Immunology Flashcards

1
Q

What is innate immunity?

A

An instinctive non-specific immune response present from birth, which does not rely on lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is adaptive immunity?

A

A specific learned immunity present in higher organisms, which requires lymphocytes and antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does the top layer of a centrifuged blood sample contain?

A

Plasma - mostly water, but also contains electrolytes, proteins, lipids, sugars etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where would you find the white blood cells in a centrifuged blood sample?

A

The white fluffy layer in the middle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does the bottom layer of a centrifuged blood sample contain?

A

Haematocrit (erythrocytes and platelets)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Where are leukocytes made?

A

In the bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the 3 types of polymorphonuclear leukocytes?

A
  1. Neutrophils
  2. Eosinophils
  3. Basophils
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What do monocytes differentiate into on leaving the bloodstream?

A

Tissue macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which type of cells differentiate into plasma cells, which secrete antibodies?

A

B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is Complement?

A

A group of about 20 different serum proteins secreted by the liver that when activated, cleave specific proteins to release cytokines, initiating a cascade of further protein cleavages.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the 3 modes of action of Complement?

A
  1. Direct lysis by activation of the MAC (membrane attack complex)
  2. Attracting more leukocytes to the site of action by secretion of chemotaxin factors (C3a and C5b)
  3. Opsonisation (C3b), which coats the surface of the microbes and makes them more tasty for phagocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What do antibodies bind to?

A

Specific antigens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which immunoglobulin is the most abundant in the blood and can get into all tissues?

A

IgG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which immunoglobulin is the first to be produced as part of an immune response?

A

IgM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which immunoglobulin is overproduced during an allergic reaction?

A

IgE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do antibodies help phagocytes to engulf microbes?

A

By acting as an adapter, binding the phagocyte to the antigen on the surface of the microbe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Name 5 types of cytokines

A
  1. Interferons
  2. Interleukins
  3. Colony stimulating factors
  4. Tumour necrosis factors
  5. Chemokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What do interferons do?

A

Induce a state of antiviral resistance in uninfected cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Interleukins are produced by many cells, what effects can they have on cells?

A

Can cause cells to divide, to differentiate and to secrete factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are colony stimulating factors involved in?

A

Directing the division and differentiation of bone marrow stem cells to form leukocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What do tumour necrosis factors do?

A

Mediate inflammation and cytotoxic reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What do chemokines do?

A

Leukocyte chemoattractants - they direct immune cells to particular parts of the body, e.g. if an infection is in a certain body part, chemokines are released in that area

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What 3 things make up the innate immune system?

A
  1. Physical and chemical barriers
  2. Phagocytic cells
  3. Blood proteins (complement)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the 6 things that need to happen in response to tissue damage?

A
  1. Stop bleeding (coagulation)
  2. Acute inflammation (immune cells to the area)
  3. Recognise and kill pathogens, neutralise toxins, limit pathogen spread
  4. Clear pathogens/dead cells
  5. Proliferation of cells to repair tissue damage
  6. Re-establish normal structure and function of tissue
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

By which process do immune cells get from the blood vessels to the tissues?

A

Extravasation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Briefly describe extravasation of a neutrophil

A

TNFa secreted, which acts on the endothelium. The endothelial wall becomes sticky rather than smooth, Integrin on neutrophil surface binds to adhesion molecule (CAM-1) on endothelial surface, stops moving through the vessel and squeezes out between endothelial cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are PAMPs?

A

Pathogen-associated molecular patterns

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are PAMPs recognised by?

A

PRRs (pattern recognition receptors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How do macrophages present antigen?

A

When a microbe is engulfed, some of its proteins are chopped up into little bits and presented on the macrophage cell surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What determines donor compatibility for organ transplant?

A

Major histocompatibility complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How does a T cell recognise an antigen?

A

An infected cell presents an antigen peptide bound to an MHC molecule on its surface, which is recognised by the T cell receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Why do we only have T cells that recognise non-self?

A

Any T cells that recognise self are killed in the fetal thymus as they mature (T cell selection)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What happens when a T cell is activated?

A

IL-2 is secreted by the T cell and binds to the IL-2R receptors (autocrine function); this then leads to diffusion, differentiation, effector functions and memory.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What are CD8 cells?

