Immunotherapy in the prevention and treatment of infection Flashcards
Define immunotherapy
Immune system can be manipulated in order to help fight or prevent infection
Define active immunisation/vaccination
Administration of antigen in order to induce active production of immunity and thus protection from disease.
What is meant or referred to by the ‘active immunity’ produced by vaccination?
T and B cell lymphocytes (Ag recognition) and their immunological memory.
What are the characteristics and advantages of active immunisation/vaccination?
Immunity is specific for antigen given
Immunological memory is induced (adaptive)
Immunity involves antibody and/or T cell responses
Systemic and/or mucosal immunity can be induced
What is a disadvantage of active immunisation/vaccination?
Protection is not immediate (days/weeks)
What is meant by adaptive immunity?
Immunity that arises from recognition of antigen, and induces immunological memory - bigger, faster response second time infection is seen.
What is meant by systemic immunity?
Activation of lymphocytes by antigen recognition in secondary lymphoid tissue i.e. liver and spleen.
How do B cells initiate immunity?
Recognise epitopes of antigen by the Ig/abs
How do T cells initiate immunity?
Recognise antigenic peptides/proteins which are presented to T-cell receptors by antigen presenting cells Peptides are associated with HLA proteins on the surface of APCs.
CD4 + helper T-cells associated with?
HLA Class 2 associated peptides
CD8+ cytotoxic t-cells associated with?
HLA class 2 antigen associated peptides
Define passive immunisation
Administration of pre-formed antibody in order to protect from disease.
Characteristics and advantages passive immunisation
Protection is immediate
Ab therapy which provides immunological protection for patients
Characteristics and disadvantages of passive immunisation
No immunological memory generated, not long lasting.
No immune response stimulated in recipient
What is a toxoid?
Inactivated form of toxin.
Toxoid is harmless version of toxin, but similar antigenic structure of toxin allows recognition by lymphocytes and generates immunological memory which will be active against the toxin itself.
Descrive the principle of vaccination with a toxoid vaccine?
Toxoid vaccination administered.
Primary ab response produced to toxoid antigen - B cells recognise antigen and produce mainly IgM antibodies.
Natural infection - B-cells recognise toxin quickly, reactivate and more cells available -> bigger and quicker response. After B-cell activation, class switching of IgM to IgG occurs and mainly IgG produced.§
Example of toxoid vaccine
Tetanus
What is a live attenuated vaccine?
Vaccine which contains organisms which are no longer able to induce disease, but still have antigenic features and structures of microbe.
Organisms multiply in host, mimicking natural infection , but causing no/mild symptoms.
Immune response mimics that generated by natural infection.
What is the immune response to a live attenuated vaccine?
IR mimics that generated by natural infection
Systemic/mucosal immunity
Long lasting memory
symptoms caused by live attenuated vaccine?
None or mild - flu like
Oedema/redness at injury site
How many doses required for live attenuated vaccine?
one
Risks of using live attenuated vaccine?
Potential for severe infection in immunodeficiency - opportunistic
Potential to revert to virulent strain - significant danger, safe guards and monitoring in place
Storage conditions crucial for stability
How do the storage temperatures of live attenuated vaccine affect stability?
Requires cool temperatures
Could effect shelf life
How is the virulence reduced for live attenuated organisms
Repeated culture in-vitro
Name some examples of live attenuated vaccines
MMR, BCG, oral polio (Sabin)
What is a killed vaccine?
Preparations of whole inactivated virus/bacteria. Do not multiply in the host.
What are the disadvantages to using a killed vaccine?
Do not multiply in host and not as strong immunogens as a live vaccine so:
- only systemic immunity induced
- several doses needed (booster to increase amount of Ag to provide immunological memory)
- Large amount of antigen needed - risk of reaction
How is the large amount of Ag required in a killed vaccine partly overcome?
Using adjuvants in the vaccines.
What is an adjuvant?
Any material that helps to boost the immune response in a non-specific way e.g. prolong, accelerate or enhance antigen-specific immune response.
They stimulate the ability of APCs to present antigen -> lymphocyte stimulation.
Also mimic PAMPs in order that they are recognised by the immune system and increase its response.
Name an example of an inorganic adjuvant and its function
Alum = aluminium hydroxide
stimulates protein complexes in cells called inflamasomes > production of cytokines IL-1 > promotes Ab production> boost immune response.
What are the problems with killed vaccines?
inactivation process may alter structure and therefore antigenic nature.
not suitable for all organisms.
Examples of killed vaccines
Killed polio (salk), influenza, pertussis
What is a sub-unit/recombinant vaccine?
Consists of parts/products of organisms i.e. single proteins or molecules.
Produced by molecular biology technology or by fractionation of microbes.
What is the immune response to a sub-unit/recombinant vaccine?
Does not mimic natural infection, but does induce response which prevents disease
What are the risks/disadvantages of sub-unit vaccines?
Only systemic immunity induced
Several doses needed
Adjuvant needed
What are the advantages to using sub-unit vaccines?
No risk of infection
no risk of reversion to virulence
no unwanted components in the vaccine
Examples of sub-unit vaccines
Tetanus toxoid, Hepatitis B, Hib, Group C meningococcus
What is a sub-unit conjugate vaccine?
