Immunology Flashcards
1
Q
What if familial mediterranean fever causes by?
A
Familial Mediterranean fever is an autosomal recessive disease resulting from biallelic pathogenic mutations in the MEFV gene, coding for pyrin. It is understood that mutations in the MEFV gene cause gain of function of pyrin protein such that it propagates inflammation following a relatively insignificant trigger, and without needing an external toxin or infective agent.
2
Q
What are the three features of Muckle Wells?
A
periodic fevers, progressive hearing loss and amyloidosis nephropathy
3
Q
What is the mechanism by which propranolol causes hypos in babies?
A
Propranolol causes inhibition of hepatic glucose production promoted by
sympathetic nervous stimulation and inhibits glycogen breakdown especially
in the context of illness and fasting
4
Q
WHat is the most common allergen in babies and toddlers?
A
Milk
5
Q
What type of reaction is Steven Johnson syndrome
A
Type 4 hypersensitivity
6
Q
What cells make the innate immunity system?
A
Dendritic cells, phagocytes, complement, NK cells, neutrophils and complement
7
Q
What does the innate immunity recognise? Ie what do the cells respond to?
A
PAMPs and DAMPs
8
Q
A defect in which toll-like receptor causes HSV encephalitis
A
TLR3 deficiency
9
Q
What is the key defect in leukocyte adhesion deficiency? And what is the classic presentation?
A
Delayed cord separation.
Defect in neutrophils- not as sticky
10
Q
What are the four hypersensitivity reactions mediated by? Hint each one is different
A
Type 1: IgE mediated
Type 2: antigen-antibody binding
Type 3: immune complexes
Type 4: T cell mediated hypersensitivity, delayed
10
Q
What are the four hypersensitivity reactions mediated by? Hint each one is different
A
Type 1: IgE mediated
Type 2: antigen-antibody binding
Type 3: immune complexes
Type 4: T cell mediated hypersensitivity, delayed
11
Q
What are central vs peripheral lymphoid organs
A
Central- generation lymphocytes ie thymus and bone marrow
Peripheral- for developing adaptive immune response ie spleen, lymph nodes, MALT
12
Q
What cells come from lymphoid progenitors
A
T cells
B cells and NK cells
13
Q
What are the three types of phagocytes
A
monocytes/macrophages
neutrophils
dendritic cells
14
Q
Name 3 professional antigen presenting cells?
A
Macrophage, B cells and dendritic cells- activate T cells
15
Q
What are CD19/20 cells?
A
Immature B cells that sit in the blood until they are activated by an antigen, after which they become a plasma cells
Plasma cells are CD27
16
Q
What are TRECs a marker of?
A
Essentially T-cell receptor excision circles which are made from excision of intervening gene segments during the VDJ recombination of TCR- indicates normal T cell development and thymic function. Used as marker for SCID
17
Q
What does AIRE do?
A
Autoimmune regulator so essentially simulates thymic expression of many self-antigens. Lack of AIRE–> APECED
18
Q
What is APECED
A
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy
Autoimmune polyendocrinopathy, candidiasis , hyopparathyroidism and aderenal gland insufficiency
19
Q
What is the process by which high reactive T cells to self antigen (MHC) undergo apoptosis
A
Negative selection
20
Q
Which MHC is on professional APCs
A
MHC II
21
Q
Which MHC is on CD4 vs CD8 T cells
A
Remembers always have to multiple to be 8 so.
CD4 = MHC 1
CD8= MHC2
22
Q
What does a deficiency in IRAK4/MyD88 lead to?
A
Essentially these are invlved in the signal transduction pathway in the innate immune system. Deficiency or mutation –> recurrent pyogenic infections in early life.
23
Q
What does a failure of the classical complement pathway lead to?
A
type 3 hypersensitivity
Because immune complexes build up. Can cause lupus.
C1q is the main player.
24
What does an MBL def lead to?