A

When activated, become cytotoxic T cells, which can kill intracellular pathogens directly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What are CD4 cells?

A

Helper T cells, which differentiate into Th1 and Th2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What do Th1 cells do?

A

Secrete IL-2 and IFN-gamma, which helps kill intracellular pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What do Th2 cells secrete?

A

IL-4,5, 10 and 13

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How do cytotoxic T cells kill infected host cells?

A

By forming proteolytic granules, releasing perforins and granulysin into the cell and inducing apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What happens when an APC presents antigen with MHC2 to a naive CD4 cell?

A

Stimulation with high levels of IL-12 activates the naive CD4 cells to become Th1 cells, which travel to secondary lymphoid tissue (spleen lymph nodes) and proliferate. The Th1 cells recognise the antigen on infected cells via CD4 receptor and secrete INF-gamma, which activates macrophages.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Why are humans born with more than 10^9 immature B cells?

A

Because each B cell can only make one antibody that will bind one epitope on one antigen; humans therefore have enough to cover all combinations and to detect every single possible epitope on all antigens ever.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What happens to B cells that recognise self?

A

They are killed in the bone marrow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What happens when a primed Th2 cell binds a B cell presenting antigen via MHC II?

A

The Th2 cell secretes cytokines IL-4,5,10 and 13, which cause B cells to divide (clonal expansion) and then differentiate into plasma cells and memory B cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What 3 things can a specific secreted antibody do?

A
  1. Neutralise a toxin by binding to it
  2. Increase opsonisation via phagocytosis
  3. Activate complement
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What risks might come with mutations in TLRs?

A

Increased risk of infections, some variants associated with increased risk of chronic inflammatory diseases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What do TLRs do?

A

They recognise structurally conserved molecules derived from microbes and trigger an immune response by recruiting adaptor proteins to propagate the antigen-induced signal pathway, which eventually leads to the upregulation/suppression of genes that regulate inflammation/transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

At what point would a TLR recognise a microbe?

A

When physical barriers have been breached

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Why is TLR4 important?

A

It recognises lipopolysaccharide, which is present in many gram negative bacteria and some gram positive bacteria. It also recognises several viral proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Besides TLRs, name 3 other PRRs

A
  1. C-type lectin receptors
  2. Mannose receptor on macrophages
  3. Dectin-1 and Dectin-2 (widespread on phagocytes, help recognise beta glucans in fungal walls)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What do Nod-like receptors recognise?

A

PAMPs and DAMPs (damage-associated molecular patterns)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What happens when a Nod-like receptor recognises a PAMP or a DAMP?

A

It cooperates with TLRs to regulate inflammatory and apoptotic responses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What specific peptide does NOD2 recognise?

A

Muramyl dipeptide (MDP), which is a breakdown product of peptidoglycan (forms cell wall of most bacteria)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

NOD2 activates inflammatory signalling pathways. Name 2 conditions that can be caused as a result of mutations in NOD2.

A
  1. Crohn’s disease, caused by non-functioning mutations

2. Blau syndrome, caused by hyperfunctioning mutations.

53
Q

What does RIG-I help the body to recognise?

A

Viruses

54
Q

What is the role of TLR in damage repair?

A

TLRs can be activated by cellular damage products and therefore will activate the immune system to initiate tissue repair - may also enhance local antimicrobial signalling.

55
Q

How are TLR agonists used in vaccines?

A

As adjuvants, to trigger the immune response.

56
Q

Give 2 ways in which PRRs may be implicated in disease.

A
  1. Recognition of host molecules in autoimmune disease

2. Failure to recognise pathogens/increased inflammatory responses

57
Q

What is passive immunisation?

A

The transfer of pre-formed antibodies to an individual; could be natural (e.g. via placenta/breastmilk) or artificial (e.g. treatment with pooled normal human IgG/immunoserum)

58
Q

When might passive immunisation be used?

A
  • When an individual has acquired B cell defects
  • When there is no time for active immunisation to give protection e.g. in the case of a pathogen with a short incubation time
  • When there is an acute danger of infection
59
Q

Why can’t we vaccinate against toxins?

A

Natural immunity to toxins is difficult to achieve as even tiny doses can be lethal; therefore anti-toxins have to be given following exposure instead.

60
Q

How does tetanus prevent relaxation of the muscles?

