Immnunology Flashcards by Learning Paediatrics

Difference between Anaphylaxsis and anaphylactoid?

Identical signs and symptoms

Different activation of MAST

Anaphylaxsis - IgE mediated - preformed antigen made by B-cells then bound to MAST awaiting degranulation

VS.

Direct activation of MAST - Virus/Drugs/Hormones/Complement

No role for skin prick testing

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What is Mepolizumab/Resilzumab

Anti IL-5 (Limiting interaction of IL-5 with IL-5 receptor, Which sits on the surface of Eosinophils)
Trade name - Nucala//Cinqair//Cinqaero
Indications:
Eosinophilic Asthma

Under Ix for:
Eosinophillic Eosphagitis

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Widespread Urticaria, new welts on scratching?

Cutaneous mastocytosis - If given a mast cell degranulator like an opiod may release histamine +++

Dermatographism

Scabies

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Adrenaline Receptors Role in anaphylaxsis?

Alpha-1 receptor
- Vasoconstrictior, increase BP, decrease odema

Beta-2 receptor

Bronchodilator
Reduces generation of mediators from MAST cells

(Also) B-2 - Increase HR, increase cardiac contraction

Relevant if have a beta-blocked patient

Dose - 0.01mL/kg of 1:1000 = 10mcg/kg
20Kg and under = EpiPen Junior (150mcg)
>20kg EpiPen (300mcg)

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Glucagon, indication for anaphylaxsis?

In setting of refractory or

Adjunct IF BETABLOCKADE

Glucagon receptor in heart, cAMP, independent of adrenaline

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STEM: 2 yo M p/w axillary abscess
PMHx cervical lymphadenitis age 7/12
Brother and Father recurrent abscess
Grows serratia marcesses

?Diagnosis

Chronic granulomatous disease
NADPH Oxidase (Phox)
Rare 1: 250,000
Failure to generate ROS

Pathognomic with liver abscess
Organisms are catalase positive of aspergillus (Or norcardia/burkholderia)

Rx
Bacterial prophylaxis - Bactrim
Fungal prophylaxsis - Itraconazole
Stem cell transplant

Natural Hx : 50% survival age 30

Association: Inflammatory bowel disease

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STEM:
11 month old with broad ulcer in nappy area
Very little pus
WCC 48
PMHx delayed cord separation

Leucocyte adhesion disorder
= Failure to exit endothelium to get to site of required action

LAD1 - CD 18 beta-integrin genes
LAD2 - CD 15
LD3 - KINDLIN3

Automsomal recessive

Recurrent bacterial
Peripharl leucocytosis
Absent pus formation
Delay cord separation

Rx
Aggresive Rx of infections
Stem cell transplant offered

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Isoagglutins - Which class, what function?

Predominately IgM (So don’t cross placenta)
Anti-A and Anti-B
Develop by 12/12 in setting of cross reactivity

Test as raw function of ability to make IgM

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ASOT Antibody
Which class
Which pathogen

IgG

Group A Streptococcus

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In a protein losing state - which immunoglobulin levels are diminished?

IgG is most diminished
It has longest half life (23 days) so production is gradual and a loss of circulating antibody is apparent

Vs.
IgM/A (5 days) IgE (2days)
Which are rapidly replenished regardless of losing state

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Relevant proportion of immunoglobulins circulating?

IgG - 75% (5g/L)
IgA 15% (0.3g/L)
IgM 5-10% (0.3g/L)
IgE 0.00002

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In setting of low immunoglobulin:

How to determine protein losing state vs. primary immunodeficiency?

Do an albumin

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Regarding interleukins:

Function/Origin of IL-2?

From dendritic cells
From T cells

For signalling T cells

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Regarding interleukin:

Origin/Function of IL-12?

From antigen presenting cells

For Th1 Response
TNF - Alpha
Interferon Gamma

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Macrophages love which cytokine?

Interferon Gamma - they turn into super macrophages

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Immunologically: Th1 cells trigger what?

Release which cytokines
To stimulate what
And cause?

IL-2
IFN-gamma
LT

Stimulate Macrophages
And also IgG class 1 and 3
Which heavily stimulates complement

And also provide CD40L to b cells ro encourage maturation and isotype switching

Cause INFLAMMATION
TISSUE DAMAGE
Associated with auto-immunity

Th2 response?

