Immunology Flashcards

1
Q

What are the causes of inflammation?

A

Necrosis/infarction/direct trauma
Infection (bacterial, viruses, fungi, protozoa, parasites)
Chemical or other physical agents, including radiotherapy
Autoimmune reactions, particularly hypersensitivity states.

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2
Q

What is a granuloma?

A

A granuloma is a tiny cluster of white blood cells and other tissue that can be found in the lungs, head, skin or other parts of the body in some people. Granulomas are not cancerous. They form as a reaction to infections, inflammation, irritants or foreign objects.

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3
Q

What is the major issue with chemotherapy?

A

As well as killing the fast-dividing cancer cells, it also damages fast dividing cells in the hair marrow and GI tract and the immune cells that govern the inflammatory response.
This means the patient experiences low immunity, hair falling out and diarrhoea.

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4
Q

What is peritonitis?

A

Peritonitis is an inflammation of the peritoneum, the tissue that lines the inner wall of the abdomen and covers and supports most of your abdominal organs. Peritonitis is usually caused by infection from bacteria or fungi.
Left untreated, peritonitis can rapidly spread into the blood (sepsis) and to other organs, resulting in multiple organ failure and death.

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5
Q

What is gastritis and what commonly causes it?

A

Gastritis is an inflammation, irritation, or erosion of the lining of the stomach. It can occur suddenly (acute) or gradually (chronic).
Gastritis can be caused by irritation due to excessive alcohol use, chronic vomiting, stress, or the use of certain medications such as aspirin or other anti-inflammatory drugs.

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6
Q

What is inflammation?

A

A reaction to injury or infection involving cells such as neutrophils and macrophages.
Inflammation is good in infection to start off healing process, but inflammation can also be bad in the context of auto-immunity and the fact that it causes pain.
ACUTE: sudden onset, short duration (usually neutrophil)
CHRONIC: slow onset or sequel, long duration (usually macrophage/leukocyte)

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7
Q

What are neutrophil polymorphs?

A

Short-lived cells first on the scene of acute inflammation.
Cytoplasmic granules full of enzymes that kill bacteria.
Usually die at the scene of inflammation, but release chemicals that attract other inflammatory cells such as macrophages.

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8
Q

What are macrophages?

A

Long-lived cells (weeks to months).
Phagocytic properties - ingest bacteria and debris.
May carry debris away and present antigen to lymphocytes.
Different names according to their location.

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9
Q

What are lymphocytes?

A

Long-lived cells (years).
Produce chemicals which attract other inflammatory cells.
Immunological memory for past infections and antigens.
Able to produce clones.

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10
Q

What happens to endothelial cells in inflammation?

A

Endothelial cells line capillary blood vessels in areas of inflammation. They become sticky so inflammatory cells adhere to them. They become porous to allow inflammatory cells to pass into tissues. They grow into areas of damage to form new capillary vessels.

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11
Q

What are fibroblasts?

A

Long-lived cells.
Form collagen in areas of chronic inflammation and repair.
Produce scars.

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12
Q

What is acute appendicitis?

A

Unknown precipitating factor.
Neutrophils appear, blood vessels dilate, inflammation of serosal surface occurs, pain felt.
Appendix is either surgically removed, inflammation resolves or appendix bursts with generalized peritonitis and possible death.

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13
Q

What happens after inflammation?

A

Usual result is resolution
Excessive exudate - discharge of pus
Excessive necrosis - repair and organisation leading to fibrosis
Persistent causal agent - chronic inflammation

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14
Q

What’s the difference between T and B cells?

A

T cells: mature in thymus, 80% lymphocytes, involved in cell-mediated immunity, identify viral antigens outside the infected cells.
B cells: mature in bone marrow, contain surface antigens, involved in humoral-mediated immunity, identifies surface antigens on viruses.

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15
Q

Which drugs treat inflammation?

A

Aspirin was one of the first anti-inflammatory drugs,
Ibuprofen is commmonly used.
Drugs that inhibit prostaglandin synthase (prostaglandins initiate inflammation).
Corticosteroids used to bind to DNA and upregulate inhibitors of inflammation and downregulate promoters of inflammation.

