Immunology Theme 4 Flashcards
(92 cards)
1
Q
what are the Aims of tissue and organ transplantation, what can be the issue with this
A
• Transplants must be physiologically viable
• The process should not harm the recipient
• The transplant should not be rejected by the recipient’s immune system
- Must mitigate for successful transplantation
But: immunosuppression to prevent rejection is not selective
- Susceptible to infections/cancers
2
Q
outline the hypersensitivity mediated by 1st phase of rejection - hyperacute rejection
A
Type II hypersensitivity caused by preexisting antibodies binding to the graft
3
Q
outline what occurs in the 1st phase of rejection - hyperacute rejection
A
- Pre-existing antibodies (IgG) to non-self antigens bind vascular endothelium of transplant and activate complement causing endothelial damage and haemorrhage of graft.
- Activation of clotting cascade causes vascular blockage.
- Anti-HLA antibodies may arise as the result of pregnancy, multiple blood transfusions and previous transplants
- Rejection circumvented by antigen cross matching and serological testing
4
Q
specifically, what is hyperacute rejection caused by
A
ABO or HLA Class I antigen mismatch
Preexisting antibodies (IgG) to ‘non-self’ antigens bind vascular endothelium of transplant and activate complement causing endothelial damage and haemorrhage of graft. Activation of clotting cascade causes vascular blockage.
graft becomes engorged and purple due to hemorrhage
5
Q
why might Anti-HLA antibodies may arise
A
as the result of pregnancy, multiple blood transfusions and previous transplants
6
Q
Outline Alloreactions in transplant rejection and graft-versus-host reaction
A
Type 4 hyposensitivity reactions – T cell mediated (delayed)
• Graft vs host – transplant anything to do with blood, with T cells in it from the donor, which cause a reaction with the host tissue. Common form of morbidity/mortality in transplants due to leukaemia. The T cells attack the recipient’s tissues and there is a potentially fatal graft vs host reaction
(occurs when a kidney is transplanted or heamotopeitc cells)
7
Q
what is an Alloreaction:
A
immune response by one individual to the alloantigens of another caused by alloreactive T-cells
8
Q
what is an alloantigen
A
antigens that vary between the individuals of the same species e.g. HLA because this is the most polymorphic gene area (differs most) in the make up. These are recognised by the recipient in transplantations.
9
Q
outline Preparation for transplantation
A
- MHC is the overview term for HLA and other things lol so can use interchange
- Limit ischaemia (inadequate blood supply) which leads to tissue damage and inflammation within the organ
- Cadaveric vs live donation
- Limit HLA I and II mismatch
10
Q
how do CD8 and CD4 cells respond if there is a mistmatch. what form of hypersensitivity is this
A
- Alloreactive CD8+ T-cells respond to HLA class I differences
- Alloreactive CD4+ T-cells respond to HLA class II differences
Organ attacked and destroyed leading to acute rejection - a form of type IV hypersensitivity
11
Q
what is the Gross appearance of an acutely rejected kidney
A
• May be rejected by Type IV reaction
• Red areas of haemorrhage
• Grey areas of necrosis
• Overall swollen appearance
• Immunosuppressive drug cover before AND after surgery
- This increases likelihood of infections so individuals must be kept in hospital
12
Q
how may Acute progress to chronic rejection and what hypersensitivites are involved
A
- Hyperacute - antibodies (type II)
- Acute - T- CELLS mediated T-cell mediated (type IV)
- Chronic rejection - Involves type III rejection
13
Q
outline Chronic rejection of a kidney transplant, what hypersensitivites are involved
A
Type III hypersensitivity reaction - deposition of immune complexes
- Immune complexes between Alloantibodies and HLA molecules (form within vessels of organ). this recruits inflammatory cells then t cell immunity. immune effectors enter wall of artery due to the damage and cause more damage
- Fibrosis - key feature of chronic rejection
fibrosis: body attempted to repair – however this is not regeneration compromised function failure and rejection.
