Download IMMUNE SYSTEM. PECULIARITIES of ITS FUNCTIONING

IMMUNE SYSTEM.
PECULIARITIES of ITS
FUNCTIONING.
INSPECTION METHODS IN
CHILDREN. SEMIOTICS.
СARE FOR PATIENTS
The immune system includes the primary
lymphoid organs (thymus, bone marrow,
and probably liver) and the secondary
lymphoid organs (lymph nodes, spleen,
and gut-associated lymphoid tissue
[GALT]).
The functions of the immune
system
are basically two types: nonspecific and
specific. Nonspecific immune defenses
are activated on exposure to any foreign
substance but react similarly regardless of
the type of antigen; they are unable to
identify the antigen. The principal
component of this system is phagocytosis,
the process of ingesting and digesting
foreign substances. Phagocyte cells are
composed of neutrophils and monocytes
Specific defenses are those that have the
ability to recognize the antigen and
respond selectively. The components of
adaptive immunity are humeral immunity
and cell-mediated immunity. The cells
responsible for these two forms of
immunity are the lymphocytes, specifically
B-lymphocytes and T-lymphocytes.
Humoral immunity
Humeral immunity is involved with antibody
production and complement. The principal cell
involved in antibody production is the Blymphocyte. Five classes of antibodies or
immunoglobulins (lg) have been identified: G, M,
A, D, and E, each serving a specific function .
On initial exposure to an antigen, the Blymphocyte system begins to produce antibody,
predominantly lgM, which appears in 2 to 3
days. This process is referred to as the primary
antibody response.
Cell-mediated immunity
Cell-mediated immunity is involved in a variety of
specific functions mediated by the T-lymphocyte.
The T-lymphocyte is so named because it
passes through the thymus during the
differentiation process, which leads to the
mature T-cell. T-lymphocytes do not carry typical
immunoglobulins on their surfaces as do the Bcells. However, they are functionally
heterogeneous in that several subsets have
been identified, including cytotoxic T-cells,
memory T-cells, helper T-lymphocytes, and
regulator T-lymphocytes.
Cell-mediated immunity
Specific functions of T-lymphocytes include:
 protection against most viral, fungal, and
protozoan infections and slow-growing bacterial
infections, such as tuberculosis,
 rejection of histoincompatible grafts, mediation
of cutaneous delayed hypersensitivity reactions,
such as in tuberculin testing,
 and probably immune surveillance for malignant
cells.
 In addition, they also have regulatory functions
within the immune system.
Cell-mediated immunity
The immunologic system undergoes numerous changes
during the first year. The newborn receives significant
amounts of maternal lgG, which confers immunity for
about 3 months against antigens to which the mother
was exposed. During this time the infant begins to
synthesize his own lgG, and about 40% of adult levels
are reached by 1 year of age.
Significant amounts of lgM are produced at birth, and
adult levels are reached by 9 months of age.
The production of IgA, IgD, and IgE is much more
gradual, and maximum levels are not attained until early
childhood.
Cell-mediated immunity
Immunoglobulin G (lgG), which neutralizes microbial
toxins, reaches adult levels by the end of the second
year of life. Passive immunity from maternal transfer
disappears by the beginning of toddlerhood,
necessitating the use of artificial immunizations.
Immunoglobulin M (lgM), which responds to artificial
immunizing techniques and combats serious infection,
attains adult levels during late infancy.
Immunoglobulins A, D, and E increase gradually, not
reaching eventual adult levels until later childhood. Many
young children demonstrate a sudden increase in colds
and minor infections when entering nursery school or
kindergarten because of the exposure to new antigens.
The terms in immunology



immunity An inherited or acquired status in
which an individual is resistant to the occurrence
or the effects of a specific disease, particularly
an infectious agent.
natural immunity Innate immunity or
resistance to infection or toxicity.
acquired immunity Immunity from exposure
to the invading agent, either bacteria, virus, or
toxins.
