Hillary Revision Flashcards by Jordan Rolt

What are the 6 adjuvants approved for use in humans

Alum
ASO1
ASO3
ASO4
MF59
CpG ODN

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What is a prime boost

Administratoring a second, different vectored vaccine to boost responce.
First vector will induce vector-specific responce.
Homologous - same second vector
Heterologous - different second vector

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Meningitis vaccine coverage - which strains have good coverage

A, C, W, X, Y

B does not

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Meningococcal disease - what type of infection leads to shedding and trasmission?

Carrige - asymptomatic infection keadsnto shedding.

Symptomatic infection does not lead to transmission.

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Meningococcal clonocal complexes- what determines the CC?

Housekeeping genes

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Why is there poor immune responces to serogrouop B and poor vaccine coverage?

B has similarity to human antigens

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Which HIV type and clade causes pandemics?

HIV-1 clade M

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HIV DNA type? And baltimore group

+ ssRNA

Baltimore group 6 - reterovirus

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Number of HIV mature proteins?

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The open reading frames of HIV?

gag
pol
env

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The proteins produced by Gag and there function?

P24 - capsid
P18 - structual envelope protein
P6 - chaperones RNA genome

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The proteins produced by Pol and there function?

Protease - cleaves gag-pol precursor
rt - catalyses DNA production
RNA acetyl - degrades RNA genome template
Integrase - catalyses proviral integration

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What are the proteins produced by Env and there function?

Receptor binding and membrane fusion protein

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Other HIV orf’s - function of Tat

Transactivates viral gene transcription

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Other HIV orf’s - function of Rev

Regulates viral RNA splicing

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Other HIV orf’s - function of Nef

Inhibits SERINC5
Immune evasion via MHC1 down regulation and CD4 evasion.
Lowers the threshold for CD4 activation.

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Other HIV orf’s - function of vif

Overcomes deaminase APOBEC

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Other HIV orf’s - function of VPU

Downregulates tetherin to increase viral release

Downregulates CD4 by connecting it to a E3 ligase

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Other HIV orf’s - function of VPR

G2 cell cycle arrest and appoptosis in proliferating cells

Nuclear import of pre integration complex - required for viral replication in non-proliferative cells (macrophages)

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8 stages of the HIV lifecycle

Attachment and entry
Reverse transcription
Nuclear import
Integration
Transcription
Translation
Assembly
Budding

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Which HIV protein facilitates cell entry, and what is the structure of the protein?

Glycoprotein ENV receptor.

Tetramer of dimers.

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ENV is expressed as a single polyprotein gp160 cleaved into what two proteins?

gp120 and gp41

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How do gp120 and gp41 allow HIV entry?

gp120 binds CD4 then CCR5/CXCR4. This causes a conformational change in the gp120 complex
gp 41is then exposed and pierces cell membrane to fuse the membranes.

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HIV cellular tropism types?