14
Q
what can Chronic rejection also caused by
A
ischaemic reperfusion injury, viral infection (Due to immunosuppressant drugs) and relapse of original disorder (e.g. leukemia where you don’t get rid of the original disease failure of bone marrow)
15
Q
outline the importance of Polymorphism in the human major histocompatibility complex (MHC) in relation to transplantation
A
Ch 6 - HLA present which codes for MHC
- Very unlikely that HLA genes will be identical between individuals
- When considering transplantation, we look for individuals with a degree of similarity rather than with identical genes.
HLA matching improves the survival of transplanted kidneys
16
Q
outline how there is Differential sensitivity of organ transplant procedures to HLA matching
A
- Simple (corneal) transplant - doesn’t require much of a HLA match (more less HLA neutral) unlike bone marrow
- The eye is immune privaleged site like the CNS – don’t get immunocompetent cell therefore the corneas are available for anyone
- Liver is tolerant to HLA mismatch
- Bone marrow – full of WBC expressing a lot of HLA (class II) designed to undergo immune responses so matching is a requirement
- Chemotherapy to kill cancer cells and kill recipient bone marrow (to prevent host vs graft reaction) – bone marrow replenished by graft bone marrow
17
Q
outline Conventional immunosuppressive drugs in clinical use
A
corticosteroids- mimic natural hormones (may be given in severe acute inflammation e.g. to footballers)
Cyclosporin A
- Side effects headaches, gingival overgrowth , diarrhoea, nausea and vomiting, kidney dysfunction, tremor, hirsutism (excessive growth of hair in women in a male-like pattern)
18
Q
outlinee Examples of Immunological diagnosis and therapy
A
- ELISA
- Immunofluorescence direct and indirect
- FACS
- Monoclonal antibodies
- Cytokines
- N.B. vaccination/immunosuppression
19
Q
outline The unique specificity of antibodies is the basis for detection of specific proteins in the lab
A
- Antibodies will recognise specific proteins
- Binds specific molecules to detect them
- Fc- crystalline fragment – binds to receptors in cells
- constant regions differs between classes
- variable regions- very diverse
20
Q
outline the Production of specific antibodies
A
Conventional immunisation- mixed specificity and limited quantity
Monoclonal antibodies- - limitless supply of antibodies of a single specificity (homogenous) with very good quality.
Recombinant antibodies- limitless and single specificty but DNA technology used to make better
- humanise antibodies
- Manipulate IgG genes,
- make mice immunoglobulin into human immunoglobulin
21
Q
outline the Production of monoclonal antibodies for use in clinical assays and therapeutically
A
immunise mouse with antigen and extract cells from it (from spleen)
fuse with cancer cell (myeloma) - tumour of b cells NOT same and myeloid
this means they become immortal can live for lots of generations and maintain their properties (hybridoma cells – cells which ultimately produce the monoclonal antibodies)
grow in drug containing medium where myeloma die and b-cells die - important antibody cells survive
select for antigen specific hybridoma
clone the selected hybridoma cells
22
Q
How are immunodeficiencies diagnosed?
A
Measure levels of IgG, IgM, IgA and IgE – used in diagnosis and therapy
Lymphocyte count
Flow cytometry to characterise deficiency
If you suspect someone has immunodeficiency, then count their Ig levels, and WBC levels)
23
Q
what does flow cephalometry allow for
A
uses monoclonal antibodies to identify/numeral WBC specific cell types in a mixed population.
FC allows you to enumerate the number of cells that are expressing a specific protein on its surface
The 1% of cells claiming to express IgM and TCR are likely to be false positives as there are no cells which express both.
24
Q
outline the Diagnosis of X-linked agammaglobulinaemia using flow cytometry
what is expressed on all T-cells
A
- Patient with XLA has very little CD19 – marker for B cells
- Cells in the box on the lower left express neither CD3 or CD19 – neutrophils, monocytes or eosinophils
CD3 expressed on all T-cells
CD4 Is just on helper tcells
CD8 is just on cytotoix
25
what are the 2 ways autoimmune diseases analysed/diagnosed?
