Immunodeficiencies Flashcards

(101 cards)

1
Q

Warning signs for adult primary immunodeficiency disorders

A

4 or more infections requiring anitbiotics within one year - otitis, bronchtiis, sinusitis, penumonia
Recurring infections or infection requiring prologned antibiotic therapy
2 or more severe bacterial infections - osteomyelitis, menignitis, speticaemia, cellulitos
2 or more radiologically proven pneumonia within 3 yrars
INfection w unusual localisation or pathogen
PID in family
FTT in paeds

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1
Q

Ass features primary immunodeficiency

A

Atypical eczema
Chronic diarrhoea
FTT
Telangiectasia - ataxic
Hepatosplenomegaly
Endocrinopathy
Chronic osteomyeltisi/deep seated abscess
Mouth ulcers
AI
FH

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2
Q

Scondary antibody deficiency causes

A

Etrems of age
Urameia
Toxins
Acute and chronic infections
Burns - lose skin
Myotonic dystrophy
Protein-losing states
Lymphangiectasia

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3
Q

Examination for immunodeficiencies

A

Weight and heigh t- FTT
Structural damage from infections w look or scan eg ears, lungs, sinuses
AI features - vitiligo, alopecia, goitre
Absent tonsils - XLA
lymphadenopathy
Hepatosplaenomegaly
Other potnetial diagnositc features - telagniectasia, eczema

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4
Q

Features of immunodeficiencies

A

Increased susceptibility to infection
Susceptibility to cancers
Increased AI diseases
What deficiency is

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5
Q

First investigations for immunodeficiencies

A

FBC - individual white cells not just overall count
IgG, IgA, IgM
Serum electrophoresis
Lymphocyte surface markers - T cell (CD4/CD8), B cells, NK cells, B cell subclasses - naive, memory, class switched
Specific antibody responses

Later - genetics, complement AP100/CH100, neutrophil burst assay, lymphocyte prolif assay

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6
Q

Complement investigation

A

AP100/CH100

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7
Q

Neutrophil investigation

A

Neutrophil burst assays - can go oxidative burst to kill pathogens?

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8
Q

Lymphocyte investigations

A

Lymphocyte proliferation assays - if can proliferate on exposure to pathogen

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9
Q

Humoral deficiency presentations

A

Antibody deficiency
Recurrent sinopulmonary infections
Chronic GI infections
Bactaraemias
Meningitis
Como pathogens incl encapsulated bacteria

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10
Q

Common pathogens causing humoral deficiency

A

S.pnuemoniae, H.influenzae type B, N.meningitidis
Giardia, cryptosporidia, campylobacter

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11
Q

Conditions causing humoral (antibody) deficiency

A

Selective IgA def
Common variable ID
Specific AB D
XLA
X lymphoprolif disease
Hyper IgM syndrome
Hyper IgE syndroe

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12
Q

What immunodef is most common

A

Hypogammaglobulunaemia

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13
Q

Size of Igs

A

IgM - pentameter
IgA - dimer
IgG - monomer

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14
Q

What Ig deficient if losing through gut or kidney

A

IgG - monomer - smallest

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15
Q

When is low IgM noraml

A

Older age/normal variation
V low in lymphoprolif disease

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16
Q

How assess functioning of Igs

A

Response to vaccines
baseline serology
give pneumovax vaccine
assess antibody level weeks later
Use pneumococcal IgG antibodies

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17
Q

Which vaccines are easier to make an immune repsonse to

A

Proetin
Prevenar can be used if necessary for antibody respone testing but elss helpul than pneumova

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18
Q

How diagnose sepcific antibody deficiency

A

Pneomovax vaccination - below 4 x greater antibodyes 4-6 weeks later than baseline
Check at 6 months in case of loss

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19
Q

What measure if use conjugated pneumococcal vaccine to test for specific antibody deficinecy

A

Number of serotypes immune system responded to -
normal = >7 >0.35mcg/ml

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20
Q

Causes of reduced production of immunoglobulins

A

Primary ID - CVID, XLA - genetic
Medications
Malignancy - multiple myeloma, lymphoma, leukaemia
Systemic illness - sev infection -> bone marrow supression

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21
Q

Medications causing reduced production of immunoglobulins

A

Prednisolone
Azathioprine
Methotrexate
Rituximab
Anti-epileptics
Antipsychotics

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22
Q

Causes o increased loss of Igs

A

Nephrotic syndrome
Coeliac disease,
IBD
Peritonneal dialysis

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23
Q

How diagnoise CVID

A

> 4 years old
Low IgG
Low IgA+/- IgM
Poor or absent repsonse to immunisation
Exclusion of other immunodeficiencies

