Immunology Flashcards
1
Q
A 35 year old woman presents with persistent itchy wheels for the last 2 months. She noticed that when this is at its worst, she also has a fever and feels generally unwell. After an acute attack, she has bruising and post-inflammatory residual pigmentation at the site of the itching.
A
Chronic Urticaria
Type II (IgG) note acute uritcaria is Type I
Persitent Itchy wheels
Angiodema can occue
Increased ESR
TX: Responds well to histamine. If it does not respond it is not Chronic Urticaria.
Q) WHy not acute? Acute urticaria lasts less than 6 weeks.
2
Q
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction.
She has longstanding hypertension and received a renal transplant two years previously. She has no history of a_llergic disease_. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
What is the condition?
A
Acute angioedema
3
Q
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
What is the condition?
A
Acute angioedema. This woman has angioedema of the tongue, without symptoms suggestive of a generalised allergic reaction. Isolated angioedema may be allergic in origin, but 94% of cases angioedema presenting to A&E are drug induced and the majority of these are associated with ACE inhibitors (eg captopril).
4
Q
A 19 year old male presents to A&E with increasing breathlessness. On examination his BP is 90/55 mmHg and his respiratory rate is 28/min. He shows you a generalised red itchy skin rash, and examination of his chest reveals bilateral inspiratory and expiratory wheezes throughout.
A
IM adrenaline 1 mL of 1:1000
5
Q
A 35 year old woman presents with a two day history of a red itchy skin rash which started soon after her first scuba-diving lesson. She is otherwise well.
What is it? How would you treat it?
A
PO antihistamines -acute urticaria type I
6
Q
A 22 year old woman is presents with this intermittently itchy and desquamating skin rash which is unresponsive to antihistamines
A
None of the above
7
Q
A 40 year old man complains of loss of smell with nasal itching and discharge over 4 weeks. He also describes morning sneezing. He is otherwise in good health. On examination his nasal mucosa are swollen and hyperaemic.
A
PO antihistamines
Allergic
Rhinitis
8
Q
This 45 year old woman presents to A&E with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
A
IM adrenaline 0.5 mL of 1:1000
Elevate Legs
100% Oyxgen
- IM Adrenaline 500 mcg
- Inhaled bronchodilators
- Hydrocortisone 100mg IV,
- Chlorphenamine 10mg IV,
- IV Fluids, Seek Help
9
Q
Cytokines exerting an anti-viral effect
A
infereron
10
Q
Immunoglobulin dimer
What other types of IgG do you knw?
A
IgA:
IgA: mucosal areas, saliva, tears, breast milk
IgE: allergy – histamine release from mast cells
IgG: can cross from placenta to foetus
IgM: on surface of B cells
Immature B cells express only IgM.
Human normal Ig has a half life of 18 days
11
Q
MHC associated with Th1 cells
A
Major histocompatibility complex class 2
Reminder – Immune Recognition
T-Cells (TCs) recognise antigen with
MHCs on APCs
B-Cells (BCs) can recognise just
antigen
12
Q
Acts on hepatocytes to induce synthesis of acute phase proteins in response to bacterial infection (complement activation)
A
IL6
13
Q
Arise in the first few days after infection and are important in defence against viruses and tumors
A
Natural Killer cells
14
Q
MHC associated with Th2 cells
A
Major histocompatability complex class I
15
Q
MHC associated with cytotoxic T cells
A
Major histocompatability complex class 1
16
Q
Along with IgD, is one of the first immunoglobulins expressed on B cells before they undergo antibody class switching
A
IgM
17
Q
The most abundant (in terms of g/L) immunoglobulin in normal plasma
A
IgG
18
Q
Deficiencies in this predispose to SLE
A
Classical complement pathway: C2 and C4 measured by CH 50
19
Q
Kostmanns syndrome is a congenital deficiency of which component of the immune system?
A
Kostmann Syndrome-no pus
- Severe congenital neutropenia
- Mainly Autosomal Recessive (HAX-1)
- 1-2 cases per million
Patients have infections shortly after birth
Diagnosis based on chronicallLlow Neutrophil count and bone marrow test showing an arrest of neutrophil precursor maturation
- Treatment includes G-CSF, prophylactic antibiotics and BMT if G-CSF is ineffective
20
Q
Which infection is most common as a consequence of B cell deficiency?
A
Bacterial
21
Q
Meningococcal infections are quite common as a result of which deficiency of the component of the immune system?
A
Complement
22
Q
Produced by the liver, when triggered, enzymatically activate other proteins in a biological cascade and are important in innate and antibody mediated immune response?
Which interleukin acts on the liver to activate complement?
A
Complement
Answer: IL-6
23
Q
A complete deficiency in this molecule is associated with recurrent respiratory and gastrointestinal infections.
A
Selective IgA Deficiency
Most common defiency
Reccurent gastro and resp infections
Affects 1 in 600 Caucasians
70% are asymptomatic
24
Q
Leukocyte Adhesion Deficiency is characterised by a very high count in which of the white cells? What other findings would be?
