PEDIATRICS

IMMUNOLOGY 1
SEPTEMBER 27, 2016

Immunity
derived from the Latin word immunitas
historically means protection from disease, and
more specifically, infectious disease
a reaction to foreign substances, including
microbes, macromolecules such as proteins and
polysaccharides, regardless of the physiologic or
pathologic consequence of such a reaction.

Immune system composed of cells and molecules
responsible for immunity

Immune response the collective and coordinated
response of the immune system to the introduction
of foreign substances

Immunology is the study of immunity and of the
cellular and molecular events that occur after an
organism encounters microbes and other foreign
macromolecules

A SHORT HISTORY OF IMMUNOLOGY
430 B.C. : Peloponesian War, Thucydides
describes plague (first mentioned immunity to
an infection)
15th century: Chinese and Turks use dried crusts
of smallpox as vaccine
1798 : Edward Jenner smallpox vaccine
Since 1901 there have been 19 Nobel Prizes for
immunological research.

FEATURES OF THE IMMUNE SYSTEM

1. Immune Memory
made possible by the clonal expansion
of lymphocytes in response to
stimulation by antigens
can protect against harmful microbial
agents despite of infection being
separated by prolonged periods of time,
even decades
on interaction of antigens, the activated
lymphocytes make millions of long-lived
clones of themselves
immediate recognition of same antigens
by memory cells

USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

2. Surveillance
the immune system is in a perpetual
state of vigilance, screening, and
rejecting any nonself entity that
appeared in the body

3. Tolerance (Central vs. Peripheral)
the immune system is programmed to
eliminate foreign substances such as
microbes, toxins, and tissues but to
accept self-antigens
Immunologic self-tolerance is not
complete at birth but is actively
acquired and maintained during life.
Central tolerance: occurs in lymphoid
tissue
o Mechanism: Clonal deletion
(results in the elimination of
self-reactive immature T
lymphocytes in the thymus and
self-reactive B lymphocytes in
bone marrow)
Peripheral tolerance: maintained by
clonal deletion, anergy, suppression and
clonal ignorance

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

1

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

COMPONENTS OF THE IMMUNE SYSTEM

INNNATE
ADAPTIVE
Humoral/
Physical
Barriers: Antibodies: IgM,
Soluble
Cathelicidins,
IgG, IgA, IgE
proteins
defensins, lysozymes
Circulating Proteins: Cytokines: IL-2,
Complements,
IL-14
pentraxins
Cytokines: TNF, IL-1,
IL-12
Cellular
Epithelial
cells, Lymphocytes: T
Elements
intraepithelial cells, cells,
B
killer cells, B1 cells
cells/Plasma
Phagocytes
cells,
Antigen
Presenting
Cells(APCs),
macrophages,
dendritic cells
Receptors
Fc receptors
T cell receptor,
and
Pattern integration MHC II proteins
Recognition receptors
Co-stimulator
Proteins
MHC I proteins
proteins
and
Complement receptor receptors


PHYSICAL BARRIERS OF INNATE IMMUNITY
1. Integrity of cutaneous and mucosal
2. Mucociliary movement of ciliated columnar
epithelial lining of respiratory tract
3. Peristalsis of nonciliated columnar cells
4. Flow of secretory fluids
5. Desquamation of skin

The above anatomical features secrete peptides
with antimicrobial properties:
o Cathelicidins
o Defensins
Kills bacteria
Direct cytotoxicity
Activate the immune
cells of the innate
immunity
Synthesis is triggered by
cytokines
and
microbial
products

Other chemical barriers
o Gastric acidity
o Fatty acids
USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

Secretions from sebaceous glands

Bile acid secretion from liver into small
bowels
o Pulmonary surfactant

CIRCULATING PROTEINS OF INNATE IMMUNITY
Soluble proteins in plasma
Promote further inflammatory response
and destruction of microbes

Complement system
Group of proteins that is activated by
microbes and other foreign bodies

Pentraxins (PTX)
Plasma proteins that recognize
microbial structures

1. C-reactive proteins (CRP)
2. Serum amyloid proteins (SAP)
3. PTX 3 protein molecules produced by
endothelial cells, dendritic cells, and
phagocytes
TNF, CRP, SAP are called acute phase
reactants
PTX3 is not

