15. Immunopharmacology, neuro- and psychoimmunology Flashcards Preview

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Flashcards in 15. Immunopharmacology, neuro- and psychoimmunology Deck (37)
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1
Q

Therapeutic agents

A

1) NSAIDs
2) Corticosteroids
3) Anti-allergy drugs
4) Cytostatic drugs
5) Non-cytostatic immunosuppressive drugs
6) Other antiinflammatory drugs
7) Biologicals

2
Q

NSAIDs effects + side effects

A

Most important effect:

  • Inhibition of arachidonic acid metabolism
  • Inhibits COX => no prostanoid metabolism => decreased inflammation

Side effects:

  • Main: Peptic ulcer, erosive gastritis-duodenitis
  • GI: vomit, diarrhea, obstipation, ulcer, erosions
  • Liver: toxic hepatitis
  • Kidney: decreased function, interstitial nephritis
  • CNS: head ache, tremor, depression, psychosis
  • Blood: bone marrow depression, hemolytic anaemia, haemophilia
  • Allergy:, exanthema, asthma
  • Other: drug interactions
3
Q

Symptoms of aspirin overdose

A
  • CNS: Restlessness, irritability, excessive unorganized talking, fear or nervousness, dizzy, confusion, excited mood, hallucinations, drowsiness, loss of consciousness
  • Systemic: fever
  • Eyes: double vision
  • Muscles: uncontrollable shaking, seizures
  • Throat: burning, pain
  • Stomach: vomiting, pain
  • Kidneys: decreased urination
4
Q

COX-1

A

Constitutional, makes cytoprotective prostaglandins
Inhibitors:
- NSAIDs (non-COX-2)
- Aspirin

5
Q

COX-2

A
Inducible, makes inflammatory prostaglandins
Inhibitors:
- COX-2 inhibitors
- NSAIDs (non-COX-2)
- Aspirin
Inducers: 
- Cytokines
- Growth factors
6
Q

Corticosteroids functions

A

1) Transactivation
- GRE: glucose response element
- Transcription: Annexin 1, SLPI (secretory leukoprotease inhibitor), IL-10
2) Transrepression
- Switching off inflammatory genes

7
Q

Use of cortisol (hydrocortisone)

A
  • Rarely and locally

- It’s synthetic derivatives are administered per os (orally), parenterally or locally

8
Q

Cortisol effects

A

1) Decreased inflammation (Decreased IL-1, TNFα, GM-CSF, IL-3, IL-4, IL-5, IL-8)
2) Decreases NO (Decreased NOS)
3) Decreased PGs and LTs (Decreased phospholipase A2 and COX-2, increased lipocortin-1)
4) Reduced emigration leukocytes from vessels (Decreased adhesion molecules)
5) Induction apoptosis in lymphocytes+eosinophils (Increased endonucleases)

9
Q

Antiallergic drugs

A

1) Antihistamines
- H1 R antagonists: dermatological diseases, allergic rhinitis (e.g Claritine, side effects: somnolence, reduced concentration)
- H2 R antagonists: inhibit gastric HCl secretion (Cimetidine, Rantidine, Famotidine)
2) Leukotriene inhibitors: therapy bronchial asthma

10
Q

Antiallergic drugs targets mast cell

A
  • IgE: Anti-IgE
  • cKit: cKit antagonists or blocking SCF Ab
  • Syk kinase: Syk kinase inhibitors
11
Q

Cytostatic drugs

A

“Cell stopping drugs”

1) Alkylating agents: bind to DNA and prevent DNA synthesis (Cyclophosphamide, chlorambucil. Major side effects: bone marrow depression)
2) Folic acid antagonists: Methotrexate
3) Purine antagonists: Azathioprine (Imuran)
4) Pyrimidine antagonists: Leflunomide
5) Vinca alkaloids: anti-mitotic, anti-microtubule agents (Vinblastin, Vincristin)

12
Q

Non-cytostatic immunosuppressive drugs

A

Cyclosporine A and tacrolimus (!)

  • Inhibit calcineurin => no dephosp of NFATc (cannot move to nucleus as a transcription factor)
  • Used in the case of transplanted patients
  • Affects T cells, B cells and granulocytes (immunosuppressive)
13
Q

Other antiinflammatory drugs

A

Primarily base therapy of RA: DMARDs (disease modifying antirheumatic drugs)

  • Gold compounds
  • Penicillamine
  • Anti-malaria agents
  • Sulfasalazine
  • Dapson
  • Thalidomide
14
Q

Biologicals (therapeutic agents)

A

1) Vaccines: against oncogenic or potentially oncogenic virus infections
2) Tolerization:
3) Cytokine therapy and cytokine antagonists
4) Antibody therapy
5) IVIG (Intravenous immunoglobulin)
6) Stem cell transplantation
7) Gene therapy

15
Q

Monoclonal Ab therapies

A

Use laboratory-made monoclonal Ab’s to attack specific targets (e.g cancer cells)

