Overview and Classification of Immunological Diseases Flashcards

1
Q

Immunological disease

  • Immune system may fail to … infection
    • … factors (evasion mechanisms)
    • … factors (immunodeficiency)
  • Immune system may cause disease …
    • Failure of … (eg allergy/ autoimmunity)
    • Immune system inappropriately activated for unknown reasons (eg inflammatory bowel disease) or for reasons that are known but poorly understood (eg asbestos or cigarette smoke) or during infection
A
  • Immune system may fail to control infection
    • Pathogen factors (evasion mechanisms)
    • Host factors (immunodeficiency)
  • Immune system may cause disease directly
    • Failure of tolerance (eg allergy/ autoimmunity)
    • Immune system inappropriately activated for unknown reasons (eg inflammatory bowel disease) or for reasons that are known but poorly understood (eg asbestos or cigarette smoke) or during infection
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2
Q

Immunological disease

  • Immune system may fail to control infection
    • Pathogen factors (evasion mechanisms)
    • Host factors (immunodeficiency)
  • Immune system may cause disease directly
    • … of tolerance (eg allergy/ autoimmunity)
    • Immune system … … for … reasons (eg inflammatory bowel disease) or for reasons that are known but poorly understood (eg asbestos or cigarette smoke) or during infection
A
  • Immune system may fail to control infection
    • Pathogen factors (evasion mechanisms)
    • Host factors (immunodeficiency)
  • Immune system may cause disease directly
    • Failure of tolerance (eg allergy/ autoimmunity)
    • Immune system inappropriately activated for unknown reasons (eg inflammatory bowel disease) or for reasons that are known but poorly understood (eg asbestos or cigarette smoke) or during infection
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3
Q

Mechanisms-based approach to classifying immunologically-mediated disease

  • Gell and Coombes proposed a system to classify immunologically-mediated diseases in 1963
  • Known as Gell and Coombes … reactions types …-…
  • It’s important to realise that the underlying immunological processes are all normal immune functions: the classification refers to mechanisms of disease when the immune system is … activated
  • The terminology is very seldom used in clinical medicine – it’s rather a classification system that helps to understand the underlying immunology
A
  • Gell and Coombes proposed a system to classify immunologically-mediated diseases in 1963
  • Known as Gell and Coombes hypersensitivity reactions types 1-4
  • It’s important to realise that the underlying immunological processes are all normal immune functions: the classification refers to mechanisms of disease when the immune system is inappropriately activated
  • The terminology is very seldom used in clinical medicine – it’s rather a classification system that helps to understand the underlying immunology
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4
Q

Mechanisms-based approach to classifying immunologically-mediated disease

  • … and … proposed a system to classify immunologically-mediated diseases in 1963
  • Known as … and … hypersensitivity reactions types 1-4
  • It’s important to realise that the underlying immunological processes are all normal immune functions: the classification refers to mechanisms of disease when the immune system is inappropriately activated
  • The terminology is very seldom used in clinical medicine – it’s rather a classification system that helps to understand the underlying immunology
A
  • Gell and Coombes proposed a system to classify immunologically-mediated diseases in 1963
  • Known as Gell and Coombes hypersensitivity reactions types 1-4
  • It’s important to realise that the underlying immunological processes are all normal immune functions: the classification refers to mechanisms of disease when the immune system is inappropriately activated
  • The terminology is very seldom used in clinical medicine – it’s rather a classification system that helps to understand the underlying immunology
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5
Q