The terms in immunology



active immunity: individual actively forms immune
bodies against specific antigens, either naturally by his
having had the disease clinically or subclinically or
articifically by the introduction of an antigen (vaccine)
into the individual.
passive immunity: temporary immunity by transfusing
plasma proteins either artificially from another human or
an animal that has been actively immunized against an
antigen or naturally from the mother to the fetus via the
placenta.
antibody: a protein found mostly in serum that is
formed in response to exposure to a specific antigen.
The terms in immunology




antigen: a variety of foreign substances,
including bacteria, viruses, toxins, and foreign
proteins that stimulate the formation of
antibodies.
antitoxin: antibody formed in response to a
toxin (antigen).
toxin: a poisonous substance usually produced
by the invading microorganism.
toxoid: a toxin that has been treated to destroy
its toxic properties but retain its antigenic
quality.
The terms in immunology


vaccine: collectively a term to denote any type
of active immunization, such as toxoids or
attenuated live viruses; specifically a suspension
of disease-causing bacteria or viruses that acts
like an antigen, stimulates antibody production,
and produces active acquired immunity.
attenuate: reduction of the virulence
(infectiousness) of a pathogenic microorganism
by such measures as treating it with heat,
chemicals, or cultivating it on a certain media.
Specific (adaptive) defenses
are those that have the ability to recognize
the antigen and respond selectively. The
components of adaptive immunity are
humoral immunity and cell-mediated
immunity. The cells responsible for these
two forms of immunity are the
lymphocytes, specifically B-lymphocytes
and T-lymphocytes
Normal development of the
immune system
After birth, the infant is rapidly colonised by organisms and challenged by
waves of transient pathogens. Cellular immunity is active from birth, and
although the neutrophil count is relatively low, infants are able to respond to
bacterial infection with a leucocytosis. Humoral immunity is less well
developed but the maturing system is initially supported by transplacental
maternal-derived IgG antibodies and potentially by breast milk factors
including IgA. Ig M does not
cross the placenta but infants can produce it in response to infection. In an
intact immune system the waning of maternally derived IgG is matched by
gradual enhancement of endogenous production but there is a nadir of
circulating IgG levels at age 2-3 months. The emergence of specific
endogenous antibodies reflects the process, of natural immunisation, and
this is accelerated during the preschool years as children average 6-12
short-lived infections each year.
Abnormal development of the
immune system
Immunodeficiency is suggested by a history of unusually frequent or severe
infections, or by unusual patterns of infection especially if caused by
organisms of low pathogenicity. A positive family history is also a powerful
guide. Failure to thrive rather than overt infection may be the main
manifestation. Modern immunology laboratories are equipped with the
tools to test the integrity of each of the main pathways of the immune
system, and the classification of disorders has become increasingly
functional. Successful management depends upon swift recognition and
classification of the disorder, initiation of specific treatments where
indicated and meticulous attention to bacteriological and virological
investigation of all infectious episodes. Where indicated, life-long
immunoglobulin replacement can be very effective.
Clinical manifestations
Obviously the most common manifestation is
susceptibility to infection early in life, most often
by 3 months of age when maternal immunity is
low. Specifically the disorder in children is
characterized by chronic infection, failure to
completely recover from an infection, frequent
reinfection, and infection with unusual agents. In
addition, the history reveals no logical source of
infection. Failure to thrive is a consequence of
the persistent illnesses.
If the child should receive a foreign tissue, such
as blood supplements, signs of graft-versus-host
assey reaction, such as fever, skin rash,
alopecia, hepatosplenomegaly, and diarrhea,
are expected. Since the reaction requires 7 to 20
days for tissue damage to become evident, the
symptoms may be mistaken for an infection.
However, the presence of a graft-vs-host
reaction increases the child's susceptibility to
overwhelming infection and, therefore, is a grave
complication.
Diagnostic evaluation
Diagnosis is usually based on a history of
recurrent, severe infections from early infancy, a
familial history of the disorder, and specific
laboratory findings, which include lymphopenia,
lack of lymphocyte response to antigens, and
absence of plasma cells in the bone marrow.
Documentation of immunoglobulin deficiency is
difficult during infancy because of the normally
delayed response of the infant to produce his
own immunoglobulins and maternal transfer of
immunoglobulin G.
