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Phase 2a pre clinical > immunology > Flashcards

immunology Flashcards

1
Q

innate immunity

A

non specific

instinctive

does not depend on lymphocytes

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2
Q

adaptive immunity

A

specific

acquired

requires lymphocytes

antibodies

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3
Q

origin of blood cells

A

all haemopoietic cells derived from pluripotent stem cells

gives rise to two main lineages- myeloid and lymphoid

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4
Q

neutrophils

A

polymorphonuclear leukocyte
phagocytosis
2 intracellular granules:
-primary lysosomes (myeloperoxidase, muramidase, acid hydrolases and defensins)
-secondary granules (lactoferrin and lysozyme)

can kill microbes by secreting toxic substances (superoxides)

size=10-14 micro-metres
3-11,000 per mm3 blood (65%)
lifespan= 6hr-12days

expresses CD66b

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5
Q

monocytes

A

mononuclear leukocyte
phagocytosis and Ag presentation
differentiate into macrophages in tissues

size=14-24 micrometres
100-700/mm3 blood (5%)
lifespan=months

presents CD14
FC, complement receptors, PRR, TLR and mannose receptors

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6
Q

macrophages

A

‘Large eaters’

Reside in tissues, Lifespan – months/years e.g. Kupffer cells – liver, microglia - brain

Phagocytosis & Ag presentation

Main role – remove foreign (microbes) and self (dead/tumour cells) Have
lysosomes containing peroxidase (free radicals)

Have Fc, complement receptors also Scavenger, Toll-like and mannose
receptors – can bind all kinds of microbes

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7
Q

eosinophil

A

Polymorphonuclear leukocyte

Size = 10-14 micrometres
100-400 per mm3 blood (5%) Lifespan – 8-12d

express CD125

Mainly associated with parasitic infections and allergic reactions

Granules contain Major Basic Protein – potent toxin for helminth worms
Granules stain for acidic dyes (eosin)

MBP – activates neutrophils, induces histamine release from mast cells &
provokes bronchospasm

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8
Q

basophil

A

Polymorphonuclear leukocyte

Size= 10-12 micrometres
20-50 per mm3 blood (0.2%) Lifespan – 2d

Granules stain for basic dyes
Very similar to mast cells

Express high-affinity IgE receptors

Binding of IgE to receptor causes de-granulation releasing histamine –
main cause of allergic reactions
Mainly involved in immunity to parasitic infections and allergic reactions

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9
Q

mast cell

A

Size 10-14 micrometres
Only in tissues (precursor in blood)
Very similar to basophils

Express high-affinity IgE receptors
Binding of IgE to receptor causes de-granulation releasing histamine –
main cause of allergic reactions
Mainly involved in immunity to parasitic infections and allergic reactions

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10
Q

T cells

A

Mononuclear leukocyte
Size= 5-12 micrometres
300-1,500 per mm3 blood (10%)
Lifespan= hrs – yrs,

Mature in thymus (T) 
Express CD3 (T cell receptor complex)

Play major role in Adaptive Immunity
-Recognise peptide Ag displayed by Antigen Presenting Cells (APC)

4 main types
o T helper 1 (CD4 – ‘help’ immune response intracellular pathogens) (cell medicated)
o T helper 2 (CD4 – ‘help’ produce antibodies – extracellular pathogens) (humoral)
o Cytotoxic T cell (CD8 – can kill cells directly)
o T reg (FoxP3) – regulate immune responses ‘dampen’

Found in blood, lymph nodes and spleen

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11
Q

B cells

A

Mononuclear leukocyte

Size =5-12 micrometres
300-1,500 per mm3 blood (15%)
Lifespan= hrs to yrs,
mature in bone marrow (B)

Express CD19 + 20 (depends on maturity)

Play major role in Adaptive Immunity

  • Recognise Ag displayed by Antigen Presenting Cells (APC)
  • Express membrane bound antibody on cell surface
  • Differentiate into plasma cells that make Antibodies

Found in blood, lymph nodes and spleen

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12
Q

Natural killer cells

A

Account for 15% of lymphocytes

Express CD56, Found in spleen/tissues

Look like ‘large granular lymphocytes’
NK cells recognise and kill:
o Virus infected cells
o Tumour cells

Kill by apoptosis – programmed cell death

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13
Q

soluble factors of the immune system

A

complement

antibodies

cytokines

chemokines

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14
Q

complement (C’)