A

By preventing the release of inhibitory neurotransmitters glycine and GABA

61
Q

What are the 4 steps involved in active immunisation?

A
  1. Engage the innate immune system (neutrophils, NK cells, dendritic cells, macrophages)
  2. Elicit ‘danger’ signals that activate the immune system, e.g. through activation of TLRs
  3. Activate specialist antigen-presenting cells
  4. Engage the adaptive immune system - generate T and B cells, activate T cell help
62
Q

What is the goal of immunisation?

A

To achieve initial exposure to the antigen without the risks of actual infection

63
Q

Which immunoglobulin predominates during the initial response?

A

IgM (low affinity)

64
Q

Which immunoglobulin predominates during the secondary response

A

High affinity IgG

65
Q

At what point during the immunisation process are memory T and B cells generated?

A

During the primary response, when IgG levels rise

66
Q

Why are infants and the elderly more vulnerable to infections?

A

Plasma cell differentiation is limited in these age groups. In early life, IgG response duration is limited due to exposure to large load of environmental antigens and restriction of plasmablasts towards a limited set of plasma cell survival niches in bone marrow.
Elderly individuals have increasing titres of autoantibodies (byproducts of earlier responses to pathogens)

67
Q

Why does the flu vaccine need to be given every year?

A
  1. The rapid onset means that high levels of neutralising antibody need to be maintained in the circulation.
  2. Annual ‘escape’ variants require the generation of new vaccines
68
Q

Why does the polio vaccine last for a long time?

A

It takes three days to establish infection in the nervous system, which provides an opportunity for memory cells to be activated and for the body to produce neutralising antibodies

69
Q

Give two examples of live attenuated vaccines (whole pathogen)

A
  1. BCG (Bacilus Calmette-Guerin), produced from mycobacterium bovis grown for 13 years on a medium containing bile, which became adapted and had reduced virulence.
  2. Polio Sabin, virus grown on monkey kidney epithelial cells, prolonged culture led to adaptation and a strain with reduced virulence in humans.
70
Q

Give 5 advantages of whole attenuated pathogen vaccines

A
  1. Sets up a transient infection
  2. Activation of a full natural immune response
  3. Prolonged contact with the immune system leads to prolonged and comprehensive protection
  4. Activates a memory response in T and B cell compartments
  5. Often only a single immunisation is required
71
Q

Give 3 disadvantages of whole attenuated vaccines

A
  1. Immunocompromised patients may become infected as a result of immunisation
  2. Risk of complications, e.g. 1 per 1,000,000 live measles vaccine recipients develop post-infectious encephalomyelitis
  3. Occasionally the attenuated organism can revert to a virulent form
72
Q

Give 3 advantages of whole inactivated pathogen vaccines

A
  1. No risk of actual infection
  2. No requirement for special storage
  3. Wide range of different antigenic components are present so a good immune response is possible
73
Q

Give 4 disadvantages of whole inactivated pathogen vaccines

A
  1. They tend to just activate humoral responses (lack of T cell involvement)
  2. Without transient infection, the immune response can be quite weak
  3. Repeated booster vaccinations may be required
  4. Patient compliance can be an issue
74
Q

Why are pathogens for use in vaccines inactivated by chemical treatment (such as formaldehyde) instead of heat?

A

Heat inactivation can alter the conformation of target antigens

75
Q

What are the 3 major types of subunit vaccines?

A
  1. Inactivated exotoxins
  2. Capsular polysaccharides (e.g. men C)
  3. Recombinant microbial antigens (e.g. Bexsero)
76
Q

Give 3 advantages of subunit vaccines

A
  1. They are safe as only parts of the pathogen are used
  2. There is no risk of infection
  3. They are easy to store and preserve
77
Q

Give 3 disadvantages of subunit vaccines

A
  1. Immune response is less powerful
  2. Repeated vaccinations and adjuvants required
  3. Need to consider the genetic heterogeneity of the population for antigen choice (HLA/cytokine expression)
78
Q

What is an exotoxin?

A

A toxin secreted by bacteria

79
Q

What is a toxoid?

A

A toxin that has been heat treated or chemically modified to eliminate toxicity

80
Q

How is polysaccharide used in conjugate subunit vaccines?

A

Polysaccharide is a weak antigen; it can be linked to a carrier protein to increase its immunogenicity for use in a vaccine.

