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Pathology Year 5 > Immunology > Flashcards

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.

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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

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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).

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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

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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

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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

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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

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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
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9
Q

Cytokines exerting an anti-viral effect

A

infereron

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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

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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

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12
Q

Acts on hepatocytes to induce synthesis of acute phase proteins in response to bacterial infection (complement activation)

A

IL6

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13
Q

Arise in the first few days after infection and are important in defence against viruses and tumors

A

Natural Killer cells

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14
Q

MHC associated with Th2 cells

A

Major histocompatability complex class I

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15
Q

MHC associated with cytotoxic T cells

A

Major histocompatability complex class 1

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16
Q

Along with IgD, is one of the first immunoglobulins expressed on B cells before they undergo antibody class switching

A

IgM

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17
Q

The most abundant (in terms of g/L) immunoglobulin in normal plasma

A

IgG

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18
Q

Deficiencies in this predispose to SLE

A

Classical complement pathway: C2 and C4 measured by CH 50

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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
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20
Q

Which infection is most common as a consequence of B cell deficiency?

A

Bacterial

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21
Q

Meningococcal infections are quite common as a result of which deficiency of the component of the immune system?

A

Complement

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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

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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

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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.

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25
Q

Which crucial enzyme is vital for the oxidative killing of intracellular micro-organisms?

A

NADPH oxidoase

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26
Q

Which complement factor is an important chemotaxic agent?

A

C3a

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27
Q

What is the functional complement test used to investigate the classical pathway?

A

CH50

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28
Q

Graves Disease

antibodies

treatment

type of hypersentivity reaction

A

Type II – Antibody mediated

anti-TSH

carbimazole

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29
Q

SLE

Type Hypersnsitivity

antibodies present (6)

A

D.

  • Type III – Immune complex mediated
  • ANA
  • antiSM
  • anti dsDNA
  • Beta-2-glycoprotein
  • Anti-cardiolipin
  • Lupus anti-coagucalant.
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30
Q

Rheumathoid artheritis

type of reaction

A
  • 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
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31
Q

Asthma

type of reaction

pathology involved

A
  • 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).
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32
Q

Type 1 diabetes

A

Type IV – T-cell mediated

Pancreatic Beta Cell proteins. (Glutamate Decarboxylase GAD)

Insulitis

Beta Cell Destruction

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33
Q

Immune thrombocytopaenic purpura

How does it present?

What sort of reaction it is?

Where antibodies bind to?

A
  • Type II - abnomral IgG** 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
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34
Q

/ABO hemolytic transfusion reaction. What type of reaction is it?

A

Type II – Antibody mediated

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35
Q

Hepatitis C associated membranoproliferative glomerulonephritis type I

Q) Type of immune reaction it is

Q)

A
  • 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

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36
Q

GOOdpasture’s syndrome?

1) What type of reaction is it?
2) How does it present?

3)

A

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.

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37
Q

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?

A

Myaesthenia gravis

Type II – Antibody mediated

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38
Q

Recurent bacteria infections 3 months after birth.

What is the model of inheritance?

What is lacking?

Which gene is mutated?

A

Bruton’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
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39
Q

DiGeorge’s Syndrome

1) how does ir present?

2) what sort of infections is he predisposed to?

A

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.

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40
Q

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)

A

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

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41
Q

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?

A

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.

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42
Q

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?

A

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

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43
Q

Boys present first years of life with

recurrent bacterial infections esp.

Pneumocystis carinii & failure to thrive

What is the mechanism?

A

Hyper IgM

Activated T-cells cannot interact with B-cells to class switch

􏰂Therefore B-Cells cannot make IgA and IgG, but elevated IgM

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44
Q

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.

A

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
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45
Q

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.

A

BARE LYMPHOCYTE SYNDROME

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46
Q

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?