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16
Q

What is the difference between innate immunity and adaptive immunity?

A

Innate: instinctive, non-specific, does not depend on lymphocytes, present from birth.
Adaptive: specific, acquired/learned immunity, requires lymphocytes and involves antibodies

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17
Q

What is present in a blood sample?

A

TOP: Plasma - 90% water, electrolytes, proteins, lipids, sugars
MIDDLE: Buffy coat - made up of leukocytes
BOTTOM: Haemocrit - erythrocytes and platelets

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18
Q

What is serum?

A

Plasma without fibrinogen and other clotting factors

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19
Q

What are leukocytes?

A

White blood cells
Derived from multipotent haematopoietic stem cells(haemocytoblast) in the bone marrow. Different factors secreted to give different routes.
Polymorphonuclear leukocytes: neutrophil, eosinophils, basophils.
Mononuclear leukocytes: monocytes (macrophages), T cells and B cells.

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20
Q

What are mast cells?

A

Cells that are filled with basophil granules. Found in connective tissue and induce inflammation through the release of histamine and heparin.

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21
Q

What are natural killer cells?

A

Cells that circulate in blood and migrate into tissues. Able to kill tumour-cells or virus-infected cells.

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22
Q

What are dendritic cells?

A

Cells that present antigens on their surfaces, triggering adaptive immunity. Present in epithelial tissue.

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23
Q

What are the 3 soluble factors in the immune system?

A

Complement
Anitbodies
Cytokines and chemokines

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24
Q

What is the complement system?

A

Group of about 20 serum proteins secreted by the liver that need to be activated to be functional.
Have 3 modes of action: direct lysis, attraction of more leukocytes to the site of infection or coat invading organisms.

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25
Q

What are antibodies?

A

AKA Immunoglobulins
Can be soluble, secreted or bound to B cells as part of the B cell antigen receptor.
Bind specifically to antigens.
5 types: IgG, IgA, IgM, IgD and IgE

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26
Q

What are the different types of antibodies:

A

IgG: most predominant in human serum (70-75%). Present anywhere in the body.
IgM: pentamer with 10 binding sites. Accounts for 10% of Ig in serum. Mainly involved in the primary immune response (mIgM present as an antigen-specific receptor). Mainly found in blood as too big to cross endothelium.
IgA: usually a monomer. Accounts for 15% of serum. Predominant Ig in mucous secretions such as saliva, colostrum, milk, bronchiolar and genitourinary secretions.
IgD: transmembrane monomer present on mature B cells. Accounts for 1% of serum.
IgE: expressed by basophils and mast cells. Accounts for only 0.05% of serum. Binding the Ag triggers release of histamine in hypersensitivity reactions.

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27
Q

What are interferons?

A

Group of signalling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumour cells.
Induce a state of antiviral resistance in uninfected cells and limit the spread of viral infections.
IFNa and B produced by viral-infected cells. IFNy released by Th1 cells.

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28
Q

What are interleukins?

A

Group of cytokines that are produced by leukocytes to regulate immune response. Can be pro-inflammatory (IL-1) or anti-inflammatory (IL-10). Can cause cells to divide, differentiate and secrete factors.

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29
Q

What are colony stimulating factors?

A

Secreted glycoproteins that bind to receptor proteins on the surfaces of hemopoietic stem cells, thereby activating intracellular signaling pathways that can cause the cells to proliferate and differentiate into a specific kind of blood cell.

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30
Q

What are tumour necrosis factors?

A

Multifunctional cytokine produced by immune system cells. Act to promote the inflammatory process and can also induce necrosis in tumour cells (name’s sake).

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31
Q

What are chemokines?

A

Group of about 40 proteins that direct movement of leukocytes (and other cells) from the bloodstream into the tissues or lymph organs by binding to specific receptors on cells.
CXCL - mainly attract neutrophils
CCL - mainly attract monocytes, lymphocytes, eosinophils, basophils
CX3CL - mainly attract T lymphocytes and NK cells
XCL - mainly T lymphocytes

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32
Q

What 3 things make up innate immunity?