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24
Treating low IgG levels
Reverse underlying cause Give prophylactic antibiotics Vaccination - avoid live vaccines! Replace immunoglobulin - IV or subcut, ONLY IgG GIVEN
25
What immunoglobulin can be replaced by IV/SC
IgG
26
Dosage and goal of IgG replacement
0.4g/kg/month Target trough level IgG>6g/L - shoudnt go below
27
Prophylacitv antibiotics in CVID
Azithromycin Co-trimoxazole
28
How do cell mediated immunodeficiencies present
Infections with ordinarily 'benigng' viruses, opportunistic IC pathogens, fungi
29
Common pathogens causing infection in cell mediated immunodeficiency
CMV, EBV, herpes virus Mycobacteria Fungo - candida, cryptococcus, oneumocystisis
30
Diseases casuing cell mediated immunodeficiency
SCID Chronic mucutaneous candidiasis Di george syndrome Wiskott aldrich syndrome
31
What cells are affected in SCID
T cells always +/- B cells +/- NK cells
32
Genetic causes of chronic mucocutaneous candidiasis
AIRE deficiency, Dectin-1, CARD-9
33
What causes di george syndrome
22q11.2 deletion -> absent thymus -> T cell lymphopaenia
34
Deficiencies of innate immunity
Phagocyte disorders NK cell defects Cytokine disorders Toll-like receptors Complement deficiency
35
Complement functions
Ability to lyse cells Ability to opsonize particles (easier to engulf) When activated -> inflammatory proteins
36
What complement pathway is antidbody indpendent vs depndent
Classical = antibody triggeres Alternate = pathogen triggers - antibody independent
37
Complemetn oathways outcome
C3 -> membrane attack complex -> transmembrane pore -> cell lysis
38
Classical complement pathway deficiency what causes
C1,C2,C4 def -> systemic AI disease incl SLE
39
What bacteria does classical complement deficiency increase risk infection of
Encapsulated bacteria eg S.pneumonia, H.influenzae, Neissieria meningitidis
40
What causes alternate pathway deficneicny
Properdin deficiency - regulates C3 and C5 convertases - if deficient rapud decay of convertases, less efficeient, cant do pathway
41
Features of alternate pathway deficinecy
X linked Recurrent severe bacterial infection in childhood eg meningitis due to neissieria meningitisides - ifmore than one = red flag
42
What causes lectin oathway deficiency
Mannan binding lectin
43
Features of lectin pathway deficiency
Increased risk encapsulated bacteria < 2 years Asymptomatuc in adults - adaptive immune system overtakes In CF - worse prognosis
44
Presentation of C3 deficiency - common pathwya deficiency
Life threatening recurrent infections starting in early childhood Particuarly susceptible to encapsulated organsisnsm Ass w immune complex disease - 1/4 - renal disease, AI disease eg SLE
45
MA complex deficiencies what is it
Deficiency of any terminal componenets complement -> susceptibility to gram negative bateria esp neisseria species
46
What does CD59 deficiency cause pathology
CD59 is inhibitory protein for MAC complex to our own cells If deficient -> lysis of cells
47
What condition is caused by CD59 deficiency due to aquired PIGA gene mutation
Paroxysmal nocturnal haematuria
48
PNH presentation
Red urine first thing in morning- Haemolysis as urine condensed overnight red most obvious in morning Anemia - tired, breathless Increased thrombosis incidence Rare and life threatening
49
What does Radial immunodifusion assays CH200/AP100 do
Classical pathway complement - CH100 Alternative pathway complemetn - AP100
50
Results of CH100/AP100 normal
Clear zone formed around well - patient serum has lysed foreign RBC in agar
51
What results indicate alternate vs classical pathway deficiency AP100/CH100
Lysis in CH100 assay w no lysis AP100 = alternate deficiency Lysis in AP100 w no lyssi CH100 = classical deficiency
52
What results in AP100/CH100 suggest terminal componenet deficiency
No lysis in AP100 or CH100
53
Investigations for complement deficiency
AP100/CH100 If abnormal total lysis assay -> C3/C4 complement measuring Genetics
54
How does neutrophil/grnaulocyte deficiency present
Recurrent invasive skin and soft tissue infetions Focal abscesses requiring incision and drainage esp in llvier/lung Granulomas/granulomatous disease
55
Common pathogens in neutrophil deficiency
S.aureus, gram negative bacilli Aspergillus, nocardia
56
Priamry immunodeficiencies causing granulocyte/neutropgil deficiency
Chronic granulomatous disease Leukocyte adhesion afects Chediak Higashi dyndrome
57
Key features of chronic granulomatous disease
Early presentation Skin abscess and deep seated lung, lymph, liver and bone infections Linked to IBD
58
pathogens seen in chronic granulomatous disease
Catalase + bacteria - staph, kelbsiella, serratia and burkholderia Fungal - aspergillus
59
Neutrophil oxidative burst assay
Stimulate neutrophils to oxidative burst - if cant do so problem Healthy control - peak will shift on graph Patient - peak stays the same
60
Carrier of neurtophil deficiency
50% of cells can undergo oxidative burst, 50% cant X linked or autosomal recessive, can pass on
61
Treatment for CGD
Prophylactic antibiotics and antifungals Interferon gamma Bone marrow traansplantion ?Gene therapy?
62
Bcterial pathogens seen in combined T and B cell deficiencies