81
Q

What is the aim of DNA vaccines?

A

To transiently express genes from pathogens in host cells, thereby generating an immune response similar to natural infection, leading to T and B cell memory responses.

82
Q

How do DNA vaccines work?

A

A DNA vector carries genetic information coding for antigen into a cell. Transcription takes place, mRNA is translated into protein in the cytoplasm, which is degraded into peptides. The peptides bind to MHC1 and peptide antigen/MHC1 complexes are presented on the cell surface, inducing a cell-mediated immune response.

83
Q

Give 3 advantages of DNA vaccines

A
  1. Safe (especially in immunocompromised patients)
  2. No requirement for complex storage and transportion.
  3. Drug delivery can be simple and adaptable to widespread vaccination programmes
84
Q

Give 2 disadvantages of DNA vaccines

A
  1. DNA vaccines are likely to produce a mild response and require subsequent boosting.
  2. No transient infection
85
Q

What is the aim of recombinant vector vaccines?

A

To imitate the effects of transient infection with a pathogen, but using a non-pathogenic organism.

86
Q

How do recombinant vector vaccines work?

A

Genes for major pathogen antigens are introduced into a non-pathogenic or attenuated microorganism and introduced into the host.

87
Q

Give 4 advantages of recombinant vector vaccines

A
  1. Ideal stimulus to the immune system
  2. Produces immunological memory
  3. Flexible - different components can be engineered in
  4. Safe relative to live attenuated pathogen
88
Q

Give 3 disadvantages of recombinant vector vaccines

A
  1. Can cause illness in compromised individuals
  2. Immune response to virus in subjects can negate effectiveness
  3. Requires refrigeration for transport
89
Q

What are adjuvants?

A

Substances added to vaccines to stimulate the immune system.

90
Q

What are the 3 main components of vaccines?

A
  1. Active ingredients
  2. Adjuvants
  3. Antibiotics
91
Q

What are the 6 characteristics of the ‘ideal’ vaccine?

A
  1. Safe
  2. Induce a suitable immune response, e.g. if pathogen uses mucosal route, vaccine should also use this route
  3. Generate T and B cell memory
  4. Stable and easy to transport
  5. Should not require repeated boosting (improves patient compliance)
  6. Affordable and accessible
92
Q

What is a type I hypersensitivity reaction?

A

Immediate response, mediated by IgE in response to a soluble antigen, effected by mast cell activation - e.g. allergic rhinitis, asthma, systemic anaphylaxis

93
Q

What is a type II hypersensitivity reaction?

A

Primarily IgG dependent, response to cell/matrix associated antigen, effected by phagocytes and NK cells - some drug allergies e.g. penicillin

94
Q

What is a type III hypersensitivity reaction?

A

IgG/IgM dependent immune complex formation, response to soluble antigen, effected by FcR+ cells and complement - seen in serum sickness and Arthus reaction

95
Q

When is a type IV hypersensitivity reaction seen?

A

Contact dermatitis, tuberculin reaction, chronic asthma, chronic allergic rhinitis.

96
Q

Give 4 types of symptoms related to allergy

A
  1. Skin symptoms (oedema, pruritus, erythema)
  2. Airway symptoms (excess mucus production, bronchoconstriction)
  3. GI symptoms (abdominal bloating, vomiting, diarrhoea)
  4. Anaphylaxis (usually systemic, can involve airway, breathing, circulation)
97
Q

What is allergy?

A

An abnormal response to harmless foreign material (allergens)

98
Q

What is atopy?

A

A tendency to develop allergies

99
Q

Name 7 allergic diseases

A
  1. Anaphylaxis
  2. Allergic asthma
  3. Allergic rhinitis
  4. Atopic dermatitis
  5. Allergic conjunctivitis
  6. Oral allergy syndrome (food allergy)
  7. Angioedema
100
Q

Roughly what proportion of the UK population is affected by allergy?

A

About 20%

101
Q

Which cells can be involved in hypersensitivity reactions?

A

Mast cells, eosinophils, basophils, lymphocytes, dendritic cells, epithelial cells (e.g. skin barrier), smooth muscle, fibroblasts

102
Q

What are the mediators of hypersensitivity reactions?

A

Cytokines, chemokines, lipids and small molecules

103
Q

Atopic individuals can have greatly elevated serum concentration of which immunoglobulin?