A
Physical and chemical barriers
Phagocytic cells (neutrophils and macrophages)
Blood proteins (complement system and acute phase)
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33
Q

What is inflammation?

A

A series of reactions that bring cells and molecules of the immune system to the site of infection or damage.
The hallmarks of inflammation include increased blood supply and vascular permeability and increased leukocytes transendothelial migration (extravasation).

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34
Q

Name some of the actions that may occur in the inflammatory response?

A

Initiates a response to:
Stop bleeding (coagulation)
Acute inflammation (leukocyte recruitment)
Kill pathogens
Neutralise toxins
Limit pathogen spread
Clear pathogens/dead cells (phagocytosis)
Proliferation of cells to repair damage
Remove blood clot (remodel extracellular material)
Re-establish normal structure/function of tissue

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35
Q

What are the two types of inflammation?

A

Acute: complete elimination of a pathogen followed by resolution of damage, disappearance of leukocytes and full regeneration of tissue.
Chronic: persistent, unresolved inflammation.

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36
Q

What are Toll-like receptors?

A

Type of pattern recognition receptor.

Recognise pathogen-associated molecular patterns expressed by microbes.

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37
Q

What are the 3 complement activation pathways?

A

Classical: Ab is bound to microbe
Alternative: complement binds to microbe
Lectin: activated by mannose binding lectin which binds to the microbe

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38
Q

What is the membrane attack pathway?

A

C5 convertase cleaves C5 into C5a and C5b. C5D binds to C6 which then binds to C7, C8 and C9 to form the Membrane Attack Complex which forms a transmembrane channel that disrupts the cell membrane leading to cell death.

39
Q

What are the 3 possible outcomes of the complement pathway?

A

Cell lysis by the MAC
Chemotaxis via C3a and C5a
Oponization via C3b: bind to the bacterial membrane and coat it, making it easier to phagocytose.

40
Q

What is extravasation?

A

Infection present in tissue.
Macrophages bind but recognise they need more cells to be called in.
Macrophages secrete TNF-a which activates the endothelium making it sticky.
This means that neutrophils stick and tether.
Endothelial cells also secrete chemokines to tell neutrophil to stop. Held on by integrins.
Neutrophils enter through gap and migrate up the concentration gradient of chemokines.

41
Q

What are the two mechanisms of microbial killing?

A

Oxygen dependent: reactive oxygen intermediates like superoxides are converted to H2O2 then OH (free radical).
Nitric oxide is also anti-microbial

Oxygen independent: enzymes (lysozyme), proteins (defensins insert into membranes), TNF, pH

42
Q

What are the two types of adaptive immunity?

A

Cell-mediated - T cells (intracellular microbes)

Humoral - B cells (extracellular microbes)

43
Q

What is cell-mediated immunity?

A

Interplay between antigen presenting cells (macrophages, dendritic cells, B cells) and T cells.
T cells only respond to intracellular ‘presented antigens’.

Naive T cells are converted into activated effector T cells after encountering antigen-presenting cells (APCs). These APCs, such as macrophages, dendritic cells, and B cells, load antigenic peptides onto the MHC of the cell, in turn presenting the peptide to receptors on T cells. T cell receptor (TCR) recognises foreign antigens in association with the major histocompatibility complex and binds to them. Activated T cells can become Cytotoxic T cells, which kill infected target cells by apoptosis without using cytokines, TH1 cells, which primarily function to activate macrophages, and TH2 cells, which primarily function to stimulate B cells into producing antibodies.

44
Q

What is the major histocompatibility complex?

A

A set of genes that code for cell surface proteins that bind to antigens derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.
MHC coded for by Human Leukoctyes antigen (HLA) genes.
MHC I - glycoproteins on all nucleated cells (8-10 AA)
MHC II - glycoproteins only on APC (13-24 AA)Wh, code for secreted proteins (complement).

45
Q

What does a Tc (CD8) cell do?

A

It can release chemokines to recruit more inflammatory cells, release IFNy to activate macrophages (intracellular killing) or it can release perforin and granulysin to lead to apoptosis and killing of pathogens.

46
Q

What does a Th1 (CD4) cells do?

