Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Paediatrics RACP written exam > Immunology > Flashcards

Immunology Flashcards

1
Q

The most common type of Hyper IgM syndrome?

A

X-linked CD40 ligand deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Recurrent infections, FTT and steatorrhoea (due to pancreatic dysfunction), neutropenia - cause is?

A

Schwachman Diamond syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Presents at 6 months to 2 yrs
Low or absent B cells
IgA, IgM, IgG, IgD, IgE all low

A

X-linked agammaglobulinaemia:
Recurrent bacterial infections after 6 months when maternal immunoglobulins have gone
Unusual enterovirus infections (chronic meningoencephalitis)
Tonsils, adenoids, lymph nodes small or absent
Acquired infections with pyogenic organisms (e.g. Strep pneumo, Haemophilus influenza unless given Abs or IVIG)
Pneumocystis carinii rarely seen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Recurrent infections, short stature and an erythematous photosensitive facial rash

A

Bloom syndrome:
Autosomal recessive
Increased risk of malignancy
Erythematous photosensitive rash in the first two years of life

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Features of the innate immune system

A

Rapid but non-speciifc.

Made up of acute phase proteins, cytokines, complement, neutrophils, macrophages, NK cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Mechanism of PAMPs

A

Pathogen-associated molecular patterns
Neuts/NK cells/macrophages have receptors (pathogen-recognition receptors PRRs) that recognised PAMPs - produce cytokines - activate inflammation (CRP, complement)
Complement protein activates pathogen uptake by phagocytic cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Features of the adaptive immune system

A

Slower, but antigen-specific and development of immunological memory.
B and T cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Functions of antibodies (immunoglobulin)?

A
  • Produced by B cells
  • Neutralise toxins released by pathogens
  • Opsonise pathogens to facilitate uptake by phagocytes
  • Activate complement to cause cytolysis of pathogen
  • Direct NK cells to kill infected cells by antibody-mediated cytotoxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Function of T cells?

A
  • Kill virus-infected cells and cancer cells
  • Activate macrophages to kill intracellular organisms
  • Help with B-cell antibody synthesis and memory B cell formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Antigen presenting cell types and role

A

Macrophages and dendritic cells are APCs that activate T cells and initiate adaptive immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Dendritic cell role

A

Takes up pathogen at site of infection and becomes activated, migrates to peripheral lymphoid organs, presents antigens to naive T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Types of phagocytes

A

Monocytes/macrophages
Neutrophils
Dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the process of B cell differentiation?

A

B cells develop in the bone marrow where assembly of pre-B cell and B-cell receptors by V(D)J (variable, diversity and joining) immunoglobulin gene rearrangement occurs. Immature B cells migrate to peripheral lymphoid organs where activation by antigens leads to proliferation and differentiation into antibody-producing plasma cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the process of T cell differentiation?

A

T cell precursors migrate from the bone marrow to the thymus where V(D)J recombination of T-cell receptors occurs, and T-cell precursors develop into naive CD4 and CD8 T cells. These naive cells emigrate from thymus into peripheral lymphoid organs where activation, clonal expansion, and differentiation into effector T cells occurs upon antigen encounter (priming).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

T-cell receptor excision circles

A

Surrogate marker of recent thymic output, indicator of normal T cell development.
Excision of the intervening gene segments during V(D)J recombination of TCR generates T-cell receptor excision circles.
Used as a marker for SCID in newborn screening

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Induction of self-tolerance

A

Occurs in the cortex of the thymus.
T cells that bind strongly to self cell-surface antigens are removed.
Cells that have low affinity are removed.
Only interactions with an intermediate affinity lead to CD4 or CD8 lineage commitment (positive selection) , followed by passage into the thymic medulla and exit into the periphery.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

3 important factors of innate immunity?

A

Recognition - PAMPs (pathogen-associated molecular patterns) recognised by PRR (pathogen-recognition receptors) on macrophages, neutrophils, dendritic cells

Acute inflammatory response - pathogens engulfed and killed, secretion cytokines and chemokines to recruit more effector cells to site of infection

Induction of adaptive immune response - activated antigen presenting cells migrate to lymphoid organs where antigens are presented to B and T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the complement pathway

A

Links innate and adaptive immunity.
Classical pathway: C1q, C1r, C1s, C4, C2, C3.
Lectin pathway: mannose-binding lectin (MBL), MASP 1 and 2, C4 and C2.
Alternative pathway: factor B, factor D, properdin (upregulating factor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Examples of cytokines

A

Interleukins, interferons, tumour necrosis factor (TNF).
Mediate signalling between immune cells (c.f. chemokines which attract and recruit neuts, monocytes to site of infection, eg CXCL, CCL).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Neutrophils ingest…

A

Pyogenic bacteria and fungi

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Macrophages kill…

A

Intracellular organisms e.g. TB, toxo, legionella, salmonella

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

NK cells control…

A

Cytotoxic activity against virus- infected cells and cancer cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Complement activation causes…

A
  • Recruitment of inflamm cells and provoke inflamm response (C3a, C5a)
  • Opsonisation of pathogens and removal of immune complexes (C3b, C4b)
  • Killing by lysis of pathogens and cells (membrane attack complex: C5b, C6, C7, C8, C9)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Adaptive immune system is divided into humoral and cellular responses. What are these?