Contains 2 different antigenic compounds that are covalently linked together in order to increase the immunogenicity of a vaccine. Used when bacteria has polysaccharide outer coating.
Why do polysaccharide coatings cause an issue for vaccines?
Not good for stimulating immune response as they disguise a bacterium’s antigens so that the immature immune systems of infants and younger children can’t recognize or respond to them. i.e. don't stimulate CD4+ t-cells as no Ag peptides bound to HLA class 1 molecules on surface of APC. Can still stimulate B- cells to produce Ab to polysaccharide
Why does there need to be a physical bond between the polysaccharide and adjuvant/conjugate components of a conjugate vaccine?
The linkage of antigen/toxoid helps the immature immune system react to polysaccharide coatings and defend against the disease-causing bacterium i.e. potent stimulator of T-cells for immunological memory
Explain how meningococcal group C vaccine works and its components.
Compromised of diphtheria protein conjuhgated to men Groip C capsular polysaccharide.
Dip protein - potent stimulator of helper T- cells in order tp stimulate T-cell response and create immunological memory
Men group C capsular poly - main Ag component that stimulates B-cells to produce neutralising Abs adjacent men C.
Explain how meningococcal group B vaccine works and its components
Composed of three outer membrane proteins of meningococci, two of which bound to proteins to form fusion proteins. Also contains outer membrane vesicles.
Immunity to meningococcal disease is mediated primarily by serum antibodies that are specific for bacterial surface components, and are capable of activating complement once bound, resulting in bacteriolysis.
Contraindications of all vaccines
acute illness - make worse/not work
severe reaction to previous dose of same vaccine
Contraindications of live vaccines
Pregnancy - dangerous to foetus
Primary immunodeficiency
Secondary immunodeficnecy
Examples of allergens contained in vaccines/vaccine components - contraindication
Influenza - traces of egg protein
Abx traces such as neomycin or polymyxin
What circumstances might vaccines not work in?
Live typhoid vaccine given to patients on abx - killed vaccine typhoid
Patients receiving IgG therapy
Live vaccines given close together - after immune response peaked for first vaccine, period of immunosuppression follows > body would suppress effective response to vaccine given closely.
Key ages/stages of vaccine schedule
Two months, Three months Four months, Approx 12 months, Approx 13 monhts, Three years and four months, Girls 12-13 years = HPV 13 - 18 years = tetanus, diptheria and polio
What additional vaccines are given to medical students and HCWs?
Hep B
What additional vaccines are given to splenectomy patients?
Pneumovax for pneumococcal infection
What sort of infections are vaccinated against in foreign travellers?
Yellow fever,
Japanese encephalitis,
Hep A
What is human normal IG replacement therapy?
IV IG or subcutaenous IG - passive immunotehrapy ie. immunity provided.
Normal ABS present in humans through normal environmental exposures to microbes
IgG is extracted from the plasma of large number of individuals.
Commercial IVIG preparations contain
estimated 10 million Ab specificities - confer passive protective against common env microbes
High titres of Abs against bacteria, viruses and toxins which activate complement and opsonise for phagocytosis, neutralise viruses and toxins
indications for use of IG replacement therapy in primary ab deficiencies (don’t produce Ab/low no’s)
common variable immunodeficiency,
x-linked agammglobulinaemia
hyper-IgM syndrome
primary T cell deficiencies
indications for use of IG replacement therapy in secondary ab deficiencies (dec Abs due to other malignancies)
Chrnonic lymphocytic leukaemia,
Multiple myeloma,
HIV inf children with recurrent viral or bacterial infections
Premature infants with recurrent infs (passive IgG levels dec )
Early onset neo-natal sepsis
What is the half life of Ab/IgG
3 weeks
What is a hyperimmune or specific IG preparation?
Selected for very high titers of Abs to specific microbes, used to give protection against specific microbe.
What are hyperimmune or specific IgG preparations prepared from?
Plasma pre-screened for high tires of specific abs e.g. Hep B IG high titre >1:100,000 of anti-HBsAg
Vaccinated volunteers e.g. rabies IG
Examples of uses of hyperimmune IG for PEP/treatment
Hepatitis Rabies RSV Tetanus Varicella zoster for babies at risk/premature/ CMV - immunosuppresed tx patients
What are monoclonal Abs?
Artificially produced Abs of a single specificity derived from a single B cell clone
Advantages for the use/production of MAbs?
endless supply = production industrial
Fully homogenous and characterised reagent: highly specific for target Ag and selected for neutralising activity
Reduced risk of transferring infection.
Uses for MAbs and example
Autoimmune and Cancer treatment.
Palivizumab - RSV prevention in infants at HR.
Biological activities of cyotkines
Stimulation of cells of immune system
Stimulation of inflammation
Stimulation of haematopoiesis
anti-viral and anti-proliferative activities
What anti-viral activities does IFN alpha have?
Inhibition of viral replication and protein synthesis in infected cells
Stimulation of anti-viral immune response.
When is IFN alpha used?
Chrnoic hep B - ltd response rate
What is used to enhance circulating neutrophil levels?
granulocyte colony stimulating factor and granulocyte-macrophange colony stimulating factor
