Immune system in health

Question 1

What are the properties of an ideal vaccine?

Answer 1

Safe to the patient
Prevent infection in all cases
Cross reactive
Lifelong protection
Easy to administer
Stable
Not too expensive (global health)

Question 2

What are the risks of live attenuated vaccines? Examples?

Answer 2

Risk of reverting to the wild type pathogenic genotype e.g. live attenuated type 3 Sabin polio vaccine

Question 3

What are the two types of vaccination?

Answer 3

Passive and active

Question 4

What is an example of passive immunity?

Answer 4

Transfer of maternal IgG into the foetal blood during the last trimester - esp important for protection against encapsulated bacteria (requires TI2 antibody responses which do not develop until later in life)

Question 5

How is protection against specific microbes achieved in passive vaccination?

Answer 5

Pooled serum donors with high titres of neutralising antibody are used

Question 6

What are examples of human serum vaccines?

Answer 6

Rabies, Rhesus D, VZV

Question 7

What is an example of animal serum vaccine?

Answer 7

Tetanus

Question 8

What is the problem with animal serum vaccines?

Answer 8

Risk of hypersensitivity reactions against the animal immunoglobulin which is recognised as foreign

Question 9

What does active vaccination involve?

Answer 9

Injecting the infectious organism (or parts of it) into the individual before exposure to the infectious organism

Question 10

What are examples of whole micro-organism vaccinations?

Answer 10

Live attenuated - BCG, Yellow Fever,VZV, MMR

Dead - whole-cell Pertussis, Rabies

Question 11

What are examples of vaccines with subunit of micro-organism?

Answer 11

Inactivated toxin - tetanus, diphtheria toxoid
Recombinant proteins - Hep B, HPV
Polysaccharide - pneumococcus, meningococcus, haemophilus
Conjugate vaccines polysaccharide combined with more immunogenic conjugate to elicit T cell help

Question 12

What are adjuvants?

Answer 12

Materials injected with vaccine antigen to enhance immune response

Question 13

What is the most widely used adjuvant?

Answer 13

Alum - onto which the microbial antigen is adsorbed?

Question 14

How do adjuvants work?

Answer 14

Convert the soluble protein to particulate material, which is more readily phagocytosed by APC. It provides a depot of slow release of antigen

Question 15

What is an example of co-administration of vaccines?

Answer 15

Pertussis with diphtheria & tetanus toxoid

Question 16

What is an incomplete Freund’s adjuvant?

Answer 16

Water in oil emulsion

Question 17

What is a complete Freund’s adjuvant?

Answer 17

Composed of inactivated mycobacteria emulsified in oil

Question 18

What are conjugate vaccines?

Answer 18

Infants can’t produce antibody responses against bacterial capsular polysaccharides - so the polysaccharide is conjugated to protein antigens like Diphtheria and Tetanus toxoids. B cells can internalise the conjugate and present the protein, and obtain help from T cells

Question 19

At what stage of life are lymphocyte numbers highest? What are these lymphocytes like?

Answer 19

Just after birth

Naive, do not respond well to antigen

Question 20

What is the most prominent antibody class in neonatal period?

Answer 20

IgM

Question 21

What problems are associated with Congenital Rubella?

Answer 21

Sensorineural deafness
Eye disease - retinopathy, cataract, microphthalmia
Congenital heart disease

Question 22

What are other congenital transplacental infections?

Answer 22

Toxoplasmosis, CMV, Herpes, Syphilis

Question 23

When is transplacental IgG important for the foetus?

Answer 23

First 3-6 months of life

Question 24

When do maternal IgG get transported across the placenta?

Answer 24

Last trimester of pregnancy

Question 25

What antibodies do not cross the placenta?

Answer 25

IgA & IgM

Question 26

What is the problem with placental IgG?

Answer 26

Transmission of IgG mediated autoimmune disease e.g. Neonatal myasthenia gravis (IgG against acetylcholinesterase), Neonatal heart block in RO positive SLE patients (RO antibody destroys nerve conduction fibres in foetus)

Question 27

What is transient hypogammaglobulinaemia of infancy (THI)?

Answer 27

When there is a delay in the infant developing IgG, thus total IgG concentrations remain low

Question 28

What are the benefits of vaccination against pertussis for pregnant women?

Answer 28

Boost their IgG antibody levels so that these can be transmitted to foetus

Question 29

What does human milk contain that help protect against early infections?

Answer 29

Secretory IgA antibodies, bactericidal proteins (e.g. lactoferrin), cytokines

Question 30

What is done to overcome difficulties with infant immmunisation schedules?

Answer 30

Use of conjugate rather than polysaccharide vaccines

Question 31

What is immunosenescence?

Answer 31

Gradual deterioration of the immune system with age

Question 32

What changes occur in haematopoiesis?

Answer 32

Number of haematopoietic cells ↓, and those that remain are biased towards myeloid lineage therefore number of lymphoid cells ↓ (not pathological)

Question 33

What do changes in cytokines cause?

Answer 33

Immuno-ageing (increased inflammation)

Question 34

What are the changes with cytlkines?

Answer 34

↑ level of circulating PRO-inflammatory cytokines and CRP | ↓ level of ANTI-inflammatory cytokine (IL-10)

Question 35

What are the pro-inflammatory cytokines that increase with age?

Answer 35

IL-1B, IL-6, TNF

Question 36

What does inflamm-ageing contribute to?

Answer 36

Many age-related conditions e.g. CVD, insulin resistance, sarcopenia, dementia

Question 37

What are the causes of inflamm-ageing?

Answer 37

↓ sex hormones, production of cytokines by senescent cells, low level of production by macrophages

Question 38

What happens to neutrophils with age?

Answer 38

Number not changed ↓ bactericidal processes used by neutrophils Chemotaxis reduced --> ↑ time taken for neutrophils to reach site of infection Phagocytosis ↓ Ability to generate reactive oxygen species ↓(cytotoxic effects)

Question 39

What happens to monocytes with age?

Answer 39

``` ↑ circulating monocyte number, but decreased function ↓ TLR-induced cytokines ↓ phagocytosis ↓ ROS generation ↓ production of IL-6 ```

Question 40

What happens to NK cells with age?

Answer 40

↑ number ↓ proliferation in response to IL-2 ↓ Cytotoxicity ↓ Telomere length

Question 41

What happens to T lymphocytes with age?

Answer 41

↓ T cell producing capacity --> ↓ naive cells ↑ memory T cells ↓ Production of and response to IL-2 ↓ telomere length --> ↓ proliferative capacity ↓ co-stimulatory molecule CD28 on surface Acquire NKG2D (normally receptor of NK cells) Acquire ability to induce apoptosis in other cells Lose their helper function

Question 42

What happens to B lymphocytes with age?

Answer 42

↑ memory B cells ↓ telomere length ↓ ability to proliferate ↓ ability to produce high affinity antibodies via the germinal centre reaction ↓ diversity of antibodies produced ↑ autoreactive antibodies due to peripheral tolerance

Question 43

What are the main consequences of immunosenescence for health?

Answer 43

Increased susceptibility to infections Decreased response to vaccination Increased autoimmunity (↑ autoantibodies e.g. rheumatoid factor, anti-ssDNA antibodies)