Initial Immunologic Testing of the
Child with Recurrent Infections
Complete Blood Count, Manual Differential, and Erythrocyte
Sedimentation Rate
 Absolute lymphocyte count (normal result makes T-cell defect unlikely)
 Absolute neutrophil count (normal result precludes congenital or
acquired neutropenia and (usually) both forms of leukocyte adhesion
deficiency, in which elevated counts are present even between
infections)
 Platelet count (normal result excludes Wiskott-Aldrich syndrome)
 Howell-Jolly bodies (presence suggests asplenia)
 Erythrocyte sedimentation rate (normal result indicates chronic
bacterial or fungal infection unlikely)
Screening Tests for B-Cell Defects
 IgA measurement; if abnormal, IgG and IgM measurement
 Isohemagglutinins
 Antibody titers to tetanus, diphtheria, H. influenzae, and S. pneumoniae
Initial Immunologic Testing of the
Child with Recurrent Infections
Screening Tests for T-Cell Defects
 Absolute lymphocyte count (normal result indicates Tcell defect unlikely)
 Candida albicans intradermal skin test: 0.1mL of a
1:1,000 dilution for patients older than 6 yr, 0.1mL of
a 1:100 dilution for patients younger than 6 yr
Screening Tests for Phagocytic Cell Defects
 Absolute neutrophil count
 Respiratory burst assay
Screening Test for Complement Deficiency
 CH50
Diagnostic criteria of primary
immunodeficient conditions
Clinical:
A. Suggestive T-cell deficit:
a) systemic illness following vaccination with any alive virus or BCG;
b) unusual life-threatening complication following infection caused by ordinary
benign viruses (e.g., giant rubella pneumonia; varicella pneumonia);
c) chronic oral candidiasis after 6 months of life;
d) chronic mucocutaneous candidiasis;
e)
fine, thin hair, short-limbed dwarfism with characteristic
radiographic features of cartilage-hair hypoplasia (CHH);
f)
intrauterine graft-versus-host disease - the most characteristic
feature is scaly erythroderma and total alopecia (absence of eyebrows
is quite striking);
g)
graft-versus-host disease after blood transfusion;
h) hypocalcemia in newborn (Di George anomaly, especially with characteristic
faces, ears and cardiac lesions);
i) small (less than 10 mm in diameter) lymphocytes count persistently less than
1500/mm3, must rule out gastrointestinal loss of them or loss from the
lymphatic vessels.
Diagnostic criteria of primary
immunodeficient conditions
B. Suggestive R-cell defect
a) recurrent proved bacterial pneumonia, sepsis or meningitis;
b) nodular lymphoid hyperplasia.
C. Suggestive B- and T-cell deficiency (combined immunodeficient
disease - CID)
a) all the above mentioned features except chronic mucocutaneous candidiasis and
nodular lymphoid hyperplasia;
b)features of Wiskott-Aldrich syndrome (draining ears, trombocyto-penia and
eczema);
c) features of ataxia-telangiectasia.
P. Suggestive immunodeficiency without clearly implicating T-or B-cell defect
a) Pneumocystis carinii pneumonia;
b) intractable eczema;
c) ulcerative colitis in infants less than 1 year old;
d) intractable diarrhea;
e) unexplained hematological deficiency (RBC, WBC, platelet);
f) severe generalized seborrheal dermatitis (Leiner's disease) suggests
C5 deficiency; seborrhea is common in combined immunodeficient disease;
g) recurrent pyogenic infections seen in C3 deficiency.
Diagnostic criteria of primary
immunodeficient conditions
E. Suggestive biochemical defect
a) features of combined immunodeficiency with characteristic bony
lesions (adenosine deaminase deficiency);
b) features of Blackfan-Diamond aplastic anemia (nucleoside
phosphorylase deficiency).
F. Suggestive abnormality of polymorphonuclear leukocytes
a) primary skin infections (if associated with asthma, eczema and
coarse faces, think of Buckley syndrome);
b) chronic osteomyelitis caused by Klebsiella or Serratia species,
draining lymph nodes (chronic granulomatous disease).