A

IgE

104
Q

To which receptor does IgE bind with very high affinity?

A

FceRI

105
Q

To which receptor does IgE bind with low affinity?

A

FceRII / CD23

106
Q

FceRII is expressed in B cells, T cells, monocytes, eosinophils, platelets and neutrophils. What are its three functions?

A
  1. Regulation of IgE synthesis
  2. Triggering of cytokine release by monocytes
  3. Antigen presentation by cells
107
Q

Which cells express FceRI?

A

Mast cells

108
Q

Where are mast cells found?

A

Only in tissues

109
Q

Which protein do mast cells need in order to develop?

A

c-kit

110
Q

What condition can be caused by mutations in c-kit?

A

Systemic mastocytosis

111
Q

Which 4 types of compounds do mast cells release immediately upon activation?

A
  1. Histamine
  2. Chemotactic factors
  3. Proteases
  4. Proteoglycans
112
Q

What type of compounds do mast cells release within minutes of activation?

A

Lipid-derived mediators

113
Q

What types of compounds do mast cells release within hours of activation?

A

Transcription/translation cytokines

114
Q

What do mast cell chemotactic factors do?

A

Attract and activate eosinophils

115
Q

How do mast cells increase IgE production?

A

Mast cell derived cytokines promote a Th2 response and can lead to B cell class switching, the B cells then start producing IgE antibodies.

116
Q

Which system is geared towards fighting parasites?

A

Th2 via the release of cytokines IL-3, 4, 5 and 10, which leads to an IgE response

117
Q

How can allergic reactions result in tissue damage?

A

Through mast cells being activated in the wrong place

118
Q

What 5 rapid events occur in anaphylaxis?

A
  1. ABCDE: airway, breathing, circulation, disability, exposure (systemic)
  2. Mast cell/basophil activation (either through IgE or direct activation)
  3. Cardiovascular: Vasodilation, increased vascular permeability, lowered BP
  4. Respiratory: Bronchial smooth muscle contraction, mucus
  5. Skin: Rash, swelling
119
Q

What slow onset symptoms can occur in anaphylaxis?

A

GI symptoms: pain, vomiting etc.

120
Q

What are the six potential treatment strategies for hypersensitivity?

A
  1. Avoid allergens
  2. Desensitisation to allergen
  3. Prevent IgE production
  4. Prevent IgE interaction with receptor
  5. Prevent mast cell activation
  6. Inhibit mast cell products
121
Q

What is Lumiliximab used for?

A

To help treat leukaemia - lumiliximab is an anti-CD23 antibody that can decrease IgE levels

122
Q

What is Xolair (omalizumab)?

A

A recombinant DNA derived humanised IgG1K monoclonal antibody that selectively binds to human IgE, inhibiting binding of IgE to FceRi receptor

123
Q

Some studies suggest Xolair (omalizumab) may be an effective treatment for allergic asthma. Why is it not commonly used?

A
  1. Very high cost
  2. Slight increase of cancer incidence
  3. Anaphylaxis in 0.1% of cases
  4. Not recommended in regions where intestinal parasites may be acquired
124
Q

What is mepolizumab and what can it be used to treat?

A

IL-5 antibody, NICE guidelines allow it to be used to treat adults with severe asthma.

125
Q

What is daclizumab and what can it be used to treat?

A

IL-2 antibody, approved for use in MS

126
Q

What is infliximab, what is the therapeutic effect and what are the risks?

A

TNF-alpha antibody, can improve lung function, risks of infection and cancer

127
Q

Give 5 mediators of mast cell activity

A
  1. Mast cell stabilisers (e.g. sodium cromoglycate) reduce mediator release
  2. Beta-2 agonists (e.g. salmeterol) increase cAMP
  3. Glucocorticoids (e.g. budesonide, prednisolone) inhibit gene transcription and may have long term effecits
  4. Calcium channel blockers
  5. Signalling inhibitors e.g. Syk kinase, MAP kinase inhibitors
128
Q

Give 4 potential mediators of mast cell products

A
  1. H1 antagonists (although this has numerous target cells)
  2. Leukotriene antagonists e.g. montelukast (inhibit activation of Th2 cells)
  3. Tryptase inhibitors (prevent airway smooth muscle activation)
  4. Protease-activated receptor (PAR)-2 antagonists (numerous target cells)