Whcih molecule is dysfunctional in this syndrome?
What would be the presentation?
A
Neutrophils
B2-integrin
A) Deleyed umbilical cord separation, and high neutrophil count.
25
Which **crucial enzyme** is vital for the oxidative killing of **intracellular** micro-organisms?
**NADPH oxidoase**
26
Which complement factor is an important **chemotaxic agent**?
**C3a**
27
What is the **functional complement test** used to investigate **the classical pathway?**
CH50
28
**Graves Disease**
antibodies
treatment
type of hypersentivity reaction
**Type II –** Antibody mediated
**anti-TSH**
**carbimazole**
29
SLE
Type Hypersnsitivity
antibodies present (6)
D.
* **Type III** – Immune complex mediated
* ANA
* antiSM
* anti dsDNA
* **Beta-2-glycoprotein**
* **Anti-cardiolipin**
* Lupus anti-coagucalant.
30
**Rheumathoid artheritis**
**type of reaction**
* Type **III** and Type **IV**
* **type IV -** delayed hypsensitivity **_T-cell_** mediated
* **Type III** - **IgM** antibodies vs **Fc** region of **IgG.**
RF (+)
* **Anti-CCP** (95% specific)
* **Increased ESR**
31
**Asthma**
**type of reaction**
**pathology involved**
* non-immune mediated
* SM cell hyperplasia
* excess mucus
* **inflammation**=Group of immune-mediated lung disorders caused by **intense/prolonged exposure** to inhaled **ORGANIC antigens** → widespread ALVEOLAR inflammation (cf asthma = airway inflammation).
32
**Type 1 diabetes**
**Type IV** – **T-cell mediated**
Pancreatic **Beta Cell proteins.** (Glutamate Decarboxylase GAD)
**Insulitis**
**Beta Cell Destruction**
33
Immune thrombocytopaenic purpura
How does it present?
What sort of reaction it is?
Where antibodies bind to?
* **Type II** - abnomral **I**_gG_**** and **_IgA_**
* Generally asymptomatic illnes following **_viral infection_** or immunisation in children **_less than \<10_** years and **_adults\>65_**
* Petchial Rash
* Low platelets is the only finding. In adults you need to do bone marrow biopsy to exclude myoplastic syndrome.
* Glycoprotein **_IIb/IIIa_** on platelets
* Bruising/ Bleeding (Purpura)
* **_Anti-Platelet Antibody_**
* _**Steroids, IVIG**,_ Anti-D Antibody, splenectomy
34
**/ABO hemolytic transfusion reaction. What type of reaction is it?**
**Type II** – Antibody mediated
35
**Hepatitis C** associated membranoproliferative **glomerulonephritis type I**
## Footnote
**Q) Type of immune reaction it is**
**Q)**
* **Type III** – **Immune complex mediated**
* _**Mixed Essential** **Cryoglobuinaemia**_
* gM against IgG +/- **hepatitis C** antigens
Joint pain, splenomegaly, skin, nerve and kidney involvement. Associated with Hep C.
A mixture of clinical and biopsies
NSAIDs, Corticosteroids and plasmaphoresis
36
G**_OO_**dpasture's syndrome?
1) What type of reaction is it?
2) How does it present?
3)
**Type II** – **Antibody mediated**
a) of pulmonary renal syndrome: **pulmonary haemorrhage** with **rapidly progressive glomerulonephritis. so hemoptysis and blood in the pee.**
**b) Remeber always two things in GOODPASTURE**
**c) Linear smooth IF staining og IgG deposit in BM.**
37
**A 32yr old woman** complains of **fatiguability** in many muscles and double vision. She is thought to be at risk of other **_autoimmune diseases_** as she has a family history of various **autoimmune diseases** and herself has **autoimmune** **hypothyroidism.** Her thyroid function is normal because she is well replaced with **thyroxine.** What might be causing her muscle weakness?
**What type of reaction it is?**
**Myaesthenia gravis**
**Type II** – Antibody mediated
38
Recurent bacteria infections **3 months** after birth.
What is the model of inheritance?
What is **lacking**?
Which gene is mutated?
****_B_**ruton’s Agammaglobulinemia**
* X-Linked Tyrosine Kinase Defect
* Mutation in BTK gene
* Failed production of _mature **B-Cells** and antibodies. T cells would be present_
* No antibodies
* Symptoms after 3-6 months
39
**DiGeorge’s Syndrome**
**1) how does ir present?**
**2) what sort of infections is he predisposed to?**
**_DiGeorge’s Syndrome (CATCH 22)_**
**__**Impaired development of the **3rd** and **4th** pharyngeal pouches (oesophagus, thymus, heart)
**22q11.2 deletion** – **75% sporadic**
**Low set ears, cleft lip and palate**
**Low calcium** *\>* seizures
** Susceptibility _to viral infection_
V. low numbers of mature T cells**
**(absent thymus)
Treated by thymus transplant**
Treatment of T cell deficiencies: infection prophylaxis, Ig replacement if necessary, specific other treatments.