Physiological dysfunction-
e.g. deficiency in endocrine or musculature issues (autoimmune diseases often treat in endocronine clinic as hormone replacement needed)
E.g. ptosis (eyelids droop over eyes) in myasthenia gravis (treated by neostigmine)
E.g. hyperthyroidism in Graves’ disease (autoantibodies to TSH receptor producing too much thyroid hormone tachycardia/sweaty palms/jumpy)
Autoantibody detection - use ELISA (below)
26
what does ELISA (enzyme linked immunosorbent assay) detect
* Detect serum autoantibodies and antigens
| * Use a spectrophotometer
27
what does Immunofluorescence detect for and what we looking for in the case of an autoimmune disease
Can look at tissue sections
uses Fluorescently labelled antibodies
In the case of autoimmune disease, you are looking for antibodies attached to the tissues (not ones that are free in the blood).
28
outline how Indirect immunofluorescence can be used for biopsy material in good pastures sydrome
autoantibody detection-
| immune complexes deposited in the glomeruli causing inflammation and damage
29
How are allergies diagnosed- what are the controls
• Intradermal skin test – place suspect antigen into skin
* Saline – negative control (for injections)
* Histamine – positive control - shows what result we would expect in an allergic reaction.
There to mimic the hypersensitivity reaction (mast cells secrete when degranulate)
* Put suspected antigen in (positive/negative result)
* Looking for wheal (swelling) and flare (red area)
30
what are some agents used to manipualte the immune response
hormones
antibodies
adjuvants
cytokine- cytokine signalling pathway inhibitors e.g. Tofacitinib for rheumatoid arthritis
31
what are therapeutic monoclonal antibodies
• Anything with -mab at the end
32
how can the follwing be treated with monoclonal antibodies :
- rheumatoid arthiritis
- chronic asthma
- lymphoma
RA- anti-TNFa can dampen down joint inflammation
asthma- Anti igE- removes igE required for mass cells degranulation
lymphoma- antiCD20 can get rid of b-cells
33
what are the Anti-inflammatory effects of anti-TNFα in rheumatoid arthritis
RA is systemic – it affects joint and all body too!- activation of liver proteins – this antibody supresses inflammation caused by this
34
what is C reactive protein is an indication of
protein produce in the liver, used as an indicator of peripheral cytokines (mediating inflammtion)
35
what is the action of Action of Omalizumab (therapeutic and experimental)
Therapeutic anti-IgE
• Anti-IgE prevents mast cell from acquiring cell-surface IgE (cant bind to its receptor)
• So when they encountered the environmental antigen that trigger asthma Mast cell cannot be activated as all the IgE is mopped up.
Experimental anti-IgE:
•Anti-IgE cross-links IgE bound to receptor and activates mast-cell deregulation
•Inflammatory response
36
what is the difference between benign and malignant cancers
Benign – contained within a particular area (doesn’t cause harm but can depend on location e.g. benign tumour in CNS may spread and cause harm or in the brain)
Malignant- Proliferation and invasion of tissues are key features of malignant cancer - change in morphology
37
what are the characteristics of caner
• Very similar immunologically to healthy tissue
- Self cells hidden from the immune system
• Grows/progresses slowly - compare this to infectious pathogens
- Less recognition by the immune system
• Survival rates are increasing may be a manageable chronic disease
38
How do we know the immune response can recognise and reject tumours?
• Immunodeficient animals have increased incidence of cancer
• Immunosuppressive therapy and infections increase cancer incidence
• Cancer incidence increases with age due to immunosenescence/dysregulation
-Zinc important micronutrient
• MHC differences influence tumour survival
39
outline 2 ways cancer cells can become transformed which allows the immune system to recognise them- why is this important
Peptide antigens presented by MHC class I on normal cells , but the cell undergoes a mutation and becomes cancerous
1. Tumour specific antigen- new antigen (body not seen before) due to the mutation- therapeutic targets
2. Tumour associated antigen- reactivation of embryonic genes not normally expressed in the differentiated cell.
Overexpression (quantitative change) of normal self protein by a tumour cell changes density of self-peptide presentation, allowing recognition by T-cells
Need to be able to recognise cancerous antigens to evoke an immune response
40
outline how HPV, HeptB and - Epstein- Barr virus can be associated with cancer
- HPV - certain strains can cause warts (benign) and rare cases can transform cells causing cancers of urogenital tract.