A

Humoral immunity: production of specific antibody against an invading pathogen or vaccine antigen.
Cellular immunity: T-cell dependent macrophage activation, cytotoxic T cells (CD8)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

CD8 T cells (cytotoxic T cells) work by…

A

Recognising viral peptides via MHC-I, triggers apoptosis, releases cytotoxic granules. Effector molecules: IF gamma, TNFa, perforin, granzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Naive CD4 T cells work by…

A

Recognising antigens presented by MHC-II, differentiate into Th1 and Th2 cells.
Th1: activate macrophages to kill engulfed intracellular pathogens via IF gamma, TNFa, GMCSF, CD40 ligand, Fas ligand. Cell-mediated immunity
Th2: coordinate humoral immune response with Th1 cells by inducing differentiation of naive B cells into antibody-producing plasma cells via IL 4,5,13, CD40 ligand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Immunoglobulin types and complement pathway activation

A 
IgG - classical pathway
IgM - classical pathway
IgA - alternative pathway
IgD - none
IgE - none
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Recurrent sinopulmonary infections with encapsulated bacteria suggest a defect in?

A

Antibody-mediated immunity (B-cells) because these pathogens evade phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Chronic diarrhoea, failure to thrive, malabsorption and infections with opportunistic pathogens suggest…

A

T-cell immunodeficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Recurrent infections with less virulent organisms such as viral, fungal, or protozoal infections suggests…

A

T-cell or NK-cell deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Deep-seated abscesses and infections with staph, serratia and aspergillus suggests…

A

A disorder of neutrophil function, such as CGD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Delayed separation of the umbilical cord (esp with omphalitis and later onset peridontal disease) in addition to poorly formed abscesses indicates…

A

Leucocyte adhesion deficiency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Neisserial infections or early onset autoimmunity suggests…

A

Complement defect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Timing of presentation of immunodeficiency disorders.

  • First few months of life?
  • > 3 months of life?
  • Older child?
A
  • Neutrophil defects in first few months eg congenital neutropenia, leukocyte adhesion deficiency.
  • Antibody defects and T-cell defects after first 3 months once maternal antibody levels have waned e.g. agammaglobulinaemia, SCID
  • CVID in adolescents or young adulthood, although milder phenotype of primary immunodeficiency can present later
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Immunodeficiency with congenital heart disease and hypocalcaemia?

A

DiGeorge syndrome, 22q11.2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Immunodeficiency with abnormal gait and telangectasia?

A

Ataxia-telangectasia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Immunodeficiency with atopic dermatitis?

A

Hyper-IgE syndrome, Omenn syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Immunodeficiency with eczema, easy bruising or a bleeding disorder?

A

Wiskott-Aldrich syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Absence of lymphoid tissue eg. tonsils suggests…. and increased size of lymphoid tissue suggests….

A

Absence - agammaglobulinaemia or SCID

Increased - CVID, CGD, HIV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Immunodeficiency with eczema and IBD?

A

X-linked (IPEX) syndrome - immune regulation with polyendocrinopathy and enteropathy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Describe the classical features of B cell defects

A
  • Recurrent pyogenic infections with encapsulated organisms e.g. strep pneumona, haemophilus, GAS
  • Recurrent sinopulmonary infections
  • Diarrhoea due to giardia
  • Minimal growth retardation
  • Survival to adulthood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are the features of complement defects?

A
  • Recurrent infections with encapsulated organisms e.g. strep pneumona, haemophilus, GAS
  • Recurrent Neisseria infections
  • Increase autoimmune disease
  • Severe recurrent skin or resp tract infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What are the features of T cell defects?

A
  • Recurrent infections less virulent organisms e.g. viruses, protozoa, fungal
  • Growth retardation, malabsorption, diarrhoea, FTT
  • Susceptible to GvHD from non irradiated blood
  • Fatal reactions from live vaccines
  • Increased incidence malignancy
  • Poor survival beyond infancy or early childhood
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What types of infections are associated with neutrophil defects?

A
  • Recurrent skin infections with staph, pseudomonas, E.coli, aspergillus
  • Abscesses in subcut, lymph nodes, lung, liver
  • Abscess and pneumatoceles in lungs
  • Bone and joint infections
  • Delayed separation of umbilical cord
  • Absence of pus at site of infection
  • Poor wound healing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Describe a serum sickness-like reaction?