40
**_Infants present_** with recurrent infections, **_failure to thrive_**, and _**chronic diarrhoea**._
1) what is it?
2) what is lacking?
3) what is model of inheritance?
4)
**IL-2**
* **Severe Combined Immune Deficiency (SCID)**
* **lymphoid tissue precursors IL-2 receptor**
* **pattern of inheritence**
* **Failure to thrive and _persistent diarrhoea_ & _early infant death_**
* Low or **normal B cell numbers,** reduced **T cells**, low antibodies
BMT only established treatment
45% are X-linked
41
**_Small platelet size_ is the one consistent feature. _Eczema_ and _reccurent infections_ are common.**
Q) What is it?
Q) What is the model of inheritence?
Q) What does it increases the risk of?
Wiskott-Aldrich Syndrome
X-linked condition characterised by thrombocytopenia.
Small platelet size is the one consistent feature.
Eczema and recurrent infections are common.
There is an increased risk of haematological malignancies.
42
1) Failure to thrive by the age of three months
2) The child presents with jaundice and hepatosplenomegaly
2) Which Immunoglubins will be low?
3) Which Immunoglobulin will be normal?
**Bare Lymphocyte Syndrome**:
**Bare lymphocyte syndrome**
Absent expression of **HLA molecules** within **thymus**
lymphocytes fail to develop
** Type 1:** MHC I absent - ↓CD8 cells
** Type 2: MHC II absent - ↓CD4 cells**
BLS type 2 more common:
**B-cell** class switch needs **CD4** therefore less **I_gA_** and **_IgG_** made.
IgM would be normal
* Associated with Sclerosing Cholangitis
Unwell by 3 months of age
43
**Boys** present first years of life with
recurrent bacterial infections esp.
**Pneumocystis carinii & failure to thrive**
**What is the mechanism?**
**Hyper IgM**
**Activated T-cell**s cannot interact with B-cells to class switch
Therefore **B-Cells** cannot make **IgA** and **IgG,** but elevated **IgM**
44
A **25 year old woman** comes to her **GP about family planning**. She is worried because she had an older brother who died before she was born and her grandmother lost two children which she things were both boys. Her GO thinks there may be a genetic disorder in her **family affecting the IL-2 receptor.** If correct she has a 50% of inheriting the trait from her mother and being a carrier herself. And there would be a 50% chance of passing it to her children. If inherited, her daughters would be carriers and her sons would require treatment which is usually a bone marrow transplant but gene therapy is sometimes used.
**Severe Combined Immune Deficiency (SCID)**
* Defects in lymphoid precursors e.g. Adenosine Deaminase Gene; **IL-2 receptor**
* Recurrent infections
* Failure to thrive and persistent diarrhoea & early infant death
* Low or normal **B cell numbers**, **reduced T cells,** low antibodies
* BMT only established treatment
* 45% are X-linked
45
**A jaundiced** 8 month old child presents with failure to thrive, and a history of **recurrent infections (viral, bacterial and fungal).** On examination there is **hepatomegally** and blood tests show a raised alk phos and low CD4 count. A defect is found in the proteins that regulate **MHC Class II transcription.**
BARE LYMPHOCYTE SYNDROME
46
Patient X’s GP writes inquiring about whether to **vaccinate**. The patient suffers from recurrent respiratory tract infections and has been diagnosed with one of the **B-cell maturation defects**. For which one is immunisation still effective?
Selective **IgA** Deficiency
Most **common** defiency
Reccurent **gastro** and **resp infections**
Affects 1 in 600 Caucasians
70% are asymptomatic
47
For which disorder would a bone marrow transplant be unhelpful but **a thymic transplant** may provide a cure?
DIGEORGE CATCH-22
48
A difference in this between host and recipient is the main cause of transplant rejection
HLA
49
Along with anti-HLA antibodies, the most important screen to ensure a match before transplantation
ABO blood type
50
Risk factor for chronic allograft rejection
Hypertension
Hyperlipidaemia
51
Transplanting an ABO incompatible kidney will result in ___ rejection
1) Why
2) what would be the consequence?
3) How it could be prevented?
**Hyperacute**
**Preformed Ab** which activates complement
**Thrombosis and Necrosis**
**Prevention:** Crossmatch (ABO groups) HLA-matching
52
You are about to see a gentelman following **kidney transplant developng _vascullitis_ following _2 weeks of his transplant._**
**1) What is it?**
**2) Wha is the mechanism?**
**2) What is the treatment?**
Acute organ transplant
**B cell producion and antibody attacking the blood vessls leading to vasculitis**
**The treatment would be to remove the antibody = plasmapharesis and immunospuression**
53
**Treatment of _acute cell_ mediated rejection**
**what is the pathology involved?**
**How does it work?**
High dose corticosteroids
CD4 activating a Type IV
reaction
Cellular
Infiltrate
T-Cell
Immunosuppression
54
The **3 most** important **HLA types** to screen for in renal transplantation when matching donor and recipient, in order of importance
HLA DR \> B \> A
55
The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance
B.
