Immunotherapy in the prevention and treatment of infection

Question 1

Two main forms of immunisation

Answer 1

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

Question 2

Characteristics of active immunisation

Answer 2

• Immunity is specific for a antigen
• memory T/B cells generated
• May induce systemic or mucosal immunity
• Not immediate, at least weeks

Question 3

Characteristics of passive immunisation

Answer 3

• Preformed antibodies for immediate protection
• No memory generated, limited duration
• NO IMMUNE RESPONSE STIMULATED IN RECIPIENT

Question 4

Define toxoid

Answer 4

Toxoid: is an inactivated or attenuated toxin

Question 5

Role of Ig subclasses in active immunisation

Answer 5

Mainly IgM following toxoid delivery, then class switching of naive lymphocytes to IgG on exposure to toxin .

Question 6

Define live attenuated vaccine

Answer 6

Live: contains live microbes

Attenuated: microbes have been somewhat disabled to not include disease-causing property

Question 7

Advantages of live attenuated vaccines

Answer 7

Multiply in host, mimic response of a real infection

Can therefore stimulate systemic/mucosal immunity

Usually only require one dose

Question 8

Risks associated with live attenuated vaccines

Answer 8

• Potential for severe infection in immunodeficient
• Potential to revert to virulent strain
• Storage conditions critical for stbaility

Question 9

Examples of live attenuated vaccines

Answer 9

MMR

BCG

Oral polio (Sabin)

Question 10

Define: killed vaccines

Answer 10

Whole microbes, but dead.

Question 11

Advantages of killed vaccines

Answer 11

• NO risk of infection
• NO risk of reversion to virulence
• More stable for storage

Question 12

Disadvantages of killed vaccines

Answer 12

• Usually only systemic immunity
• Several doses needed
• Large amounts of antigen needed
• Inactivation process may alter antigen structure
• Not suitable for all organisms

Question 13

Examples of killed vaccines

Answer 13

Killed polio (Salk)

Influenza

Pertussis

Question 14

Define: Subunit vaccine

Answer 14

• Part organism/product of organisms
• Immunisation does not mimic natural infection but induces a response which prevents disease

Question 15

Pros/cons of subunit vaccines

Answer 15

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

Question 16

Examples of subunit vaccines

Answer 16

Tetanus toxoid

Hep B

Hib

Group C meningococcus

Question 17

Structure of groupC meningococcus vaccine

Answer 17

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.

Question 18

Contraindications to immunisation

Answer 18

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)

Question 19

Circumstances in which vaccines may not work

Answer 19

• Live typhoid vaccine given to patients on ABs
• Patients receiving immunoglobulin therapy
• Live vaccines given close together

Question 20

6-in-1 Vaccine

Answer 20

3 doses of:

Diphteria

Hep B

Hib

polio

tetanus

Whooping cough

Question 21

Pneumovax given to

Answer 21

Spleectomy patients

Question 22

Define: Human normal immunoglobulin replacement therapy

Answer 22

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

Question 23

WHO criteria ofIVIG preparations

Answer 23

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)

Question 24

Indications for use of Ig replacement therapy

Answer 24

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

Question 25

Situations when hyperimmune or specific immunoglobulin preparations are useful

Answer 25

When immediate protection towards particualr infections required

Question 26

Sources of Hyperimmune or specific immunoglobulin preparations:

Answer 26

• 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.

Question 27

Examples of uses of hyperimmune immunoglobulin for post-exposure treatment and/or for prophylaxis

Answer 27

hepatitis

rabies

respiratory syncitial virus

tetanus (susceptible wounds)

varicella zoster

cytomegalovirus

Question 28

Monoclonalanitbodies as passive immunotherapy

Answer 28

‘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.

Question 29

Biological activities of cytokines making them suited for passive immunisation

Answer 29

• stimulation of cells of the immune system
• stimulation of inflammation
• stimulation of haematopoiesis
• anti-viral and anti-proliferative activities

Question 30

Anti-viral properties of interferon-a

Answer 30

• 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.

Question 31

Passive immunisation by enhancing neutrophil levels

Answer 31

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;

Question 32

Passive immunisation by Enhancement of phagocyte function by interferon-g

Answer 32

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.