the immune system and disease

lecture 1 to 6

infectious vs non-infectious disease

Infectious: bacterial, viral, parasitic 

Non-infectious: reproductive, allergy, asthma, autoimmunity, cancer, cardiovascular, neurological 

Non-specific defences (defenses of non-immune cells and tissuse) 

• physical barreirs

• chemical and physiological barriers

• microbiological barriers

• these are intrinsic barriers ^

• inflammatory barriers (covered by innate defences)

Physical barriers - skin 

eg mucus membranes

1. Prevent approach and deny access to pathogens 

2. Barrier:keratin (dead skin cells form waxy barrier 

3. Acidity: skin secretions 

4. Tight junctions between cells 

Ailments driven by breach of physical barrier include allergy: eczema 

chemical barriers

Sweat 

Acid in stomach and urine 

Lysozyme 

• breaks down carb 

• In tears, saliva, mucus 

Antimicrobial proteins 

• Small peptides –defensins 

• Proteins- transferrin 

microbial barriers

• Commensal bacteria: normal ‘good’ bacteria 

• Adapted to grow in a particular niche 

• Inhabit skin, gut, mouth, nose 

• Elimination of this ‘normal flora’ can allow pathogenic bacteria to establish 

Commensal bacteria can enhance skin barrier, help eczema, and in gut help inflammatory bowel disease 

breaking/bypassing intrinsc barriers

• Cut or break in skin 

• Direct injection via insect bite 

• Breakdown skin to enter directly (found in worms) 

• Ingestion of food or waterborne pathogens 

• Inhalation of air-borne pathogens 

• Infect epithelial cells in airway or gut 

Infectious disease 

• Each microbe infects and causes disease by a different mechanism 

• Thus the immune system recognizes and targets each microbe differently 

• eg respiratory vs skin disease

innate immune system

• Possessed at birth 

• Inborn rather than learnt through experience 

 

• Rapid response (hours) 

• Limited specificities 

• Constant during response 

adaptive immune system

• Capacity for adaptation 

• Improves through experience 

• Remembers 

 

• Slow response (days to weeks) 

• Numerous, highly selective specifities 

• Improves during response 

Immune cells (innate) 

All start from pluripotent hematopoietic stem cell from bone marrow 

From there become progenitors in bone marrow (stage 2), then mature and can be found in blood or tissue

phagocytes

(uptake and destruction of microbes or particles) 

Mature dendritic cells 

Monocytes (circulate in blood, if recruited devleops into macrophage) 

Macrophage (tissue) 

Neutrophil (in blood)

mature dendritc cells

• Antigen uptake inperipheral sites 

• Antigen presentation and cytokine production 

• Main function is activate adaptive immune system thru antigen presentation to T cell 

monocytes

• Phagocytosis and activation of bactericidal mechanisms 

• Antigen presentation and cytokine presentation 

• circulate in blood

macrophage

tissues

• Phagocytosis and activation of bactericidal mechanisms 

• Antigen presentation and cytokine presentation 

neutrophil

in blood

• Phagocytosis and activation of bactericidal mechanims 

• First cell to be recruited to site of infection, has multilobbed nucleus 

• Most abundant white blood cells

immune cells in blood

adaptive:

• b and t cells

innate:

granulocytes:

• neutrophil

• eosinophil

• basophil

• monocyte

• platelets

• immature dendritic cells

immune cells in tissue

adaptive: effector cells

• plasma cell

• activated t cell

innate

• mast cell

• macrophage

• immature dendritic cell

Granulocytes

• Eosinophil 

• basophil

• mast cell

• neutrophil

eosinophil

• speacilised for killing of antibody-coated parasites (worm infections) 

• In blood, can migrate to tissue 

• Pathogenic in allergy and asthma 

• Has granules that stain pink with eosin

basophil

• Promotion of allergic responses and augmentation of antiparasitic immunity 

• In blood, function unclear\granules contain histamine, cytokines, and distructive enzymes 

mast cells

• Release of granules containing histamines and active agents 

• In tissues, esp in skin (just underneath), mucosa granules containing histamine cytokines, and destructive enzymes 

• initial release of cytokines and Vasoactivators 

•  brings in other immune cells 

neutrophil

• Phagocytosis and activation of bactericidal mechanism 

• First cell to be recruited to site of infection, has multilobed nucleus 

• Most abundant white blood cells 

natural killers cells

directly kill infected cell

• Releases lytic granules that kill virus infected cells 

• In blood, can migrate ti tissues, innate lymphocyte, functions similar to T cell 