Recurrent sinopulmonary infections
25
What does a deficiency in C1 inhibitor (part of complement pathway) lead to?
Episodic angioedema
Treat with C1 ie Berinet
26
What is the classical complement pathway driven by>
Antigen-antibody complexes
27
What is the risk of complement def? (In terms of pathogens)
Neisseria- gono or meningitides
28
What are the two main triggers for release of interferon?
viral illness and neoplasm
29
What is the relationship between IBD and IL-10
Present in kids with IBD <10 months of age. 10x worse prognosis.
30
How do APCS deliver antigens to T cells?
On MHC
31
What makes up an immunologlobulin molecule?
2 heavy and 2 light chains.
32
What region of the immunoglobulin defines the isotype and effector function
The constant region of heavy chain
33
Which Ig crosses placenta?
IgG
IgG GOES across the placenta
34
What is C1 related to?
Calcium.
35
What does C3 do
Central role in forming MAC
36
What is the action of C3a and C5a
chemotaxins and anaphylotxins
37
What does a deficiency in C1-C4 present with?
Can't remove antigen antibody complexes- causes lupus like illness, CKD and repeated infections
ALso strep
38
What does C5-9 def present with
No MAC so Neisseria infections. Note C9 not AS important as the others
39
What does C3b do?
Opsonin- marks cells and acts as a sticky agent to pahgocytes to destroy
40
Difference between hypertrophy and hyperplasia?
Hypertrophy= enlarged cells
Hyperplasia= increased NUMBER of cells
41
What are actions of bradykinin
vasodilation, increased vascular permeability and pain. Also lowers BP.
ACE inhibitors act by reducing degradation of bradykinin to continue BP lowering effect.
42
How do steroids affect the elucoyte adhesion cascade
Block selections and integrins from the endothelial wall which enable leukocytes to adhere to the wall and become activated. So essentially neutrophils are stuck and can't get to the right area
43
What does CGD present with and what is the pathophys
Recurrent candida abscess.
Essnetially cant produce the NADPH oxidative burst required- which makes reactive oxygen species
44
Issue in what cell causes HLH
NK cells. Loss of killing function causes massive uncontrolled inflammatory response
45
When do T cell defect immunodeficiencies present
AT birth.
46
What infections are commonly associated with T-cell def
mycobacteria, pseudomonas, CMV, EBV, varicella, enterovirus, phemocystis jiroveci, FUNGAL
47
Presentation for T cell def?
FTT, dairrhoea and candidiasis
48
What is the onset age of PID associated with B cell defects
~5-12 monnths after maternal antibodies are done.
49
What infections are commonly associated with B cell defect?
Strep pneumoniae, Hib, Staph aureus, Enterovirus, Giardia
50
When do phagocytic defects present
Younger age
51
Common infections related to phagocytic defects? ie CGD
Staph, aspergillus, nocardia, candidia, pseudomonas
THINK INTIAL BARRIER
52
What do complement def present with
Typically Neisseria/recurrent meningococcal, also others associated with loss of clearance ie lupus , CKD etc.
53
What is the difference between antigenic drift and shift?
Antigenic shift involves genetic reassortment and is associated with pandemics, such as the emergence of SARS-Cov2.
Antigenic drift involving point mutations of viral haemagglutinin or neuraminidase are associated with the epidemics typically associated with Flu and necessitate updating vaccine antigen composition; e.g. the emergence of variants of SARS-Cov2.
SHIFT= SARs COV
54
What is Chediak Higashi associated with?
ALBINISM, EASY BRUISING, RECURRENT INFECTIONS
Chediak Higashi are associated with oculocutaneous albinism, easy bruising, recurrent infections. It is a result of abnormal function of natural killer cells due to mutation in the lysosomal trafficking regulator gene. There are large lysosomal granules noted in the WBC and bone marrow on biopsy.
55
What is properdin?