A

group of around 20 serum proteins that need to be activated to be functional

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15
Q

antibodies

A

bind to antigens (Ag)

Immunoglobulin (Ig)= soluble and bind to B cells as part of B cell antigen receptor
Glycoproteins
5 different classes:
-IgG (1-4)
-IgA (1&2)
-IgM
-IgE
-IgD
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16
Q

antibody definition

A

protein produced in response to antigen

can only bind with antigen that induced its formation

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17
Q

antigen definition

A

molecule that reacts with preformed antibody and specific receptors on T and B cells

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18
Q

epitope definition

A

part of antigen that bind to antibody

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19
Q

affinity

A

measure of binding strength between epitope and antibody binding site

higher the affinity the better

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20
Q

antibody structure

A

antigen recognition:

  • fab regions= variable in sequence
  • bind different antigens specifically

antigen elimination:

  • FC region= contant in sequence
  • binds to complement, FC receptors on phagocytes, NK cells etc.

variable and constant regions are encoded by different exons
Multiple variable region exons in genome can recombine and mutate during B cell differentiation to give different antibody specificity

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21
Q

IgG

A

main class in serum and tissues (70-75%)

important in secondary/memory responses

crosses placenta

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22
Q

IgA

A

15% of Ig
80% of IgA is a monomer

predominant Ig in Mucous such as saliva, milk and genitourinary secretions (secretory IgA, protects mucosal surfaces)

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23
Q

IgD

A

present at low levels
1% of Ig
transmembrane monomeric form is present on mature B cells

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24
Q

IgE

A

around 0.05% of Ig
basophils and mast cells express IgE receptor so continually saturated with IgE

allergic and parasitic

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25
Q

IgM

A

10% of Ig

pentamer

mainly found in blood as too large to cross endothelium

mainly primary response

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26
Q

cytokines

A

proteins secreted by immune and non-immune cells

Interferons:

  • induce state of antiviral resistance in uninfected cells
  • alpha and beta are produced by virus infected cells
  • gamma released by activated Th1 cells

Interleukins:

  • over 30 types
  • pro-inflammatory (IL1) or anti-inflammatory (IL10)

CSF:

  • colony stimulating factors
  • direct division and differentiation on bone marrow stem cells
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27
Q

chemokines

A

chemotactic cytokines

around 40 proteins that direct movement of leukocytes from blood stream into tissues

attract leukocytes to site of infection

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28
Q

features of innate immunity

A

primitive
does not depend on immune recognition
no long lasting memory

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29
Q

defences

A

physical and chemical barriers
phagocytic cells
serum proteins

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30
Q

physical and chemical barriers

A

anatomical barriers:

  • epidermis and dermis
  • sebum (skin secretes), pH 3-5

mucous membranes:

  • saliva
  • tears
  • secretions entrap
  • cilia
  • commensal colonies

physiological:

  • temperature (pyrexia)
  • pH
  • gastric acidity
  • oxygen tension
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31
Q

sensing microbes

A

in blood: monocytes and neutrophils

in tissues: macrophages and dendritic cells

receptors involved= PRR and PAMP and TLR

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32
Q

complement proteins activation pathways:

A
  • classical= antibody bound to microbe
  • alternative= C’ binds to microbe
  • lectin= activated by mannose binding lectin to microbe
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33
Q

extravasation

A

leukocyte migration across endothelium

diapedesis:
-process of neutrophils moving out of vascular system

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34
Q

diapedesis process

A

tethering and rolling:

  • slow neutrophil down (CD15 and E-selectin)
  • neutrophil senses and binds to chemokines

secondary adhesion:
-neutrophil becomes static via binding its integrins and adhesion molecules on endothelial cells

spreading:
-neutrophil changes shape

extravasation:
-it squeezes through gap junction in endothelial cells along chemotactic gradient to site of infection

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35
Q

phagocytosis

A

binding
engulfment
phagosome formation
lysosome formation (phagolysosome and digestion)
membrane disruption/fusion
antigen presentation of non-self antigens that have been degraded

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36
Q

mechanisms of killing

A

O2 dependent:

  • reactive oxygen intermediates
  • superoxides (O2) converted to H2O2 then OH free radical
  • nitric oxide (NO) vasodilates and increases extravasation

O2 independent:

  • enzymes
  • proteins
  • pH
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37
Q

inflammation accessory molecule

A

acute phase proteins

C reactive protein:

  • serum protein produced by liver, binds to some bacterial cells walls (pneumococci)
  • promotes opsonisation, binding to C1q and activating C’

mannose binding lectin

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38
Q

need for adaptive immunity

A

microbes evade innate immunity

intracellular viruses and bacteria and hide from innate immunity

need memory to specific antigen so it’s faster

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39
Q

cell mediated immunity

A

interplay between APCs (macrophages, dendritic cells, B cells) and T cells

requires:
- intimate cell-cell contact
- MHC
- intrinsic/endogenous antigens
- extrinsic/exogenous antigens
- recognition of self and non-self

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40
Q

T cells

A

only responds to presented antigens not soluble antigens

if they recognise self they are killed in foetal thymus

T cell receptors recognise foreign antigens

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41
Q

Major histocompatibility complex

A

display peptides from self or non-self proteins on cell surface

Ag is bound to MHC and T cell receptor recognises MHC and peptide

MHC I= all nucleated cells

MHC II= only on APC

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42
Q

T cell Ag recognition

A

involved co-stimulatory molecules

required for full activation

leads to division, differentiation, effector functions and memory

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43
Q

Tc (CD8) activation

A

CD8 and MHCI/peptide = Tc/CTL effector cell

forms proteolytic granules

kills cells by inducting apoptosis

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44
Q

Th1 (CD4) activation

A

APC presents Ag with MHCII to CD4 cell

stimulation with high levels of IL2 activates naive cells to TH1 cells

proliferate (clonal expansion)

recognises Ag on infected cells and secretes interferon gamma to stop viral spread

help B cells make antibodies

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45
Q

Humoral adaptive immunity (B cell activation)

A

express Ig (D or M)

can only make one antibody that will only bind to one epitope on one Ag

born with 10^9 immature B cells

Bcells that recognise self are killed in bone marrow

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46
Q

B cells presenting Ag to T cells

A

monomeric IgM or MigD bind to Ag

phagocytosis

peptide displaced on surface with MHCII

TCR of naive TH binds to MHCII

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47
Q

T helper cells

A

APC eats Ag and presents it to naive CD4+ Tcells (turn into Th2 cells)

Th2 cells bind to B cells that present Ag

now secrete cytokines (IL-4,5,10,13)
these cause B cells to divide (clonal expansion and differentiate into plasma cells or memory B cells)

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48
Q

Ab effector functions

A

specific secreted antibody may:

  • neutralise toxin when binding
  • increase opsonisation (phagocytosis)
  • activate complement
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49
Q

patterns in pattern recognition

A

limited characteristics
gram +ve/-ve
dsRNA
CpG motifs

50
Q

PRR family

A

secreted and circulating PRRs

cell-associated PRRs =more traditional

51
Q

secreted and circulating PRRs

A

antimicrobial peptides secreted in lining fluids, from epithelia and phagocytes:

  • defensins
  • cathelicidin

lectins and collectins= proteins containing carbohydrate that find carbs or lipids in microbe walls:

  • improve phagocytosis
  • mannose binding lectin
  • surfactant A and D
52
Q

cell associated PRRs

A

receptors present on cell membrane or in the cytosol of cells

recognise a broad range of molecular patterns

Toll like receptors are main family

53
Q

TLRs

A

polymorphisms in TLR4 affect endotoxin responsiveness

inflammatory pathways
interferon pathways (viral infections)
54
Q

nod-like receptors

A

rapidly expanding family of another 22 human proteins

detect intracellular microbial pathogens

detection of peptidoglycan, muramyl dipeptide etc.

best known = NOD1, 2, and NLRP3

55
Q

NOD2

A

widespread expression

recognises muramyl dipeptide- breakdown product of peptidoglycan

activated inflammatory signalling pathways

nonfunctioning= crohns disease

hyper-functioning= blau syndrome

56
Q

Rig like receptors

A

RIG-1 and MDA5- detect intracellular double stranded viral RNA and DNA

couple effectively to activation of interferon production, enabling antiviral response