• Kills infected cells (viral and bacterial) and tumor cells (altered self) 

detecting innate activation

Fever 

1. Increase in body temp 

2. Caused by pyrogens 

Endogenous (some cytokines, TNF, IL-1) 

Exogenous (made by pathogen, lipopolysaccharide , LPS) 

3. Act on hypothalamus to regulate heat production and heat loss 

Fever restricts growth of pathogens, denatures proteins, speeds up repair mechanisms 

eg (give syphillis patients malaria, causes fever, kills syphillis, then treat malaria, cured) 

Decide whether to treat fever or not depend on if beneficial. Guideline shift depending on age 

2. Inflammation signs

1. RUBOR—redness (increases blood flow to area, vasodilation) 

2. TUMOR – swelling (increased fluid, vascular permeability) 

3. CALOR—heat (increases blood flow to area, vasodilation) 

4. DOLOR – pain (increased pain receptors) 

5th is loss of function, added recently

inflammation vs fever

Inflammation is local:

• blood flow,

• immune cells,

• pathogen killing,  

• wound healing

fever is centrally mediated

• fever

• fatigue

• nausea

• sweating

• aches

process of infection (innate immunity)

1. break in barrier

2. entry of pathogen

3. innate immunity response

4. inflammation

5. fever

How does immune system recognise pathogen? 

Recognise what is not you, then determine what is harmless or potentially harmful why recognising distinct motifs in building blocks of life (protein, sugar, lipds, DNA) 

• Innate receptors are pattern recognition receptors that recognise conserved microbial structures called pathogen associated molecular pattern s(PAMPs).  

• These can include outer membrane proteins, flagellar proteins, carbohydrates, DNA motifs.  

Bacteria recognition 

Gram negative:

• Pattern recognition receptor TLR2 recognises peptidoglycan

• TLR5 recognises flagellin protein

Gram positive:

• Pattern recognition receptor recognised peptidoglycan (TLR2) and lipopolysaccharide (TLR4)

Toll-like receptors (TLR) 

• Family of pattern recgntion receptors 

• Highly conserved structure – monomer or dimer 

• Evolutionarily conserved, found in flies, sea urchin as well as humans. 

• humans have at least 10 members 

conserved motifs in viruses

virus nucleic acids 

• double stranded RNA (TLR3) 

• single stranded DNA 

• double stranded DNA 

TLR specificities

• TLR-2: cell wall of gram positive bacteria

• TLR-3: dsRNA of viruses

• TLR-4: lipopolysaccharide of gram negative bacteria

• TLR-5: flagellin in bacteria

Binding of pathogen structures to pattern recognition receptors leads to: 

• Innate cell activation (eg macrophages- phagocytosie, cytokine secretion) 

• Inflammatory environment (eg cytokine secretion – blood flow, migration) 

• Adaptive cell activation (via dendritic cells- lecture 3) 

innate effector mechanisms

macrophage activation by bacteria leads to either phagocytosis or secreted factors

effecotr mechanisms acheived through: 

1. phagocytosis 

2. Extracellular cell killing 

3. Soluble factors  

• complement system 

• degranulation  

• cytokines  

• chemokines 

4. Migration 

Phagocytosis 

Four steps: 

1. Recognition (easy) 

2. Adherance (difficult, improved via opsonisation) 

3. Ingestion 

4. Digestion 

Last stages 

• Residual body secretion (N) 

• Antigen presentation (DC and M) 

opsonization

Alteration of the surface of a pathogen or other particle so that it can be ingested by phagocytes. Antibody and complement opsonise extracellular bacteria for destruction by neutrophils and macrophages 

Mediated by:

•  acute phase proteins 

• Complements 

• antibodies 

natural killer cells

• Kill intercellular pathogens 

• Activated by interferons secreted by virus infected cells 

• Activated NK cell releases granule contents, inducing apotosis in target cells 

secreted factors

• Cytokines, 

• Toxic mediators or enzymes 

• Lipid mediators 

• Chemokines 

Factors can be ready  made (degranulation, minutes) or require synthesis (transcription (DNA ot RNA), translation (RNA to protein), secretion – hours) 

degranulation

Degranulation is process of granulocytes (neutrophils, eosinophil, basophil, mast cell). Most other immune cells secrete soluble mediator by other methods and must first initiate gene transcription

cytokines

• Immunological hormones, also called interleukin (IL) 