Binding and regulator of alternative complement pathway by stabilising C3/C5 convertase
56
What does properdin deficiency present with? What is the inheritance of this condition?
X-linked, essentially unable to regulate alternate complement pathway.
Presents with FAST onset of infection- usually meningococcal septicaemia
57
What is CD3 a marker of?
Thymic T cells (before they switch to CD4 and CD*)
58
Defiencies in which type of cells normally leads to fungal infections? Ie candidate, giardia etc
B cells. T Cells and Macrophage cerlls
59
What are the 4 most common PID
HIV/AIDs
MBL def
Selective IgA def
CVID
60
How long do the antibodies last when crossed from placenta in third trimester
4 months
61
What is the second disease vaccinated to mums that has reduced all cause mortality in paeds
Influneza
62
Half life of IgG
25 days
63
What is Bruton's syndrome? or X-linked agammaglobunaemia?
Pan hypo immunoglobulins with low B cell numbers.
64
What is the pathophys behind Bruton's syndrome
Bryton tyrosine kinase defect which prevent B cells signal transduction pathways --> B cell differentiation arrest at pre B cell stage
BTK gene.
Think no immunoglobulins BTS
65
When and what does Bruton
s syndrome present with
Absent lymph node, sinopulmonary infections , poor vaccine response. Low B cell numbers.
66
What is IgA deficiency?
Lack of IgA only- increased risk of mucosal infections
67
What is a special consideration for transfusing blood to someone who has IgA def
use washed RBCs because there is compensatory elevated IgE
68
What does IgA def present with
Increased infection esp associated with saliva, sweat, intestinal juices. No protection against carcinogens
69
What is transient hypogam of infancy?
Low IgG, normal specific antibodies, normal lymphocyte number and function
Usually outgrow by 1st birthday
70
When does transient hypogam of infancy present and how does it present
6 months and resolves by 4 years.
Recurrent sinopulmonary infections
71
What is the most common B cell disorder
CVID
72
Definition of CVID
Def in >2 Ig subtypes with recurrent sinopulmonary infections and impaired vaccine response in kids >2yo
73
What are the common infections that kids with CVID present with
sinopulmonary infections caused by encapsulated bacteria (strep), gastro (giardia, campylobacter), VZV,
74
4 chronic complications of CVID
bronchiectasis
chronic diarrhoea with malabs
GI obstruction
increased risk of malignancy (NHL, gastric cancers)
75
What will happen to CD 19 in CVID
Low
Reduced class switched B cells. CD 19 on mature B cells
76
What is Kostmann syndrome?
Severe persistent neutropenia, presents with bacterial infections, fever, perianal abscess, ginigivitis in first few months of life.
Monocytosis with eosinophilia
KOSTLY to have NO Neutrophila
Kostmann - no neutrophils
77
What is the time frame for post-viral neutropenia?
In first two days of infection, persist for 3-8 days
78
What is Scwanman-Diamond syndrome
Pancreatic insufficiency and bone marrow dysnf.
--> Neutropenia with anaemia and thrombocytopenia
79
What is the immunological defect in DiGeorge? And what pharyngeal arches are affected in this syndrome?
Absent thymus= no T cells
Arches 3 and 4
CATCH 22- 3,,3 pharyngeal arches
80
What is the defect in hyper IgM
CD40 ligand defect- T cells cant bind B cells so no class switching.
81
Inheritance for hyper IgM
X linked.
82
Common presentation for Hyper IgM
Recurrent pyogenic infections esp sinopulmonary, PJP, cryptosporidium enteritis .
NORMAL B and T cell numbers.
83
What is the triad for Hyper IgE syndrome?
High levels of IgE (and eosinophilia), eczema, recurrent skin and pulmonary infections.
