Immunotherapy in the prevention and treatment of infection Flashcards
Two main forms of immunisation
Active - vaccination; administration of specificantigens in order to induce active production of immunity
Passive - Administration of pre-forned antibody in order to protect from disease
Characteristics of active immunisation
- Immunity is specific for a antigen
- memory T/B cells generated
- May induce systemic or mucosal immunity
- Not immediate, at least weeks
Characteristics of passive immunisation
- Preformed antibodies for immediate protection
- No memory generated, limited duration
- NO IMMUNE RESPONSE STIMULATED IN RECIPIENT
Define toxoid
Toxoid: is an inactivated or attenuated toxin
Role of Ig subclasses in active immunisation
Mainly IgM following toxoid delivery, then class switching of naive lymphocytes to IgG on exposure to toxin .
Define live attenuated vaccine
Live: contains live microbes
Attenuated: microbes have been somewhat disabled to not include disease-causing property
Advantages of live attenuated vaccines
Multiply in host, mimic response of a real infection
Can therefore stimulate systemic/mucosal immunity
Usually only require one dose
Risks associated with live attenuated vaccines
- Potential for severe infection in immunodeficient
- Potential to revert to virulent strain
- Storage conditions critical for stbaility
Examples of live attenuated vaccines
MMR
BCG
Oral polio (Sabin)
Define: killed vaccines
Whole microbes, but dead.
Advantages of killed vaccines
- NO risk of infection
- NO risk of reversion to virulence
- More stable for storage
Disadvantages of killed vaccines
- Usually only systemic immunity
- Several doses needed
- Large amounts of antigen needed
- Inactivation process may alter antigen structure
- Not suitable for all organisms
Examples of killed vaccines
Killed polio (Salk)
Influenza
Pertussis
Define: Subunit vaccine
- Part organism/product of organisms
- Immunisation does not mimic natural infection but induces a response which prevents disease
Pros/cons of subunit vaccines
Pro: No risk of infection
No risk of reversion to virulence
No unwanted components in the vaccine i.e only relevant antigens, and no immunsuppressant microbial components present
Cons: Usually only systemic immunity
Several doses
Adjuvant needed e.g. Alum, trigger inflammosomes; IL-1
Examples of subunit vaccines
Tetanus toxoid
Hep B
Hib
Group C meningococcus
Structure of groupC meningococcus vaccine
Human response to meningococcal requires a very strong response to capsular polysacc to be effective, especially complement actiavtion.
Polysaccs on their own are very weak and poor antigens, Th only react to peptides bound to HLA proteins, which polysaccs are not.
Diphteria used as is a known strong stimulator of Th.
Contraindications to immunisation
All vaccines: Acute illness, previous reaction to vaccine
Live vaccines:
- Pregnancy
- Primary immunodeficiency
- 20 immunodef. e.g. high dose steroids, chemo, HIV
Allergies: (Influenza vac may contain traces of egg)
Circumstances in which vaccines may not work
- Live typhoid vaccine given to patients on ABs
- Patients receiving immunoglobulin therapy
- Live vaccines given close together
6-in-1 Vaccine
3 doses of:
Diphteria
Hep B
Hib
polio
tetanus
Whooping cough
Pneumovax given to
Spleectomy patients
Define: Human normal immunoglobulin replacement therapy
A form of passive immunisation: Intra-venous immunoglobulin (IVIG) or subcutaneous immunoglobulin.
contain high titres of antibodies against a number of bacteria, viruses and
toxins, which: activate complement and opsonise for phagocytosis neutralise viruses and toxins
WHO criteria ofIVIG preparations
Derived from: pooled plasma of at least 1000 donors (usually 6-10,000)
The IgG must be: at least 90% intact
- normal ratio of subclasses (IgG1, IgG2, IgG3, IgG4)
- biologically active (activates complement, binds FcR)
Free of:
- inflammatory mediators
- infectious agents (Hepatitis B and C; HIV)
Indications for use of Ig replacement therapy
Primary antibody deficiencies:
- common variable immunodeficiency
- X-linked agammaglobulinaemia
- hyper-IgM syndrome
- Also in: primary T cell deficiencies
Secondary antibody deficiencies:
- some patients with chronic lymphocytic leukemia or multiple myeloma
- HIV infected children with recurrent viral or bacterial infections
- Premature infants with recurrent infections
- Early-onset neonatal sepsis
Situations when hyperimmune or specific immunoglobulin preparations are useful
When immediate protection towards particualr infections required
Sources of Hyperimmune or specific immunoglobulin preparations:
- plasma pre-screened for high titres of specific antibodies, eg. hepatitis B
- immune globulin has a titre of >1:100,000 of anti-HBsAg. - vaccinated volunteers, eg. rabies immunoglobulin.
Examples of uses of hyperimmune immunoglobulin for post-exposure treatment and/or for prophylaxis
hepatitis
rabies
respiratory syncitial virus
tetanus (susceptible wounds)
varicella zoster
cytomegalovirus
Monoclonalanitbodies as passive immunotherapy
‘Artificially’ produced antibodies of a single specificity derived from a single B cell clone.
- endless supply
- fully homogeneous and characterised reagent: highly specific for the target
Eg. Palivizumab (Synagis) is a monoclonal antibody indicated for the prevention of respiratory syncytial virus infection in infants at high risk of infection.
Biological activities of cytokines making them suited for passive immunisation
- stimulation of cells of the immune system
- stimulation of inflammation
- stimulation of haematopoiesis
- anti-viral and anti-proliferative activities
Anti-viral properties of interferon-a
- inhibition of viral replication and protein synthesis in infected cells
- stimulation of the anti-viral immune response
Interferon-a is used in the treatment of chronic hepatitis B but its use is limited by a response rate of less than 50%, and relapse is frequent.
- Ribavirin can be used in combination with peginterferon-a for the treatment of chronic hepatitis C; ribavirin monotherapy is ineffective.
- Both peg-interferon-a and ribavirin are used with the new protease and polymerase inhibitors for therapy of HCV infection.
Passive immunisation by enhancing neutrophil levels
granulocyte colony-stimulating factor granulocyte-macrophage colony stimulating factor
•reduction in duration of neutropenia and incidence of febrile neutropenia in cytotoxic chemotherapy for malignancy (except chronic myeloid leukaemia and myelodysplastic syndromes);
•reduction in duration of neutropenia (and associated sequelae)
in myeloablative therapy followed by bone-marrow transplantation;
Passive immunisation by Enhancement of phagocyte function by interferon-g
eg. in chronic granulomatous disease (CGD)
CGD is a primary immunodeficiency disease involving defects in genes encoding components of phagocyte NADPH oxidase involved in the generation of reactive oxygen metabolites.
The activity of the NADPH oxidase is upregulated by interferon-g.