The Gell and Coombes classification of hypersensitivity

A
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6
Q

Fill in the gaps

A
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7
Q

Fill in the gaps

A
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8
Q

Give an example of Type 1 hypersensitivity

A

Seasonal rhinitis, Cat allergy

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9
Q

Give an example of Type 2 hypersensitivity

A

Autoimmune haemolysis, haemolytic disease of newborn

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10
Q

Give an example of Type 3 hypersensitivity

A

Serum sickness, hypersensitivity, pneumonitis, Systemic lupus, erythematosis

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11
Q

Give an example of Type 4 hypersensitivity

A

Contact dermatitis, tuberculin reaction

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12
Q

Type 1 hypersensitivity: IgE-mediated allergy

  • B cells … switch to IgE antibody. Secreted IgE is picked up by tissue … cells and circulating basophils
  • …-linking of allergen-specific IgE antibodies by allergen activates the mast cell
  • Mast cell rapidly ‘degranulates’ releasing …, tryptase and other pre-formed mediators
  • Pharmacological effects of … lead to symptoms in the affected organ(s)
  • In health, believed to assist with parasite immunity
A
  • B cells class switch to IgE antibody. Secreted IgE is picked up by tissue mast cells and circulating basophils
  • Cross-linking of allergen-specific IgE antibodies by allergen activates the mast cell
  • Mast cell rapidly ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators
  • Pharmacological effects of histamine lead to symptoms in the affected organ(s)
  • In health, believed to assist with parasite immunity
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13
Q

Type 1 hypersensitivity: IgE-mediated allergy

  • B cells class switch to IgE antibody. Secreted IgE is picked up by tissue mast cells and circulating …
  • Cross-linking of allergen-specific IgE antibodies by allergen … the mast cell
  • Mast cell rapidly ‘…’ releasing histamine, tryptase and other pre-formed mediators
  • Pharmacological effects of histamine lead to symptoms in the affected organ(s)
  • In health, believed to assist with … immunity
A
  • B cells class switch to IgE antibody. Secreted IgE is picked up by tissue mast cells and circulating basophils
  • Cross-linking of allergen-specific IgE antibodies by allergen activates the mast cell
  • Mast cell rapidly ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators
  • Pharmacological effects of histamine lead to symptoms in the affected organ(s)
  • In health, believed to assist with parasite immunity
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14
Q

Type 2 hypersensitivity: AB blood system and transfusion medicine

  • Refers to pathology directly mediated by …
  • … blood transfusion reactions are an example of type II hypersensitivity
  • IgM antibodies against AB antigens develop during first year of life
  • The antibodies are an example of isoantibodies – develop against similar antigens on surface of gut bacteria and cross-react with red cell antigens
A
  • Refers to pathology directly mediated by antibodies
  • Mismatch blood transfusion reactions are an example of type II hypersensitivity
  • IgM antibodies against AB antigens develop during first year of life
  • The antibodies are an example of isoantibodies – develop against similar antigens on surface of gut bacteria and cross-react with red cell antigens
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15
Q

Type 2 hypersensitivity: AB blood system and transfusion medicine

  • Refers to pathology directly mediated by antibodies
  • Mismatch blood transfusion reactions are an example of type II hypersensitivity
  • Ig… antibodies against AB antigens develop during first year of life
  • The antibodies are an example of … – develop against similar antigens on surface of gut bacteria and cross-react with red cell antigens
A
  • Refers to pathology directly mediated by antibodies
  • Mismatch blood transfusion reactions are an example of type II hypersensitivity
  • IgM antibodies against AB antigens develop during first year of life
  • The antibodies are an example of isoantibodies – develop against similar antigens on surface of gut bacteria and cross-react with red cell antigens
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16
Q

Blood Type - Group AB are potentially universal …

A

Blood Type - Group AB are potentially universal recipient - no pre-formed antibody against A or B

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17
Q

Blood Type - Group … are potentially universal donors

A

Blood Type - Group O are potentially universal donors - blood wont react with circulating antibodies in the recipient

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18
Q

Type 2 hypersensitivity: haemolytic disease of the newborn

  • Major blood group system is …
  • ‘D’ antigen (Rhesus) is a secondary classification
  • Majority of the population are D…
  • Mother may be … by exposure to fetal red cells during pregnancy
    • Parturition
    • Trauma
  • Antibodies may cause disease in subsequent pregnancies
A
  • Major blood group system is ABO
  • ‘D’ antigen (Rhesus) is a secondary classification
  • Majority of the population are D+
  • Mother may be sensitised by exposure to fetal red cells during pregnancy
    • Parturition
    • Trauma
  • Antibodies may cause disease in subsequent pregnancies
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19
Q