A
  • Secondary to medications, usually cefaclor
  • Not due to immune complex formation and deposition (like true serum sickness)
  • Usually <6y
  • Can occur days - weeks after exposure
  • Fever, malaise, urticarial rash, facial swelling, joint pain and/or swelling, which is usually symmetrical
  • The rash may also atypical and has been reported as being morbilliform, scarlatiniform and erythema multiforme-like
  • Tx: stop medication, symptomatic relief
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Nijmegen breakage syndrome (NBS)

A
  • Severe microcephaly, IUGR
  • Immunodeficiency with recurrent sinopulmonary infections
  • Lymphoma susceptibility
  • Radiation hypersensitivity is found in both lymphocytes and fibroblasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

CD40 ligand deficiency

A
  • Also known as Hyper IgM
  • Associated with cryptosporidium infection
  • Risk of cholangiocarcinoma
  • Susceptible to peripheral neuroectodermal tumours of the gastrointestinal tract
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

X-linked lymphoproliferative disease (XLP)

A
  • Caused by mutations in the signalling lymphocyte activation molecule (SLAM)-associated protein (SAP) gene
  • T and NK cell defect and an uncontrolled cytotoxic T-cell immune response to EBV
  • Fulminant infectious mononucleosis during the preschool years, fatal in 50%
  • HLH with fever, HSM, lymphadenopathy, hepatic necrosis, cytopenia
  • Can develop lymphoma, dysgammaglobulinaemia, aplastic anaemia
  • Tx: immunosuppression, chemotherapy, HSCT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What are some immunodeficiency tests and what are we looking for?

A
  • FBC - neutropenia, anaemia, lymphopenia, eosinophilia
  • Serum immunoglobulin levels - low (normal age, immunodef), high (may indicate CGD, CF, HIV, autoimmune disease)
  • Vaccine responses - conjugate and polysaccharide vaccine responses
  • Skin prick tests - tests presence of antigen-specific T cells and functional APCs
  • Lymphocyte phenotyping by flow cytometry - looking at T (CD3 and 4), B (CD19+20), NK cell subsets (CD56)
  • Complement assays - CH50 test (classic pathway, C1-4), AH50 (alternative, C3, factor B, properdin). If both abnormal then likely defect in common pathway (C5-9)
  • Neutrophil oxidative burst - NBT and DHR to look for oxygen radicals produced by activated neutrophils. In CGD, no blue stain (NBT) or fluorescence (DHR)
  • Genetic testing - to confirm diagnosis e.g. 22q11 or ataxia-telangectasia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Diagnostic imaging in immunodeficiency?

A

Absence of a thymus on CXR suggests DiGeorge or other defects in T-cell development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Describe agammaglobulinaemia

A
  • 85% X-linked (mutation BTK gene), rest AR (u heavy chain, BLNK)
  • Onset 6-9m
  • Arrest in B-cell differentiation at pre-B level
  • Recurrent sinopulm infections by encapsulated bacteria
  • Diarrhoea due to giardia
  • Chronic enteroviral meningoencephalitis
  • Absent tonsils and lymph nodes
  • Decr IgG, IgA, IgM, absent vaccine response, CD19 B cells <2%
  • Tx: immunoglobulin replacement (aim trough IgG >7-8), early treat infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Describe CVID

A
  • Majority sporadic, 10-25% AR or AD
  • Adolescence or early adulthood
  • Issue with differentiation at mature B-cell level
  • Recurrent sinopulm infections by encapsulated bacteria
  • Diarrhoea due to giardia and campylobacter
  • Severe VZV, recurrent HSV
  • Autoimmune disease: AIHA, ITP, SLE, graves, Chron’s, granulomatous disease
  • Splenomegaly, lymphadenopathy , normal or large tonsils
  • Inc risk NH lymphoma, gastric cancers
  • Decr 2 of IgG, IgA, IgM, poor vaccine response, CD19 B cells >1%
  • Tx: immunoglobulin replacement, early treat infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is the age of development of different immunoglobulins?

A

IgM is detected by 1 week of age, reaches adult by 12m
IgA detected by 2 weeks of age, reaches adult by 7y
IgG reaches adult levels by 7-12y

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Describe transient hypogammaglobulinaemia of infancy

A
  • Temporary prolongation of physiological hypogammaglobulinaemia of infancy
  • Accentuated nadir at 6m age, reaches normal levels by age 2-4 years
  • Inc viral, sinopulmonary infections, usually mild
  • Normal B and T cell numbers, normal vaccine responses
  • Frequently in families with other immunodeficiencies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What are the causes of low immunoglobulins?

A
  • Primary antibody deficiencies (XLA, CVID, THI, hyper IgM, IgA def)
  • Prematurity <36/40
  • Excessive losses (protein losing enteropathy, nephrotic syndrome)
  • Drug-induced (anti-malarials, captopril, carbemazapine, phenytoin)
  • Infections (EBV, HIV, congenital CMV and toxo)
  • Others (malignancy, SLE)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What are the types of class-switch recombination defects?