HLA DR \> B \> A
56
Lymphocyte that responds to foreign **HLA DR** types
P.
CD4+ T cells
57
Lymphocyte that responds to foreign **HLA A t**ypes
CD8+ T cells
58
Prevents **DNA** replication especially of **T cells?**
## Footnote
**How it can prevent replication?**
**What is it used for?**
Mycophenolate Myofeti
Prevents Guanine Synthesis
Transplantation
Autoiimune
Vascullitis
59
Causes a transient increase in neutrophil count
Prednisolone
60
**Monoclonal** antibodies inhibiting the actions of **cytokines**
Infliximab
61
Can cause **_gingival hypertrophy_** as a side effect
how does it work?
****_C_**iclosporin**
**inhibits **_C_**alceurin**
**whihc normally activates the transcription of Il-2, thus reduces T cell proliferation**
62
Administration of this may boost the immune system
Immunoglobulins
63
prevent **lymphocyte** proliferation by inhibiting **DNA replication,** affects B cells more than T cells.
Q) What is it used for?
**Cycloophoshamide.** Both **mycophenolate mofetil** and **cyclophosphamide** prevent lymphocyte proliferation by inhibiting DNA replication. However, **mycophenolate mofetil** is more **selective for T cells**, whereas **cycophosphamide *affects B cells more than T cells.***
Note that **cyclophosphamide** at high doses will affect all cells with a high turnover.
**b) connective tissue disease, vascullitis**
Bone marrow **suppresion**, **infection**, **malignancy**
64
***_Corticosteroids,_** as well as being directly lymphotoxic in high doses, icell via which other mechanism?*
***_What else does it do?_***
* Blocking cytokine synthesis
* Inhibits PLA12, hence blocks archaidonic acids
* Reduces prostaglandin synthesis
* Inhibits phagocyte trafficing
* Phagocytocis and relase of proteolytic enzymes
65
The antiproliferative drug cyclophosphamide inhibits lymphocyte proliferation by which mechanism?
Inhibition of DNA synthesis
66
**Plasmapheresis** may be indicated in which conditions?
**Goodpasture’s syndrome-** removal of anti-GBM antibody
**Myasthenia Gravis -** nACHR antibodies
**Vascular Transplant rejection** - hyperacute but aapears 6 days afterwards
67
Example of a vaccine that should NOT be given to a severely immunocompromised patient.
POLIO
MMR BOY
68
A condition where **antigen desensitization** therapy **may be indicated.**
**Bee/wasp venom allergy**
69
The main side effect of this drug is diabetogenic drug
How does it work?
is also used in the treatment of other **T cell-mediated diseases** such as **eczema (for which** it is applied to the skin in a medicated ointment), severe **refractory uveitis** after bone marrow transplants, exacerbations of minimal change disease, and the **skin condition vitiligo.**
**T**acrolimus
Inhibits calceurin, which normally inhibits synthsis of IL-2 thus T lymphocyte proliferation.
How does it work?
70
Main SE Predinolone
Transistent neutrophilia
Hypertension
Glaucoma
71
**Antimetabolite agent**
Metabolised by liver to 6 mercaptopurine,
blocks d**e novo _purine_ (eg adenine, guanine)**
synthesis – prevents replication of DNA,
preferentially inhibits T cell activation &
proliferation
## Footnote
**What is its main side effetc?**
**_Azathropine_**
_**Bone** **marrow** **supression**_
72
**inhibits dihydrofolate reductase (DHFR),** therefore **decreases DNA synthesis**
**Methotrexate**
**B**one **M**arrow **S**upression
Pnemottis, Pulmonary Fibrosis, Cirhiosis
73
What is **conjugate vaccine vaccine?**
**Pneumococcal vaccine**
**A conjugate vaccine** is created by covalently attaching **a poor antigen** to a **strong antigen** thereby eliciting **a stronger** immunological response **to the poor antigen.** Most commonly, the **poor antigen is a polysaccharide** that is attached to **strong protein antigen.**
74
A live attenuated viral vaccine
Live attenuated: BCG, MMR,
typhoid
75
**Inactivated** preparations of the **bacteria**
**Whole cell typhoid vaccine**
* Yellow fever
* BCG
* Typhoid
76
Extracts of or **detoxified exotoxin** product by **a micro-organism.**
**tetanus vaccine**
**Diphtheria, Tetanus**
77
**Vaccine t**hat is made using recombinant **DNA technology.**
**Hepatitis B** virus vaccine
78
An antigen assembled in a multimeric form and saponin that provokes a strong serum antibody response.
Immunostimulatory complexes (ISCOMS)
79
**The general name for a compound which increases the immune response without altering its specificity.**
Adjuvant
80
A vaccine given only to sero-negative women
**Rubella vaccine**
**Management**
* women normally have their immunity checked before becoming pregnant
* rubella immunity is routinely checked at the booking visit. If the no immunity is demonstrated pregnant women need to keep away from people who might have rubella
* non-immune mothers should be offered the MMR vaccination in the post-natal period
81
**A central cytokine involved in immunological central memory**
**IL2**
82
Which type of vaccine generally achieves immunisation with a single dose and is not suitable for pregnant and immunocompromised patients?