IL4
IL5
IL13

Allergy phenotype

IL4 isotype switches to IgE
IL 5 activates eosinophils?

Th17 does what?

Release IL 17
Neutrophil recruitment
Autoimmune disease

What do T-Reg cells do?

TGF -beta
IL-10

Regulates and dampens immunity response

What does TFH cell do?

T-Follicular-Helper

Helps B-Cell high affinity response(plasma or memory)

Lives in germinal centre of lymphoid gissue

B cell has MHC2 molecule
Binds to Tfh cell( an activated cd4 distinct from thr other Th cells)
TFH PROVIDES CD40L AND IL21 and Il4 to

Toculizimab?

Indications?

Anti IL6
Refractory Systemic JIA, refractory polyarticular JIA, Rheumatoid arthritis

TB absolute contraindication

Anakinra
Canakinumab
Rilonacept

All target?

Targeting IL-1 components
Anakinra IL-1 Receptor antagonist

Indicated for rhematoid arthritis/stills

Pathophysiology of Herediatry angioedema?

Deficiency of C1 Esterase inhibiotr
Too much C1 Action
Too much bradykinin

Angioedema

Fingolomod?

Multiple Sclerosis Rx
Inhibits leucocyte movement

Orally active anti-leucocyte
Keeps lympocytes sequestered in their lymph nodes and unable to leave

If sick just stop meds, short half life, preveent sepsis

Target is Sphingosin-1-PO4

Small molecule (Not MAB)

Natalizumab?

Anti leucocyte trafficing monoclonal antibody for multiple sclerosis Targets alpha-4-beta-1 (VLA4) Blocks adhesion of activate T-cells to blood/brain barrier

What does CXC or CC signify in immunology?

Chemokine - guides migration of cells around body

What are Toll-Like Receptors?

Highly confined German ‘Toll” = “wow/cool” So when german scientists knocked out innate cell immunity in drosphillia to give a fuzzy green (fungally infected) fly they were like “Super Cool” - Sehr Toll. TLR1-9, we got the same, recognise pathogen associated molecular patterns, - cell membrane bound (for extracellular) and endosome membrane bound for RNA/DNA (for intracellular viral)

Pro Inflammatory Cytokines? From innate immnity

``` IL-1beta TNF alpha IL 6 CXCL8 IL 12 ```

Membrane attack complex?

``` C5b C6 C7 C8 C9 ``` Punches holes

Alternative complement pathway - key molecules?

Activated by pathogen surface THEN C3, B, D -Always ticking over - needs regulation Gets to C3 Convertase then common C3a, C4a, C5a (chemo attracts) C3b opsonises C5b-C9 (MAC)

Eculiziumab

Blocks C5 in C5a Risk of can’t form MAC Risk of Nisseria

TMA, Renal failure, organ failure? ADAMTS13? Shiga Toxin?

If -ve then not TTP If -ve then not infection induced - HUS So then aHUS - genetic deficiency in Complement Factor H, or I

Avacopan?

Blocks C5 receptor Orally active Use in place of prednisolone for vasculitis (In trial, in adults)

How many different TCRs possilbe?

10^23 - aka almost any protein segment you could place in front of it.

TCR Structure

alpha chain, beta chain - DIMER by disulphide bond Variable region pokes out Constant region close to membrane -RANDOM RECOMBINATION of 5x GENES - Shuffled like card, VDJ

T-Cell - How big and what does it recognise What does it attach to?

10-16 peptides Presented by ANTIGEN PRESENTING CELL, extracellular place on MHCII - to CD4 CYTOSOLIC PROTEIN processed onto MHC1 = presented to CD8 Only in setting of danger APC - DC(dendritic cells), B cells, Macrophage

Thymic Purging of self recognising?

Thymic epithelial cells contain IRE - which is a transcription factor to express most self peptides - e.g. insulin (just this and pancreas) If strong binding (as 70% do) then apoptosis After this selection, and some maturation, naive CD4 and CD8 leave to begin immune surveillance.

Immunoglobulin, levels, dosage, halflife

IGG 10g/l serum, 400mg/kg dose, 21-28 day half life