Type 2 hypersensitivity: haemolytic disease of the newborn

  • Major blood group system is ABO
  • ‘D’ antigen (Rhesus) is a secondary classification
  • Majority of the population are D+
  • Mother may be sensitised by exposure to fetal red cells during pregnancy
    • During …
    • Or during … events
  • Antibodies may cause … in subsequent pregnancies
A
  • Major blood group system is ABO
  • ‘D’ antigen (Rhesus) is a secondary classification
  • Majority of the population are D+
  • Mother may be sensitised by exposure to fetal red cells during pregnancy
    • Parturition
    • Trauma
  • Antibodies may cause disease in subsequent pregnancies
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20
Q

The majority of the population are D… (rhesus + or -?)

A

D+ (rhesus positive)

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21
Q

Type 2 hypersensitivity: Haemolytic disease of the newborn

  • Illustration
A
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22
Q

Haemolytic disease of the newborn

  • Autoimmune haemolysis highly deleterious to fetus:
    • … retardation, … failure, ‘hydrops fetalis’, … from high bilirubin levels
  • Rhesus-negative mothers with rhesus+ partner are given …-D IgG during pregnancy
    • At … weeks routinely
    • After accidents, miscarriage or surgical delivery
  • Binds to fetal red cells entering circulation; fetal red cells then destroyed, preventing sensitisation
  • Risk of maternal sensitisation reduced from 16% per pregnancy to 0.1%
A
  • Autoimmune haemolysis highly deleterious to fetus:
    • Growth retardation, cardiovascular failure, ‘hydrops fetalis’, neurotoxicity from high bilirubin levels
  • Rhesus-negative mothers with rhesus+ partner are given anti-D IgG during pregnancy
    • At 28 weeks routinely
    • After accidents, miscarriage or surgical delivery
  • Binds to fetal red cells entering circulation; fetal red cells then destroyed, preventing sensitisation
  • Risk of maternal sensitisation reduced from 16% per pregnancy to 0.1%
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23
Q

Haemolytic disease of the newborn

  • Autoimmune haemolysis highly deleterious to fetus:
    • Growth retardation, cardiovascular failure, ‘hydrops fetalis’, neurotoxicity from high bilirubin levels
  • Rhesus-negative mothers with rhesus+ partner are given anti-D IgG during pregnancy
    • At 28 weeks routinely
    • After accidents, … or surgical delivery
  • Binds to fetal red cells entering circulation; fetal red cells then …, preventing sensitisation
  • Risk of maternal sensitisation reduced from 16% per pregnancy to …%
A
  • Autoimmune haemolysis highly deleterious to fetus:
    • Growth retardation, cardiovascular failure, ‘hydrops fetalis’, neurotoxicity from high bilirubin levels
  • Rhesus-negative mothers with rhesus+ partner are given anti-D IgG during pregnancy
    • At 28 weeks routinely
    • After accidents, miscarriage or surgical delivery
  • Binds to fetal red cells entering circulation; fetal red cells then destroyed, preventing sensitisation
  • Risk of maternal sensitisation reduced from 16% per pregnancy to 0.1%
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24
Q

Rhesus-… mothers with rhesus… partner are given anti-D IgG during pregnancy

A

Rhesus-negative mothers with rhesus+ partner are given anti-D IgG during pregnancy

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25
Q

When are •Rhesus-negative mothers with rhesus+ partner given anti-D IgG during pregnancy?