A
  • Defective CD40 ligand (X-linked, account for 70%) and CD40 (AR) interactions: opportunistic infections
  • Defect in CD-40 mediated NF-KB activation: anhidrotic ectodermal dysplasia with immunodeficiency (NEMO gene): increased susceptibility esp meningitis and atypical mycobacteria
  • AID and UNG defects (no opportunistic infections)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Describe HyperIgM syndrome

A
  • Most due to CD40 ligand deficiency = X-linked
  • Decr ability to switch from IgM to IgG, A, E
  • Recurrent sinopulm infections, opportunistic PCP (40%) and crypto, recurrent viral HSV, CMV, parvovirus
  • Cryptosporidium enteritis and sclerosing cholangitis, liver failure
  • Haematological and liver malignancy
  • Autoimmune: ITP, IBD, arthritis
  • Neutropenia - ulcers and gingivitis
  • Normal B and T cell numbers (c.f. SCID), absent CD40 ligand on flow cytometry. Reduced vaccine response.
  • Tx: Immunoglobulin, cotrimoxazole for PCP prophylaxis, may need stem cell transplant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

What is the most common form of SCID?

A

X-linked SCID caused by IL-2 gamma chain deficiency due to mutation on Chr Xq13.1, JAK3 (all remaining forms are autosomal recessive). T cell defect due to defect in IL-7 receptor and NK cells due to IL-15 receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What causes lymphopenia and hypogammaglobulinaemia?

A

SCID. Lymphocyte count <2.5 is abnormal in infants and indicates likely SCID

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Describe SCID

A
  • Defect in T cell development, may have absent or present B cells, however cannot work without T cell interaction (can be T-B+ or T-B-)
  • Most common is X-linked
  • Severe infections first few months of life
  • Resp infections, opportunistic eg. PCP, chronic oral and perineal candidiasis, BCG-related abscess, chronic diarrhoea and FTT, disseminated viral infections, eczema-like skin rash from maternofetal engraftment, absent lymphoid tissue
  • Lymphopenia <2.5, low IgG, A, M (may have maternal IgG)
  • Need to rule out HIV
  • Tx: prophylaxis, treat infections, Ig replacement, HSCT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Describe DiGeorge Syndrome

A
  • 22q11.2 deletion (detect via FISH)
  • CATCH 22 (cardiac abnormalities, abnormal facies, thymic hypoplasia, cleft palate, hypocalcaemia)
  • Hypocalcaemia, absent thymus, parathyroid hypoplasia, conotruncal abnormalities
  • Usually partial T-cell defect, improves with age, 1% have complete aplasia with SCID phenotype
  • Increased autoimmune diseases (cytopenia, arthritis, endocrinopathies)
  • May need prophylaxis, Ig replacement, thymic transplant, don’t respond well to HSCT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Describe the different antibody types

A

IgM - pentomeric, first immunoglobulin produced in infection, intravascular
IgG - crosses placenta, 80% of antibodies, goes to site of infection
IgA - 2nd most abundant, is secreted in breast milk, tears, saliva, mucous
IgE - low levels, involved in type 1 hypersensitivity reactions
IgD - minimal role except early B cell receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Describe Omenn Syndrome

A
  • Type of SCID
  • Exaggerated inflammatory response caused by oligoclonal T-cell populations, often autoreactive in nature
  • Generalised erythroderma with alopecia, loss of eyebrows/lashes
  • Chronic diarrhoea, lymphadenopathy, hepatosplenomegaly
  • May have lymphocytosis rather than lymphopenia because of clonal T-cell expansion, raised IgE and eosinophils
  • Often due to RAG1 or 2 deficiency, T-B-
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

Describe Wiskott-Aldrich Syndrome

A
  • X-linked disorder, Xp11.22, abnormal expression WASP protein
  • Thrombocytopenia, eczema, combined immunodeficiency
  • High IgE and IgA, decr IgM, small and decr platelets, poor vaccine responses, waning T cell function and numbers over time
  • Opportunistic infections, sinopulmonary, viral eg CMV
  • Bleeding - can be fatal in 1/3rd due to ICH
  • Autoimmune: AIHA, neutropenia, nephropathy, arthritis/vasculitis
  • Tx: prophylaxis, treat infections, IVIG or steroids for plts, Ig replacement, HSCT (better outcomes if <5yo)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Describe Ataxia Telangectasia

A
  • Mutation in ATM gene on 11q22.3, DNA-repair defect, AR
  • Onset age 2-5 years
  • Recurrent OM, pneumonia, meningitis with encapsulated organisms
  • Cutaneous and conjunctival telangectasia over age 2, progressive cerebellar ataxia (early onset), choreoathetosis.
  • Lymphopenia, antibody deficiency, decr IgA and IgE, incr AFP, variably depressed T cell function
  • Very sensitive to radiation, risk leukaemia and lymphoma
  • Tx: antibiotics, Ig replacement
66
Q

Type 1 reactions

A
  • Allergic reactions
  • IgE antibodies bind to mast cells and cause degranulation
  • e.g. asthma, food allergies, anaphylaxis hayfever
67
Q

Type 2 reactions

A
  • Cytotoxic antibody-dependant reactions
  • IgM (type 2) or IgG (complement)
  • AIHA, ABO incompatibility, thrombocytopenia, Goodpasture’s, Grave’s, myasthenia gravis
68
Q