A

Activated in high levels of IL-12.
Th1 cells travel to secondary lymphoid tissue (lymph nodes and spleen) to proliferate through clonal expansion. It is able to recognise Ag on infected cells (with MHCII) via the TCR. Can also secret INFy to causes apoptosis to stop a virus spreading.

47
Q

What is humoral immunity?

A

B cells express membrane bound Ig (IgM or IgD monomer). Each B cell can only make one Ab that will bind one epitope on one antigen. We are born with loads of immature B cells.
When a B cell encounters an antigen, it will internalize the attached microbe, degrade the organism, and present peptide degradation products of the microbe on its surface with MHC II molecules.
CD4+ T-cells survey the MHC II displayed on B-cells and determine if their T-cell Receptor can recognize the microbial peptides. If it cannot, the B-cell will simply move on to the next lymph node. If it can, it will secrete IL-4 and IL-5, inducing intense proliferation of the B-cell.
One population of the B cells will become plasma cells
which secrete enormous amounts of their antibody (generally IgM, may be IgG later). Others develop into quiescent B memory cells

48
Q

What are the major problems with our immune system?

A

We need a rapid response to pathogens but:

  • Immunological memory takes a long time
  • We live in a continual relationship with pathogens
  • Adaptive immunity is highly specific
49
Q

What are the two types of pattern recognition receptors?

A

Secreted and circulating PRRs

Cell-associated PRRs

50
Q

What are secreted and circulating PRRs?

A

Antimicrobial peptides secreted in living fluids from epithelia and phagocytes.
Can lead to direct killing or activation of an immune response.

51
Q

What are lectins and collectins?

A

Carbohydrate-containing proteins that bind carbohydrates or lipids in microbe walls. Activate complement and improve phagocytosis
e.g. mannose binding lectin, surfactant proteins

52
Q

What are pentraxins?

A

Proteins like CRP which have some antimicrobial actions. Can activate complement and promote phagocytosis.
Can react with C protein of C. Pneumococci

53
Q

What are cell-associated PRRs?

A

Present on the cell membrane or in the cytosol of cells. Recognise a broad range of molecular proteins. TLRs are the main family, different TLRs respond to different bacteria and viruses.

54
Q

What are Nod-like receptors?

A

Rapidly expanding family of 22 proteins that setect intracellular microbial pathogens. Detections of peptidoglycans, muramyl dipeptide etc.
NOD1, NOD2 and NLRP3 are the best known.

55
Q

What does NOD2 do?

A

Widespread expression.
Recognise muramyl dipeptide which is a breakdown product of peptidoglycan.
Activates inflammatory signalling pathways.
Non-functioning mutations lead to Crohn’s disease.
Hyperfunctioning mutations lead to Blow’s syndrome (chronic granulomatas)

56
Q

What are rig-like receptors?

A

Best known are Rig-1 and MDA5 whose roles are to detect intracellular dsRNA and DNA. They couple to active interferon production, enabling an antiviral response.

57
Q

What roles do TLRs have?

A
  • Blood neutrophil numbers
  • Induction of endotoxin tolerance in the newborn gut
  • Maturation of the normal immune system
  • Maintaining a balance of commensal organisms
58
Q

How are TLRs involved in damage recognition?

A

Recognise a range of endogenous damage molecules which may share characteristics of hydrophobicity.
Damage molecules include:
-Extracellular (fibrinogen, hyaluronic acid)
-Intracellular (HMGB1, mRNA, heat shock proteins, uric acid)
Leads to initiation of tissue repair and perhaps enhance local antimicrobial signalling.

59
Q

How can knowledge about PRRs be translated into therapy?

A

Enhance TLR signalling to improve immunity (adjuvants)
Inhibit TLR signalling in sepsis syndromes, inflammation and arthritis
Modify adaptive immune response

60
Q

What is the immunological theory?

A

Infection with an organism leads to the generation of protective substances in the serum. This protection persists (memory) and can be transferred to other subjects (passive immunity). Protective substance identified as circulating globulin (antibody).

61
Q

What are the two types of passive immunity?

A

Passive immunity is the transfer of preformed antibodies.
NATURAL: maternal antibodies across the placenta to the developing foetus/breast milk. Protection against MMR, tetanus, diptheria.