G. Suggestive secondary deficiency
a) concomitant or preceding viral infection;
b) lymphoid malignancy (chronic lymphatic leukemia, Hodgkin's
disease, myeloma).
Diagnostic criteria of primary
immunodeficient conditions
Laboratory:
a) genealogical anamnesis;
b) common blood analysis (not only total but absolute quantity
of different leukocytes);
c) investigation of numeral link of immunity:
 gamma globulin concentration;
 immune serum globulins by Manchini;
 Immunoelectrophoresis of serum proteins;
 tillers of different antibodies, blood group, liter of isohemagglu-tinins;
 secretory immunoglobulins;
 surface immunoglobulins of antiserum lymphocytes, marked with fluoroscein;
 EAC-rosellas.
d) investigation of cellular link of immunity:
 E-rosellas;
 reaction of blast transformation (in unspecific stimulation with FHA, in stimulation with
antigens, in mixed lymphocyts culture);
 depression of macrophages migration;
 reaction of hypersensitivity of a delayed type (intracutaneous tests with 2,4-dinitroftorbenzol,
streptokinase, odoriase, antigen; Shieck's reaction).
Diagnostic criteria of primary
immunodeficient conditions
e) special investigations:
 functions of T-helpers and T-suppressors;
 hystochemical determination of adenosine-deaminase's activity;
 transcobalamin's content.
 X-ray of the chest including side positions and tomo-gram of
mediastinum for revealing the thymus;
 biopsy of the lymph nodes with the use of hystotogical and
hystochemical methods;
h) investigation of complement's system (total complement, its
factors);
i) investigation of phagocytosis function (opsonization bacteria's
killing, a test with blue tetrazolium, cytochemical methods of
determination of enzyme's activity etc.)
Primary immunodeficient conditions.
Classification of primary immunodeficient
conditions
1. Prevalence of antibodies deficiency:
a) sex-linked agammaglobulinemia;
b) sex-linked agammaglobulinemia and growth hormone
deficiency;
c) autosomal recessive agammaglobulinemia;
d) selective immunoglobulin deficiency:
- with elevated level of IgM and IgD;
- IgA deficiency.
e) selective deficiency of other isotypes of Ig;
f) kappa-chains deficiency;
g) immunodeficiency on the background of thymoma;
h) transitory hypogammaglobulinemia in children.
Primary immunodeficient conditions.
Classification of primary immunodeficient
conditions
2. Combined immunodeficiency:
a) total variable immune deficiency:
with primary antibody deficiency;
with primary deficiency of cellular immunity.
b) severe combined immunologic deficiency:
- reticular dysgenesis;
-deficiency of T- and B-lymphocytes (earlier the Swiss type of IDC).
c) T-lymphocyte deficiency (earlier Nezelof syndrome);
d) adenosindeaminase deficiency;
e) purine-nucleotide-phosphorylase deficiency;
f) absence of HLA-antigens of the 1st class (syndrome of "naked"
lymphocytes);
g) absence of HLA-antigens of the 2nd class.
Primary immunodeficient conditions.
Classification of primary immunodeficient
conditions
3. Immunodeficiency in combination with other
congenital defects:
a) Wiscott-Aldrich syndrome;
b) ataxia-telangiectasia (Louis-Bar, syndrome);
c) syndrome of 3nd-4,h pockets of branchial arch (Di
George syndrome);
d) transcobalamin-2 deficiency;
e) mmunodeficiency due to congenital anomalous
reaction at Epstein-Barr virus.
Therapeutic management
The only definitive treatment is a histocompatible bone marrow
transplant. The perfect donor is an identical twin because the
human lymphocyte antigens (HLA) are exactly the same. The
second best choice is a sibling. The procedure consists of
aspirating several samples of bone marrow from the donor and
infusing the marrow intravenously into the host. However, bone
marrow transplants are usually done at medical centers where
measures to control posttransplantation infection, such as a
sterile environment, and other specialized facilities are available.