84
What is the mutation in autosomal dominant HyperIgE syndrome
STAT 3
IgE causes STAT inflammation 3
85
What syndrome is assocaited with cutaneous cold abscess and neonatal eczema
Hyper IgE
86
What are the typical facies for Hyper IgE
Prominent forehead and chin, deepset eyes, bulbous nose, coarse facial features, facial asymmetry and high palate
87
What is more common- AD Hyper IgE syndrome or AR?
AD more common.
AR develops more viral cutaneous infections
88
What is Netherton syndrome- include presentation
severe eczema, atopy, recurrent infections and FTT. THIN HAIR AND EYEBROWS> High IgE and multiple food allergies.
THINK OF LEO
89
What happens to primary teeth in hyper IgE syndrome
Retained primary teeth
90
What is the mutation in chronic mucocutaneous candidiasis?
Gain of function STAT-1 mutation
91
What is Omen syndrome
TYPE of SCID. But instead of no T cells, there are HIGH number of T cells that are not functional and also autoreactive==> eczema
92
Mutation in Omens
*Hint: What is a bad omen*
RAG1/RAG2 - gene deficiency
Being a RAG is a bad OMEN
93
What happens to eosinophils in Omen syndrome
UP
94
What is maternofetal engraftment?
Variant of SCID.
Essentially lack of functional T cells--> maternal lymphocytes entering the circulation which then attacks baby
95
What is always a lab finding in SCID
T-cell agenesis (and hence absent lymphoid tissue)
96
What is the curative treatment for SCID
BMT
97
What is the mutation in X-linked agammaglobunaemia (XLA)
deficiency in BTK gene. No tonsils.
98
Apart from delayed cord separation, what are 2 other features of leukocyte adhesion disorder
Poor wound healing and gingivitis
99
Triad for Wiskott-Aldrich Syndrome?
Small platelets, eczema and immuno def
100
Mutation in what gene in Wiskitt-Aldrich?
WASP
Wiskott Aldrich syndrome protein
101
What happens to the Igs in WAS?
Low IgM
High IgA and IgE
102
What are some PRIMARY causes of HLH
Due to inherited genetic conditions ie PERFORIN deficiency (remember can't stabilise alternate complement pathway)
Perforin DIFF to Properdin which has fast onset of infections
103
What are some secondary causes of HLH
CMV, EBV, MAS and malignancy
Also X linked lymphoproliferative disease which increases susceptibility to EBV
104
Treatment for hereditary angioedema?
Remember low C1 inhibitor
So give C1 inhibitor- barinet OR bradykinin inhibitor= Katibant
105
What are the 5 bugs most commonly causing infeciton in CGD (chronic granulomatous disease)
Aspergillious, staph, burkholdaria, serratia, nocardia
106
Problem in CGD
mutation in structural component of NADPH oxidase
107
What is commonly deranged in bloods for HLH
RAISED Ferritin
RAISED LDH
Deranged LFTs
Raised triglycerides
108
The risk of what is increased post EBV in patients with X linked lymphoproliferative disorder
lymphoma
109
What are some protein losign states that can cause secondary/ancquired immunodef?
Nephrotic syndrome
severe burns
Lymphangiectasia
110
What is the gold standard for diagnosis of food allergy
food challenge
111
What is the most common cause of elevated IgE levels
Atopy/eczema
can be hyper IgE syndrome, helmonth infection, scabies, atopy etc
112
What diametre of wheal in SPT is suggestive of allergy
>3mm
113
What is the usual time frame POST food ingestion within which FPIES occurs
2-4 hours post ingestion
Usually diary or soy based products
114
Name 2-3 examples of a type 1 hypersensitivity reaction
Ig E mediated
So allergy, anaphylaxis, hayfever
115
Name 2-3 examples of type II hypersensitivity reactions
This is cytotoxic or antigen-antibody mediated.