A

Selective IgA Deficiency

􏰂 Most common defiency

􏰂 Reccurent gastro and resp infections

􏰂 Affects 1 in 600 Caucasians

􏰂 70% are asymptomatic

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47
Q

For which disorder would a bone marrow transplant be unhelpful but a thymic transplant may provide a cure?

A

DIGEORGE CATCH-22

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48
Q

A difference in this between host and recipient is the main cause of transplant rejection

A

HLA

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49
Q

Along with anti-HLA antibodies, the most important screen to ensure a match before transplantation

A

ABO blood type

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50
Q

Risk factor for chronic allograft rejection

A

Hypertension

Hyperlipidaemia

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51
Q

Transplanting an ABO incompatible kidney will result in ___ rejection

1) Why
2) what would be the consequence?
3) How it could be prevented?

A

Hyperacute

Preformed Ab which activates complement

Thrombosis and Necrosis

Prevention: Crossmatch (ABO groups) HLA-matching

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52
Q

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?

A

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

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53
Q

Treatment of acute cell mediated rejection

what is the pathology involved?

How does it work?

A

High dose corticosteroids

CD4 activating a Type IV
reaction
Cellular
Infiltrate
T-Cell
Immunosuppression

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54
Q

The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance

A

HLA DR > B > A

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55
Q

The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance

A

B.

HLA DR > B > A

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56
Q

Lymphocyte that responds to foreign HLA DR types

A

P.

CD4+ T cells

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57
Q

Lymphocyte that responds to foreign HLA A types

A

CD8+ T cells

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58
Q

Prevents DNA replication especially of T cells?

How it can prevent replication?

What is it used for?

A

Mycophenolate Myofeti

Prevents Guanine Synthesis

Transplantation

Autoiimune

Vascullitis

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59
Q

Causes a transient increase in neutrophil count

A

Prednisolone

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60
Q

Monoclonal antibodies inhibiting the actions of cytokines

A

Infliximab

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61
Q

Can cause gingival hypertrophy as a side effect

how does it work?

A

Ciclosporin

inhibits Calceurin

whihc normally activates the transcription of Il-2, thus reduces T cell proliferation

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62
Q

Administration of this may boost the immune system

A

Immunoglobulins

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63
Q

prevent lymphocyte proliferation by inhibiting DNA replication, affects B cells more than T cells.

Q) What is it used for?

A

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

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64
Q

_Corticosteroids,_ as well as being directly lymphotoxic in high doses, icell via which other mechanism?

What else does it do?

A
  • Blocking cytokine synthesis
  • Inhibits PLA12, hence blocks archaidonic acids
  • Reduces prostaglandin synthesis
  • Inhibits phagocyte trafficing
  • Phagocytocis and relase of proteolytic enzymes
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65
Q

The antiproliferative drug cyclophosphamide inhibits lymphocyte proliferation by which mechanism?

A

Inhibition of DNA synthesis

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66
Q

Plasmapheresis may be indicated in which conditions?

A

Goodpasture’s syndrome- removal of anti-GBM antibody

Myasthenia Gravis - nACHR antibodies

Vascular Transplant rejection - hyperacute but aapears 6 days afterwards

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67
Q

Example of a vaccine that should NOT be given to a severely immunocompromised patient.

A

POLIO

MMR BOY

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68
Q

A condition where antigen desensitization therapy may be indicated.

A

Bee/wasp venom allergy

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69
Q

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.

A

Tacrolimus

Inhibits calceurin, which normally inhibits synthsis of IL-2 thus T lymphocyte proliferation.

How does it work?

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70
Q

Main SE Predinolone

A

Transistent neutrophilia

Hypertension

Glaucoma

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71
Q

Antimetabolite agent
Metabolised by liver to 6 mercaptopurine,
blocks de novo purine (eg adenine, guanine)
synthesis – prevents replication of DNA,
preferentially inhibits T cell activation &
proliferation

What is its main side effetc?