  • Most of the Ab is human, but parts of the variable region are exchanged with mouse Ab parts
    1) Murine: fully mouse (muromonab-CD3)
    2) Chimeric: Fc is human, variable part of Fab is mouse
    3) Humanized: only CDR (complement determining region) is mouse, rest is human
  • Longer half-life
  • Reduced immunogenicity
  • More efficient (ADCC, complement) effector mechanisms
    4) Fully human
16
Q

Denosumab

A
  • Fully human monoclonal Ab
  • IgG2
  • High affinity and specificity to human RANKL
    => inhibit osteoclast => inhibit bone resorption/prevent osteoporosis
17
Q

Omalizumab

A
  • Humanized monoclonal Ab
  • Anti-IgE
  • Reduce sensitivity to inhaled/ingested antigens
  • Used for asthma
18
Q

Abatacept

A
  • Fusion protein (monoclonal Ab therapy)
  • Human IgG1 Fc part + extracellular part of CTLA4
  • Inhibit T cell activation (CD80/86-CTLA4)
  • Used for rheumatoid arthritis
19
Q

Cytokine antagonists

A

1) IL-1R antagonists
- Anakinra (RA)

2) TNFα-blockers (RA, ankylosing spondylitis, psoriasis)
- Infliximab (chimera - also Crohn’s disease, ulcerative colitis)
- Adalimumab (human)
- Etanercept (fusion molecule: 2 TNF R + Fc of IgG1)
- Golimumab (human)
- Certolizumab (pegol - PEGylated, mainly against Crohn’s and RA)

20
Q

PEGylation of Certolizumab

A

Fab of a monoclonal antibody that has been conjugated to polyethylene glycol (PEG)
=> Longer halflife
=> Protection: from degrading enzymes and Ab’s
=> Reduced immunogenicity

21
Q

Other immunsuppressive agents

A

Sirolimus (rapamicin)
- mTOR inhibition
=> Inhibition of B and T cell proliferation
- After transplantation

22
Q

Anti Rh(0)-D immunoglobulin

A
  • Prevent morbus haemolyticus neonatorum

- Given to Rh- mother within 24-72 hrs postpartum

23
Q

Side effects of immunosuppressive agents

A
  • Increased susceptibility to infections
  • Bone marrow and mucosal membrane damages
  • Cyclosporine may cause kidney damage
  • Late consequence: elevated freq of malignant diseases
24
Q

Immunstimulant agents

A

1) Natural
- Cytokines
- Endogen regulators and their derivatives
2) Synthetic
- Inosiplex
- Imiquimod: TLR7/8 agonist

25
Q

Immunstimulant cytokines

A

1) Interferons
- IFN α: antiviral, anti-tumor
- IFN β: multiple sclerosis
- IFN γ: Increased IL1 production, chronic granuloma
2) Colony stimulating factors
* Induces colony formation of bone marrow stem cells
- G-CSF: filgrastim
- GM-CSF: molgramostim, sargramostim
3) Interleukins
- IL2 (aldesleukin): metastatizing kidney tumors
- IL11 (oprelvekin): thrombocytopenia by tumor chemotherapy
4) Other cytokines: TNF

26
Q

Desenzitation - allergen-specific immuntherapy

A

Subcutaneous or sublingual administration of the allergen: stepwise increasing teh dose

27
Q

IVIG therapy requirements

A
  • Should be from at least 1000 different human donors
  • All 4 IgG subclasses should be represented
  • IgG activity for >21 days
  • Not contain HIV, hepB/C
  • Should be handled in a way that destroys viruses
28
Q

Inflammatory bowel disease important inducer

A

Psychological distress

29
Q

HPA axis

A

Hypothalamus: CRH => ACTH => cortisol => decr. IL-6

30
Q

Stress

A
  • Acute: fight/flight
  • Short: days-weeks
  • Chronic: months-years
  • Stress can be a part on the inducers of chronic inflammation
31
Q

Effects of stress on immune response

A

Increases immune response in acute and short

Decreases in chronic

32
Q

Impact of stress enhanced in

A
  • Elderly
  • People with depression
  • People who recieve low psychological support (lonely)
33
Q

Caregiver of Alzheimer patients effect (chronic stress)

A
  • Enhanced telomer erosion
  • Decreased T cell proliferation
  • Increased IL-10
  • Increased TNF α
34
Q

Physical exercise

A

Advantageous psychological and immunological

  • Efficient first line treatment for mild or intermediate depression
  • Reduces depression symptoms caused by stress
  • Reduces inflammation and oxidative stress
35
Q

Vitamin D3

A

Antiinflammatory effect, antidepressant

  • Increase monocytes/macrophages
  • Decrease dendritic cells
  • Decrease effector or memory T cell
  • Decrease B cells or ASC (APC?)
36
Q

Activation induced cell death (AICD)

A

Fas -> apoptosis

37
Q

Regulatory T-cells

A

Tr1: IL-10 producing regulatory T cells
CD4+/CD25+ regulatory T-cells
TH3 cells: TGF beta