Type 3 reactions

A
  • Antigen-antibody complexes, 1-3w post exposure
  • Antibody-antigen immune complexes are deposited in tissues which triggers complement activation causing causing tissue damage
  • e.g. RA, SLE, serum sickness (cefaclor, penicillin, cotrimoxazole- fever, arthralgias, LAM, erythema multiforme, decr C3+C4)
69
Q

Type 4 reactions

A
  • Delayed-type hypersensitivity reactions. 2-7d post exposure
  • Cell mediated reaction involving CD8+ cytotoxic T cells and CD4+ helper T cells
  • e.g. contact dermatitis, type 1 DM, Steven Johnson’s, Mantoux test, chronic transplant rejection, GvHD
70
Q

High IgE, eosinophilia, eczema, recurrent skin and pulmonary infections

A

Hyper-IgE syndrome

71
Q

Describe Hyper-IgE syndrome

A
  • Markedly elevated IgE levels (>1000), atopic dermatitis, eosinophilis (>0.8) and staph abscesses of skin, lung, joints, viscera
  • Sinopulm infections, candidia and aspergillus
  • Associated coarse facial features, joint laxity, fractures, pneumatoceles, retained primary teeth, newborn pustular rash
  • Normal IgG, IgA, IgM. Poor vaccine response
  • Most are AD (Jon syndrome, STAT3 mutation), rest AR (TYK2 and DOCK8 mutation)
  • Tx: staph and fungal prophylaxis
72
Q

Describe chronic mucocutaneous candidiasis

A
  • Extensive candida infections of skin, nails, mucous membranes
  • Related to defects of dendritic cells or impaired Th1 and Th17 immune response
  • Tx fungal prophylaxis
  • May be associated with autoimmune endocrinopathies (APECED)
73
Q

What are suggestive signs of a neutrophil disorder?

A

Gingivitis, abscesses in skin and viscera, absence of pus, poor wound healing, delayed separation of umbilical cord, lymphadenitis

74
Q

How do neutrophils kill ingested pathogens?

A

Using granular enzymes or by activation of oxygen radicals

75
Q

Describe congenital neutropenia

A
  • Multiple syndromes, most severe is Kostmann Syndrome
  • Maturational arrest at promyelocyte stage. May have monocytosis
  • Presents 1st year life
  • Cellulitis, abscesses, osteomyelitis, colitis, sepsis, meningitis
  • Neutropenia <0.5 for over 3 months
  • Tx: aggressively treat infections. GCSF.
  • Long term risk leukaemia and myelodysplastic syndromes
  • May requires HSCT
76
Q

What is the gene defect in Kostmann Syndrome?

A

Autosomal recessive
Mutation in HAX-1 gene
Severe congenital neutropenia

77
Q

Schwachman-Diamond Syndrome

A 
Autosomal recessive
Pancreatic exocrine insufficiency, skeletal abnormalities, short stature, recurrent infections lung/bone/skin.
Neutropenia, 25% have panyctopenia.
Inc risk leukaemia, myelodyspasia.
HSCT may be curative.
78
Q

Cyclical neutropenia

A

Neutropenia for 3-6 days every 21 days, associated with stomatitis, oral ulcers, bacterial infections, severe debilitating bone pain when neutropenic.
AD, linkes to ELA2 and ELANE elastase genes
Can use GCSF when neutrophils are low

79
Q

Leukocyte adhesion deficiency (LAD)

A

Neutrophils cannot bind to and migrate therefore lack of pus at sites of infection.
Paradoxical high neutrophil count in blood.
LAD1 most common, AR, ITGB2 (defect in common beta chain of beat 2 integrin), decreased CD18 and CD11
Failure separation umbilical cord, omphalitis, sepsis.
Severe orogenital infections, gingivitis, fungal
Absent pus
Tx: treat infection, prophylaxis, HSCT

80
Q

Chronic granulomatous disease (CGD)

A
  • Defect in intracellular killing as unable to activate respiratory burst. Hyperinflammatory state.
  • 2/3rds X-linked, more severe, gp91 phox deficiency. 1/3rd AR, p47,22,67,40 phox deficiencies (inc AR in Maori)
  • FTT, severe bacterial infections, abscesses, osteo
  • Staph, pseudomonas, nocardia, aspergillus, burkholderia
  • Granulomas, IBD, lymphadenopathy, hypergammaglobulinaemia, chronic dermatitis
  • Use NBT or DHR tests, flow cytometry
  • Treat with antifungal + Ab prophylaxis, steroids, interferon gamma infusions, HSCT, maybe gene therapy in future
81
Q

Lack of pus at a site of infection usually indicates what/

A

Neutrophil migration defect

82
Q

LAD 2 additional features?

A

Impairment of neutrophil rolling.
Dysmorphism
Growth and mental retardation

83
Q

LAD 3 additional features?

A

Defective neutrophil adhesion.

Thrombocytopenia

84
Q

Most common organisms in chronic granulomatous disease?