Since the host's immunologic system is incompetent, graft
rejection is not a problem. However, a graft-vs-host reaction is
always a possibility in a nonidentical twin graft, and once it
occurs, little can be done to reverse the process.
IMMUNISATION
Protection against some of the infectious diseases is available in
the form of immunization which is given at various stages
during childhood. Immunizations for different diseases are
scheduled to
balance the risks of disease with the child's ability to produce a
good immunological response; Immunization should not be
given if the child is acutely unwell or if a severe reaction has
occurred to a previous dose of that vaccine. Live attenuated
vaccines (e.g. poliomyelitis, measles, mumps, rubella, BCG)
should not be given to children" with immune deficiency states
including those on cytotoxic drugs and high doses of
corticosteroids, because of the risk of severe generalised
infection. Three weeks should elapse between live vaccines to
ensure adequate immune responses to the second one.
National immunisation schedule
Derived from Salisbury DM, Begg NT 1996
Immunisation against infectious disease- Department of
Health, HMSO, London
INFANT
 Birth

tuberculosis
2 months
BCG for babies in Asian and other immigrant families
.with high TB rates and those in contact with active respiratory
Polio + diphtheria /tetanus/ pertussis (DTP) +
Haemophilus influenzae B (Hib)
 3 months
Polio + DTP + Hib
 4 months
Polio + DTP + Hib
 12-15 months Measles, mumps and rubella (MMR)
PRE-SCHOOL
 3-5 years
Booster polio + diphtheria/tetanus (DT) + MMR 3 years after
primary course
SECONDARY SCHOOL
 10-14 years
BCG after tuberculin skin test
SCHOOL LEAVING
 15-19 years
Polio + tetanus/diphtheria (Td) MMR if not received previously
Panhypogamma-globuliriaemia
This presents as recurrent sinopulmonary infection,
recurrent otitis media, bronchiectasis or giardiasis
infection. It may be 'early,onset' in the first two years,
which is almost always the X-linked disorder
described by Bruton, or 'late onset' where the
presentation is more variable and the inheritance
pattern less certain. Failure to thrive, gastrointestinal
disorders and autoimmune disorders may complicate
the clinical course. Gamma globulin replacement
therapy often results in a dramatic improvement.
Selective IgA deficiency
This presents with recurrent upper and lower
respiratory, and gastrointestinal tract
infections. Low serum IgA levels are found in
between 1 in 400 and 700 children, but the
deficiency disorders only occur in around 1 in
15 000,: this subgroup having associated
abnormalities in IgG production. They too
benefit-from gamma globulin administration.
T-cell deficiencies
These conditions present with frequent and severe
infections with herpes simplex, measles, varicella,
cytomegalovirus, Pneumocystis and fungi such as
nocardia, Candida and aspergillus. T-cell deficiencies
may be isolated or part of extensive
immunodeficiency states in which humoral immunity
is also impaired. Di George syndrome is an
example of T-cell deficiency associated with
congenital absence of the thymus. T-cell function is
defective in Wiskott-Aldrich syndrome, ataxia
telangiectasia and chronic mucocutaneous
candidiasis. Bone marrow transplantation may be
used to replace T-cell deficiencies, although it is of
high risk especially in patients with a strong previous
history of recurrent infections.
Severe combined immune deficiency
This presents with failure to thrive in the first year of life,
-
recurrent sinopulmonary infection,
-
persistent candidiasis,
-
Pneumocystis infections,
-
persistent diarrhea,
-
severe recurrent systemic infections
-
disseminated viral infections.
It is a rare condition and is inherited as autosomal recessive or X-linked. First cases in families
are difficult to diagnose and almost, always have established infection. A low lymphocyte
count (<2.8xl0*9) is an important clue worthy of further investigation. Subsequent
pregnancies may be offered antenatal diagnosis and immediate postnatal investigation.
Deficiency of adenine deaminase (ADA) or purine nucleoside phosphorylase (PNP) are
found in certain subtypes. For children with severe combined immune deficiency (SCID)
successful treatment depends upon the presence of an HLA matched bone marrow donor.