A.
Live attenuated
83
Which vaccine is usually given to children at 12-15 months?
MMR vaccine
84
**_Which vaccine_** is normally given to infants under the **_age of 13 month_**_s_ in the form of **three doses** at monthly intervals to protect against an infection that has symptoms similar to **meningitis** and predominantly occurs in children **_\< 5 years?_**
Haemophilus influenzae **type b** vaccine
85
**Conjugate vaccine** routinely given to neonates in the UK.
H. influenzae B
86
**Agent** used in humans that promotes a **predominantly antibody** response through the release of **Il-4 t**hat primes **naïve B-cells**.
**Alum**
87
**Diploid cell vaccine** containing inactivated virus given before or after exposure to those considered at risk.
Rabies
88
Live attenuated vaccine that is no longer given as standard in the UK since the rates of reverse mutation are higher than those of active disease.
Polio (Sabin)
89
Subunit vaccine given to the elderly and immunocompromised
H.
## Footnote
Influenza
90
Which is recommended in all individuals over 65 years of age?
Influenza vaccine
91
Sterility in adult males may occur if a particular vaccine is not administered. Which one is it?
Mumps vaccine
92
Which vaccine is given to the mother to prevent congenital c**ardiac defects, eye lesions** (particularly cataracts), **microcephaly**, **mental handicap** and deafness of her newborn baby?
**Rubella vaccine**
93
Which group of patients are at particularly high risk of **pneumococcal disease**, and are the major group that need **Pneumovax revaccination** after 5 years.
patients \> 54
patients\<65 with chronic conditions such as chronic lung disease
diabetes
94
**Live, attenuated vaccines:**
**Measles, mumps, rubella** (German measles), polio (Sabin vaccine), chicken pox, yellow fever, BCG
**Adv:** Produces a strong immune response so can provide life-long immunity with 1–2 doses.
**Disadv:** Not safe for people with compromised immune systems. Needs refrigeration to stay potent
95
**2) Inactivated 'killed' vaccines**
_**C**holera, **F**lu, hepatitis **A**, **R**abies, **P**olio (Salk vaccine)_
Remember **SCAR** (_**S**alk vaccine_, _**C**holera_, _Hep **A**,_ _**R**abies)_
**Adv:** Safe for people with compromised immune systems. Easily stored and transported; does not require refrigeration.
**Disadv**: Usually requires booster shots every few years to remain effective.
96
Subunit Vaccines, example, adv and dis
This is a **vaccine** made of **recombinant protein.**
**Adv:**
Disadv:
***Hepatitis B***
Lower chance of adverse reaction.
Research can be time-consuming and difficult.
97
**Conjugate Vaccines**
Haemophilus influenzae B (or Hib) and pneumococcal vaccine
**Adv**:Safe for people with immune compromised systems
**Disadv:** Usually requires booster shots every few years to remain effective.
98
A water-in-oil emulsion containing mycobacterial cell wall components that could be used to increase the immune response of a vaccine.
Freund's adjuvant
99
This type of vaccine activates all phases of the immune response, has the most durable immunity and is the most cross-reactive.
Live attenuated
100
This test measures the immune response to the BCG vaccine.
Mantoux
101
This form of immunity is induced by vaccination.
Active immunity
102
**Monocytes and Macrophages**
Monocytes are produced in bone marrow, circulate in blood and migrate to tissues where they differentiate to macrophages
**Liver**
**Kidney**
**Bone**
**Spleen**
**Lung**
**Neural tissue**
**Connective tissue**
**Skin**
**Joints**
**Capable of presenting processed antigen to T cells**
Kupffer cell
Mesangial cell
Osteoclast
Sinusoidal lining cell
Alveolar macrophage
Microglia
Histiocyte
Langerhans cell
Macrophage like synoviocytes
103
Thic cytokin deficiency may cause susceptibility to mycobacterial infections
IL12, IL12R, IFNg or IFNg R
104
Recurrent infections with high neutrophil count on FBC but **no abscess formation**
Leukocyte adhesion deficiency
105
Recurrent infections with **_hepatosplenomegaly**_ and _**abnormal dihydrorhodamine test_**