- HeptB- chronic infection can transform liver cells - hepatic carcinoma
- Epstein- Barr virus- chronic infection leading to lymphomas (cancer of mature lymphocytes not like leukemia immature WBC).
41
outline how Viruses can cause cancer
They set up chronic infections- induce hyperplasia (over growth of tissues)
Virally encoded proteins can interfere with normal mechanisms for controlling division (first step to transformation)- cell proliferation can lead to cancer
42
outline which bacterial infection can cause stomach ulcers and stomach cancer
. Helicobacter pylori
43
outline the Aetiology and progression of HPV-associated cervical cancer
As you go from left to right, you get an increasing event of transmalignant carcinoma. Disruption of the normal architecture, and micro-anatomy. Cells get larger, shape changes, prominent nuclei and starting drilling into the tissues below.
16&18 HPV strains associated with cancers - vaccination offered with these strains (70% of cervical cancer caused by these strains)
44
outline the Mechanism of the association between HPV and cervical cancer
* Human papilloma virus (HPV) infect epithelial cells
* It inhibits tumour suppressor mechanisms (p53) which protects genome as it delays the cell cycle allowing for repair mechanisms- Mutations not repaired – transformation can occur
* Cells proliferate beyond normal regulatory mechanisms
45
why has there been an improvement in HPV cervical cancer
Vaccination, screening and surgery
46
why may the vaccine for HPV not prevent cervical cancer incidence
• Due to latency period of 5-15 years
47
how can hept b and hept c infection be passed on
• Blood, blood contaminated instruments, mother to child
48
what do hept b and hept c viruses cause
liver cirrhosis (scarring, fibrosis and loss of function) and hepatocellular carcinoma
Both infections have long incubation period (may be clinically silent)
49
what is the mechanism of hept c
inhibits activation of dendritic cells (knock on effect: lack of specific T-cells and impaired viral clearance)
HCV mutates rapidly
• HBV and HCV promote Treg cell activity
50
how can Monoclonal antibodies be used to target specific antigens in cancers
- Target cancer molecules: killing of B-cells in lymphoma (Rituximab)
- Target host immune system to boost performance: checkpoint inhibitor drugs (e.g. ipilmumab)
- identify size and location of tumour (conjugated to radioactive isotope)
51
what are the types of bone marrow transplants-
allogenic- HLA matched from donor (non-self)
autologous (self)
52
outline whether allogenic or autologous BMPTs ones may cause graft versus host reaction (GVHR) and which ones give graft versus leukaemia (GVL) effect - are these effects good?
allogenic (non self)
- may get GVHR and you can die lol :)
- BUT also get beneficial GVL- donor cells attack leukaemia cells too
autologous (self)
- don't get GVHD :)
- also don't get GVL :(
- higher relapse rate :(
53
what do New BMT regimens involving therapeutic use of donor T-cells promote
- Promote GVL effect
- Give donor T-cell primed to attack the cancer
- Replace stem cells (reconstruction of haemopoiesis) but also giving T cells to kill any of the cancerous cells which cause the problem
54
outline An example of adoptive T-cell therapy
Adoptive t- cell therapy KILLS leukaemia cells – adding to cells to benefit patient
Chimeric antigen receptors – modified t-cell receptors to target tumour cells and kill them - confer antitumor specificity to a patient's lymphocytes
55
outline Importance of the mouth in terms of immune responses
• Proximal region of the both the alimentary and respiratory tracts
• Principle point of entry of pathogens (along with the nose) -70% enter by this route
• Common anatomical features with other mucosal surfaces (which are…list)
- Mouth part of mucosal immune system
• They are all lined by glandular epithelia bathed in secretions e.g. saliva
• But the mouth has a unique anatomy…. Teeth!
