines antigen specificity, what it can bind and what viruses it can recognize

(Antigen-binding)

29
Q

What is the Fc region of an antibody

A

Determines antibody class (lgA, lgG, lgM)

Different classes are recognized by different immune cell types through specific receptors for each class
Determines a different immune response

30
Q

Describe the structure of the antibody’s Fab region

A

Variable, creating specificity for different antigens

Made up of the light chain with a bit of the heavy chain

31
Q

Describe the structure of the antibody’s Fc region

A

Conserved

Made up of only the heavy chain

32
Q

How are antibody-based therapies created

A

Antibodies are raised in other animals, however, if used as they are they will be rapidly degraded by the immune system before they can have an affect

33
Q

What is humaization/chimerization

A

Replacement of the conserved region (Fc) of the mouse monoclonal antibody with the corresponding sequence (Fc) from human antibodies.

The monoclonal antibody will not be recognized by the immune system
Reduces their antigenicity (Ability to induce an effect)
Increases their lifetime in the body

34
Q

What are the naming conventions of therapeutic monoclonal antibodies

A

-umab / -zumab for humanized antibodies
-imab / -ximab for chimeric products

Murine (mouse) monoclonal antibodies

35
Q

What is the difference between humanization and chimerization

A

Humanized: Non-human antibody containing protein sequence to make it more human like

Chimerized: Antibody containing a conserved region from a human antibody and a variable region from a non-human species

36
Q

Alemtuzumab

A

Humanized lgG1 that recognizes and binds to CD52 found on many different immune cell types

NK cells, complement, and phagocytic immune cells (macrophages, neutrophils, dendritic cells) recognize the lgG1 Fc domain.
Leads to cell death by lysis or phagocytosis

Effect: Labels cells early in immune response and targets them for destruction

Side Effect: Targets both healthy and destructive T and B cells for destruction

37
Q

Basiliximab

A

Chimeric mouse-human lgG1 that binds to CD25 which is part of the IL-2 receptor (the alpha chain), on activated lymphocytes

Interferes with activation of IL-2 receptor
IL-2 antagonist that blocks IL-2 from binding to activated lymphocytes

Ultimately causes immunosuppression

PMCOL 200 Final (5 decks)

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