Which infections are patietns predisposed to? \>
**C**hronic **g**ranulomatous **d**isease
**PLACESS**
**P**seudomonas
**L**isteria
**A**spergillius
**C**andidia
**E**.Coli
**S**taph Aureus
**S**erratia
106
•Recurrent infections shortly after birth with **n**o **n**eutrophils on FBC
•Kostma**nn** syndrome
107
**Infection** with atypical mycobacterium. **Normal FBC**
I**FN gamma receptor deficiency, IL-12 = cytokine deficency**
108
•Membranoproliferative nephritis and bacterial infections
**•C3 deficiency** with presence of a nephritic factor
109
**•Meningococcus meningitis** with family history of sibling dying of same condition aged 6
**•C9 deficiency**
110
•Severe childhood onset **SLE** with normal levels of **C3** and **C4**
**•C1q** deficiency
111
**Recurrent infections** when receiving chemotherapy but previously well. This pathway has two names
**_MBL_** pathway deficency
**_Leptin_** Pathway Deficency
112
**Antibodies** to **Thyroglobulin** and **Thyroperoxidase**
**Hashimoto**
113
Shared epitope in RA
114
P gingivalis
C. Expresses PADI enzymes capable of deiminating arginine to form citrullinated proteins
115
**_Anti-CCP_** antibody, where does it bind to? What is specific for?
Binds to **_citrullinated_** proteins and has ~95% specificity for development of **_rheumatoid arthritis_**
116
Anti-CCP antibody or ACPA
D. Binds to citrullinated proteins and has ~95% specificity for development of rheumatoid arthritis
117
Where does Rheumatoid factor bind to?
Binds to Fc region of IgG
118
Molecular Patterns. Where to they occur? 'Lump-Bumby' versus smooth linear pattern?
119
**Antibodies** may occur in **SLE**
* ANA(+)
* anti-SM
* dsDNA
* anti-Ro, anti-La, U1RNP (specled)
* **anti-cardiolipin**
* **anti-phospholipid**
120
How to differentiate between active and inactive SLE disease?
The activity of SLE is relaiting to the complement deficiencies.
In the active disease, the C4 will be reduced, wheres in severe active disease both C3 and C4 will be monitore
121
Two major types of **_anti-phospholipid antibodies_**
* **cardiolipin**
* **B2 glycoprotein**
* **lupus anti-coagucalant**
122
ANA staining is an important prognostic indicator in
XXXXX
**Systemic Scleriosis**
123
Which antibodies are **ENA (+)**?
anti-**Ro**, **La, Sm, SNP**
**SCL70**
**CREST**
124
A. Screening test for a connective tissue disease
**ANA**
125
Sometimes positive in patients with **idopathic inflammatory myopathy** particularly if they **have interstitial lung disease**
* Anti-Jo-1 (t-RNA synthetase)
* Also positive in dermatomyosistis and polymyositis
126
This is very important:
Which antibodies are a ) organ specific
b) ANA positive
c) ANCA associatted vascullitis
**_b) all starting with S_**
- **Sy**stemic scleriosis
- **Sj**orgen Syndrome
- **SL**E
- **De**rmatomyositis/polymyositis
127
What is **human Immunoglobulin**?
1. Prepared from **pools of \>1000 donors**
2. Contains preformed **IgG** antibody to a wide range of unspecified organisms
128
What is **S**pecific **I**mmunoglobulin?
Human immunoglobulin used for **_post-exposure prophylaxis_** (passive immunisation)
Derived **from plasma donors** with **high titres of**
**_IgG_** antibodies to specific pathogens
**_•Hepatitis B_** immunoglobulin
**_•Tetanus_** immunoglobulin
**_•Rabies_** immunoglobulin
**_•Varicella Zoster_** immunoglobulin
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What is the clincal use of **cytokines**?
* **_Interferon alpha_** -HEP C, HEP B, Kaposi Sarcoma
* _**Interferon beta** -_ Relapsing MS
* **_Interferon gamma_** - Chronic granulamtous Disease
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B. Part of treatment for Hepatitis C
IFN alpha
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X-linked SCID treatment
Blood Marrow Transplant
132
Chronic Granulotamous Disease Treatment
IFN-gamma
133
**EBV-specific** CD8 T cells
A. **Post-transplant** lymphoproliferative disorder
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**Human normal immunoglobulin**
C. X linked **hyper IgM** syndrome
135
**G. What are two treatment options for Metastatic melanoma ?**
* **Blocking immune checkpoints**
* **_Ipilimumab_** – antibody specific for **CTLA4** – blocks immune checkpoint and allows T
cell activation; indications: **advanced melanoma**
_ **Pembrolizumab/Nivolumab**_ – antibody specific fo**r PD-1 -** blocks immune checkpoint