Collectins and Ficolins
Serve as opsonins and activators of
complement
Collectins
MBL (Mannose Binding Lectin)
SPA, SPD (Pulmonary
surfactants)

CYTOKINES OF INNATE IMMUNITY
Synthesized in
o Macrophages
o Natural killer cells
o Neutrophils
o Vascular endothelial cells
o Epithelial cells

ADAPTIVE IMMUNITY
Also called specific immunity or acquired
immunity
Has very large diversity and has memory
Nonreactive to self
Specificity: for antigens of microbes and for
nonmicrobial antigens
o
o

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

2

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

2 Types:
o Humoral Immunity
Mediated by antibodies
produced by B cells
o Cell-mediated immunity
Mediated by T cells

HUMORAL IMMUNITY
defends primarily against the extracellular
phases of bacterial and viral infections
o Cellular elements consist of B
lymphocytes and plasma cells
o Serum factors include
immunoglobulins or antibodies

CELLULAR IMMUNITY
defends against intracellular organisms and
provide immune surveillance against malignant
cells and foreign tissue
o Cellular elements consist of T-
lymphocytes
o T-cell derived factors lymphokines,
interleukins, helper and suppressor
factors

2 cells that are common in both adaptive and innate
immunity:
Natural killer T- cells
beta-T cells

ADAPTIVE IMMUNITY
Feature
Functional Significance
Specificity
ensures that distinct antigens elicit
specific responses
Diversity
enables immune system to respond
to a large variety of antigens
Memory
leads to enhanced responses to
repeated exposures to the same
antigens; e.g varicella, measles, etc.
Specialization
generates responses that are
optimal for defense against
different types of microbes
Self-limitation
allows immune system to respond
to newly encountered antigens
Nonreactivity to prevents injury to the host during
self
responses to foreign antigens

ACTIVE IMMUNE DEFENSE
USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

Innate Immunity
Adaptive Immunity
Invariant
Variable
(generalized)
(custom)
Early, limited
Later, highly
specificity
specific
The first line of
remembers
defense
infection

ORGANS OF THE IMMUNE SYSTEM
Primary Lymphoid Organs
o Also called central lymphoid organs
o It is where immature lymphocytes
develop
o Organs where differentiation,
proliferation and maturation of stem
cells into immunocompetent cells take
place
o Thymus and bone marrow

Secondary Lymphoid System
o It is where antigen is localized so that it
can be effectively exposed to mature
lymphocytes
o Initiate adaptive immune response

Includes: spleen, lymph nodes, appendix,
tonsils, peyers patches

A. Thymus
Central lymphoid organ
An organ located in the upper chest
It is where the immune lymphocytes are
educated to become mature T-lymphocytes
Its absence or defective development results in
severs immunodeficiency and autoimmune
disease states
Function: generate and select T cells that will
protect body from infection

Thymic Shadow
An important feature to recognize in the
pediatric chest is the normal thymic tissue in
the anterior mediastinum. Normal thymic
tissue, as demonstrated on this image, should
not be confused with a mediastinal or
pulmonary mass. This is known as the sail
sign.

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

3

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

B. Bone marrow
Home of the precursors of blood cells mostly
involve in immunity.
Location where all immature immune cells
begin their development
Site of B-cell maturation

Function: responsible for the production of the immune
system cells e.g. B-cell







SECONDARY
LYMPHOID ORGANS:

C. Lymph Nodes
Small encapsulated nodular aggregates of
lymphoid tissues
Distributed
along
lymphatic
channels
throughout the body
Where specific immune responses are
generated when antigens are delivered via
lymphatics
Present are both T- cells and B- cells


Function: acts as an immunologic filters and drain the
lymph node from most body tissues and filter out or
eliminate antigen present in them, before allowing the
lymph to return to the circulation

e.g. infection in the ear causes enlargement of
USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

the lymph nodes

Enlargement of the lymph node occurs due to
the infection because there is an antigen
brought by antigen-cell reaction.
Cells increase and proliferate due to the
presence of the antigen causing the lymph node
to enlarge
Tonsils enlarge due to the proliferation of the
cell in response to an antigen.

Tuberculosis also cause enlargement of the
lymph nodes in the cervical area along the
lungs.