Complement (C 5,6,7 and 8)
deficiencies
In general deficiencies do not normally
present with recurrent infections but are
found as a result of investigation of the
immune system for other disorders, for
example vasculitis. Recurrent neisseria
infections can be a presenting feature
because of the specific need for components
of complement to clear-this group of
organisms.
Chronic granulomatous
disease
This presents as recurrent staphylococcal infections
with abscesses in and around liver, lungs and bones,
or. infection with uncommon organisms, or chronic
lymphadenopathy and hepatosplenomegaly. Chronic
granulomatous disease (CGD) is an X-Iinked disease
in which phagocytes can ingest pathogens but are
unable to mount the oxidative burst of intracellular
metabolism necessary to kill them. It used to be fatal
but continuous administration of antibacterial agents
like trimethoprim together with vigorous antibiotic
therapy for each new infection has improved the
outlook in children diagnosed early and monitored
closely.
Acquired immunodeficiency syndrome (AIDS)
AIDS is caused by human immunodeficiency
virus (HIV) of type 1 (HIV-1). HIV-1 infects
CD4+ T-lymphocytes predominantly.
Depletion of CD4+ lymphocytes results in
immunodeficiency.
The clinical picture of AIDS is the final phase
of HIV infection and its manifestation, with a
wide spectrum of clinical disorders. The
majority of them is nonspecific.
Clinical manifestations of HIV
infection in children
 Persisting generalized
lymphadenopathy

Persisting hepatomegaly

Persisting splenomegaly
 Persisting diarrhea
 One or more nodes have
size more than 1 cm and
exist longer uian 1 month
(especially substantial is
enlargement of auxiliary
lymph nodes)
 Enlargement of the liver,
registered for 3 months and
more
 Enlargement of the spleen,
registered for 3 months and
more
 Stool is three times a day for
more than 1 month
Clinical manifestations of HIV
infection in children
 Fever
 Persisting enlargement of
salivary glands
 Thrombocytopenia

Serious bacterial infections
 t = 38 CC for 4 weeks and
more, 2 and more episodes
of fever of obscure nature
 For 3 months and more
 Amount of thrombocytes is
less than 100 000 per ml
twice and more times
 2 and more episodes of
exacerbation or chronization
of an infection (for more than
3 days in spite of the
treatment)
Clinical manifestations of HIV
infection in children
 Retardation of
 Progressing hypotrophy,
development
 Persisting or recurring
oral candidiasis
encephalopathy
 It lasts for 2 months and
more or relapses after
the course of treatment
 Signs of heart
insufficiency
 Nephrotic syndrome
(proteinuria,
hypoalbuminemia)
 Cardiomyopathy
 Nephropathy
CARE OF A CHILD WITH IMMUNODEFICIENT
CONDITIONS
A report of certain communicable diseases
must be filed with the city health
department upon the admission of the
child.
Personnel giving direct care to the child with a
communicable disease should seek
protection when immunization measures
are; available. Frequent handwashing is
essential.
Isolation Gowns
When isolation gowns are used, a fresh gown
should be used for each patient contact.
Organization of activities is essential for the
economical use of supplies.
CARE OF A CHILD WITH
IMMUNODEFICIENT CONDITIONS
Isolation Masks
If a mask is used, it should cover both the nose and the
mouth, be worn no longer than 30 minutes, and be
discarded immediately after use. Disposal of
Wastes
Paper bags for the disposal of tissues should be
available within the unit. All contaminated waste
should be wrapped securely and discarded in a
special receptacle marked "isolation."
Bedpans may be emptied into the community sewage
system, using the bedpan flusher. The flusher
should be handled with paper barriers. Waste cans
should be lined with paper and kept covered.
All reusable equipment should be cleaned, wrapped,
labeled "isolation," and sterilized before routine
reprocessing. Infusion bottles should be discarded
after use
CARE OF A CHILD WITH
IMMUNODEFICIENT CONDITIONS
Care of Dishes
Disposable dishes maybe requested
through the dietary department. If
regular dishes are used, they should
be returned to the kitchen for
processing in the dishwashing
machine. Formula bottles should be
washed and returned to the
reception area of the formula
kitchen.