Download Document

Vaccines
Dr T. Espanol
Immunology Unit
University Hospital Vall d´ Hebron
Barcelona
Effective vaccines: rapid decrease in infections in the general
population
If protective immune response levels are high in the general
population, the possibility of dissemination of an infection is low.
For this reason it is so important to follow the immunisation programmes
until the infection can be considered erradicated
Measles cases / protection
Red cells
SpecificPlatelets
response
Specific response
Innate response / inflammation
How and where the infections enter the body
Distribution and recirculation
A main characteristic of the immune response is its ability to
recognise antigens in any part of the body and distribute effector
cells and antibodies throughout the organism
Most cells of the immune response recirculate throughout the
body and in lymph nodes they mature to produce antibodies or
cytotoxic cells that leave the lymph nodes for any part of the body
Acute inflammatory signs: fever
oedema
swelling....
Innate response
Specific T-cell response
Specific T-cell response begins with recognition of the “intruder”
by monocyte/macrophages (through some receptors), and the
presentation of antigens (part of the proteins) to the super-specific
T-cell receptor
1st
2nd
Innate response/inflammation is essential to elicit a specific response
The antigen is presented to the T cells to begin complex cell activation,
induce several effector mechanisms, collaborate with B cells to produce
antibodies and secrete cytokines that mature cytotoxic cells, etc
HLA antigens are inherited characteristics of all human cells
(except red cells and the cornea) and their function is to recognise
the “identity” of our cells versus foreign cells or cells with
foreign antigens
Correlation between some HLA characteristics and diseases
The job of cytotoxic cells is to kill the cells recognised as “foreign”
(transplants) or which have foreign “particles” in the membrane
(virus-infected cells)
A high proportion of plasma cells mature in lymph nodes
Immunoglobulins are proteins with several functions
The Fab segment is able to recognise many different antigens
Total diversity: Ig´s
T-cell receptors:
Main characteristics of the immune response:
- immunological memory (used in vaccination)
- high specificity (used in vaccination)
- recirculation (oral vaccines)
- a very high energy-consuming system
If there is a chronic inflammatory
response and no antibodies to
eliminate the bacteria, lesions appear
in different organs
Extracellular bacteria: pneumococcus
haemophilus
streptococcus, etc
Intracellular bacteria: tuberculosis
salmonella, etc
Viral infections : polio
measles
HIV, etc
Vaccines to produce antibodies to bacterial infections and toxins
e.g. Pneumococcus, tetanus toxins  must stimulate the
maturation of B cells (a T-cell collaboration is needed!)
Vaccines to prevent viral infections e.g. measles, polio, HIV
must stimulate cytotoxic cells (T cells)
Most of them are very effective in healthy persons.
- HIV vaccine not achieved to date due to the extreme
variability of the virus and because it is a retrovirus
- Anti-’flu vaccines. Effective but the antigen must be
changed periodically due to changes in the virus
Vaccines against parasites (e.g. Malaria) very difficult to achieve
Not much research has been done ( affects poor countries !!!)
Types of vaccines :
Attenuated (“live “ vaccines) BCG, measles, chicken pox...
Inactivated most anti-bacterials, polio i.m., ‘flu...
Toxoids  tetanus
Conjugated (polysaccharides and proteins)  Haemophilus
Recombinant Hepatitis B
DNA vaccines  under development
New vaccines :
Human Papilloma virus recombinant
Rotavirus  attenuated
Different types of vaccines and their efficacy
Therapeutic vaccines : to stimulate the immune response to a
specific microorganism that is infecting a patient with poor response
- Anti-tumour “vaccines”: Use of presenting cells with incorporated
tumoral antigens  to induce a stronger specific response
- Immunotherapy in allergic diseases: to inhibit specific IgE synthesis
with small and repeated amounts of the allergen (tolerance)
PID diseases. A molecular and genetic approach.2007. 2nd ed. H.Ochs et al
GENERAL RULES :
- if an antibody response or a T-cell response cannot be produced,
vaccines will not be useful
- live or attenuated vaccines can produce the same disease in an
immunodeficient or immunocompromised individual (e.g. oral
polio)
Vaccines against bacteria are of no use in antibody deficiency
syndromes. In these cases, theoretically, vaccines against
virus COULD (?) be given , but there is no way to know
whether they are effective.
In any event, inactivated or recombinant vaccines should
ALWAYS be used !!!
Clinical focus on PID – IDF October 1998
Clinical focus on PID – IDF October 1998
And it is important for PID patients that national levels of
protection against the majority of microorganisms are optimum.
Some references
- François G et al. Vaccine safety controversies and the future
vaccination programs. Ped Infect Dis J 2005; 24(11) 953-61
- Ada, G. Vaccines and vaccination. N. Engl.J. Med 2001; 345: 10421053.
- Ljungman, P., Engelhard, D., de la Camara R, et al. Vaccination of
stem cell transplant recipients: recommendations of the Infectious
Diseases working party of the EBMT. Bone Marrow Transplant 2005;
35: 737-46.
- Nachman S, Kim S, King J, et al. Safety and immunogenicity of a
heptavalent pneumococcal conjugate vaccine in infants with human
immunodeficiency virus type 1 infection. Pediatrics 2003; 112: 66-73
- Witney, CG, Farley, MM, Hadler, J. et al Decline in Invasive
Penumococcal Disease after the Introduction of Protein-Polysaccharide
Conjugate Vaccine. N.Engl.J.Med 2003; 348: 1737-46