D. Spleen
An organ vital for immune responses to blood-
borne antigens
Functions as a waste disposal system where red
pulp macrophages clear the blood of unwanted
foreign substances
Organ of the immune system composed of B
cells, T cells, NK cells, macrophages, dendritic
cells and red blood cells
It is a production site of antibodies and
activated lymphocytes, which are delivered to
the blood
Earlier in life, an active hematopoietic organ
until the bone marrow takes over - T-cells and
B-cells are present

Function: filters the blood and entraps foreign
materials (antigens); provide defense against
blood-borne antigens

Largest organ in the lymphatic system

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

4

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

E. Tonsils
Lymphoid tissue which is a lymph nodes

Two masses of soft glandular on either side or

back of the mouth; traps bacteria and viruses
from inhaled air
Inflammation in this organ is an indication of
infection and might also produce exudates

F.
Appendix
Thin dead end tube
3-4 inch in length; hang in cecum

Function: help tell the lymphocytes exactly where to
head over to attack infection and it also enhances the
massive intestines defense to a range of food and drugs.

G. Tonsils
- Soft masses of glandular tissue on either side or the
back of the mouth
- Function: traps bacteria and viruses from inhaled air
- Is a also a lymphoid organ that reacts with antigen
Tonsillitis: 5-6x a year is still normal (more often than
that, Patient may have RHD)

These are nodules of lymphatic cells that

combine form bundles/patches.
Appear at the lowest part of intestine/ileum
Function: they detect antigens and mobilize
highly specialized white blood cells to produce
antibodies.

Immunit
y
Innate

Adaptive

Cellular
Humoral Components
Components
Phagocytic
Complement
cells
Acute phase reactants
(monocytes,
(APR)
macrophages
Immunosuppressic
, neutrophils)
e acidic protein
Natural killer
(IAP)
(NK) cells
C-reactive protein
Mast cells
(CRP)
Antigen
Cytokines
Presenting
Cells (APC)
T
Immunoglobulins
lymphocytes
Helper T
(CD 4)
Killer T
(CD 8)
Memory T
Suppresso
r T
B
lymphocytes

H. Peyers Patches
USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

From the bone marrow, your hematopoietic stem cells

differentiate into myeloid and lymphoid progenitor
cells.

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

5

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

Lymphoid progenitor cells are involved in adaptive
immunity (T lymphocytes, B Lymphocytes, Natural Killer
cell and Dendritic cells).

Myeloid progenitor cells all the white blood cells, red
blood cells and platelets.

Lymphocytes: serve as memory and effector cells
Types of lymphocytes: B and T lymphocytes

Priniciple of the T cell development:

From the bone marrow, cells interact with cells of the
thymus and then go to the thymus to become double
positive thymocytes, which are attached to your TCR.
Double postive thymocytes may be differentiated upon
recognition of your Major Histocompatibility Complex
(MHC). The negative or positive selection depends on
the affinity of T lymphocytes to your MHC. MHC
involves proteins that detect pathogen. MHC is a
complex containing peptide proteins from your
pathogens and then for it to be recognized by your cells.
Ideally, these cells must not be attached to your MHC.

Affinity should not be strong for it to be positively
selected. Those that are not attached/ does not
recognize the MHC, will be positively selected and
become CD4 or CD8 single positive thymocytes.
Gamma/delta T cells will go to the circulation.

Those that react with MHC are negatively selected and
eventually dies

USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

T CELL COMPONENTS
CD4- protein present on the surfaces of T-helper cells
CD8- found on both mature cytotoxic T cells and NK
cells
MHC- Major Histocompatibility Complex, host surface
molecules

MHC I- present intracellular antigen
MHC II- present extracellular antigen

CELLULAR ELEMENTS

T-cell Function:
Signal B cells to make antibody by producing
cytokines and membrane molecules that can serve
as ligands to B cell surface molecules
Kills virally infected cells or tumor cells
For malignancy, T cells are used

Helper/ Inducer cells: CD4+
- Have an amplifying effect on both cellular and
immune responses
- Its key role in immunity is evidenced by the
devastating effect of its depletion in AIDS
- Measure for HIV

Th cells- subdivided according to cytokines they
produce upon activation
- Th1 cells- produce interleukin-2, ITF (interferon)
which promotes cytotoxic T cell or delayed
hypersensitivity type of response
- Th2 cells- produce IL-4, 5, 6, 13 and 21 which

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

6

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

promote B cell response and allergic

sensitization

Regulatory cells
- Like a switch of your T cell function
- They suppress other T lymphocytes
- For example, in lymph nodes there are already
many T lymphocytes are produced and they are
the one who will suppress to production.

