Immunology Flashcards
Cytokines function = IL 1
Name 2 IL-1 inhibitors
Uses?
Fever, induces other cytokines,
T cell stimulation
Canakinumab (SC)
Anakinra (SC)
Used in RA, periodic syndromes
Which cells express MHC Class 1?
What does this activate?
Basically all somatic cells
CD8 cytotoxic T cells
What is the 2 signal model of T cell activation?
2 signals required for T cell activation.
Signal 1 = interaction of CD3 with MHC
Signal 2 = costimulation (e.g. CD28 with B7)
What types of immune response are Th1 cells most active in?
Pro-inflammatory
Involved in:
- eradication of intracellular organisms e.g. viruses, mycobacteria
- Type IV hypersensitivity
What types of immune response are Th2 cells most active in?
Important in IgE / eosinophil synthesis
Involved in:
- parasitic infections
- allergy and asthma
What types of immune response are Th17 cells most active in?
Involved in:
- early response to extracellular pathogens
- chronic inflammatory responses
What main cytokines are produced by Th1 cells?
IFN-gamma
TNF-alpha
What main cytokines are produced by Th2 cells?
IL-4
IL-5
IL-6
IL-13
What main cytokines are produced by Th17 cells?
IL 17
IL 21, 22, 23
What main inhibitory cytokines are produced by Treg cells?
IL-10
TGF-beta
What is the main interleukin involved in gout pathogenesis?
IL-1
What does TLR3 pathway deficiency result in?
Severe HSV encephalitis
What defect causes chronic granulomatous disease?
Molecular defect in 1 or more subunits of NADPH oxidase. This is what is usually responsible for respiratory burst by neutrophils to kill intracellular organisms
What is the classical complement pathway triggered by?
Antibody-antigen complexes with IgM or IgG
What is the lectin pathway of complement triggered by?
Mannose-binding lectin binding to mannose on pathogen surfaces
What is the alternative pathway of complement triggered by?
Background low level of C3 circulating, which spontaneously activates to C3b. Then comes across pathogen surface and binds, leading to pathway activation
What is opsonisation?
Coating of target by C3b to promote its elimination -> enhanced uptake by phagocytic cells
What is eculizumab?
What is it used in?
C5 monoclonal antibody
Atypical HUS
PNH
What are the classical conditions found with early complement pathway deficiencies?
SLE, GN
Immune complexes diseases in general -> complement has role in clearing these from the circulation
What are the classical conditions found with late complement pathway deficiencies?
Disseminated neisseria infections
What is the pathophysiology of Hereditary angiooedema?
Main management?
Deficiency of C1 esterase inhibitor, which usually controls complement activation.
Thus -> Excessive classical pathway activation -
- Bradykinin release -> angio-oedema
Mx = Icatibant = bradykinin 2 receptor antagonist
What are the 5 antibody heavy chain isotypes?
Which can cross the placenta?
IgG IgM IgA IgE IgD
IgG crosses placenta
Which cells express MHC Class 2?
Professional APCs
- dendritic cells
- macrophages
- B cells
What do VDJ genes code for?
The variable portions on immunoglobulin
Where does affinity maturation of B cells occur?
Germinal centres -> secondary lymphoid tissue
What is isotype switching of B cells?
Activated B cells changing surface immunoglobulin isotype expression -> e.g. from IgM to IgG
What infections are commonly seen in CVID?
Recurrent sinopulmonary infection
GIT - diarrhoea
Skin
What non-infective complications are seen in CVID?
Autoimmunity
Malignancy -> NHL, gastric
Which immunoglobulins are most commonly low in CVID?
IgG, IgA, sometimes IgM
What are the live vaccines? (5)
Measles, mumps, rubella (MMR combined vaccine) Rotavirus Smallpox Chickenpox Yellow fever
What is the key defect which causes X-linked agammaglobulinaemia?
Mutation or absence of Bruton’s Tyrosine Kinase, which is essential for B cell development
When is the onset of X-linked agammaglobulinaemia clinically noted?
6 months of age, when maternal IgG wears off
Why can IgA deficienct patients get anaphylaxis from blood products?
If blood contains IgA -> patient may have Anti-IgA antibodies
How is specific antibody deficiency detected?
Response to vaccination is impaired
What cell marker is present on all T cells?
CD3
What is the role of AIRE ?
Autoimmune regulator - required to turn on tissue-specific self-antigens in thymus, to educate T cells to detect self vs non-self. For avoidance of autoimmunity
What are the 3 key features found in APECED (autoimmune poly-endocrine syndrome Type 1)?
Chronic mucocutaneous candidiasis
Hypoparathyroidism
Addison’s
What is Abatacept?
CTLA-4 Ig
- this binds to B7 to turn off T cells / prevent activation
Used for RA
What is Hyper IgM Syndrome caused by?
Absent CD40 to CD40 Ligand co-stimulation
This is key for B cell differentiation, so without this, B cells cannot isotype switch.
Thus high IgM, no IgG or IgA
What is the key growth factor for T cell expansion?
IL-2
What is the key regulatory factor for Treg cells?
FOXP3
What is the key defect in IPEX?
Defect in FOXP3, which is required for Treg cells
Thus will get rampant autoimmune manifestations
What infection does deficiency of Th1 cells put you at risk of? (2)
Non-tuberculous mycobacteria
Invasive salmonella
Which T cells are most important in fighting candida infection?
Th17 cells
Which interleukin is most central to Psoriasis?
IL-17
Which T cells are most involved in atopic disease?
Th2 cells
What is the pathophysiology of SCID?
Deficiency in a component critical for T cell function and development
Leads to vulnerability to infections, plus increased risk of malignancy and autoimmunity
What are the two main functions of NK cells?
To kill
- virally infected cells
- tumour cells
Other than AChR antibodies, what antibody can be tested for in myasthenia gravis?
Anti-MuSK
What are the key antibodies to test for in suspected SLE?
ANA
Anti-sm antibody
Anti-dsDNA
What is Anti-mitochondrial antibody associated with?
Primary biliary cirrhosis
What is Anti-VGCC ab associated with?
Lambert-Eaton Myasthenic Syndrome
What is Liver kidney microsome type 1 antibodies (anti-LKM-1) associated with?
Autoimmune hepatitis
What are anti-smooth muscle (SM) antibodies associated with?
Chronic autoimmune hepatitis
What is anti-U1RNP ab associated with?
Mixed connective tissue disease
What is the most common infection associated with urticaria?
Mycoplasma
What is expressed on plasma cells?
CD38
Who needs tetanus Ig after a dirty wound?
Uncertain vax hx
Humoral immunodeficiency