R5 - infects CCR5+ cells

X4 - infects CXCR4+ cells

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HIV integrase structure

Dimer of dimers | 3 domains - N terminal, catalytic core, C terminal domain

6 types of antireteroviral drugs

``` 1 Reverse transcriptase inhibitors 2 Non-nucleoside reverse transcriptase inhibitors 3 Protease inhibitors 4 Fusion inhibitors - inhibits entry 5 CCR5 inhibitors - inhibits entry 6 Integrase inhibitors ```

First line cART is mare up of what antiretroviral drug types

2 RTI plus 1 NNRI / PI / INI

Salvage cART therapy is made up of what antiretroviral drug types?

Fusion inhibitor and CCR5 inhibitor

The different uses of cART

Pre exposure prophylactic (PrEP) Post exposure prophylactic (PEP) Treatment as prevention (TasP)

Where does HIV home to?

The GALT

what does IEI mean

inborn errors of immunity

Gene responsible for XLA?

BTK - brutons tyrosine kinase

Wiskott-Aldrich syndrome, mode of inheritance?

X-linked reccesive

Wiskott-Aldrich syndrome, gene defect?

WASp gene

Wiskott-Aldrich syndrome, immune defect?

Defective anti-polysaccharide antibody impaired T cell activation Treg dysfunction

Hyper-IgM syndrome, gene defect?

CD40/ligand NEMO NEMO - NFkappaB modulator

Hyper-IgM syndrome, immune defect?

No isotype switching and somatic hypermutation | T defects

Hyper-IgE syndrome, gene defect

STAT3

Hyper-IgE syndrome, immune defect

block in Th17 differentiation | elevated IgE

Cronin 1A defficiency, immune phenotype

T-B+NK+

Reticular dysgenesis, gene defect?

AK2 - controls mitochondrial metabolism

common gamma chain, cytokines signalling via IL2R

IL2,4,7,9,15,21

Defects in V(d)J recombination?

RAG1/2, Artemis, DNS-PKcs, DNA ligase IV, | Cernunnos (xlf) - not clear

AIDs diagnosis requires

CD4 count < 200 cells / microL

AIDs defining malignancies and virus associated with them

Kaposi Sarcoma - KSHV NHL - EBV Cervical cancer - HPV

Functional T cells secrete which cytokines

IL2, IFNgamma, TNF

Markers of T cell exhaustion?

PD-1, LAG-3, CD160

LCMV model, control associated with what type of t cells

multispecific, low CD39 and PD-1 expression

In HCV, what cytokine and cell type are associated with a reduces viremia?

IFNgamma, CD8

Protective HLA molecules against HCV infection

HLA - B27 & A3

Alpha herpesviruses

herpessimplex 1 and 2

beta herpesviruses

CMV HHV6 HHV7

gamma herpesvirus

KSHV | EBV

type of herpesviruses which achive true latency?

gamma herpesviruses

What is the genetic structure of EBV

dsDNA

What is the genetic structure of CMV

dsDNA

IRAK 4 mutations, lead to susceptibility to what infections

Bacteria - pyogenic, gram positive

Assay for IRAK 4 mutation

CD62L shedding assay. Cleavage of CD62 is the normal function when bound to PAMP.

UNC93B common presentation

Herpes simplex encephalitis | On CD62L assay - no response to intracellular agonists.

NLRP3 mutation Is associated with what conditions?

Cryopyrin associated periodic syndrome

NOD 2 mutation is associated with what disease?

Crohns

HOil1 deficiency has what presentation?

Autoimmunity and immunodeficiency

HOIL is associated with what complex and what is its role

LUBAC - ubiquitinates regulatory proteins of NFkappaB

Defects in IL12/IFNgamma leads to susceptivity to what infection

Non Tb pyogenic bacteria and salmonella

Infections associated with complement classical pathway defects

pneumococcal

Infections associated with complement common pathway defects

Meningococcal

Causes of angioedema in complement defects

C1 inhibitor deficiency - bradykinin increase

CD59 function in complement

Prevents c9 binding c5 - c8

PNH deficiency, what component is affected? And it’s function

PIG-A, synthesises GPI

Glycol phosphatidyl inositol (GPI) function? And how is it relevant in PNH deficiency

Anchor on RBCs for Decoy accelerating factor, CD59, CD55. | Prevents CD59 expression on CS, therefore increased MAC formation and RBC haemolysis

TIMs, secrete what pro-angiogenic factors

VEGF, TNFa and IL8

XLP is a responce to what infection

EBV

Gene responceible for inherated XLP

SH2D1A

MRSA gene responsible for methesilin and beta lactam resistance

mecA

Vaccines given to old folks?