and allows **T cell activation**; indications: advanced melanoma
136
**When would you use the V**aricella **z**oster **i**mmunoglobulin?
Immunosuppressed seronegative individual **after chicken pox exposure**
137
Indications for **plasmapheresis**
* **Severe antibody-mediated disease**
Goodpastures syndrome
**•Anti-glomerular basement membrane antibodies**
Severe acute myasthenia gravis
**•Anti-acetyl choline receptor antibodies**
Severe vascular rejection
**•Antibodies directed at donor HLA molecules**
138
Cyclophosphamide SE
Infertility
139
Azathropine SE
Neutropenia particularly if TPMT is low
140
Cyclosporin SE
Hypertension
141
**M**ycophenolate **M**ofetil SE
Progressive **Multifocal Leukoencephalopathy**
142
Antibody specific for **CD25** which inhibits T cell activation and is used to prevent rejection
**B**asiliximab (**Anti-IL2** receptor) CD25 is the alpha chain of IL-2
143
Inhibits T-cell activation and is effective at Rheumatoid Artheritis (CTLA4-Ig fusion protein)
**Abatacept**
144
**Depletes Mature B** cells and is effective in treatment of B cell l**rheumatoid arthritis**ymphomas and
**R**ituximab (Anti-CD20)
145
**_Inhibtis_** T-cell **_migration_** (integrin and rollling prevention) but can be used in **_relapsing/remitting MS_**
**Natalizumab** (Anti-a4 integrin)
146
**anti-IL-6** receptor. Inhibits function of l**ymphoid** and **myloid cells**
and is used in management of RA and Castelman Disease
**Tocilizumab** (Anti-IL6 receptor)
147
B. Treatment options include inhibition
## Footnote
**IL12/23:**
**TNF alpha:**
**IL17A:**
**For which conditions these medications can be used for?**
**Psoriasis**
**IL12/23: Ustekinumab**
**TNF alpha: Entarecept,**
**IL17A: Secunimab**
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C. Treatment options include inhibition of **_IL6_**, **_TNF alpha_** and **_depletion B cells_**
**_Rheumatoid arthritis:_**
* **anti-IL** (6) Toclizumab
* **TNF-alpha** (infliximab)
* **B-cells Depletion:** Rituximab
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**_A. Treatment options include inhibition of RANK ligand_**
## Footnote
**a) name the condition**
**2) name the medication**
**a) Osteoporosis**
**b) Densumab**
150
•Severe recurrent infections from **_3 months,CD4_** and **_CD8_** T cells absent, B cell present but immature phenotype, **some IgM** present, IgA and IgG absent. Normal facial features and cardiac echocardiogram
•X-linked SCID
151
•Young adult with chronic infection with **Mycobacterium marinum**
**•IFN gamma receptor deficiency**
152
•Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, normal IgM, borderline low IgA and IgG
•DiGeorge syndrome CATCH22
153
6 month baby with two recent serious bacterial infections. **_T cells present_** _– but only **CD8+ population.**_ B cells present. **IgM** present bu_t **IgG** absent_
**B**are **L**ymphocyte **S**yndrome
154
Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE
•Common variable immunodeficiency
155
Recurrent bacterial infections in a child, episode of **pneumocystis pneumonia**, T and B cells present, high IgM, absent IgA and IgG
•**X linked hyper IgM syndrome** due to CD40ligand mutation
156
1 year old boy. Recurrent bacterial infections. **CD4 and CD8 T cells present. B cells absent, IgG, IgA, IgM absent**
•Bruton’s X linked **hypo**gamma**globulinaemia**
157
Recurrent respiratory tract infections, absent IgA, normal IgM and IgG
•IgA deficiency
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A. Single gene mutation involving MEFV and affecting the inflammasome complex, resulting in recurrent episodes of serositis
B. +++ **production of IL-1 → _attacks of fever and inflammation of serosal_**
**_surfaces (pleura, peritoneum, synovium)_**
**Familial Mediterranean Fever:**
## Footnote
**FAMILIAL AMYLOIDOSIS**
● Several kinds, all rare
● Most common = Familial Mediterranean Fever (AR)
● **+++ production of IL-1** → attacks of fever and inflammation of serosal
surfaces (pleura, peritoneum, synovium)
**●** Associated gene encodes pyrin
**●** AA amyloid, predominant renal deposition
**Clinical features: caused by amyloid deposits in various organs:
(1) KIDNEY: nephrotic syndrome = most common presentation
(2) HEART: conduction defects, heart failure, cardiomegaly
(3) LIVER/SPLEEN: hepatosplenomegaly
(4) TONGUE: macroglossia in 10%
(5) NEUROPATHIES: incl carpal tunnel**
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C. Single gene mutation involving **FOXp3** resulting in abnormality o**f T reg cells.**
**X- linked** so affects boys only
**IPEX (**immune dysregulation, polyendocrinopathy, enteropathy, X linked)
**IPEX syndrome**
* Immune dysregulation, Polyendocrinopathy, Enteropathy and X-linked inheritanc syndrome + autoimmune diseases
* Eczematous dermatitis, nail dystrophy and autoimmune skin conditions such as alopecia universalis and bullous pemphigoid
* Most affected children die within the first 2 years of life.