A
  • At 28 weeks routinely
  • After accidents, miscarriage or surgical delivery
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26
Q

Type III hypersensitivity

  • Describes disease caused by complexes of … and …
  • Such complexes are a normal phenomenon
    • Usually …, removed in spleen
  • In some situations (below) they become insoluble and cause disease
    • Large quantity of antigen
    • Large quantity of antibody
    • Interaction between the two is very strong
    • Complexes are of the correct size
A
  • Describes disease caused by complexes of antibody and antigen
  • Such complexes are a normal phenomenon
    • Usually soluble, removed in spleen
  • In some situations (below) they become insoluble and cause disease
    • Large quantity of antigen
    • Large quantity of antibody
    • Interaction between the two is very strong
    • Complexes are of the correct size
27
Q

Type 2 hypersensitivity: autoimmune haemolysis

  • … formation of antibodies against our … cells
  • Macrophage see opsonised red cell, phagocytose it, destroy it - … haemolysis
  • May activate complement - … haemolysis
A
  • Spontaneous formation of antibodies against our red cells
  • Macrophage see opsonised red cell, phagocytose it, destroy it - extravascular haemolysis
  • May activate complement - intravascular haemolysis
28
Q

Autoimmune haemolysis - 2 clinical signs

A

jaundice and anaemia

29
Q

Type III hypersensitivity

  • Describes disease caused by complexes of antibody and antigen
  • Such complexes are a normal phenomenon
    • Usually soluble, removed in spleen
  • In some situations (below) they become … and cause disease
    • Large quantity of antigen
    • Large quantity of antibody
    • Interaction between the two is very …
    • Complexes are of the correct size
A
  • Describes disease caused by complexes of antibody and antigen
  • Such complexes are a normal phenomenon
    • Usually soluble, removed in spleen
  • In some situations (below) they become insoluble and cause disease
    • Large quantity of antigen
    • Large quantity of antibody
    • Interaction between the two is very strong
    • Complexes are of the correct size
30
Q

In what circumstances may complexes of antibody and antigen become insoluble? (type 3 hypersensitivity) - 4 circumstances

A
  • In some situations (below) they become insoluble and cause disease
    • Large quantity of antigen
    • Large quantity of antibody
    • Interaction between the two is very strong
    • Complexes are of the correct size
31
Q

Local immune complex disease

  • … lesions in the fingertip pulp due to deposition of circulating immune complexes
  • May be seen in infective … (Osler’s nodes)
  • May be seen in other diseases with immune complex deposition eg SLE
A
  • Painful lesions in the fingertip pulp due to deposition of circulating immune complexes
  • May be seen in infective endocarditis (Osler’s nodes)
  • May be seen in other diseases with immune complex deposition eg SLE
32
Q

… nodes are painful, red, raised lesions found on the hands and feet. They are associated with a number of conditions, including infective endocarditis, and are caused by immune complex deposition.

A

Osler’s nodes are painful, red, raised lesions found on the hands and feet. They are associated with a number of conditions, including infective endocarditis, and are caused by immune complex deposition.

33
Q

Osler’s nodes are painful, red, raised lesions found on the hands and feet. They are associated with a number of conditions, including infective …, and are caused by immune complex …

A

Osler’s nodes are painful, red, raised lesions found on the hands and feet. They are associated with a number of conditions, including infective endocarditis, and are caused by immune complex deposition.

34
Q

Type III hypersensitivity: Serum sickness

  • A ‘generalised’ transient immune complex-mediated syndrome
  • Mainly results from … of certain immunogenic drugs or anti-sera produced in animals eg after … evenomation
    • Rash
    • Arthritis
    • Glomerulonephritis
A
  • A ‘generalised’ transient immune complex-mediated syndrome
  • Mainly results from injection of certain immunogenic drugs or anti-sera produced in animals eg after snake evenomation
    • Rash
    • Fever
    • Arthritis
    • Glomerulonephritis
35
Q

Type III hypersensitivity: Serum sickness

  • A ‘generalised’ transient immune complex-mediated syndrome
  • Mainly results from injection of certain immunogenic drugs or anti-sera produced in animals eg after snake evenomation
    • Fever
    • Glomerulonephritis
A
  • A ‘generalised’ transient immune complex-mediated syndrome
  • Mainly results from injection of certain immunogenic drugs or anti-sera produced in animals eg after snake evenomation
    • Rash
    • Fever
    • Arthritis
    • Glomerulonephritis
36
Q

