Immunology Flashcards
What type of vaccine is HPV vaccine?
Recombinant (uses virus-like particles)
Protects against 9 types of HPV: 6, 11, 16, 18, 31, 33, 45, 52 and 58.
MMR vaccine type
Live attenuated
Which complement is common to all pathways?
C3
Growth factor in granular tissue in a wound
VEGF
Which Immunoglobulin is a pentamer?
IgM (Ig with highest molecular weight)
IgG: % of total Ig pool? Structure? Subtypes?
75% total Ig pool
Monomer
4 subtypes: IgG1, IgG2, IgG3, IgG4
IgA: % of total Ig pool? Structure? Isoforms? Where is it found?
20% total Ig pool
Dimer
2 isoforms
Found in mucosal epithelium (GIT, respiratory tract, urogenital tract)
IgM: % of total Ig pool? Structure? Where is it found?
5% of total Ig pool
1st Immunoglobulin produced during infection, pentamer, confined to intravascular pool
IgE: Structure? Function?
Monomer
Binds to basophils and mast cells
Involved in allergy and parasitic infections
IgD: % of total Ig pool? Structure?
<1% total Ig pool
Monomer
Hepadnavirus containing DNA, can be transmitted via needle sharing and blood transfusion
Hep B
Interpretation of Hep B serology
HBsAg (surface Ag)= current infection (acute/ chronic = >6 months)
HBeAg= acute (early) infection
anti HBe Ab = indicates acquired natural immunity (from previous infection only)
anti HBs Ab = immunity (either previous infection or vaccination)
Anti HBc Ab (IgM)= acute infection, early or resolving
Anti HBc Ab (IgG)= acute/ chronic/ immune (immune secondary to infection, not vaccination)
Main cell types in the adaptive vs innate immune system
Adaptive (acquired): B and T cells that have immune memory
Innate: NK cells and some types of T cells (gamma and delta)
Rhesus D immunoglobulin treatment utilises what class of antibody?
IgG
What type of vaccination is the varicella vaccine?
Live attenuated
Examples of live/ inactivated/ toxoid/ polysaccharide and subunit/ GM vaccines?
Live: MMR, varicella, BCG, polio, rotavirus, BCG, typhoid, cholera
Inactivated: influenza, Hep A, pertussis
Toxoid: diphtheria, tetanus
Polysaccharide: HIB, meningococcal A&C, pneumococcal, typhoid
Subunit/ GM: hep B
Why does RA improve in pregnancy and SLE worsen?
Progesterone suppresses Th-1 cells and RA is Th-1 dependent
Humoral immunity tends to dominate (Th-2 cell mediated) and SLE is Th-2 dependent.
How does the placenta help to prevent immune rejection of the foetus?
The foetus is a semi-allograft
The placenta acts as an immunological barrier between the mother and the foetus. It is able to tolerate foreign antigens without provocation of immune response. A number of mechanisms help with this:
- MHC (HLA complex) antigen expression:
- In trophoblast cells MHC class II antigens are not presented
- MHC class I HLA genes can be classed as 1a (HLA-A, -B and -C) or 1b (HLA- E, -F, and -G)
- In extravillous trophoblast cells only HLA-C is expressed from 1a group along with all three types of 1b genes (-E, -F and -G)
- HLA-G in particular has several roles in immune suppression such as reduction of NK cell killing activity, reduction of IFN-y production, regulation of cytokine production and suppression of cytotoxic T lymphocyte killing activity and T-helper activity - Complement Protein Inhibition
- DAF, MCP and CG59 are proteins expressed by the placenta that inhibit complement proteins. Complement is an important part of the immune system in graft rejections. - T-cells/ T-helper cells:
- changes to both the cell populations occur during pregnancy. Increased T regulatory cell (TREG cell) populations occur. These cells both up and down regulate various immune responses.
- Th2 levels increase during pregnancy
- Th1 levels decrease during pregnancy - Phosphocholination:
The addition of phoshocholine molecule to glycoproteins inhibits T and B lymphocyte responses. - PDL1: cell signalling molecule that down regulates T cell response
- Progesterone: thought to play a role in immune suppression by stimulating lymphocytes to produce a blocking factor that mediates cytokine production
Other mechanisms: placental exosomes, retroviral envelope proteins and CRH may all play a role in maternal immune tolerance
At what gestation foes maternal IgG transfer to foetus start?
12 weeks
At what gestation does fetal production of IgM start?
Week 10-11
Which is the first antibody type to be synthesised by neonates?
IgM
Which Ig is secreted in breast milk and resistant to stomach acid breakdown?
IgA
Which Ig crosses the placenta?
IgG
What are APCs? What are the three types?