A

Azathropine

Bone marrow supression

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72
Q

inhibits dihydrofolate reductase (DHFR), therefore decreases DNA synthesis

A

Methotrexate

Bone Marrow Supression

Pnemottis, Pulmonary Fibrosis, Cirhiosis

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73
Q

What is conjugate vaccine vaccine?

A

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.

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74
Q

A live attenuated viral vaccine

A

Live attenuated: BCG, MMR,
typhoid

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75
Q

Inactivated preparations of the bacteria

A

Whole cell typhoid vaccine

  • Yellow fever
  • BCG
  • Typhoid
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76
Q

Extracts of or detoxified exotoxin product by a micro-organism.

A

tetanus vaccine

Diphtheria, Tetanus

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77
Q

Vaccine that is made using recombinant DNA technology.

A

Hepatitis B virus vaccine

78
Q

An antigen assembled in a multimeric form and saponin that provokes a strong serum antibody response.

A

Immunostimulatory complexes (ISCOMS)

79
Q

The general name for a compound which increases the immune response without altering its specificity.

A

Adjuvant

80
Q

A vaccine given only to sero-negative women

A

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
Q

A central cytokine involved in immunological central memory

A

IL2

82
Q

Which type of vaccine generally achieves immunisation with a single dose and is not suitable for pregnant and immunocompromised patients?

A

A.

Live attenuated

83
Q

Which vaccine is usually given to children at 12-15 months?

A

MMR vaccine

84
Q

Which vaccine is normally given to infants under the age of 13 months 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?

A

Haemophilus influenzae type b vaccine

85
Q

Conjugate vaccine routinely given to neonates in the UK.

A

H. influenzae B

86
Q

Agent used in humans that promotes a predominantly antibody response through the release of Il-4 that primes naïve B-cells.

A

Alum

87
Q

Diploid cell vaccine containing inactivated virus given before or after exposure to those considered at risk.

A

Rabies

88
Q

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.

A

Polio (Sabin)

89
Q

Subunit vaccine given to the elderly and immunocompromised

A

H.

Influenza

90
Q

Which is recommended in all individuals over 65 years of age?

A

Influenza vaccine

91
Q

Sterility in adult males may occur if a particular vaccine is not administered. Which one is it?

A

Mumps vaccine

92
Q

Which vaccine is given to the mother to prevent congenital cardiac defects, eye lesions (particularly cataracts), microcephaly, mental handicap and deafness of her newborn baby?

A

Rubella vaccine

93
Q

Which group of patients are at particularly high risk of pneumococcal disease, and are the major group that need Pneumovax revaccination after 5 years.

A

patients > 54

patients<65 with chronic conditions such as chronic lung disease

diabetes

94
Q

Live, attenuated vaccines:

A

​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
Q

2) Inactivated ‘killed’ vaccines

A

Cholera, Flu, hepatitis A, Rabies, Polio (Salk vaccine)

Remember SCAR (Salk vaccine, Cholera, Hep A, Rabies)

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
Q

Subunit Vaccines, example, adv and dis

This is a vaccine made of recombinant protein.

Adv:

Disadv:

A

Hepatitis B

Lower chance of adverse reaction.

Research can be time-consuming and difficult.

97
Q

Conjugate Vaccines

A

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
Q

A water-in-oil emulsion containing mycobacterial cell wall components that could be used to increase the immune response of a vaccine.

A

Freund’s adjuvant

99
Q

This type of vaccine activates all phases of the immune response, has the most durable immunity and is the most cross-reactive.

A

Live attenuated

100
Q

This test measures the immune response to the BCG vaccine.

A

Mantoux

101
Q

This form of immunity is induced by vaccination.