Type III hypersensitivity: Hypersensitivity pneumonitis

  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes sensitised to an environmental antigen by … exposure, producing large quantities of … antibodies
  • Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
    • Mould spores in hay (… lung)
    • Pigeon feathers and stool (pigeon-fanciers lung)
  • Initially transient, lung scarring with … exposure
A
  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
  • Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
    • Mould spores in hay (farmers lung)
    • Pigeon feathers and stool (pigeon-fanciers lung)
  • Initially transient, lung scarring with repeated exposure
37
Q

What features are seen in serum sickness? (Type III hypersensitivity) - 4

A
  • Rash
  • Fever
  • Arthritis
  • Glomerulonephritis
38
Q

Type III hypersensitivity: Hypersensitivity pneumonitis

  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
  • Immune … form in the lung upon re-exposure causing shortness of breath and …
    • … spores in hay (farmers lung)
    • Pigeon feathers and stool (pigeon-fanciers lung)
  • Initially transient, lung scarring with repeated exposure
A
  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
  • Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
    • Mould spores in hay (farmers lung)
    • Pigeon feathers and stool (pigeon-fanciers lung)
  • Initially transient, lung scarring with repeated exposure
39
Q

Type III hypersensitivity: Hypersensitivity pneumonitis

  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
  • Immune complexes form in the lung upon re-exposure causing … of … and cough
    • Mould spores in hay (farmers lung)
    • … feathers and stool (…-fanciers lung)
  • Initially transient, lung scarring with repeated exposure
A
  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
  • Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
    • Mould spores in hay (farmers lung)
    • Pigeon feathers and stool (pigeon-fanciers lung)
  • Initially transient, lung scarring with repeated exposure
40
Q

Type III hypersensitivity: Hypersensitivity pneumonitis

  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes … to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
  • Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
    • Mould spores in hay (farmers lung)
    • Pigeon feathers and stool (pigeon-fanciers lung)
  • Initially transient, lung … with repeated exposure
A
  • Also known as extrinsic allergic alveolitis (EAA)
  • Patient becomes sensitised to an environmental antigen by repeated exposure, producing large quantities of IgG antibodies
  • Immune complexes form in the lung upon re-exposure causing shortness of breath and cough
    • Mould spores in hay (farmers lung)
    • Pigeon feathers and stool (pigeon-fanciers lung)
  • Initially transient, lung scarring with repeated exposure
41
Q

Type IV hypersensitivity: Delayed-type hypersensitivity

  • Reactions are mediated by …-specific effector … cells
  • Because it takes time to process and present antigen, these reactions do not develop for at least … hours following exposure
  • In the skin, known as contact dermatitis
A
  • Reactions are mediated by antigen-specific effector T cells
  • Because it takes time to process and present antigen, these reactions do not develop for at least 24 hours following exposure
  • In the skin, known as contact dermatitis
42
Q

Type IV hypersensitivity: Delayed-type hypersensitivity

  • Reactions are mediated by antigen-specific effector T cells
  • Because it takes time to process and present antigen, these reactions do not develop for at least 24 hours following exposure
  • In the skin, known as … …
A
  • Reactions are mediated by antigen-specific effector T cells
  • Because it takes time to process and present antigen, these reactions do not develop for at least 24 hours following exposure
  • In the skin, known as contact dermatitis
43
Q

Allergic contact dermatitis is an inflammatory disease of the skin that is caused by a type … hypersensitivity reaction.

A

Allergic contact dermatitis is an inflammatory disease of the skin that is caused by a type 4 hypersensitivity reaction.