• Mostly named in order of discovery (IL-1, IL-2 etc) 

• Other common families: interferon and tumour necrosis factor 

• Each with unique factors incl inflammation, cell recruitment, killinh 

• Cytokines act locally and systematically to induce protective responses 

• bacteria activated macrophages to produce cytokines: IL-1, IL-6, TNF

virus infected cells produced interferon (innate immunity)

• Stops cellular machinery 

• Inhibits viral replication 

• Activates NK cell 

• Leads to immune cell recruitment 

• Make the cell a target for killer T cell and NK cell

complement

• Family of more than  2p proteins produced in liver 

• Activation of pathway initiates a cascade reaction 

Lead to 3 options: 

• Inflammation 

• Opsonisation 

• Lysis 

Recruitment- extravasation 

2 specific signals and locations: blood vessels by sites and gradient on tissue

1. Rolling: cell weakly binds ti selectin, rolls to site of infection 

2. Tight binding: strongly binds by LFI 1 

3. Diapedesis: migrates through barrier 

4. Migration: chemokine gradient guides cell to site of infection 

lymphatic spread and adaptive immunity

1. lymphocytes at home 

Looking for activation 

2. activating lymphocytes 

TCR, BCR and many forms of antigen 

3. B cell responses 

Complement, opsonisation, neutralisation 

4. T cells and antigen presentation 

APC, antigen location, MHC 1 and 2 

5. helper and cytotoxic T cell responses 

Pathogen-specific functions 

Lymphocytes at home (B and T cell)

B cell: 

• Mature in bone marrow, circulate in blood and lymph nodes after maturity 

• Produces antibodies 

• Humoral immunity (soluble factors, in fluids) 

T cell: 

• Made in bone marrow, migrate to thymus to mature 

• Interact with APC (must interact to become activated) 

• Cell-mediated immunity (as require cell interaction

Activation of lymphocytes

Antigen= antibody generating = any substance that induces an adaptive immune response (bad)

B cell

• Each b cell expresses unqiue BCR (B cell receptor) 

• BCR recognises antigen directly 

• The binding site on the antigen is the epitope 

• When activated, B cells secrete the BCR as an antibody 

• 2 different antibodies made by 2 different B cells can bind the same antigen (recognise different things in the same antigen) 

• Antigen B cell recognises incl. Proteins, sugars, lipids, small molecules 

B cell receptor (BCR)

• cells are activated --> proliferate-->differentiate into plasma cells (antibody factory)--> antibodies go to site of infection where each different antibody binds its specific epitope 

• BCR is an antibody (aka immunoglobiulin/Ig) 

• Upon activation, becomes antibody whose function is determined by constant region 

• specificity is specific to epitope, constant region (blue) is so it can be recognised by self, and not also killed 

Antibody functions: 

Neutralisation 

• Blocks action of toxin 

• Blocks invasion of pathogen            

Opsonisation 

• Coats pathogen 

• Promotes phagocytosis  

• Promote NK killing 

• Promote mast cell activation 

Complement activation 

• Starts classical pathway 

Antibody isotopes: 

B cell are polyclonal (many isotopes). Infection-specific function determined by isotope (Isoyope change function of antibody) 

5 isotopes: 

1. IgM 

2. IgD: 

3. IGG 

4. IgA 

5. IgE 

IgM

1. First isotpe produced 

2. Best at complement actibvvation 

3. Large (5 antibodies) 

4. Mainly in blood 

IgD

1. Developmental 

2. Function not really known (so unimportant for this course) 

IgG

1. Good at most things 

2. All three functions 

3. Small, in blood and tissues 

4. Crosses placenta, breast milk 

5. NK cell killling, stops invasion 

6. Main antibody produced 

IgE

1. Mast cell activation 

2. Opsonisation 

3. Coated antigen activates mast cells, eosinophils, basophils 

4. Pathogenic in allergy 

5. Important in worm infections

T cell: 

• Each T cell expresses unique TCR (T cell receptor) 

• TCR recognises antigen when presented by another cell (antigen presenting cell, APC, usually dendritc cell (DC)) 

• When activated, T cell interact directly with other cells 

• Antigens in T cell recognises= peptides (small pieces of protein) 

activation of T cell

• Antigens enter through site of infection --> picked up by APC --> taken to lymph node and inspected by T cell --> T cell that recognises antigen proliferate and begin immune response 