160
B. Mutation within the Fas pathway associated with lymphocytosis, lymphomas and auto-immune cytopenias
Auto-immune lymphoproliferative syndrome (ALPS)
161
B. Mixed pattern auto-inflammatory / auto-immune disease with \>90% heritability that **results in inflammation t**ypically involving t**he sacro-iliac joints** and **responds to TNF alpha antagonists**
**Which allelle is it associated with?**
Ankylosing spondylitis
Ankylosing spondylitis HLA B27
162
A. Polygenic auto-inflammatory disease. ~30% patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria.
Crohn’s disease
163
Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids
**Giant cell arteritis**
164
–Involves IgE and mast cells
•Eg Anaphylaxis, Atopic asthma
•Type I Anaphylactic hypersensitivity
165
–Involves Ab binding to cells with complement mediated host cell destruction (or inhibition/activation or receptor signalling)
•Eg Goodpasture disease, Graves disease
•Type II Cytotoxic hypersensitivity
166
–Involves deposition of Ab/Ag complexes in tissue
•Eg SLE, Serum sickness
•Type III Immune complex hypersensitivity
167
Involves T cells and cytokines: Eg Diabetes, Contact dermatitis
**Type IV:** Delayed hypersensitivity
168
SLE
type III
169
Eczema
Type I hypersensitivity
170
Type IV hypersensitivity examples
Multiple sclerosis
Type I Diabetes
Rheumatoid Artheritis
Contact Dermitis
Mantoux Tes
Crohn's
171
Goodpasture disease
Type II hypersensitivity
172
Managment of Anaphylaxis
•**Oxygen by mask**
–Improve oxygen delivery
**•Adrenalin im (0.5mg for adult and may repeat)**
–Acts on B2 adrenergic receptors to constrict arterial smooth muscle
* Increases blood pressure
* Llimits vascular leakage
* Bronchodilator
* Intravenous anti-histamines (10mg Chlorpheniramine)
–Acts to oppose the effects of mast-cell derived histamine
- Nebulised bronchodilators
- Improve oxygen delivery through bronchial dilatatio
- Intravenous corticosteroids (Hydrocortisone 200mgs
- Systemic anti-inflammatory agent.
- Effect takes about 30minutes to start, and does not peak for several hours.
- Important in preventing rebound anaphylaxi
- Intravenous fluids
- Increase circulating blood volume and therefore increase blood pressure
173
Latex has two types of sensitivity reactions
Type (I) Acute
Type (IV) Deleyed - Chronic Dermitis
174
175
What are the tests uused to describe the severity of SLE?
C4 and C3 (C4 first affected)
dsDNA
ESR
176
What is the name of this condition?
serum sicness
177
**•Presenting complaint – recurrent infections**
* 3 year old Caucasian **Male**
* **Weight and height dropping from 50th** centile to **10th centile**
**•First infection aged 3 months**
–Cellulitis of gluteal region
–Responded to antibiotics
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•64 year old lady is seen in A&E after slipping and injuring her left hip when getting out of the bath
**•Other problems**
* –Persistent back pain and generalised lethargy for 12 months
* –Three episodes of pneumococcal pneumonia in last 2 years
* –Post-menopausal – on HRT
- **High IgG**
- monoclonal band on the electroporesis
movement
–Clinically anaemic
Monoclonal band in gamma region, subsequently shown to **be IgG lambda**
**Urine electophoresis:** Free light chains detected - Bence Jones proteins
179
Q: What is the most common allergy in humans?
Allergic Rhinitis
180
## Footnote
Q1) What are the receptors required for the HIV entry?
Q2) What are the co-receptors required for the HIV entry to target cells.
* CD4 molecule/Ag is the Receptor for HIV-1.
* Most infecting strains of HIV-1 use co-receptor molecules (CCR5 and CXCR4) in addition to CD4 to enter target cells.
181
Indications for specific IgE testing
* Patients who can’t stop anti-histamine
* Patients with dermatographis
* Patients with extensive eczema
* History of anaphylaxis
* Borderline/equivocal skin prick test results
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* **Primary adjuvant utilized in humans.** Antigens are adsorbed to alum so acts
as means of slowly releasing antigen. Activates Gr1+ cells to produce IL-4, helps
prime naïve B cells (mainly antibody mediated response). Generally safe and mild
* **Activates TLRs on APCs stimulating expression of costimulatory molecules.**
* **Water-in-oil emulsion containing mycobacterial cell wall components.** Mainly for animals, painful in humans (not used clinically)
* **Cell-mediated immune response** and **humoral response.** With saponin results in strong serum antibody response.
* In individuals with **Hep-B-Sag** in order to get them to seroconvert
* ALUMN
* CPG
* Complete Freund’s adjuvant:
* ISCOMS (Immune Stimulating Complex):
* Interleukin 2
183
Episodic neutropenia occuring every ***3 weeks*** and lastiing several days.
Caused by mutation in the *ELA1 gene* (neutrophil elastase)
Treated with the mutations in the ELA1 gene
184
The most severe form of SCID
Results in absolute deficiency of neutrophils, lymphpcytes, macrophages, platlets
Reticular Dysgenesis
185
What is the atopic triad?
What type of reaction is it?
Eczema, asthma and hay fever
186
187
guanine synthesis
mycophenolate mofeyteil
188
Patients with SLE have a cross reactive antibody towards the platlets and red blood cells. Look for the signs of ITP or AIHA.
189
the first cytokine to be relased in response to allergen
IL-12
190
Pattern of antibodies in dermatomyositis
specled
191
what molecule is central to the pathogenesis of central systemic scleriosis? CREST
TGF-beta
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