56
what are Elements of the immune response in the mouth
salivary glands
- salivary IgA-adaptive immune response to streptococci
- Lactoferrin- binds iron which is a co-factor for many bacteria
- Mucin - highly glycosylated protein, coaggregates bacteria- can also allow Anchorage of antibodies and protective coat where there is lack of keratin in the oral epithelium
Epithelial cells
- make AMPs and TLRs
- exfoliate, shedding of top layer is defence as bacteria will be removed and swallowed
```
GCF
- antibodies
- complement
- cellular elements- neutrophils and AMPs
(plaque fluid is not a defence)
```
57
what is the Importance of saliva in the oral immune response
• The mouth is well-served by salivary glands
– Major (parotid; submandibular; sublingual)
– Minor (many and widely distributed)
• Note flow characteristics: bacteria must attach or multiply in fluid phase
• Saliva has many components dedicated to host defences
• Note these often act in complexes (heterotypic association)
• They also must act in different phases of the mouth: soluble phase; mucosal surface; tooth surface; plaque biofilm
58
outline the salivary host defences
```
AMPs distrust bacterial membranes
Adhesive protei- agglutination
Lactoferrin- binds iron
Cyastin- protease inhibitor
Lysozyme
```
59
how is the gingival crevicular fluid an Interface with the systemic immune defences
Junction between teeth and gingiva particularly susceptible to infection from plaque biofilm- junctional epithelial is very thin and has hight turn over
GCF a serum exudate originating in the gingival crevice
Carries locally produced elements of innate and adaptive immunity
60
how is the Oral mucosa a host defence
* Barrier function of keratinocytes (the major cell of the epithelium of the masticatory mucosa)
* Desquamation of the oral epithelium- shedding which removes bacteria stuck to this surface
* Epithelial cell products e.g. anti-microbial peptides
* Mucous layer
61
what are the Phase 1: Natural host defence- what do they all mediate
Inactivation, clearance, prevention of attachment and prevention of invasion
- Saliva and its components
- Integrity of oral mucosa
- Acquired enamel pellicle- layer of proteins from saliva, prevents bacterial attachment
- Commensal bacteria -competition for nutrients and niches (dysbiosis may occur)
- Vascularity- lots blood vessels (host defence)
62
what are the Phase 2: Innate immunity in the tissue-inflammatory responses- what do they all do
Containment, prevention of spread and clearance
* Strong innate= strong adaptive
* Elements of the GCF and the gingival tissues
* Macrophages-phagocytosis and signalling
* Neutrophils-phagocytosis (lots of blood vessels allow this)
* Complement-opsonisation and killing
* In health plaque confined to gingival margin
* If plaque accumulates and moves into the crevice inflammatory responses ensue
63
what is the role of Neutrophils in the gingiva- what cytokine are they recruited by
* Neutrophils pass through the gingiva in response to commensal bacteria (via IL-8). This is the physiological inflammation similar to that observed in the gut.
* IL-8 and therefore neutrophil emigration is substantially up-regulated in response to pathogenic microflora e.g. in periodontitis
* Individual with neutrophil defects have an Increased susceptibility to periodontitis (Neutropenia- more oral infections)
64
Compare and contrast the immune responses of the oral cavity (junctional and sulcular epithelium- JSE) with intestine
in the intestine there is a high microbial burden and bacteria are in suspension. in JSE microbial burden variable and bacteria in biofilm
INT- thick mucus
JSE- no mucin (its in oral mucosa but not crevice)
```
INT has (S)-IgA (main mucosal antibody)
SJE- has IgG instead (main circulatory antibody)
```
INT- epithelium has tight junction so difficult to get inflammation
JE- highly pours
INT- inflammation stable
JSE- damaging inflammation
65
outline a summary of the Phases of the oral immune response
Phase 1: Natural host defences in the oral cavity
- Inactivation, clearance, prevention of attachment and prevention of invasion
Phase 2: Innate immunity in the tissue-inflammatory responses
- Containment, prevention of spread and clearance
Phase 3: Adaptive immunity - Enhancement of innate immunity and provision of specific long-lasting immunity
66
what is Salivary IgA (S-IgA) involved in
• Adaptive immune response – very important!