Extracellular antigens: 

• extracellular antigens are phagocytosedand loaded onto MHC class II molecules. (bacteria, toxins, virus, worms etc) 

intracellular antigen are loaded onto MHC class I molecules. (virus, tumour etc)

cytotoxic T cell

• CD8 molecular that binds MHC class 1, recognises intercellular antigens,  

• Goes to site of infection, uses lytic granules to trigger apoptosis in infected cell 

helper T cell

• CD4 molecule that binds MHC class 2, recognises extracellular antigen 

• Activation induces proliferation and CD4 helper T cell target pathogen 

• Four different forms of T helper cells depending on type of infection,  

• in general, role is to help, not directly target pathogen, must act through other cells 

Bacteria and viruses 

• Help macrophage 

Worms 

• Promote mucus production to expell worms in gut 

Fungi, skin pathogens 

• Promotes neutrophils and antimicrobial peptide 

Extracellular pathogens 

• Help B cell produce anitbodies

cytosolic pathogens

degraded in cytosol

peptides bind to MHC class 1

presented to effector CD8 T cells, causes cell death

intravesicular pathogens

degraded in endocytic vesicles

peptides bind to MHC class 2

presented to effector CD4 T cells, which activate macrophages to kill intravesicular bacteria and parasites

extracellular pathogens and toxins

degraded in endocytic vesicles

peptides bind to MHC class 2

presented to CD4 T cells which activate B cells to produce Ig to eliminate extracellular pathogen/toxin/viruses

integrated immune responses

Success: 

• Memory 

• Homeostasis in the gut 

• Vaccination 

Failure 

• Pathogen escape 

• Hyper-sensitivity 

Homeostasis in the gut 

The gut deals with billion of microbes daily, many PAMPS, yet has no immune response 

cells maintain homeostasis: 

• Paneth cells: antimicrobial peptides 

• Goblet cells: mucus 

• Epithelial cells: tight junctions 

• Dendritic cells can do phagocytosis and activate T and B cells by extending into thelumen side of epithelial cells 

 

regulatory T cell (Treg) and paneth cells

Regulatory T cell (Treg) is a specilised T helper cells. 

Treg turns off immune cells, prevents excessive immune response 

Paneth cell is a good example of how one alteration can disrupt homeostasis and lead to disease 

Paneth cell is pattern recognistion receptor, when recognises PAMPs, antimicrobial peptides production reduced, larger immune response 

immune memory and reinfection

• Contracted lymphocytes become memory cells 

• Upon reinfection, memory cells are activated, leading to faster, larger response 

• Antibodies that are produced are antigen specific,  

• over time as response gets better and better, switch to isotypes that are much better/functional for the specific infection 

IgM vs IgG

IgM produced more on first infection, IgG produced more on second infection (as IgG gets more effective the more its activated, IgM doesn’t) 

first vs second infection

First infection 

• Naive B and T cells (never been activated) 

Second infections 

• Memory B and T cells 

• More antigen specific 

• Expand faster 

• Improved function 

vaccination

Memory is used for vaccination 

• Induction of protective adaptive response w/o infection 

• May induce antibodies (B cells) or T cells (helper or cytotoxic) 

• Use all or part of pathogen in vaccine 

• Live, attenuated (whole pathogen, alive but cannot instigate infection, replicate) 

• Killed (dead whole pathogen, cannot infect but has PAMPs, eg in rabies vaccine) 

• Protein/toxin antigen (subunit of pathogen, part of pathogen with PAMP, immune system recognizes only that PAMP) 

• mRNA of antigen (nuclei acid message of the antigen 

COVID-19 Vaccination 

• Vaccination is mRNA vaccine for spike protein on covid-19 

• MRNA put in lipid carrier for protection during injections, dissolved in muslce of recipient 

• Viral nuclei acids act as adjuvant (PAMP), induce immune response 

• Cells produce spike protein 

• B cells produced anti-spike anitbodies 

• Must be redone to keep up protection 

Immune evasion and pathogen escape 

• Some pathogens have developed strategies to evade immune response and establish infection Eg HIV 

• Error prone replication (keeps changing) eg HSV 

• Prevents MHC 1 expression (hiding) 

And parasites: 

W. bancroftic -

• Immune suppression 

T. gondii 

• Latent infection -

T. Bruceli (causes african sleeping sickness) 

• Antigenic variation (VSG) 

african sleeping sickness (Trypanosoma bruceii): Antigenic variation 

• Surface of parasite covered with one protein 

• Variable surface glycoprotein (VSG) 

• surface of parasite covered with one 

• multiple forms of VSG but only one expressed at a time 

• antibodies kill parasites with one VSG 

• parasites change VSG so antibodies are ineffective. 

antigenic drift

• small changes, occur over time make immune response not as effective (normally maintin some protection) 

• seasonal flu 

• still retain some immunity 

antigenic shift

• major changes, occur at once 

• pandenic flu 

• little to no immunity 

• Can occur when two strains of the virus infect at same time, recombine to create new strain, mean much of immunity agaisnt original virus are ineffective.  