Intracellular mycobacteria Salmonella spp
63
Fungal in combined T and B cell deficiencies
Candida spp Aspergillus spp Cryptococcus neoformans
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Protozoal
Pneumocystitis carinii Toxoplasma gondii Cryptosporisia
65
Viral causes of infection in combines T and B cell deficiencies
RSV, parainfluenzae GI - rotavirus, norovirus CMV, adenovirus
66
What would cryptosporidium infection suggest about immunodeficiency cause
CD40 ligand deficinecy =hyper IgM syndrome and liver dysfunction
67
CGD disease what infection think about
Fungal disease in pneumonia or pneumonitis Deep seated abscess eg in liver - S.aureus
68
Pathogen idenitificanion in immunodeficiency
Disease Srology - materangl Ig, Ab deficiency PCR Timeline Which site - imaging Tissue biopsy Which strain/serotype - vaccine strain Is it a contaminant Dual oathology - more than one
69
Treatment for fungal infection in extremely neutrophil deficient patient
Leukocyte orneutrophil infusions acutely
70
What prevent or treatment for RSV in SCID
Palivuzumba - anti RSV monoclonal antibody
71
Immunosupressive drugs
Steroids Ciclosporin Sirolimus Monoclonals - anakinra, infliximab
72
Curative therapy for immunodeficiency
Haematopoietic stem cell transplant Gene therapy - addition, editing, stem cells, target cells - uses viral vectors Thymic transplant Enzyme replacement therapy - adenosine diamentes or DASKD - not long term but to prep for trnasplant
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How bone marrow donor taken
GSF harvesting stem cells -> mobilise stem cells into peripheral bood and mkae easier Otherwsie from bone marrow
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Why need chemo if bone arrow in receiver patient transplant
Make space for donor cells in their bone marrow
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SCID prognosis
<12 months if no ucrative therapy
76
How does bone marrow transplantation improve survival
<5 years = same as avg population >5 years still v good survival rate even prophylactic antibiotics only 50% survival by late 20s early 30s
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What matching need for bone marrow transplant
Sibling ideal Half identical/hablo - parent
78
Risk in using habloidentical n=bone marrow transplant and how prevent
graft vs host disease T cell depletion
79
T cell depletion how done
CD3/TCRalpha-beta/CD19 depletion- TCR gmma T cells left- antileukaemia OR replete marrow w post infusion cyclophosphamide
80
Can you use a non matched donor of bone in transplant
Yes if do T cell depletion
81
Gene addition therapy how works
Bone marrow cells removed and parent cells of immune system isolated Cells infected w virus w corrected gene -> intracellular, faulty gene replaced with corrective viral gene Cells returned -> 2 weeks later immune system protected
82
Problem with gene addition therapy
Can stimulate an oncogene -> clonal proliferation of cell -> leaukaemia or myelodysplasia Now use safer retroviral vectors w self inactivation built in
83
What conditions is thymus transplantation used in
Di george Charge syndroe
84
Why is early diagnosis of primary ID important
older patients -> organ damage from mulitple infections
85
Major comorbidities form XLA
Lung diseases and bronchiectasis
86
FEATURES OF PRIMARY DEFICIENCY
lifelong history of infections Younger age of onset Concurrent AI or malignancy FH
87
FEATURES OF SECONDARY ID
Use of chemo or immunosupressants Radiation Malignancy Protein loss from gut or kindeys Malnourishment HIV
88
Bloods in immunodeficiency
FBC U+Es LFTs B12 Thyrod function HBA1c Serum immunoglobulins and electrophoress HIV lymphocyte subsets Sepcific viral antibodies and bactreria eg varicella, MMR, tetanus, pneumococcus
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Imaging for structural damage immunod
HRCT - bronchiectasis, thymoma, malignancy
90
What test need to do before give azithromycin
ECG - QT interval 2 sputum cultures to rule out acid fast bacilli which could be masked by azithromycin
91
Tests done before give IVIG
Screening for HIV, hep B and hep C - cant test after as affected Also test isohaemmaglutinins IgM against blood group antigens
92
Basic panel in flow cytometry
Number of total lymphocytes T cells B cells NK cells CD4 and CD8 T cells
93
What is cellular toxicity of NK cells and cytotoxic T cells a feature of
Haemophagocytic lymhohistiocytosis - uncontrolled proliferation of activated lymphocytes and histiocytes
94
Which diseases have high polyclonal IgM levels
Liver diseases and other inflammatory conditions
95
What causes raised IgA
Elderly Chronic infection Inflammation
96
What can cause high polyclonal IgG
Reactive state Sjrogens syndrome HIV
97
Why need electrophoresis in Igs interpretation
Ig level cant tell whether its monoclonal or polyclonal increase - electrophoresus can detect paraproteins and differentiate
98
>50,000 IgE what is it
Hyper IgE syndrome
99
What is immunofixation
Stained paraprotiens for heavy or light chain and run electrophoresis
100
Conditions causing overactive complemetn
C3G glomerulonephropathy Atypical haemolytic uraemic syndrome