ARTIFICIAL: treated with pooled normal human IgG or immunoserum against pathogens or toxins.
Used for botulism, tetanus, diptheria (anti-toxins).
Hepatitis, measles, rabies.
Snake bites, insects, jelly-fish (anti-venins).

62
Q

What is active immunisation (vaccination)?

A

Manipulating the immune system to generate a persistent protective response against pathogens by safely mimicking natural infection.
Generate immunological memory.

63
Q

What are the stages of active immunisation?

A
  • Engage the innate immune system
  • Elicit ‘danger’ signals that activate the immune system, triggers such as molecular fingerprints of infection (PAMPs)
  • Activate specialist antigen presenting cells
  • Engage the adaptive immune system - memory T and B cells
64
Q

What are the different kinds of antigen that can be used for a vaccine?

A

Whole organism: live attenuated pathogen or killed, inactivated pathogen e.g TB and Polio
Subunits: toxoids/antigenic extracts/recombinant proteins
Peptides
DNA vaccines
Engineered virus

65
Q

What are the advantages and disadvantages of a vaccine made from a live attenuated pathogen?

A

Advantages: sets up a transient infection, activation of a full natural immune response, prolonged contact with the immune system, memory response in T/B cells.

Disadvantages: immunocompromised patients may become infected, can lead to virulent form.

66
Q

What are the advantages and disadvantages of a vaccine made from a whole inactivated pathogen?

A

Advantages: no risk of infection, storage is less critical, wide range of antigenic components so good immune response is possible.

Disadvantages: only activates humoral response, can be weak, booster vaccination required, patient compliance can be an issue.

67
Q

What are subunit vaccines?

A

Purified molecular components as immunogenic agents.
Inactivated endotoxins (toxoids)
Capsular polysaccharides (MenC)
Recombinant microbial antigens (Bexsero)

68
Q

What are the advantages and disadvantages of subunit vaccines?

A

Advantages: safe to patients, no risk of infection, easier to store
Disadvantages: immune response is less powerful, repeated vaccinations and adjuvants required, must consider heterogeneity of population.

69
Q

How can bacterial exotoxins be used as subunit vaccines?

A

A number of important pathogens (like diphtheria and tetanus) produce symptoms of disease as a result of exotoxins.
Toxoid are heat treated or chemically modified to eliminate toxicity.

70
Q

How can capsular polysaccharides be used as subunit vaccines?

A

Capsular polysaccharides are highly polar, hydrophilic cell surface polymers consisting of digosaccharide repeating units. They interfere with bacterial infections with phagocytes by blocking opsonisation.

71
Q

How can synthetic peptides be used as vaccines?

A

Produce a peptide that includes immunodominant B cell epitopes and can stimulate memory T cell development.
Difficulties: knowledge of HLA presentation of peptides is essential.

72
Q

What are DNA vaccines?

A

Transiently express genes from pathogens in host cells. Generates immune response similar to natural infection leading to T and B cell memory responses.
Expression vector transfected into muscle cells, expression from episomal form or DNA may integrate into chromosomes.

73
Q

How can recombinant vectors be used as subunit vaccines?

A

Imitate the effects of transient infection with pathogen but using a non-pathogenic organism.
Genes for major pathogen antigens are introduced into a non-pathogenic or attenuated microorganism and introduced into the host.

74
Q

What are the advantages and disadvantages of DNA vaccines?

A

Advantages: safe in immunocompromised patients, no requirement for complex storage or transportation, drug delivery can be simple and widespread.
Disadvantages: DNA vaccines are likely to produce a mild response and require boosting, no transient infection.

75
Q

What are the advantages and disadvantages of recombinant vector vaccines?

A

Adavntages: creating ideal stimulus to the immune system, produce immunological memory, flexible, safe.

Disadvantages: require refrigeration for transport, can cause illness in compromised individuals, immune response to virus in subjects can negate effectiveness.

76
Q

What is a conjugate subunit vaccine?

A

Polysaccharide (a weak antigen) linked to a carrier protein to increase its immunogenicity when used as a vaccine (long-term protective response).

77
Q

What is innate immunity?