44
Q

Contact dermatitis: sensitisation

  • Sensitising agents are typically highly reactive … molecules which can … skin
  • These react with self proteins to create protein-…* complexes that are picked up by Langerhans cells, which migrate to regional lymph nodes
  • Examples are nickel and molecules in perfume/ cosmetics
A
  • Sensitising agents are typically highly reactive small molecules which can penetrate skin
  • These react with self proteins to create protein-hapten* complexes that are picked up by Langerhans cells, which migrate to regional lymph nodes
  • Examples are nickel and molecules in perfume/ cosmetics
45
Q

Contact dermatitis: sensitisation

  • Sensitising agents are typically highly reactive small molecules which can penetrate skin
  • These react with … proteins to create protein-hapten* complexes that are picked up by … cells, which migrate to regional lymph nodes
  • Examples are … and molecules in perfume/ cosmetics
A
  • Sensitising agents are typically highly reactive small molecules which can penetrate skin
  • These react with self proteins to create protein-hapten* complexes that are picked up by Langerhans cells, which migrate to regional lymph nodes
  • Examples are nickel and molecules in perfume/ cosmetics
46
Q

Nickel allergy is one of the most common causes of contact allergic ….

A

Nickel allergy is one of the most common causes of contact allergic dermatitis.

47
Q

Contact dermatitis: sensitisation (2)

  • The Langerhans cells process and present the antigen together with MHC…
  • In some susceptible individuals, the complexes are recognised as …
  • The activated T cells then migrate to the dermis
A
  • The Langerhans cells process and present the antigen together with MHCII
  • In some susceptible individuals, the complexes are recognised as foreign
  • The activated T cells then migrate to the dermis
48
Q

Contact dermatitis: sensitisation (2)

  • The Langerhans cells process and present the antigen together with MHCII
  • In some susceptible individuals, the complexes are recognised as foreign
  • The activated T cells then migrate to the …
A
  • The Langerhans cells process and present the antigen together with MHCII
  • In some susceptible individuals, the complexes are recognised as foreign
  • The activated T cells then migrate to the dermis
49
Q

Contact dermatitis: elicitation (last stage)

  • Antigen penetrates skin - haptenisation - taken up by … cells - presented to … cells
  • Preformed … Th1 cells produce IFN-gamma (delay, 24 - 72hours)
  • Inflammation produced by secretion of cytokines such as IFN-gamma and chemokines which attract other inflammatory cells
A
  • Antigen penetrates skin - haptenisation - taken up by langerhans cells - presented to T cells
  • Preformed effector Th1 cells produce IFN-gamma (delay, 24 - 72hours)
  • Inflammation produced by secretion of cytokines such as IFN-gamma and chemokines which attract other inflammatory cells
50
Q

Patch testing for contact dermatitis

  • …-impregnated patch placed on back
  • Nickel, chrome, cobalt, epoxy resin, lanolin etc
  • Results read after … days
A
  • Antigen-impregnated patch placed on back
  • Nickel, chrome, cobalt, epoxy resin, lanolin etc
  • Results read after 2 days
51
Q

Patch testing for contact dermatitis

  • Antigen-impregnated patch placed on back
  • …, chrome, cobalt, epoxy resin, lanolin etc
  • Results read after … days
A
  • Antigen-impregnated patch placed on back
  • Nickel, chrome, cobalt, epoxy resin, lanolin etc
  • Results read after 2 days
52
Q

Patch testing for contact dermatitis - results read after how many days?

A

2

53
Q

Tuberculin skin test (TST): another example of a type IV hypersensitivity reaction

  • Used to determine previous … to …
  • Tuberculin injected intradermally (tuberculin=complex mixture of antigens derived from MTB)
  • Local inflammatory response evolves over 24-72 hours if previously …
  • Mediated by Th1 cells
A
  • Used to determine previous EXPOSURE to TB
  • Tuberculin injected intradermally (tuberculin=complex mixture of antigens derived from MTB)
  • Local inflammatory response evolves over 24-72 hours if previously exposed
  • Mediated by Th1 cells
54
Q

Tuberculin skin test (TST): another example of a type IV hypersensitivity reaction

  • Used to determine previous EXPOSURE to TB
  • Tuberculin injected … (tuberculin=complex mixture of antigens derived from MTB)
  • Local inflammatory response evolves over …-… hours if previously exposed
  • Mediated by … cells
A
  • Used to determine previous EXPOSURE to TB
  • Tuberculin injected intradermally (tuberculin=complex mixture of antigens derived from MTB)
  • Local inflammatory response evolves over 24-72 hours if previously exposed
  • Mediated by Th1 cells
55
Q

Mechanism of TST (Tuberculin skin test)

  • Antigen is injected into subcutaneous tissue and processed by local antigen-presenting cells
  • A … effector cell recognizes antigen and releases … which act on vascular endothelium
  • Recruitment of … and plasma to site of antigen injection causes visible …
A
  • Antigen is injected into subcutaneous tissue and processed by local antigen-presenting cells
  • A Th1 effector cell recognizes antigen and releases cytokines which act on vascular endothelium
  • Recruitment of phagocytes and plasma to site of antigen injection causes visible lesion
56
Q

Detection of TB-specific Th1 cells in vitro by interferon gamma release assay (IGRA)

  • Alternative to TST (… … test) - as that requires patient to be present at time of test and later to read the test, difficult to read and difficult to do, does produce false positives
  • This test - Mycobacterium peptides used (…-6 OR CFP-10) - these are unique to mycobacterium TB - very … - less false +
  • These peptides are added to blood in lab - antigen presenting cell takes them up - presents them with … and secretes IL-12
A
  • Alternative to TST (tuberculin skin test) - as that requires patient to be present at time of test and later to read the test, difficult to read and difficult to do, does produce false positives
  • This test - Mycobacterium peptides used (ESAT-6 OR CFP-10) - these are unique to mycobacterium TB - very specific - less false +
  • These peptides are added to blood in lab - antigen presenting cell takes them up - presents them with MHCII and secretes IL-12
57
Q

Detection of TB-specific Th1 cells in vitro by interferon gamma release assay (IGRA)

  • Alternative to TST (tuberculin skin test) - as that requires patient to be present at time of test and later to read the test, difficult to read and difficult to do, does produce false positives
  • This test - Mycobacterium peptides used (ESAT-6 OR …-10) - these are unique to mycobacterium TB - very specific - less false +
  • These peptides are added to blood in lab - antigen presenting cell takes them up - presents them with MHCII and secretes IL-…
A
  • Alternative to TST (tuberculin skin test) - as that requires patient to be present at time of test and later to read the test, difficult to read and difficult to do, does produce false positives
  • This test - Mycobacterium peptides used (ESAT-6 OR CFP-10) - these are unique to mycobacterium TB - very specific - less false +
  • These peptides are added to blood in lab - antigen presenting cell takes them up - presents them with MHCII and secretes IL-12
58
Q

IGRA test - Previous TB exposure vs no previous TB exposure

  • Previous exposure:
    • Memory … cells recognise antigen
    • Because this is a secondary immune response, they are ‘…’ and release cytokines within this short timeframe (IFN-gamma)
  • No previous exposure:
    • No … memory T cells specific for MTB
    • No inteferon gamma produced in this short timeframe
A
  • Previous exposure:
    • Memory Th1 cells recognise antigen
    • Because this is a secondary immune response, they are ‘primed’ and release cytokines within this short timeframe (IFN-gamma)
  • No previous exposure:
    • No primed memory T cells specific for MTB
    • No inteferon gamma produced in this short timeframe
59
Q

IGRA test - Previous TB exposure vs no previous TB exposure

  • Previous exposure:
    • Memory Th1 cells recognise antigen
    • Because this is a … immune response, they are ‘primed’ and release cytokines within this short timeframe (IFN-…)
  • No previous exposure:
    • No primed memory T cells specific for MTB
    • No inteferon … produced in this short timeframe
A
  • Previous exposure:
    • Memory Th1 cells recognise antigen
    • Because this is a secondary immune response, they are ‘primed’ and release cytokines within this short timeframe (IFN-gamma)
  • No previous exposure:
    • No primed memory T cells specific for MTB
    • No inteferon gamma produced in this short timeframe
60
Q

IGRA: positive test

  • Cytokine thats produced by MTB specific Th1 cells is IFN-…
  • Capture antibody on bottom - cells and peptide all added together - If cells produce IFN-… - this is captured by antibodies on bottom of well
  • Secondary antibody is added - marker to produce colour change when substrate is added - produces the little spots
A
  • Cytokine thats produced by MTB specific Th1 cells is IFN-gamma
  • Capture antibody on bottom - cells and peptide all added together - If cells produce IFN-gamma - this is captured by antibodies on bottom of well
  • Secondary antibody is added - marker to produce colour change when substrate is added - produces the little spots
61
Q

IGRA: positive test

  • Cytokine thats produced by MTB specific Th1 cells is IFN-gamma
  • Capture antibody on bottom - cells and peptide all added together - If cells produce IFN-gamma - this is captured by antibodies on bottom of well
  • Secondary antibody is added - marker to produce … change when … is added - produces the little spots
A
  • Cytokine thats produced by MTB specific Th1 cells is IFN-gamma
  • Capture antibody on bottom - cells and peptide all added together - If cells produce IFN-gamma - this is captured by antibodies on bottom of well
  • Secondary antibody is added - marker to produce colour change when substrate is added - produces the little spots
62
Q

Gell and Coombes classification - revisited

  • Pros
    • The only successful attempt to classify disease by mechanism
    • A useful framework to describe & understand various diseases
  • Cons
    • Not particularly useful in … practice
    • … the immunology
      • Even in apparently simple situations such as autoimmune haemolysis (type II hypersensitivity), many components of the immune system are involved
    • Many diseases are much more complex, particularly … inflammatory diseases. The involve multiple immunological effector mechanisms and aren’t well-described in this framework eg
    • Rheumatoid arthritis
    • Chronic asthma
    • Inflammatory bowel disease etc etc
A
  • Pros
    • The only successful attempt to classify disease by mechanism
    • A useful framework to describe & understand various diseases
  • Cons
    • Not particularly useful in clinical practice
    • Oversimplifies the immunology
      • Even in apparently simple situations such as autoimmune haemolysis (type II hypersensitivity), many components of the immune system are involved
    • Many diseases are much more complex, particularly chronic inflammatory diseases. The involve multiple immunological effector mechanisms and aren’t well-described in this framework eg
    • Rheumatoid arthritis
    • Chronic asthma
    • Inflammatory bowel disease etc etc
63
Q

Gell and Coombes classification - revisited

  • Pros
    • The only successful attempt to classify disease by mechanism
    • A useful framework to describe & understand various diseases
  • Cons
    • Not particularly useful in clinical practice
    • Oversimplifies the immunology
      • Even in apparently simple situations such as autoimmune haemolysis (type … hypersensitivity), many components of the immune system are involved
    • Many diseases are much more complex, particularly chronic inflammatory diseases. The involve multiple immunological … mechanisms and aren’t well-described in this framework eg
    • … arthritis
    • Chronic asthma
    • … bowel disease etc etc
A
  • Pros
    • The only successful attempt to classify disease by mechanism
    • A useful framework to describe & understand various diseases
  • Cons
    • Not particularly useful in clinical practice
    • Oversimplifies the immunology
      • Even in apparently simple situations such as autoimmune haemolysis (type II hypersensitivity), many components of the immune system are involved
    • Many diseases are much more complex, particularly chronic inflammatory diseases. The involve multiple immunological effector mechanisms and aren’t well-described in this framework eg
    • Rheumatoid arthritis
    • Chronic asthma
    • Inflammatory bowel disease etc etc
64
Q

Limitations of the Gell and Coombes system

A
  • Not particularly useful in clinical practice
  • Oversimplifies the immunology
    • Even in apparently simple situations such as autoimmune haemolysis (type II hypersensitivity), many components of the immune system are involved
  • Many diseases are much more complex, particularly chronic inflammatory diseases. The involve multiple immunological effector mechanisms and aren’t well-described in this framework eg
    • Rheumatoid arthritis
    • Chronic asthma
    • Inflammatory bowel disease etc etc