A

Active immunity

102
Q

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

A

Kupffer cell

Mesangial cell

Osteoclast

Sinusoidal lining cell

Alveolar macrophage

Microglia

Histiocyte

Langerhans cell

Macrophage like synoviocytes

103
Q

Thic cytokin deficiency may cause susceptibility to mycobacterial infections

A

IL12, IL12R, IFNg or IFNg R

104
Q

Recurrent infections with high neutrophil count on FBC but no abscess formation

A

Leukocyte adhesion deficiency

105
Q

Recurrent infections with hepatosplenomegaly** and **abnormal dihydrorhodamine test

Which infections are patietns predisposed to? >

A

Chronic granulomatous disease

PLACESS

Pseudomonas

Listeria

Aspergillius

Candidia

E.Coli

Staph Aureus

Serratia

106
Q

•Recurrent infections shortly after birth with no neutrophils on FBC

A

•Kostmann syndrome

107
Q

Infection with atypical mycobacterium. Normal FBC

A

IFN gamma receptor deficiency, IL-12 = cytokine deficency

108
Q

•Membranoproliferative nephritis and bacterial infections

A

•C3 deficiency with presence of a nephritic factor

109
Q

•Meningococcus meningitis with family history of sibling dying of same condition aged 6

A

•C9 deficiency

110
Q

•Severe childhood onset SLE with normal levels of C3 and C4

A

•C1q deficiency

111
Q

Recurrent infections when receiving chemotherapy but previously well. This pathway has two names

A

MBL pathway deficency

Leptin Pathway Deficency

112
Q

Antibodies to Thyroglobulin and Thyroperoxidase

A

Hashimoto

113
Q

Shared epitope in RA

A
114
Q

P gingivalis

A

C. Expresses PADI enzymes capable of deiminating arginine to form citrullinated proteins

115
Q

Anti-CCP antibody, where does it bind to? What is specific for?

A

Binds to citrullinated proteins and has ~95% specificity for development of rheumatoid arthritis

116
Q

Anti-CCP antibody or ACPA

A

D. Binds to citrullinated proteins and has ~95% specificity for development of rheumatoid arthritis

117
Q

Where does Rheumatoid factor bind to?

A

Binds to Fc region of IgG

118
Q

Molecular Patterns. Where to they occur? ‘Lump-Bumby’ versus smooth linear pattern?

A
119
Q

Antibodies may occur in SLE

A
  • ANA(+)
  • anti-SM
  • dsDNA
  • anti-Ro, anti-La, U1RNP (specled)
  • anti-cardiolipin
  • anti-phospholipid
120
Q

How to differentiate between active and inactive SLE disease?

A

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
Q

Two major types of anti-phospholipid antibodies

A
  • cardiolipin
  • B2 glycoprotein
  • lupus anti-coagucalant
122
Q

ANA staining is an important prognostic indicator in

XXXXX

A

Systemic Scleriosis

123
Q

Which antibodies are ENA (+)?

A

anti-Ro, La, Sm, SNP

SCL70

CREST

124
Q

A. Screening test for a connective tissue disease

A

ANA

125
Q

Sometimes positive in patients with idopathic inflammatory myopathy particularly if they have interstitial lung disease

A
  • Anti-Jo-1 (t-RNA synthetase)
  • Also positive in dermatomyosistis and polymyositis
126
Q

This is very important:

Which antibodies are a ) organ specific

b) ANA positive
c) ANCA associatted vascullitis

A

b) all starting with S

  • Systemic scleriosis
  • Sjorgen Syndrome
  • SLE
  • Dermatomyositis/polymyositis
127
Q

What is human Immunoglobulin?

A
  1. Prepared from pools of >1000 donors
  2. Contains preformed IgG antibody to a wide range of unspecified organisms
128
Q

What is Specific Immunoglobulin?

A

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

129
Q

What is the clincal use of cytokines?

