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
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
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
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
5
Q
The Gell and Coombes classification of hypersensitivity
A
6
Q
Fill in the gaps
A
7
Q
Fill in the gaps
A
8
Q
Give an example of Type 1 hypersensitivity
A
Seasonal rhinitis, Cat allergy
9
Q
Give an example of Type 2 hypersensitivity
A
Autoimmune haemolysis, haemolytic disease of newborn
10
Q
Give an example of Type 3 hypersensitivity
A
Serum sickness, hypersensitivity, pneumonitis, Systemic lupus, erythematosis
11
Q
Give an example of Type 4 hypersensitivity
A
Contact dermatitis, tuberculin reaction
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
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
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
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
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
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
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
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
20
Q
The majority of the population are D… (rhesus + or -?)
A
D+ (rhesus positive)
21
Q
Type 2 hypersensitivity: Haemolytic disease of the newborn
- Illustration
A
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%
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%
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
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
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