Cytotoxic cells: CD8+
- Kill microorganisms by direct activation on their

surface

B cells
- Major function is to produce antibodies specific to
almost all foreign antigen there is (broad and
diverse)

B cell Development:
- Has two phases:
o Antigen independent Phase
o Antigen dependent Phase
So from B cell, initially, there is some surface expression
of your IgM. So this is the first antibody to recur in any
infection.
Mature B cells also express first IgM then IgD
IgM and IgD are surface antibodies

In the presence or upon exposure to antigen (bacteria,
virus), there is now antigen interaction (B cells
interacting with Antigen). So what happens there is now
production of Ig secreting B cells, memory B cells and
plasma cells. So thats

why in this reaction, there is isotype switching that
reoccur, some Ig rearrangement and other antibodies
are produced (these are your IgG, IgA and IgE which are
secretory antibodies).

So thats why when we measure an infection, IgG is late
because of this. For them to be produced, there has to
be B cell reaction.

Remember that at the end of your Antigen independent
Phase development will be your mature B cells. So this
is the area where co expression or secretion of IgM and
IgD occur. Upon the exposure of antigen, the other Igs
are produced.

USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

7

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

Immunoglobulins (Antibodies)
The complex serum proteins produced by B-
cells (surface antigens) and plasma cells
(secretory Igs)
An heterogenous groups of serum proteins
comprising approximately of 20% of the total
plasma proteins
Basic unit is monomer comprising 4
polypeptide chains, 2H or heavy chains and 2L
or light chains

IgM
First antibody to be produced
Major Ig expressed in your B cell
IgG
Most abundant
Only Ig to cross the placenta
IgA
Present in secretions
IgD
Present in very minimal amount (0.29%)
For differentiation of B cells and assist in the
switch of IgM to IgG
Present in the colostrum
IgE
parasitic and allergic reactions

USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

In the presence of an antigen, there would be antigen

presentation,
cell mediated immunity is acted on and
react by:
1. Killing directly
2. Phagocytosis
3. Releasing chemical toxins to kill pathogen

Cell mediated immune response:
Infected cell is attached to macrophage and this is
where Antigen-MHC complex is formed. Your infected
cell with your macrophage reacts to the cell of your
body and what is activated on (if this is secondary
infection, your memory cells) but here, your Th cells. Th
cells release or produce different cytokines and these
cause mitosis. After mitosis, Killer T cells are activated
and they also produce cytokines that act on infected
cell, which causes death of cell or pathogen.

Humoral Immune Response:
Cytokines are also secreted which are important for the
maturation of B cells.

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

8

PEDIATRICS
IMMUNOLOGY 1
SEPTEMBER 27, 2016

Cytotoxic T cells
memory cytotoxic and active cytotoxic T cells

Helper T cell
Active and memory helper T cells
B cells Plasma cells producing the antibodies
and memory B cells

DIFFERENCE BETWEEN PRIMARY RESPONSE AND
SECONDARY RESPONSE


Primary
Secondary
response
response
Exposure to
First exposure to After second
antigen
a specific antigen exposure to the
same antigen


IMMUNE RESPONSE
- The first exposure to a specific antigen represents
the primary immune response
- During this time, effector B cells (plasma cells) are
generated, and T cells are activated to their
effector forms
- In the secondary immune response, memory cells
facilitate a faster, more efficient response.

USE AT YOUR OWN RISK. USE OF OTHER REVIEW MATERIALS IS ADVISED.

Time of onset 1-week delay

Strength
Weak potency
Duration
Short life, for
only a few weeks

Within hours
More potent
Forms antibodies
for many months

Type of
Antibody

IgG

IgM

TRANSCRIBED BY: ESTEBAN | GAOR|MEDINA|SARMIENTO|TAN :

9