Monoclonal antibodies 

• B cell clone (one specificity) 

• Fuse to immortalized cell 

• Large amounts of antibody with a single specifity 

• grown in lab 

Used for diagnostics, 

• COVID 

• pregnancy 

• cancer 

• lupus 

Therapeutics (immunotherapy) 

• Herceptin (breast cancer) 

• Keytruda (melanoma) 

• Tysabri (multiple sclerosis) 

• Humira (rheumatoid arthritis) 

• Dupixent (asthma) 

Research 

Hyper sensitivity 

• A disorder in which the immune system reacts inappropritly, usualluy bu responding to an antigen it normally ignores 

These antigens are 

• Foreign and harmless (allergy) 

• Self proteins (autoimmunity) 

Preventing autoimmunity and allergy 

• Lymphocytes that have TCR or BCR that recognise self to not mature that prevents autoimmunity 

• Early in ( and throughout ) life lymphocytes that recognise harmless antigen are tolerised (made non-responsive) that prevents allergy 

• Genetics and environment can impact these processes 

Type 1 hypersensitivity 

• IgE mediated 

• Classic allergy 

• Allergen-specific IgE binds to IgE receptors on mast cells 

• Allergen: IgE binding to mase cells induces rapid degranulation 

• Histamine is released 

These events cause the allergic reaction but to get to this point you need the allergen-specific IgE (where does the IgE come from)

sensitization stage

First exposure to allergen 

1. Antigen presenting cells picks up allergen and presents to naive CD4 helper T cell 

2. CD4 helper T cells become activated and proliferate 

3. CD4 helper T cells differentiate into Th2 cells that produce IL-4, IL-5, IL-13 and support B cells 

4. With the Th2 cell help, B cells produce allergen-specific IgE 

allergic stage

After IgE response develops (weeks to years after sensitisation)

1. IgE on mast cells binds allergen 

2. mast cells degranulate releasing histamine 

3. histamine acts on locally to induce inflammation 

eg for dust mites

1. house dust mites have Der p1 in their feces 

2. Der p1 can cleave tight junctions between cells 

3. thus, if breathed in, it can enter the lung tissue and induce an allergic response 

Local anaphylaxis

only occurs in that location/tissue, local response

1. histamine works quickly on blood vessels 

• vasodilation (redness & heat) 

•  increased permeability (swelling) 

2. local reactions (depend upon the tissues involved) 

• reddening of skin 

• watering eyes 

• hives 

• digestive disturbances 

3. mast cells also release factors (cytokines, prostaglandins), which are longer acting and cause the late phase reactions 

systemic anaphylaxis

more widespread reactio

• occurs when there is degranulation in airways (mast cells) or the blood (basophils) 

• causes airway constriction or extreme drop in blood pressure 

• life-threatening situation 

• Treat with adrenaline/epinephrine (e.g. EpiPen) 

Site of mast cell activation by the allergen determine allergic condition 

Skin 

• Urticaria (hives) 

Lungs 

• Llergic rhinitis (hayfever) (upper airways) 

• Asthma  (lower airways) 

Gut 

• Food allergy 

allergy medication

symptom relief

• Targets the effects of mast cells activation 

• Doesn't treat underlying cause 

immunotherapy

desensitization: treating allergy

Eg oral immunotherapy (OIT) 

• key aim is to increase the threshold for an allergic reaction 

• Prevent life-threatening consequences of accidental exposure. 

• Switch from IgE to IgG 

• Extremely low doses of allergen daily increase >44 weeks 

• Allergen picked up by DC 

• Change the outcome --> Th2 to anotehr subset 

• Change the Th subset balance 

• Chnage the outcome --> Th2 to anotehr subset 

Epidemiology (disease in the population) 

Eg skin – atopic dermatitis, lungs – asthma, gut – food allergy 

• Atopy – exaggerated IgE response; is a predisposition to allergy development 

• 10-30% of people in developed countries have atopy 

• In New Zealand, 30-40% of people have some form of allergy. 