57
Q

homeostasis and PRRs

A

neutrophil numbers may be dependent on TLR4 signalling

induction of endotoxin tolerance in the newborn gut

maturation of normal immune system

maintain a balance with commensal organisms

58
Q

damage recognition and PRRs

A

TLRs recognise a range of endogenous damage molecules

appearance of host molecules in unfamiliar contexts can activate TLRs

TLR signalling by cellular damage products activates immunity to initiate tissue repair and perhaps enhance local antimicrobial signalling

59
Q

PRRs in adaptive immunity

A

activation of TLRs and PRRs drives cytokine production by APCs

increases likelihood of successful T cell activation

TLR4 agonists vaccine adjuvants

TLR7/8/9 adjuvants in development

60
Q

natural passive immunisation

A

e.g. transfer of maternal antibodies across the placenta to developing foetus
or breast milk to baby

protects against:

  • diphtheria
  • tetanus
  • rubella
  • mumps
  • polio
61
Q

artificial passive immunisation

A

treatment with pooled normal human IgG or immunoserum against pathogens or toxins

anti-toxins
anti-venoms

62
Q

vaccination

A

manipulating the immune system to generate a persistent protection against pathogens after mimicking natural infection

mobilise the appropriate arms of the immune system and generate immunological memory

achieve natural exposure without risk of actual infection

63
Q

process of active immunisation

A
  • engage the innate immune system
  • triggers molecular fingerprints of infection (PAMP etc.)
  • engage TLR
  • activate specialist APCs
  • engage the adaptive immune system by generating T and B memory cells and Th cells
  • memory cells then circulate for years
  • seconds response is therefore prompt and powerful: high levels and affinity of IgG
64
Q

types of vaccine

A

live or inactivated whole organism

subunit (toxins, antigenic proteins or recombinant proteins)

peptides

DNA vaccine

engineered virus

65
Q

whole organism

A

live attenuated pathogen

e.g. TB or polio

prolonged culture leads to adaption and a strain that has reduced virulence in humans

66
Q

whole organism advantages

A

attenuated pathogen sets up transient infection

full natural immune response

memory response

prolonged and comprehensive protection

single immunisation required

67
Q

whole organism disadvantages

A

immunocompromised patients may become infected

can occasionally revert to virulent form

68
Q

whole inactivated pathogen

A

inactivation usually by chemical treatment (formaldehyde)

heat can alter conformation of target antigens

69
Q

whole inactivated pathogen advantages/disadvantages

A

advantages:

  • no risk of infection
  • storage less critical
  • wide range of antigenic components present so good immune response

disadvantages:

  • tend to activate humoral response so no T cell involvement
  • without transient infection the immune response is weak
  • booster required (issue with compliance)
70
Q

subunit vaccine 3 types

A

purified molecular components as immunogenic agents

  • inactivated exotoxins
  • capsular polysaccarides (Men C)
  • recombinant microbial antigens
71
Q

subunit vaccine advantages/disadvantages

A

advantages:

  • safe, only parts of pathogen used
  • no risk of infection
  • easy to store and preserve

disadvantages:

  • immune response is less powerful
  • repeated vaccinations and adjuvants required
  • consider genetic heterogeneity to the population
72
Q

synthetic peptides

A

produce a peptide that includes immunodominant B cell epitopes and can stimulate T memory cell development

lack of knowledge, peptides can by stimulatory or suppressive, most B cell epitopes are conformational

73
Q

DNA vaccines

A

transiently express genes from pathogens in host cells

generates immune response similar to infection

leads to T and B cell memory response

74
Q

DNA vaccines advantages/disadvantages

A

advantages:

  • safe
  • no requirement for complex storage
  • drug delivery can be simple and adaptable to widespread vaccination programs

disadvantages:

  • DNA vaccines are likely to produce mild response and require subunit boosting
  • no transient infection
75
Q

recombinant vaccines

A

imitate effects of transient infection with pathogen byt using non-pathogenic organism

genes for major pathogen antigens are introduced into non-pathogen microorganisms

76
Q

recombinant vector vaccine advantages/disadvantages

A

advantages:

  • create ideal stimulus
  • produce immunological memory
  • flexible
  • safe

disadvantages:

  • require refrigeration
  • can cause illness in compromised individuals
  • immune response to virus in subjects can negate effectiveness
77
Q

adjuvants

A

any substance added to a vaccine to stimulate the immune system

aluminium salts- form precipitates and potentiate opsonised phagocytosis

chemicals can cause inflammation

toxoids and killed organisms trigger immune system

78
Q

the ideal vaccine

A
  • safe
  • induce suitable immune response
  • generate T and B memory cells
  • stable and easy to transport
  • should not require repeated boosting
79
Q

passive immunity

A

transfer of preformed antibodies

does not activate immunological memory so no long term protection

80
Q

general features of tumour

A

express antigens that are recognised as foreign by the immune system

immune response frequently fails to prevent the growth of tumours

the immune system can be activated by external stimuli to effectively kill tumour cells and eradicate tumours

81
Q

etiology of cancer

A

transformation of germline cells= inheritable cancers (<10%)
transformation of somatic cells= non-inheritable cells (>90%)

environmental factors= UV (skin cancer), chemicals (lung cancer), pathogens (HPV causes cervical cancer)

82
Q

hallmarks of cancer

A 
growth self sufficiency
evade apoptosis
ignore anti-proliferative signals
limitless replication potential
sustained angiogenesis
invade tissues
escape immune surveillance
83
Q

tumour immunology

A

induce clinically effective anti-tumour immune responses that would discriminate between tumour cells and normal cells in cancer patients

84
Q

cancer immunosurveillance

A

immune system can recognise and destroy nascent transformed cells, normal control

85
Q

cancer immunoediting

A

tumours tend to be genetically unstable

immune system can ill and induce changes in the tumour resulting in tumour escape and recurrence

86
Q

Tumour antigens

A

tumour specific antigen:

  • only found on tumours
  • as a result of point mutations or gene rearrangement
  • derive from viral antigens

tumour associated antigens:

  • found on both normal and tumour cells but are over-expressed on cancer cells
  • developmental antigens which become depressed
  • differentiation antigens are tissue specific
87
Q

evidence for tumour immunity

A

spontaneous regression (melanoma, lymphoma)

regression of metastases after removal of primary tumour

infiltration of tumours by lymphocytes and macrophages

higher incidence of cancer after immunosuppression or immunodeficiency

88
Q

immune responses to tumours

A

t lymphocytes

antibodies

NK cells

macrophages

89
Q

evidence for escape (detectable tumours)

A

immune responses change tumours such that the tumours will no longer be seen by the immune system (tumour escape)

tumours change the immune responses by promoting immune suppressor cells (immune evasion)

90
Q

cancer immunotherapy

A

how to kill tumour cells without killing normal cells?

to induce an immune response against the tumour that would discriminate between the tumour and normal cells (adaptive immunity)

91
Q

active immunotherapy

A

vaccination:

  • killed tumour vaccine
  • purified tumour antigens
  • DNA vaccines
  • viral vectors

augmentation of host immunity to tumours with cytokines and co-stimulators

92
Q

passive immunotherapy

A

adoptive cellular therapy

anti-tumour antibodies

93
Q

cell-based therapy

A

cellular therapies can be used to activate a patients immune system to attack cancer

do not act directly on cancer cells but work systemically to activate immune system

94
Q

dendritic cells and cancer treatment

A

found throughout body

detect and ‘chew up’ foreign proteins and then present parts of this on their surface

the blood of a cancer patient is collected and enriched to increased population of dendritic cells to make a DC vaccine

95
Q

tumour hypoxia

A

hypoxia is prominent feature of malignant tumours

inability of blood supply to keep up with growing tumour cells

hypoxic tumour cells adapt to low oxygen

96
Q

clinical indications related to allergy

A

skin- eczema, itching, redness

airways- excessive mucus production, bronchoconstriction

GI- abdominal bloating, vomiting, diarrhoea

anaphylaxis- airway, breathing, circulation

97
Q

allergy

A

abnormal response to harmless foreign material

atopy= tendency to develop allergies

98
Q

allergic disease

A 
anaphylaxis
asthma
rhinitis (hay fever)
dermatitis
food allergy
99
Q

pathogenesis

A

usually involves IgE

strong concordance in twin studies

mast, eosinophil and dendritic cells
epithelial cells
lymphocytes
fibroblasts

mediators= cytokines, chemokines, lipids, small molecules

100
Q

IgE and allergy

A

average serum conc. = 0.3-100 micrograms/ml

may reach 1000 in atopic individuals

101
Q

binding of IgE

A

one antibody binds to one receptor with high affinity

clustering causes signalling:

  • receptor cross linking causes assembly of signalling complexes
  • these are amplified causing cellular response
102
Q

low affinity IgE receptors

A

expression= B and T cells, monocytes, eosinophils, platelets and neutrophils

function= regulation of IgE synthesis, triggering cytokine release by monocytes, APCs

103
Q

high affinity IgE receptor expressing cells

A

mast cells, eosinophils and basophils are major cell types

involved in host defence

104
Q

mast cells and allergy

A

IgE mediated immunity

heterogeneity

primary role in innate and acquired immunity

involved in many disease processes

105
Q

development of mast cells

A

produced by specific cell lineage in bone marrow

characterised by requirement for c-kit protein ( cell surface receptor for stem cell factor)

106
Q

immediate mast cell functions

A

histamine- arteriolar dilation, capillary leakage, induces bronchospasm

chemotactic factors= some cytokines, IL4, CSF

proteases= tryptase, chymase

proteoglycans

typically lead to eosinophil attraction and activation

107
Q

mast cell functions (minutes)

A

lipid derived mediatiors:

  • leukotrienes= capillary endothelial contraction with vascular leakage
  • prostaglandin D2=potent induced of smooth muscle contraction
  • platelet activating
108
Q

mast cell functions (hours)

A

transcription/translation- cytokines (IL8,5,4,13 and RANTES)

mast cell derived cytokines promote Th2 response and can lead to B cell class switching

109
Q

activators of mast cells

A

indirect activators via IgE:

  • allergens
  • prior sensitisation required
  • bacterial/viral antigens

direct activators:

  • cold/mechanical deformation
  • aspirin, preservatives, latex, proteases
110
Q

mast cells and parasitic infections

A

hookworms, pinworms, flukes
IL3,4,5,10

local mast cell activation by cross linkage of IgE leads to recruitment of eosinophils and macrophages

role of IgE in parasitic infections explains presence of atopic individuals within population

111
Q

other cells and allergy

A

lymphocytes- Th2

dendritic cells- APC

neurones- coughing and sneezing

112
Q

what makes an allergen

A

particulate delivery

presence of weak pathogen-associated molecular patterns (PAMP)

nasal/skin delivery as oral delivery desensitises

low doses needed

113
Q

anaphylaxis

A

within minutes:

  • ABCDE
  • mast cell or basophil activation (IgE or direct activation, histamine elevated)
  • CV (vasodilation, lowered BP, increased vascular permeability)
  • resp (bronchial constriction, mucus)
  • skin (rash and swelling)

within hours:
-GI (pain and vomiting)

114
Q

asthma

A

narrowed airway by tightened muscles and thickened arterial walls

39 genes associated

allergens:

  • house dust mites
  • aspergillus

eosinophil influx to lungs

treatment= corticosteroids

115
Q

treatment of allergy

A
  • avoid allergens
  • desensitisation
  • prevent IgE production or interaction with receptor
  • prevent mast cell activation
  • inhibit mast cell products
116
Q

desensitisation

A

immunotherapy:
-increasing doses of antigen

risks= 23% have moderate reactions, 3% have life threatening

limited use= atopic eczema, asthma have no benefits

used only for serious conditions

117
Q

preventing IgE production

A

Th2 response can be suppressed:

  • delivery of suppressive cytokines (IL12 and 18)
  • blockade of cytokines
  • mucosal delivery of allergens fused to cholera toxin subunits
118
Q

anti-IgE therapy

A

effective for asthma

costs a lot, slight increase in cancer incidence, anaphylaxis

119
Q

anti-cytokine antibodies

A

IL5 antibody- adults with severe asthma

CD25 and IL2 antibodies- mild improvement in symptoms

IL25 antibody- reduces Th2 cytokine production in mice

120
Q

mast cell activation

A

mast cell stabilisers reduce mediator release

calcium channel blockers

beta2 agonists increase cAMP

121
Q

mast cell products

A 
histamine receptor (H1)
-numerous target cells

leukotriene antagonists
-inhibit Th2 cell activation

tryptase inhibitors
-prevent airway smooth muscle activation

122
Q

treatment of anaphylaxis

A

0.15/0.3mg of IM adrenaline (epinephrin)

beta 2 adrenergic receptor activity:

  • bronchial dilation
  • myocardial contraction
  • inhibition of mast cell activation

alpha adrenergic receptor activity:

  • peripheral vasoconstriction
  • reduction of oedema

Phase 2a pre clinical (6 decks)

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