A

Staph, pseudomonas, nocardia, aspergillus, burkholderia

85
Q

Name 5 T-cell immunosuppressant medications

A

Prednisolone, ciclosporin, tacrolimus, mycophenolate, azathioprine

86
Q

Most common mutation associated with a positive Dihydrorhodamine 123 (DHR) test?

A

gp91phox mutation - positive in 70%, X-linked, rest are autosomal recessive (p47,22,67,40 phox)

87
Q

Which immunodeficiency syndrome is associated with cryptosporidium?

A

CD40 ligand deficiency is also known as Hyper IgM and is known to be associated with cryptosporidium infection. Chronic infection and inflammation can lead to cholangiocarcinoma.

88
Q

What are the lab findings in haemophagocytic lymphohistiocytosis?

A 
Very raised ferritin, ESR, CRP.
Pancytopenia.
Hypoalbuminaemia and raised LFTs.
Low fibrinogen, raised D-dimer
Haemophagocytosis in the bone marrow
89
Q

Describe the features of Chediak-Higashi Syndrome

A
  • Lysosome-related organelle disorder, build up of giant granules in lymph/platelets/melanocytes.
  • Immunodeficiency with recurrent staph and strep infections
  • Neuro: weakness, ataxia, peripheral neuropathy
  • Oculocutaneous albinism
  • Accelerated phase driven by EBV - lymphoproliferative syndrome with haemophagocytosis, often fatal
  • Treatment with HSCT
90
Q

What does IPEX syndrome stand for?

A

Immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

91
Q

Describe IPEX syndrome

A

Enteritis - diarrhoea, FTT, villous atrophy
T1DM, hypothyroidism
Eczematous skin rash
Infections - virus, fungi, bacteria. cytopenia, raised immunoglobulins
Eosinophilia, low albumin, mutation FOX-3 gene
Tx: immunosuppression, HSCT

92
Q

Describe the classical complement pathway?

A

Antibody-dependant
Activated by antigen-antibody complexes or raised CRP
C1-C4

93
Q

Describe the alternative complement pathway?

A

Antibody-independent
Activated by C3b from classical pathway, or by hydrolysis of C3 on microbial surfaces
C3, protein B + D, properdin

94
Q

Describe the lectin pathway?

A

Antibody-independent
Activated by interaction of mannose binding lectin with microbial carbohydrate
C2-C4, mannose binding lectin

95
Q

C5-C9 complement deficiency predisposes to…?

A

Recurrent meningococcal infections

96
Q

C1, C2, C4 complement deficiency predisposes to…?

A

Encapsulated bacterial infections, SLE, glomerulonephritis

97
Q

C1 inhibitor deficiency predisposes to…?

A

Hereditary angioedema

98
Q

Factor D or properdin complement deficiency predisposes to…?

A

Recurrent neisseria infections

99
Q

Final pathway of complement system creates?

A

Opsonin
Anaphylatoxin
Chemotactic factor
Membrane attack complexes

100
Q

C3 complement deficiency predisposes to…?

A

Severe pyogenic infections, encapsulated organism infections

101
Q

Tests for complement pathway deficiencies?

A

CH50 - classical
AH50 - alternative
If both abnormal, suggests issue with terminal common pathway (C5-C9). If just one abnormal, suggests issue with early portion of that pathway

102
Q

Describe hereditary angioedema

A

AD, due to C1 esterase inhibitor deficiency
Recurrent episodes non pruritic angioedema affecting face, limbs, abdomen, airway. Can be life threatening.
Treatment with airway management, FFP or C1 esterase inhibitor concentrate, tranexamic acid or danazol prophylaxis. Antihistamines, corticosteroids not helpful. ACE inhibitors can trigger episodes

103
Q

What are the transplant outcomes in SCID?

A

90% survival if MHC-identical, 60% if haploidentical. Early transplant before acquisition of infections improves outcomes.

104
Q

Peripheral stem cells as a source for HSCT v cord blood stem cells

A

Peripheral - inc risk GvHD, can obtain large amount

Cords - decr risk GvHD, only small amount available which limits use in older children and adults

105
Q

Order of preference for allogenic transplants

A

Matched sibling > haploidentical parent > matched unrelated donor > unrelated cord blood units

106
Q

Early complications of HSCT

A

Rejection
B-cell lymphoproliferative disorder if T-cell depletion used
GvHD - fever, skin rash, diarrhoea, HSM, raised LFTs
Infections (bacterial, fungal, viral eg EBV, adenovirus, CMV)
Organ complications related to toxicities of conditioning agents

107
Q

Late complications of HSCT

A 
Chronic GvHD (>100 days)
Incomplete immune reconstitution
Growth retardation 
Endocrine issues
108
Q

Risks of preconditioning prior to HSCT

A

Pancytopenia - leading to infection and bleeding
Pulmonary toxicity
Veno-occlusive disease of the liver (alkylating agents eg cisplatin)
Mucositis
Haemorrhagic cystitis (cyclophosphamide)

109
Q

What percentage of sensitised patients (eg on RAST/SPT) are clinically allergic?