A

Does not require prior exposure to recognise something has gone wrong.
Mainly about eating bacteria and rapid responses to viruses.

78
Q

What is adaptive immunity?

A

Formation of immunological memory
Basis of vaccination - antigen-presenting cells show bits of stuff to lymphocytes.
They support the production of antibodies and also look for these molecules on tissue cells.

79
Q

What are the different antibodies known for?

A

IgM (tetramer) - made at the beginning of infection
IgG - highly specific molecules targeting single epitopes
IgE - made to things we’re allergic to
IgA - found in mucous membranes

80
Q

What are the different types of hypersensitivity reactions?

A
Type 1 (IgE) - acute anaphylaxis, hay fever
Type 2 (Ig-bound to cell surface antigens) - transfusion reactions, autoimmune disease
Type 3 (immune complexes, activation of complement) - SLE, post-streptoccoccal glomerulonephritis
Type 4 (T mediated delyaed-type hypersensitivity) - TB, contact dermatitis
81
Q

What is a Type 1 hypersensitivity reaction?

A

Immunological memory to something causing an allergic response.
Acute anaphylaxis
Hay fever
Asthma

82
Q

What are some examples of allergens that cause a Type 1 hypersensitivity?

A

Local - pollens, animals, occupational exposures

Systemic - drugs foods, treatments

83
Q

How does atopy cause a type 1 hypersensitivity reaction?

A

IgE attaches itself to IgE receptor on the mast cell.
Mast cells medators initiate release of histamine, PGD2, proteases, cytokines, IL-4, IL-13, TNFa.
Atopy is driven by histamine.

84
Q

How can you diagnose atopy?

A

Skin prick tests

RAST (radioallergosorbent test)/ImmunoCAP

85
Q

What’s the treatment for hayfever?

A

Prevent exposure
Anti-histamines
Reduction in local inflammation (steroids)

86
Q

What’s the treatment for anaphylaxis?

A

Avoid/cease exposure
Stop acute symptoms using anti-histamines
Acute resuscitation (adrenaline, fluids, bronchodilators)
Decrease ongoing inflammation (steroids)

87
Q

What is a Type 2 hypersensitivity reaction?

A

Immunoglobulins bound to surface antigens.
Goodpasture’s syndrome: autoantibodies to the a3 chain of the IV collagen which is found in basement membranes. Follows viral infections sometimes.
Can lead to pulmonary haemorrhage and glomerulonephritis (renal inflammation).

88
Q

What is a Type 3 hypersensitivity reaction?

A

Antibodies and targets circulate (e.g. chronic bacterial endocarditis).
Little lumps of antibody and target get deposited in the skin, lung, kidney and activate immunity resulting in tissue damage.
Extrinsic allergic alveolitis is a Type 3 - formation of precipitating antibodies to organic dusts.

89
Q

What are the different types of extrinsic allergic alveolitis?

A

Farmer’s lung - mouldy hay containing micropolyspora or thermoactino-mycetes
Malt worker’s lung - mouldy barlet containing Aspergillus
Mushroom worker’s lung - mushroom compost
Pigeon fancier’s lung - droppings containing Avian serum proteins

90
Q

What is a type 4 hypersensitivity reaction?

A

Formation of granulomas of T cells and macrophages, slow process but can affect many organs - lung, eyes, skin, nervous system.
Dependent upon activation of T cells.
Illustrated in reactions to TB.
Seen in granulomatous diseases such as sarcoidosis.
Also seen in drug reactions (drugs, antibodies, vaccines, herbs, blood products or combinations).

91
Q

What drugs cause type 4 reactions?

A
Amiodarone
Bleomycin
Methotrexate
NSAIDs
Nitroduranoin (antibiotic)
Novel immunoglobulin based treatments
92
Q

What is extrinsic and intrinsic asthma?

A

Extrinsic: atopy, occupational, irritant-induced, long term exposure to allergens or endotoxin
Intrinsic: nasal polyposis, aspirin sensitive, asthma

93
Q

What are the pharmacological treaments for Asthma?

A
Steroids
Anti-histamines
Anti-IgE
Novel strategies
Anti-T cell strategies