A
  • Interferon alpha -HEP C, HEP B, Kaposi Sarcoma
  • Interferon beta - Relapsing MS
  • Interferon gamma - Chronic granulamtous Disease
130
Q

B. Part of treatment for Hepatitis C

A

IFN alpha

131
Q

X-linked SCID treatment

A

Blood Marrow Transplant

132
Q

Chronic Granulotamous Disease Treatment

A

IFN-gamma

133
Q

EBV-specific CD8 T cells

A

A. Post-transplant lymphoproliferative disorder

134
Q

Human normal immunoglobulin

A

C. X linked hyper IgM syndrome

135
Q

G. What are two treatment options for Metastatic melanoma ?

A
  • Blocking immune checkpoints
  • Ipilimumab – antibody specific for CTLA4 – blocks immune checkpoint and allows T
    cell activation; indications: advanced melanoma
    􀁸 Pembrolizumab/Nivolumab – antibody specific for PD-1 - blocks immune checkpoint
    and allows T cell activation; indications: advanced melanoma
136
Q

When would you use the Varicella zoster immunoglobulin?

A

Immunosuppressed seronegative individual after chicken pox exposure

137
Q

Indications for plasmapheresis

A
  • 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
Q

Cyclophosphamide SE

A

Infertility

139
Q

Azathropine SE

A

Neutropenia particularly if TPMT is low

140
Q

Cyclosporin SE

A

Hypertension

141
Q

Mycophenolate Mofetil SE

A

Progressive Multifocal Leukoencephalopathy

142
Q

Antibody specific for CD25 which inhibits T cell activation and is used to prevent rejection

A

Basiliximab (Anti-IL2 receptor) CD25 is the alpha chain of IL-2

143
Q

Inhibits T-cell activation and is effective at Rheumatoid Artheritis (CTLA4-Ig fusion protein)

A

Abatacept

144
Q

Depletes Mature B cells and is effective in treatment of B cell lrheumatoid arthritisymphomas and

A

Rituximab (Anti-CD20)

145
Q

Inhibtis T-cell migration (integrin and rollling prevention) but can be used in relapsing/remitting MS

A

Natalizumab (Anti-a4 integrin)

146
Q

anti-IL-6 receptor. Inhibits function of lymphoid and myloid cells

and is used in management of RA and Castelman Disease

A

Tocilizumab (Anti-IL6 receptor)

147
Q

B. Treatment options include inhibition

IL12/23:

TNF alpha:

IL17A:

For which conditions these medications can be used for?

A

Psoriasis

IL12/23: Ustekinumab

TNF alpha: Entarecept,

IL17A: Secunimab

148
Q

C. Treatment options include inhibition of IL6, TNF alpha and depletion B cells

A

Rheumatoid arthritis:

  • anti-IL (6) Toclizumab
  • TNF-alpha (infliximab)
  • B-cells Depletion: Rituximab
149
Q

A. Treatment options include inhibition of RANK ligand

a) name the condition

2) name the medication

A

a) Osteoporosis

b) Densumab

150
Q

•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

A

•X-linked SCID

151
Q

•Young adult with chronic infection with Mycobacterium marinum

A

•IFN gamma receptor deficiency

152
Q

•Recurrent infections in childhood, abnormal facial features, congenital heart disease, normal B cells, low T cells, normal IgM, borderline low IgA and IgG

A

•DiGeorge syndrome CATCH22

153
Q

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_

A

Bare Lymphocyte Syndrome

154
Q

Adult with bronchiectasis, recurrent sinusitis and development of atypical SLE

A

•Common variable immunodeficiency

155
Q

Recurrent bacterial infections in a child, episode of pneumocystis pneumonia, T and B cells present, high IgM, absent IgA and IgG

A

•X linked hyper IgM syndrome due to CD40ligand mutation

156
Q

1 year old boy. Recurrent bacterial infections. CD4 and CD8 T cells present. B cells absent, IgG, IgA, IgM absent

A

•Bruton’s X linked hypogammaglobulinaemia

157
Q

Recurrent respiratory tract infections, absent IgA, normal IgM and IgG

A

•IgA deficiency

158
Q

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)

A

Familial Mediterranean Fever:

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

159
Q

C. Single gene mutation involving FOXp3 resulting in abnormality of T reg cells.

X- linked so affects boys only

A

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
Q

B. Mutation within the Fas pathway associated with lymphocytosis, lymphomas and auto-immune cytopenias

A

Auto-immune lymphoproliferative syndrome (ALPS)

161
Q

B. Mixed pattern auto-inflammatory / auto-immune disease with >90% heritability that results in inflammation typically involving the sacro-iliac joints and responds to TNF alpha antagonists

Which allelle is it associated with?