GOODPASTURES, glomerulonephritis, transfusion reaction, T2DM
116
Name 2-3 examples of type III hypersensitivity reactions
This is immune complex mediated so lupus nephritis, serum sickness, SLE, post-strep GN
ALso small vessel vasculitis ie HSP and cryoglobulamic vasculitis= antiC1q
117
What does serum sickness present with and what is one drug commonly associated with it
Fever, urticaria, arthrlagia, lymph node enlargement.
Common with Rituximab- low complements
118
What are 3 types of type IV hypersensitivity reactions?
DRESS (drug induced), tuberculin skin test, SJS, contact dermatitis
119
What is the time frame for AJEP vs DRESS vs SJS post commencement of a drug?
AJEP= 1-2 days (pustules with malaise)
SJS = <4 weeks
DRESS= 3-8 weeks post initiation
120
What virus is DRESS assocaited with
HHV -6, CMV, EBV
121
Skin involvement in SJS vs TEN
SJS is 1-10%
TEN= 10x worse - 30%
122
Skin involvement in SJS vs TEN
SJS is 1-10%
TEN= 10x worse - 30%
123
What cells would be involved in a patient with a rash ~2 weeks post Carbamexapine
Sounds like delayed hypersensitivity reaction- and time frame= SJS.
T cells
124
What are the two TYPES of drug reactions?
Type A; dose dependant, common and predictable
Type B: HOST dependant - this includes allergy and psuedollergenic ie vancomycin, aspirin
125
What do you measure to check if a reaction was a true allergy? (think in the immediate time frame)
Mast cell tryptase
126
What is the order of potency between dex, hydrocort and pred
DPH
Department of Piss Heads
127
What does Etanercept target
TNFa
128
What pathway do sirolimus and everloimus act on? What is a common condition where these medications are used?
mTOR pathways
Used in Tuberous Sclerosis
129
Apart from Pertussis, which vaccinations gives protection to baby when given in late antenatal period
Influena
130
Which vaccine gives a fever?
MenB
THINK MEN FLU
131
What type of vaccine is a Pneumovax
polysaccaride
132
What is the order of immunogenecity in terms of live vs polysaccharide vs protein subunit
Live > protein > polysaccharide
133
What is the most common type of vaccine and what cells does it trigger
Protein conjugated. Needs response from T cells for memory
134
What is excessive molluscum suggestive of?
T cell def
135
Which vaccine is given to test immune response?
Pneumovac 23
136
Difference between organic acidemia and urea cycle defects disorders
In addition, organic acidemias typically present with an anion gap metabolic acidosis, while urea cycle defects can present with a respiratory alkalosis due to ammonia stimulation of the medulla.
Organic acids are ACIDIC
OTC= Urea cycle!!!! When mum is vegan, x linked recessive
137
Syndrome with bell shaped chest and short limbs
Zelwegger
138
What is the most important Ig in breast milk? how long until baby produces their own?
IgA in milk is principally in the form of secretory IgA, which serves as a first line of mucosal defense. Maternal supply of secretory IgA is important, as infant intestinal IgA production does not begin until several months of age; and even at one year of age serum IgA levels are only 20% of adult levels.
139
Risk of anaphylaxis in patient with prev localised reaction
If he already had a systemic reaction/anaphylaxis, then the risk of a severe systemic reaction to a subsequent sting is more like 30%. But he has only had a previous local reaction, therefore his risk is 10%.
140
What are the two conditions that can cause chronic mucocutaneous candidiasis
STAT 1 mutation
APECED
141
What are the two autoimmune polyendocrinopathy complications in APECED
HypoPARAthyroidism
Adrenal insufficiency
142
What is the difference between SCID and Omenn syndrome
Omenn will have high IgE and Eczema
143
Mutation in X linked agammaglobunemia
Bruton tyrosine kinase
Think BTS there are no immunoglobulines
144
What is the mutation in aut dominant hyper IgE
STAT 3
145
What makes eosinphils in terms of cytokines
IL5
Think e is the fifth letter so IL-5
146
What do mast cells release
IL-4
4 letters in mast,