Pneumococcal vaccine (PPV) Flu Shingles

Vaccines given to teenagers?

HPV | 3 in 1 booster menACWY

6 in 1 vaccines contains?

diphtheria, tetnus, polio, pertussis, Hep B, Hib

NEMO deficiency mode of inheritance?

X linked

CGD people are susceptible to what type of bacteria

Catalyse positive

LAD1 is due to a deficiency in what?

CD18 ( beta 2 integrin)

LAD1, CD18 binds to what during extraversion?

ICAM1 on endothelium

LAD 2 is due to a deficiency in what?

Sialyl Lewis x

LAD2, Sialyl Lewis x binds to what in neutrophil extravasation?

E/P selectin on endothelium

RAC 2 deficiency results in what functional defects

Neutrophil phagocytosis, migration and oxidative burst impaired.

Whiskott Aldrich syndrome, is associated with what antibody phenotype?

Decreased IgM, increased IgA and IgE

Chediak-Higashi syndrome, is due to a mutation in what gene? And what is its function

LYST gene, protein trafficking gene.

Giant cytoplasmic granules in neutrophils is associated with what condition

Chediak higashi syndrome

Most common gene which is mutated leading to severe congenital neutropenia

ELANE

Type 2 hypersensitivity, immune complexes form when?

Excess antigen to little antibody, small ICs develop

SLE, auto antibodies bind to?

Nuclear antigens eg dsDNA

Why is crypthudia useful for SLE diagnosis

Pure source of dsDNA. No RNA

Normally immune complexes activate which complement pathway?

Classical

Antiphospholipid syndrome is associated with auto antibodies to what?

Beta 2 glycoprotein

RA autoantibodies to what proteins?

RA factor and CCP

T2 athsma diagnosed when blood ensophilia count is?

Over 300 /ml. | Under then T1

Why are ILC2s important in allergy?

Resistant to corticosteroids

HLA2 associated hypersensitivity diseases?

SLE, RA

Ankylosing spondylitis associated with what HLA

HLA B27 | Class 2

Other genes associated with ankylosing spondylitis?

IL23R and ERPI

When is ERAP associated with Ankylosing spondylitis

When HLA B27 + | - it is epistasis

CD8 important in Ankylosing spondylitis?

Nope, CD8-/- still get disease

Autoantibodies in RA

Rheumatoid factor antibody - Anti- IgGFC | CCP - Citrolinated peptides

HLA associated with RA

HLA DR4 | HLA DRB1

Autoantibodies in autoimmune hepatitis? Type 1

Anti - nuclear (chromatin) | Anti - smooth muscle

Autoantibodies in autoimmune hepatitis? Type 2

Anti - liver/kidney microsome antibodies. To crytochrome P450

IgG4 antibodies affinity to adapter proteins

Low affinity to complement and FcgammaR3

Autoantibodies in primary binary cholangitis

Anti-PDC-E2 (Mt protein)

Treatment for primary biliary cholangitis?

Treatment with bile acid

What’s a syngenic transplant?

Between genetically identical donor and recipients

Types of graft rejection

Acute Hyperacute Chronic

Warm ischemia time is?

Time since withdrawal of life support to systolic pressure below 50mmHg

autoantibodies in P. vulgaries are against

Desmoglein 3

A marker of poor outcome in breast cancer?

M-CSF

Breast cancer metastasises to which organs? and what chemokines mediate this?

lungs, liver, BM, lymph nodes. | CXCL4 homing to CXCL12

gammaDelta T cell K/O leads to susceptibility to what type of cancer?

Skin

CTLA4 ligands on the tumour cell?

CD80 and CD86

CTLA4 mutations cause haploinsufficiency, what disease is associated with this?

CHAI disease

An anti-CTLA4 antibody is called?

ipilimumab

High interstitial pressure in tumours affects vasculature?

hyperpermeability and fluids leaks into interstitium | - avoids drugs and Abs as no diffusion

Hypoxia in tumours benefit tumour survival as?

P-glycoprotein upregulated, selects for loss of P53, increased resistance to radiation.

low extravascular pH benefits tumour survival as?

VEGF release, high lactate = metastasis, reduces effect of chemotherapy, perforin release reduced

Anti-angiogenic factors?

angiostatin and endostatin

How does hypoxia affect immune cells?

oxygen radical killing impaired

testies antigens found in what tumours?

melanoma, liver cancer, lung cancer, bladder cancer,

testis antigens?

MAGE, BAGE, GAGE, NY-ESO-1

Melanocyte differentiation antigens?

MelaA, gp100, tyrosinase

Tregs are recruited to tumours by what chemokine?

CCL22