A

Ankylosing spondylitis

Ankylosing spondylitis HLA B27

162
Q

A. Polygenic auto-inflammatory disease. ~30% patients have a mutation of CARD15 which may affect response of myeloid cells to bacteria.

A

Crohn’s disease

163
Q

Polygenic auto-inflammatory disease resulting in a large vessel vasculitis and requiring immediate treatment with high dose corticosteroids

A

Giant cell arteritis

164
Q

–Involves IgE and mast cells

•Eg Anaphylaxis, Atopic asthma

A

•Type I Anaphylactic hypersensitivity

165
Q

–Involves Ab binding to cells with complement mediated host cell destruction (or inhibition/activation or receptor signalling)

•Eg Goodpasture disease, Graves disease

A

•Type II Cytotoxic hypersensitivity

166
Q

–Involves deposition of Ab/Ag complexes in tissue

•Eg SLE, Serum sickness

A

•Type III Immune complex hypersensitivity

167
Q

Involves T cells and cytokines: Eg Diabetes, Contact dermatitis

A

Type IV: Delayed hypersensitivity

168
Q

SLE

A

type III

169
Q

Eczema

A

Type I hypersensitivity

170
Q

Type IV hypersensitivity examples

A

Multiple sclerosis

Type I Diabetes

Rheumatoid Artheritis

Contact Dermitis

Mantoux Tes

Crohn’s

171
Q

Goodpasture disease

A

Type II hypersensitivity

172
Q

Managment of Anaphylaxis

A

•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
Q

Latex has two types of sensitivity reactions

A

Type (I) Acute

Type (IV) Deleyed - Chronic Dermitis

174
Q
A
175
Q

What are the tests uused to describe the severity of SLE?

A

C4 and C3 (C4 first affected)

dsDNA

ESR

176
Q

What is the name of this condition?

A

serum sicness

177
Q

•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

A
178
Q

•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

A

Monoclonal band in gamma region, subsequently shown to be IgG lambda​

Urine electophoresis: Free light chains detected - Bence Jones proteins

179
Q

Q: What is the most common allergy in humans?

A

Allergic Rhinitis

180
Q

Q1) What are the receptors required for the HIV entry?

Q2) What are the co-receptors required for the HIV entry to target cells.

A
  • 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
Q

Indications for specific IgE testing

A
  • Patients who can’t stop anti-histamine
  • Patients with dermatographis
  • Patients with extensive eczema
  • History of anaphylaxis
  • Borderline/equivocal skin prick test results
182
Q
  • 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
A
  • ALUMN
  • CPG
  • Complete Freund’s adjuvant:
  • ISCOMS (Immune Stimulating Complex):
  • Interleukin 2
183
Q

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

A
184
Q

The most severe form of SCID

Results in absolute deficiency of neutrophils, lymphpcytes, macrophages, platlets

A

Reticular Dysgenesis

185
Q

What is the atopic triad?

What type of reaction is it?

A

Eczema, asthma and hay fever

186
Q
A
187
Q

guanine synthesis

A

mycophenolate mofeyteil

188
Q

Patients with SLE have a cross reactive antibody towards the platlets and red blood cells. Look for the signs of ITP or AIHA.

A
189
Q

the first cytokine to be relased in response to allergen

A

IL-12

190
Q

Pattern of antibodies in dermatomyositis

A

specled

191
Q

what molecule is central to the pathogenesis of central systemic scleriosis? CREST

A

TGF-beta

192
Q
A

Pathology Year 5 (5 decks)

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