A

30%

110
Q

What are the three most common food allergies in children?

A

Egg white
Peanut
Milk

111
Q

Which patients are at high risk for anaphylaxis?

A

History of anaphylaxis
Poorly controlled asthma
Multiple food and drug allergies

112
Q

Timing of IgE mediated food allergy?

A

Onset minutes - 2 hours (usually <1 hr).

Resolves within 4-12 hours

113
Q

What does a skin prick test tell you?

A

Measures mast cell reaction in the skin (i.e. sensitisation) but doesn’t tell you anything about a systemic reaction - need to correlate with symptoms/history.

114
Q

What does RAST testing tell you?

A

Measures free circulating IgE, not IgE loaded onto mast cells, therefore indicates sensitisation rather than allergy.

115
Q

What is the purpose of a negative control on SPT?

A

Accounts for cutaneous dermatographism. Positive test must be >3mm above the saline control

116
Q

How do you test for a non-IgE mediated food reaction?

A

Oral food challenge (only way)

117
Q

Examples of non IgE mediated allergies?

A

FPIES
Food protein induced enteropathy
Protein induced proctocolitis
Eosinophilic oesophagitis

118
Q

Describe the difference between

  • FPIES
  • Food protein induced enteropathy
  • Food protein induced proctocolitis
A

FPIES - onset weeks-months. Starts after 2-4 hours, acutely unwell, vomiting, abdo distension, bloody diarrhoea, shock, FTT (delayed). Looks like sepsis but without fever. Characteristic = persistent retching.

Enteropathy - onset early infancy, unwell miserable baby, vomiting, diarrhoea, FTT, oedema

Proctocolitis - onset early infancy, well baby, bloody streaks in stools

119
Q

FPIES most common triggers?

A

Cow’s milk and soy milk > rice, oats, legumes, chicken

120
Q

Symptoms of eosinophilic oesophagitis?

A 
Regurgitation, vomiting
Slow eater, food refusal
FTT
Difficulty swallowing
Food impaction
Epigastric pain
121
Q

Triggers and treatment for eosinophilic oesophagitis?

A

Dairy, wheat, egg, soy most common.
Some respond to omeprazole alone. If not, then food avoidance, elimination diet, swallowed aerosolised corticosteroids + then re-scope

122
Q

Possible modifiable risk factors for food allergy?

A
  • Transcutaneous sensitisation - increased severity of eczema leads to increased prevalence of allergy
  • Timing of allergen ingestion - early exposure to allergen e.g. peanut decreases risk of allergy
  • Probiotics - probiotics from 3rd trimester - 6m age may decrease eczema but not other allergies
123
Q

Management of allergic rhinitis?

A 
Allergen avoidance/reduction measures
Oral antihistamines (ceterizine, loratidine) 
Nasal corticosteroids (mometasone, fluticasone)
124
Q

What is the risk of having an allergic reaction to a cephalosporin in a child with a SPT positive to penicillin?

A

Less than 2%.
Risk higher with first generation cephalosporins (cefazolin, cefalexin), due to chemical similarity of side chains of beta-lactam rings.

125
Q

Episodes of angioedema with NSAIDs/paracetamol (less common) can be due to?

A

COX-1 inhibiting properties of the drug - urticaria, bronchospasm, angioedema

126
Q

What are the types of severe cutaneous drug reactions?

A

AGEP
SJS/TEN
DRESS
- Cannot test for these (RAST/SPT) and re-challenge s contraindicated

127
Q

Describe DRESS syndrome

A

Onset 2-8w, itchy exanthem, erythroderma, non erosive mucositis, fever, eosinophilia, atypical lymphocytes, hepatitis

128
Q

Describe SJS/TEN

A

Onset 4-28d, painful dusky erythema, erosive mucositis, Nikolsky sign, high fever, flu-like illness, full thickness epidermal necrosis

129
Q

Describe AGEP (acute generalised erythematous pustulosis)

A

Onset <3d, pustules, high fever, oedema, neutrophilia, eosinophilia

130
Q

Omalizumab is a …….. monoclonal antibody, and is used to treat?

A

Anti-IgE antibody

Used in severe allergic asthma

131
Q

How does rituximab work?

A

Anti CD20 - knocks out B cells

132
Q

What percentage of DiGeorge syndrome have 22q11.2 deletion?

A

Up to 90%

133
Q

Which cytokine causes T-cell proliferation?

A

IL-2

134
Q

Difference between SCID and HIV?

A

HIV have normal immunoglob levels, low CD4

SCID have low immunoglob + low CD4, 8

135
Q

Deficiency of MHC-II causes?

A

Insufficient T cells functional for survival = recurrent infections. MHC-II are responsible for CD4 development in the thymus.

136
Q

Describe T-dependant vs. T-independant vaccine response

A

T-dependant (antibodies)= conjugate e.g. tetanus, diptheria, prevenar
T-independant (mainly IgM)= polysaccharide e.g. pneumovax 23

137
Q

What are the big 5 infectious organisms in CGD?