• Secreted by salivary gland (along with S-IgM)
- Prevents initiation of plaque
• Inhibition of adherence & penetration; neutralisation of viruses and virulence factors;
• Form complexes with mucins -very effective in bacterial clearance
- Mucins allow antibodies to stick to epithelium and then to be swallowed
• IgA1 subclass against proteins, IgA2 against polysaccharides
67
outline the Production of Salivary IgA from antigens in the GI tract
* Mucosal immune system is linked
* Antigens and bacteria infect mouth from mother
* Swallow and they go into peyers patches and antigen transported across the M cells in the gut . antigens presented on dendrtic cells in peyers patch
* Activate t cells, which will help B cells
* B cells move to all mucosal sites
* Develop into plasma cells which secrete IgA
* IgA comes from plasma cells (derived from gut) in salivary glands
68
what structural property of IgA allows it to be secreted
• IgA is a DIMERr- joined together by a J chain which allows it to be secreted
69
outline The signalling phases in periodontal pathogenesis
MAMPS/ PAMPS- signal innate immunity
PRR recognise signalling via TLR
signals macrophages, dendritic cells, epithelial cells, fibrobaslts which signal cytokines, chemokine, AMPs and prostanoids (this is a cycle)
secondary phase: broadcast
70
outline some PAMPS
```
LPS
lipotechoic acid
proteases
DNA
short chain fatty acids
```
71
outline the role of IL-1b in immune responses (good)
* IL-1b similar to TNF (if we inhibit TNF we inhibit inflammation e.g. in rheumatoid arthritis)
* IL1 activates neutrophils, macropahes, capillary endothelial cells and the adaptive immune response (dendritic cells- antigen presentation) - all this is good
its bad if chronic
72
outline the role of IL-1b in
| inflammation and tissue destruction in periodontal disease (bad) - what other cells are activated
response is bad when chronic e.g. persistence of plaque-
chronic activation of IL1 (high in PD) which activated other cells:
- such as osteoclasts (bone loss) ,
- fibroblasts release MMPs which remove tissue and protein(mainly collagen) – PDL is made of lots of collagen so this is problem
- neutrophils stimulation
73
why is Doxycycline an
| adjunct in PD
inhibit MMPs which destroy collagen
74
how does Infection with pathogenic viruses diminishes pre-existing immunity to other pathogens
* Measles virus infects leukocytes causing immune suppression (to infections you are immune too)
* The long-term effects of measles infection (increased morbidity and mortality) are well established
* Measles now known to reduce immune memory against many pathogens e.g. influenza, herpesviruses etc.
* Disrupts pathogen recognition
* Measles induces immune amnesia, an effect not found in MMR vaccinated children- lost previous experience in terms of vaccination
* Measles makes you more vulnerable to other infections
75
outlinee Examples of Immunological diagnosis and therapy
* ELISA
* Immunofluorescence direct and indirect
* FACS
* Monoclonal antibodies
* Cytokines
* N.B. vaccination/immunosuppression
76
outline The unique specificity of antibodies is the basis for detection of specific proteins in the lab
* Antibodies will recognise specific proteins
* Binds specific molecules to detect them
* Fc- crystalline fragment – binds to receptors in cells
* constant regions differs between classes
* variable regions- very diverse
77
outline the Production of specific antibodies
Conventional immunisation- mixed specificity and limited quantity
Monoclonal antibodies- - limitless supply of antibodies of a single specificity (homogenous) with very good quality.
Recombinant antibodies- limitless and single specificty but DNA technology used to make better
- humanise antibodies
- Manipulate IgG genes,
- make mice immunoglobulin into human immunoglobulin
78
outline the Production of monoclonal antibodies for use in clinical assays and therapeutically
immunise mouse with antigen and extract cells from it (from spleen)
fuse with cancer cell (myeloma) - tumour of b cells NOT same and myeloid
this means they become immortal can live for lots of generations and maintain their properties (hybridoma cells – cells which ultimately produce the monoclonal antibodies)
grow in drug containing medium where myeloma die and b-cells die - important antibody cells survive
select for antigen specific hybridoma
clone the selected hybridoma cells
79
How are immunodeficiencies diagnosed?