Cells that have MHC class 2 molecules in addition to type 1 and are able to stimulate CD4+ (T helper cells) and CD8+ (Cytotoxic T cells)
3 types:
- Dendritic cells
- Macrophages (derived from monocytes)
- B cells
Which IL produced in pregnancy enhance fetal survival and which ones have damaging effects (down-regulated)
IL-3 and IL 10 enhance fetal survival and promote intrauterine growth
TNF-alpha, IFN-y and IL-2 have damaging effects and in some cases result in fetal death
What do Th1 and Th2 produce? Which is suppressed and which increases during pregnancy?
Th1 produces cytokines TNF alpha, IFN-y and IL-2
Th2 produces cytokines IL-4, IL-5, IL-9, IL-10 and IL-13
Th1 is suppressed in pregnancy (as are TNF-a, IFN-y and IL2) and Th2 increases.
What complement protein is the product of all 3 activation pathways?
C3 (all pathways eventually lead to splitting of C3 to C3a and C3b)
What are the 3 complement pathways?
Classical pathway (antigen antibody complex activates C1- IgM/ IgG)
Lectin pathway (M B Lectin binds mannose on pathogen surface (C4/C2)
Alternate pathway (pathogen surface+ C3b binds, factors B&D)
What is the function of C5b?
How is C5b made?
C5b recruits C6, C7, C8 and C9 to form membrane attack complex.
C3b combines with other complement proteins to form C5 converts and convert C5 to C5a and C5b.
Which HLA’s are downregulated/ unregulated at the trophoblast to prevent rejection?
HLA-A and HLA-b are downregulated
HLA-E and HLA-G are unregulated
Type 1 hypersensitivity reaction:
- Mediators
- Description
- Examples
Mediated by IgE
Description: Fast response <1h after exposure. Antigens bind to IgE causing release of bioactive molecules
Examples: anaphylaxis, allergic asthma, atopy, some allergies e.g. latex
Type 2 hypersensitivity reaction:
- Mediators
- Description
- Examples
Mediated by IgM, IgG, complement
Description: Ig binds to host cell antigen perceived as foreign, activates release of cytotoxic mediators e.g. MAC
Examples: AI haemolytic anaemias, ITP, good pasture’s syndrome
Type 3 hypersensitivity reaction:
- Mediators
- Description
- Examples
Mediated by IgG
Description: IgG binds to antigens forming an immune complex. The immune complex often deposits in vessel walls triggering inflammatory mediators
Examples: SLE, RA
Type 4 hypersensitivity reaction:
- Mediators
- Description
- Examples
Mediated by T cells
Description: delayed hypersensitivity. T cells sensitised by antigen presented by APCs. Memory T cells activated after re-exposure. T cells activate macrophages.
Examples: contact dermatitis, graft rejection, MS, T1DM, Mantoux test
Type 5 hypersensitivity reaction:
- Mediators
- Description
- Examples
Mediated by IgM, IgG and complement
Description: instead of antigen binding, antibody binds cell surface ligands preventing cell signalling
Examples: myasthenia gravis, grave’s disease
Potentially sensitising events requiring anti-D
- Amniocentesis, CVS and cordocentesis
- APH/ PVB
- ECV
- Abdominal trauma
- Ectopic pregnancy
- Evacuation of molar pregnancy
- IUD/ stillbirth
- In-utero therapeutic interventions (transfusion, surgery etc)
- Miscarriage/ threatened miscarriage, TOP
- Delivery
- In pregnancies <12 weeks, anti-D is only indicated following an ectopic pregnancy, molar pregnancy, TOP and in some cases of uterine bleeding where this is repeated, heavy or associated with abdo pain
What type of hypersensitivity reaction best describes haemolytic disease of the newborn?
Type II (anti-body mediated)
The conversion of prothrombin to thrombin ca be inhibited by lupus anticoagulant antibodies.
What is the frequency of these antibodies in the normal UK obstetric population and the risk of fetal mortality associated with this?
2-5% normal population
85-95% fetal mortality
Natural Killer cells belong to which cell type?
Lymphocytes (bridging the innate and adaptive arms of the immune system)
Capturing, processing and presenting the antigen to T cells are the only functions of which type of cell?
Dendritic cells (APC)
- Derived from monocytes of lymphoid lineages
MOA of azathioprine/ steroids/ tacrolimus
Azathioprine:
Inhibition of nucleic acid synthesis in all mitotic cells
Steroids:
Prevent generation of cytotoxic effector cells and produce generalised anti-inflammatory response
Tacrolimus:
Blocks T cell activation
What proportion of CMV infections are asymptomatic in immune-competent patients?
Risk of fetal transmission if pregnant?
How many infected foetuses will develop symptoms?
90%
40-50%
22-38%
Cells that secrete histamine, serotonin and heparin
Basophils (largest granulocyte)
Mast cells (similar to basophils)- role in allergy and anaphylaxis
Which class of Ig is predominantly involved in activating complement?
IgM (more effective- only one unit needed)
IgG (two units needed)
Which cytokines are secreted by virally infected host cells and stimulates neighbouring cells to synthesise antiviral proteins?
Interferon-gamma
