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
When are •Rhesus-negative mothers with rhesus+ partner given anti-D IgG during pregnancy?
* At 28 weeks routinely
* After accidents, miscarriage or surgical delivery
26
_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
* 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
_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
* **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
Autoimmune haemolysis - 2 clinical signs
jaundice and anaemia
29
_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
* 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
In what circumstances may complexes of antibody and antigen become insoluble? (type 3 hypersensitivity) - 4 circumstances
* 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
_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
* **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
... 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.
**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
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 ...
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
_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 ‘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
_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 ‘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
_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
* 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
What features are seen in serum sickness? (Type III hypersensitivity) - 4
* Rash
* Fever
* Arthritis
* Glomerulonephritis
38
_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
* 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
_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
* 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
_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
* 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
_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
* 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
_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 ... ...
* 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
Allergic contact dermatitis is an inflammatory disease of the skin that is caused by a type ... hypersensitivity reaction.
Allergic contact dermatitis is an inflammatory disease of the skin that is caused by a type **4** hypersensitivity reaction.
44
_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
* 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
_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
* 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
Nickel allergy is one of the most common causes of contact allergic ....
Nickel allergy is one of the most common causes of contact allergic **dermatitis**.
47
_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
* 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
_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 ...
* 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
_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
* 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
_Patch testing for contact dermatitis_
* ...-impregnated patch placed on back
* Nickel, chrome, cobalt, epoxy resin, lanolin etc
* Results read after ... days
* **Antigen**-impregnated patch placed on back
* Nickel, chrome, cobalt, epoxy resin, lanolin etc
* Results read after **2** days
51
_Patch testing for contact dermatitis_
* Antigen-impregnated patch placed on back
* ..., chrome, cobalt, epoxy resin, lanolin etc
* Results read after ... days
* Antigen-impregnated patch placed on back
* **Nickel**, chrome, cobalt, epoxy resin, lanolin etc
* Results read after **2** days
52
Patch testing for contact dermatitis - results read after how many days?
2
53
_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
* 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
_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
* 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
_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 ...
* 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
_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
* 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
_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-...
* 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
_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
* 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
_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
* 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
_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
* 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
_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
* 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
_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
* 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
_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
* 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
_Limitations of the Gell and Coombes system_
* 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