• In addition to IgE-mediated allergies, there are many other types. 

Atopic respiratory diseases: asthma vs allergy

Both allergy and asthma, allergen is activating mast cells to release histamine, both have similar allergen types, both enter via inhalation, but have different outcomes (edema of nasal mucosa in allergy and bronchial constriction in asthma) 

They differ in allergen size, meaning that they go to different places (in allergy go to upper lungs, in asthma go to lower lungs)

immunological response of asthma

1. Like other atopic diseases, there is sensitisation – now IgE is in the lung tissue 

2. Next is acute asthma, with IgE-bound mast cells poised for activation by allergen 

Factors released by the activated mast cells (including histamine)cause: 

1. Vasodilation (standard allergic response) 

2. Increased vascular permeability (standard allergic response) 

3. bronchial smooth muscle constriction (block breathing) 

4. mucus secretion (block breathing) 

The continues presence of immune cells leasds to chronic asthama (caused by repeasted acute attack of cytokine and eosinophil products causing a sustained presence of immune cells in lungs, which can initate faster and stronger attack (since theyre already there) and cause changes to lung tissue) 

1. Chronic inflammation leads to faster and larger response 

2. Th2 cells and eosinophils become involved, that drive allergic response 

what allergens can cause asthma

One sthat can get into tge lower airways 

• Eg cat dander 

• House dust mites 

• Some pollens 

• Mould 

Can become allergen-dependent and Each person has their own triggers but common ones incl.  

• Stress 

• Exercise 

• Anger 

• Temp 

• Smoke 

• Strong odours 

• Pollution 

• Dust 

Symptom incl 

• Wheezing 

• Shortness of breath 

• Tightness in chest 

• Cough 

Can be sudden or continuous

clinical presentation of asthma

1. At the heart of the response is an IgE-mediated allergic response 

1. If inject allergen into skin, a classic allergic response will occur mediated by IgE and mast cells 

2. If the allergen enters the lungsm the allergic response can be measured by the peak expiratory flow rate (PFER) how hard can you breathe out 

 

Like classic allergic responses at skin and in the gut, asthma attacks have an immediate phase (often histamine-driven) as well as a late phase (6-8hrs later) (prostaglandins, leukotrienes) 

what happens in the lungs during an asthma attack

long-term consequences of uncontrolled asthma cause change to tissue itself: 

• Chronic inflammation (Th2 cells and eosinophils) 

• Airway hyperreactivity (part of allergy independent triggers, more sensitive) 

• Airway remodelling 

•  (tissue area becomes thicker= less air to come in,  

• more mucus=less air 

Permanent changes (due to uncontrolled asthma) 

• Airways become narrower 

• Increased smooth muscle tissue 

• Fibrosis /scarring leads to decreased elasticity 

• Increased blood vessel 

asthma treatment

• No cure, only treatment 

Two common approaches 

• Relieve and attack 

• Prevent an attack 

Treat the site (ie lungs) with an inhaler 

Two main targets 

• Immune system 

• Bronchial smooth muscle cell 

asthma meds

Symptom controllers 

• Long lasting beta-2 agonist 

Preventer 

• Take everyday 

• Make airways less hyperactive 

• Corticosteroids 

Relievers  

• Treatong attacks 

• Relax constricted bronchial msucles 

• No longer prescribed in nz unless in combo w/ corticosteroid 

Combination 

• long lasting beta-2 agonist 

• Corticosteroid 

• most consistent protection 

corticosteroids – target immune system (turn down); less airway reactivity 

beta adrenergic receptor agonists – activate beta adrenergic receptors and relax bronchial smooth muscle cells 

New asthma immunotherapies 

• Target very specific immune factors or pathways that drive Ige and esosinophils activation such as IL-4 or IL-4 signalaling (eg pitrakinra, dupilumab) 

epidemiology of asthma

• Over 600,000 Kiwis have asthma. 

• 1 in 8 adults and 1 in 7 children take medication for asthma large numbers of children (~5000 in 2021) are being admitted to hospital with asthma. (MoH 2021) 

• Highest number of people being admitted to hospital with asthma are Māori, Pacific peoples and people living in the most deprived areas. 

• The cost of asthma to the nation is over $1 billion per year (2020).