Measure levels of IgG, IgM, IgA and IgE – used in diagnosis and therapy
Lymphocyte count
Flow cytometry to characterise deficiency
If you suspect someone has immunodeficiency, then count their Ig levels, and WBC levels)
80
what does flow cephalometry allow for
uses monoclonal antibodies to identify/numeral WBC specific cell types in a mixed population.
FC allows you to enumerate the number of cells that are expressing a specific protein on its surface
The 1% of cells claiming to express IgM and TCR are likely to be false positives as there are no cells which express both.
81
outline the Diagnosis of X-linked agammaglobulinaemia using flow cytometry
what is expressed on all T-cells
* Patient with XLA has very little CD19 – marker for B cells
* Cells in the box on the lower left express neither CD3 or CD19 – neutrophils, monocytes or eosinophils
CD3 expressed on all T-cells
CD4 Is just on helper tcells
CD8 is just on cytotoix
82
what are the 2 ways autoimmune diseases analysed/diagnosed?
• Physiological dysfunction- e.g. deficiency in endocrine or musculature issues (autoimmune diseases often treat in endocronine clinic as hormone replacement needed)
E.g. ptosis (eyelids droop over eyes) in myasthenia gravis (treated by neostigmine)
E.g. hyperthyroidism in Graves’ disease (autoantibodies to TSH receptor producing too much thyroid hormone tachycardia/sweaty palms/jumpy)
• Autoantibody detection use ELISA (below)
83
what does ELISA (enzyme linked immunosorbent assay) detect
* Detect serum autoantibodies and antigens
| * Use a spectrophotometer
84
what does Immunofluorescence detect for and what we looking for in the case of an autoimmune disease
Can look at tissue sections
uses Fluorescently labelled antibodies
In the case of autoimmune disease, you are looking for antibodies attached to the tissues (not ones that are free in the blood).
85
outline how Indirect immunofluorescence can be used for biopsy material in good pastures sydrome
autoantibody detection-
| immune complexes deposited in the glomeruli causing inflammation and damage
86
How are allergies diagnosed- what are the controls
• Intradermal skin test – place suspect antigen into skin
* Saline – negative control (for injections)
* Histamine – positive control - shows what result we would expect in an allergic reaction.
There to mimic the hypersensitivity reaction (mast cells secrete when degranulate)
* Put suspected antigen in (positive/negative result)
* Looking for wheal (swelling) and flare (red area)
87
what are some agents used to manipualte the immune response
hormones
antibodies
adjuvants
cytokine- cytokine signalling pathway inhibitors e.g. Tofacitinib for rheumatoid arthritis
88
what are therapeutic monoclonal antibodies
• Anything with -mab at the end
89
how can the follwing be treated with monoclonal antibodies :
- rheumatoid arthiritis
- chronic asthma
- lymphoma
RA- anti-TNFa can dampen down joint inflammation
asthma- Anti igE- removes igE required for mass cells degranulation
lymphoma- antiCD20 can get rid of b-cells
90
what are the Anti-inflammatory effects of anti-TNFα in rheumatoid arthritis
RA is systemic – it affects joint and all body too!- activation of liver proteins – this antibody supresses inflammation caused by this
91
what is C reactive protein is an indication of
protein produce in the liver, used as an indicator of peripheral cytokines (mediating inflammtion)
92
what is the action of Action of Omalizumab (therapeutic and experimental)
Therapeutic anti-IgE
• Anti-IgE prevents mast cell from acquiring cell-surface IgE (cant bind to its receptor)
• So when they encountered the environmental antigen that trigger asthma Mast cell cannot be activated as all the IgE is mopped up.
Experimental anti-IgE:
•Anti-IgE cross-links IgE bound to receptor and activates mast-cell deregulation
•Inflammatory response