A 
Staph aureus
Aspergillus
Serratia
Burkholderia
Nocardia
138
Q

Symptoms of CGD carriers

A

If superoxide production <20% then get CGD-related infections. Carriers get autoimmune diseases, regardless of superoxide production = discoid lupus rash, aphthous ulcers, photosensitivity. X-inactivation changes with time therefore implications for use of carrier (e.g. HLA-matched sister) as a donor as may then get recurrence disease in transplant.

139
Q

At what age does the umbilical cord usually separate?

A

2 weeks

140
Q

What are the differentials for invasive pneumococcal/encapsulated organism disease?

A

Asplenia (look for Howell Joly bodies)
Complement deficiencies
B cell disorders/deficiency

141
Q

CRP production is stimulated by which cytokine?

A

IL-6

142
Q

Toll-like receptor defects

A

Invasive pneumococcal infections, <2yo
Delayed onset, weak fever and inflammatory response due to impaired production of pro-inflammatory cytokines
Low CRP
High mortality, but survivors see improvement over time a >2y/o the adaptive immune system kicks in

143
Q

Partial C4 complement deficiency

A

Common, up to 30% normal population, doesn’t usually cause an issue

144
Q

C3 deficiency causes…?

A

Severe, recurrent pyogenic infections

145
Q

What does infliximab target?

A

TNF-a

146
Q

What does rituximab target?

A

CD20 (B cells)

147
Q

What is the half-life of immunoglobulins?

A

IgM has a half-life of 5-8 days.
IgA has a half-life of 5-8 days.
IgG has a half-life of 21 days.

148
Q

What is the significance of satellite dyskeratosis?

A

Pathognomonic of transfusion related graft vs host disease

149
Q

What condition is trichorrhexis invaginata associated with?

A
  • Trichorrhexis invaginata of hair is also known as “bamboo hair” and is pathognomonic of Netherton syndrome. - Netherton syndrome is a severe disorder of cornification caused by (SPINK5) mutations
  • Eczema, recurrent infections, raised IgE
150
Q

Describe haemophagocytic lymphohistiocytosis

A
  • Overwhelming activation of normal T lymphocytes and histiocytes (immune system)
  • Primary (multiple mutations identified) or secondary (EBV most common infective trigger, other viral, blood cancer)
  • Fever, splenomegaly, >2 cytopenias, rash, weight loss, high lipids, low fibrinogen, haemophagocytosis in liver/spleen/LN/BM, low/absent NK cell activity, raised ferritin (thousands), elevated CD25 (soluble IL2 receptors)
  • May present as meningitis/ADEM-like
  • Tx: primary - chemo, allogenic SCT. Secondary - tx underlying cause, etoposide
151
Q

What are the four factors associated with intestinal failure?

A
  • Critical reduction in intestinal mass (short gut, NEC, atresia)
  • Poor tolerance of feeds (motility, gastroschisis, Hirschsprung’s)
  • Abnormal electrolyte function (microvillus inclusion disease, tufting enteropathy)
  • Multi-system disease (IPEX, mitochondrial disorders)
152
Q

What is the energy content of the 3 major food groups?

A
  • Carb - 4cal/gram
  • Protein - 4cal/gram
  • Fat - 9cal/gram
153
Q

IL-1 is primarily produced by which type of cell?

A

Macrophages

154
Q

Which cells produce IL-1, what is the target, and what are the primary effects?

A
  • Produced by: Monocytes, macrophages, epithelial cells, fibroblasts
  • Target: T cells, B cells, hypothalamus, liver
  • Effect: inflammation, fever, acute phase reactants
155
Q

Which cells produce IL-2, what is the target, and what are the primary effects?

A
  • Produced by: CD4+ T helper cells, NK cells
  • Target: T cells, B cells, monocytes
  • Effect: growth and activation, error results in SCID
156
Q

Which cells produce IL-3, what is the target, and what are the primary effects?

A
  • Produced by: T cells
  • Target: bone marrow progenitors
  • Effect: growth and differentiation
157
Q

Which cells produce IL-4, what is the target, and what are the primary effects?

A
  • Produced by: T cells
  • Target: naive T cells, T cells, B cells
  • Effect: differentiation into a T2 helper cell, growth, activation and growth, isotype switching to IgE
158
Q

Which cytokines are acute phase reactants?

A

IL-1, IL-6, TNF-a

Proinflammatory cytokine secretion

159
Q

What is the role of TGF-beta cytokine?

A

Inhibits activation and growth, “brakes” of immune system

160
Q

What is the role of GM-CSF?

A

Stimulates growth and proliferation of bone marrow progenitor cells

161
Q

Which cells produce TNF-a, what is the target, and what are the primary effects?

A
  • Produced by: T cells and macrophages
  • Acts on: T and B cells, endothelial cells
  • Effect: activation, inflammation, fever, acute phase reactant
162
Q

What is the role of IL-10?

A

Inhibits APC activity and cytokine production. Works with TGF-beta to inhibit/control immune response

Paediatrics RACP written exam (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions