LECTURE IMMUNOLOGY AND

8 PEÑAMAYOR, DOLORES O’RIORDAN

SEROLOGY MEDTECH 3-YA-6

1ST SEMESTER | MIDTERM PERIOD

CYTOKINES
- They are involved in signal
- Chemical messengers that influence
transduction, they activate genes
the activities of other cells.
for growth differentiation, and cell
- A class of non-antibody molecules, activity. They play a cardinal role
usually a low molecular weight in mediating the host’s defense
glycoproteins produced by many against internal and external
different cells in a highly antigenic insults.
regulated fashion, change the
- Many similar functions are shared by
behavior and function of many
different cytokines
different cells.
- They are derived from cells, immune
- They are regulatory and effector
or non-immune.
molecules that act at picomolar to
nanomolar concentrations on cytokine
- Cytokine action is mediated by
binding to specific receptors on
receptors expressed by target cells
target cells. They tend to be very
 Their normal values may be very low
potent.
expressed in picomolar or nanomolar
concentrations
 They are produced by various cells
ACTIONS OF CYTOKINES
of the body, although the major
producers of the cytokines are T- 1. Autocrine – effect is toward the
cells (particularly T-helper cells) same cell that produce it
 Each cytokine have their target  Ex. IL2 - produced by T-cell,
cell, one target cell have received the effect of T-cell may also
the corresponding cytokine then that be directed to T-cell which is
will create particular effects on the same cell that produce it
that particular target cells  Therefore, IL2 as a cytokine
 The action of the cytokine maybe that reacts as a autocrine
very potent and target cells manner
requires a to have a receptor for  IL5 is not autocrine cytokine
particular cytokine to bind its because it doesn’t have that
target cells same cell that produce it
 Actions of the cytokines could 2. Paracrine – effect is toward the
either be autoquin, paraquin or neighboring cells.
endoquin 
3. Endocrine – systematic effect
  Ex. IL3 – it acts in various  From pro B-cell, pre B-cell,
hematopoietic stem cells in immature B-cell, mature B-
the bone marrow, without IL3 cell, active B-cell, memory
we cannot start hematopoiesis cell, so IL-4, 5, 6 are
or the blood cell process involve
 IL-4 will activate the B-cell
so that they will undergo
FEATURES OF CYTOKINES maturation sequence
 Il-5 will promote the further
1. Pleiotropism – means a single
development of B-cells
cytokine has many different actions.
 Il-6 will differentiate B-cell
 Ex. IL-1a – it can stimulate
to become plasma cells and
lymphocyte development, it can
memory cells so that antibody
activate phagocyte, it can
formation will become possible
increase endothelial adhesion
 Without IL-4, IL-5, IL-6, they
to tissue (hindi lang isa but
cannot do their job
tatlo ang effects so IL-1a it
 Without a mature in develop B-
is a Pleiotropic cytokine)
cell, there cannot be
 Il-7 is not a pleiotropic
activation into plasma cells
cytokine because it only have
 Some set of cytokines act in
one effect
network, they have interactive
2. Redundancy – means that different
effects
cytokines often have a very similar
 They are needed for cascade of
effects.
activities or processes inside
 Ex. IL-4 and IL-6 – they are
by *hindi ko maintindihan
redundant cytokines because
guys*
both them have the same
4. Act as growth factors for
effects in terms of co-
hematopoietic cells
stimulating B-cell
 Act as growth factor during
differentiation
hematopoiesis
3. Act in networks (has interactive
 Last group of cytokines is CSF
effects)
(Colony Stimulating Factors)
 Ex. IL-4, IL-5, IL-6 – they
 For every line of blood cell
acts in networks, IL-4 is
there is a dedicated CSF
known as the B-cell activating
responsible for the appearance
factor, IL-5 is known as the
of a particular line of blood
B-cell growth factor, IL-6 is
cell
known as B-cell
 Ex. Sources of granulocytes,
differentiating factor
monocytes and macrophages in
 So in the transformation of
the human body they come from
the B-cell during the
GM-CSF (Granulocyte-Macrophage
maturation sequence
CSF)
  The presence of G-CSF and M-
CSF is important so you can be
able to have normal
development of granulocytes
and macrophages
 IL-3 is a multi-lineage
hematopoietic growth factor
 IL-7 is important during
lymphocyte growth development
and activation

FAMILIES OF CYTOKINES AND THEIR REPRESENTATIVE MEMBERS

A. INTERLEUKINS
 They are called interleukins because they promote communication between
leukocytes
 Ex. IL-1a are produced by macrophage, lymphocytes, and fibroblast which
are WBC and target cells is also WBC
 Calling them interleukins is a misnomer because not all the time that
interleukins is produced by a leukocytes then will be recognize to
another leukocyte (Ex. IL-3)
 It is very important for cytokines interleukins to know the source in
the target cells and the principal effect

CYTOKINE SOURCE TARGET PRINCIPAL EFFECT

IL-1a Macrophage, Lymphocytes, Lymphocyte co-stimulation activation,
fibroblast, macrophage, phagocyte activation, increase
lymphocytes endothelium endothelial adhesion molecules
IL-1B T-cells Other Induces fever and sleep, increase in
prostaglandin synthesis
IL-2 T-cells T-cells, B- T-cell growth and activation, NK cell
cells, NK activation, co-stimulates B-cell
cells differentiation
IL-3 T-cells, Stem cells Multi-lineage hematopoietic growth
thymic factor
epithelium
IL-4 (B-cell T-cells, bone Stem cells Co-stimulates B-cell differentiation,
activating marrow stroma stimulates MHC class II expression on B-
factor) cell and macrophage, promotes class
switch, enhances IgG1 and IgE production
IL-5 (B-cell Th2 cells B cells Stimulates in vitro antibody responses,
growth factor) enhances IgA production by stimulated B-
 cells, stimulates eosinophil
differentiation
IL-6 (B-cell Macrophage, Eosinophils, Lymphocyte growth, B-cell
differentiating endothelium, B-cells differentiation, acute phase protein
factor) Th2 cells synthesis
IL-7 Bone marrow T-cells, B- Cell activation
stromal cells cells,
hepatocytes
IL-8 Fibroblasts, Monocytes, T- Stimulates chemotaxis of target cells
monocytes, cells, and stimulates granulocytes activity
endothelium neutrophils
IL-9 CD4+ T-cells T-cells, mast Cell division, promotes development
cells
IL-10 Th2 cells Th1 cells Inhibits cytokine synthesis
IL-11 Bone marrow Stem cells, Cell division, cell proliferation, and
stroma plasma cells stimulates maturation of hematopoietic
cells
IL-12 B-cells, Th1 cells, NK Th1 cell development, activation,
macrophage cells induces IFN-gamma production from target
cells, augments cytotoxic activity of NK
cells
IL-13 Th2 cells B-cells, Division and any differentiation, blocks
macrophages inflammatory monokine production
IL-14 T-cells B-cells Cell proliferation, decrease
immunoglobulin synthesis
IL-15 Monocytes T-cells, B- Cell division, shares IL2 bioactivity
cells
IL-16 CD8+ T-cells CD4+ T-cells Chemotactic
IL-17 T-cells Many cells Pro-inflammatory

 Ex. IL-14 it produces T-cells for B-cells so they may cause the B-cell to decrease
their production of immunoglobulin synthesis or antibody synthesis because one of
the features of adaptive immunity is self-limitation
 In certain cases like IL-16 may also chemotactic properties that’s why IL-16 and
IL-8 (although they are interleukins) they can promotes chemotaxis, that’s why they
can also be classified under the second group of cytokine which is chemokines
 B. CHEMOKINES
 All of these cytokines they cause chemotaxis, movement or migration of
phagocytes or WBCs towards the site of inflammation
 Without the presence of these chemokines then chemotaxis will not occur
 Chemokines are important
 Chemoattractant – will only produce signals that will cause the
stimulus for WBC to migrate on the site of inflammation
 Chemotactic – they are the ones that will cause the movement or
migration of WBC toward the site of inflammation

CYTOKINE SOURCE TARGET PRINCIPAL EFFECTS

IL-8 (NAP-1) Macrophage, T-cells, Chemotactic
Neutrophil fibroblast, neutrophils
Activated keratinocytes
Protein
MCP-1 (MCAF) Macrophage, Monocytes, memory Chemotactic
Macrophage fibroblast, T-cells
Chemotactic keratinocytes
Protein or
Macrophage
chemoattractant
Factor
MIP 1-a Macrophage Monocytes, T- Chemoattractant
Macrophage cells, eosinophils
Inflammatory
Protein
MIP-1B Macrophage, CD8+ T-cells Chemoattractant
monocytes,
neutrophil,
endothelium
RANTES T-cells, Monocytes, memory Chemoattractant
(Regulated on platelets CD4+ T-cells
activation
normal T-cells
expressed
selected)
 C. INTERFERON
 Discovered by Alick Isaacs and Jean Lindenmann
 T-cell is more active on viruses and intracellular pathogens
 Aside from blocking the translation of viral proteins they also increase
the expression of MHC in the target cells
 Interferons has various way of fighting viral infections, they prevent
the replication and multiplication of the viruses
 They enhances the expression of HMC

CYTOKINE SOURCE TARGET PRINCIPAL EFFECTS

IFN-alpha T-cells, NK Macrophage Cell division, increased MHC
cells expression
IFN-gamma Leukocytes, T- Macrophage Anti-viral, increased MHC
cells and B- expression
cells,
macrophage
IFN-beta Fibroblast Macrophage Anti-viral, increased MHC
expression

D. CYTOTOXIC/ IMMUNOMODULATORY/ GROWTH FACTORS (TNF FAMILY) TUMOR NECROSIS FACTOR

CYTOKINE SOURCE TARGET PRINCIPAL EFFECTS

Tumor Necrosis Th1 cells, some Macrophage Local inflammation, activates
Factor-a (TNF-a) Th2 cells, NK and induces NO production
cells, Septic shock
macrophage
TNF-B Th1 cells, some T-cells, B-cell, Inhibits B-cell, enhances T-
(lymphotoxin) cytotoxic T macrophage, cell killing, activates
lymphocytes neutrophil neutrophil, activation and
induces NO production
Transforming T-cells, B-cell, Inhibits activities of T-cell,
growth factor macrophage, macrophage, NK B-cell and NK cell, activates
(TGF-B) monocyte cell neutrophil, promotes matrix
formation (wound repair),
angiogenesis
 Inflammation is important in immunity but too much inflammation is damaging to our
own tissues and cells in the human body
 Inflammation can help us in fighting against a pathogen but prolonged inflammation
is not good because what is at stake could be our organ tissues and cells
 Sepsis is the multiplication of bacteria in the body
 Septesemia is the presence of abundant or multiply bacteria in the blood
 One of the events during inflammation is increase in vascular permeability
 It will lead to septic shock or multiple organ failure
 Too much TNF-a will cause systemic inflammation instead of local inflammation
 If all blood vessels is permeable, fluids plasma will leak decreasing the volume of
blood (hypovolemia) so it will lead to multiple organ failure
 The cause of the death is the response of the immune system in the body
 Hindi mo masisisi yung immune system mo because it is natural na magresponse sila
kapag may foreign pathogen, one of that is the production of TNF-a
 Namamatay ang pasyente sa covid-19 because of overwhelming production of cytokines
or cytokines storm
 ARDS – Acute Respiratory Distress Syndrome
 Too much cytokines are producing response to covid-19
 Tocilizumab (medicine)- anti-cytokine it destroys the cytokine in the body, it’s an
inhibitor of cytokine
 If there is an infection, you have your immune system to rely on
 You still have to assist your immune system to prevent over producing of it

T-cytotoxic cell (CD8+)

2 mechanisms on how T-cytotoxic cells destroy their target cells

A. Apoptosis
a. Calcium dependent
 Calcium independent because calcium has a role in this *di ko naman
maintindihan guys*
 T-cytotoxic cells bind with their target cells
 target cell maybe a cancer cell or virally infected cell
 When the T-cytotoxic cell binds on the target cell it causes your T-
cytotoxic cell to release lymphotoxin or TNF-B
 T-cytotoxic cells releases lymphotoxin
 Secretion of high levels of calcium within cell
 Degradation of nuclear DNA
 if there’s too much calcium then that will cause the DNA to be
degraded
 If there is no DNA then there will no protein synthesis that will
cause to a cell membrane of the target cells to collapse
 Membrane blebbing/collapse
 Cell undergo apoptosis
 Major producer of lymphotoxin is T-cell particularly the cytotoxic T
lymphpocytes (CD8+)
b. Calcium independent
 Fas-FasL binding  apoptosis
 Fas – is expressed by infected cells
 FasL – is expressed by all T-cytotoxic cells (also known as T-cell death
factor)
B. Use of perforins and granzymes
E. COLONY STIMULATING FACTORS (CSF) – are synthesized by bone marrow, stromal
endothelial cells, fibroblast, macrophages, and lymphocytes. Their production is
boosted by endotoxin, antigen and phorbol esters. They are specific growth
glycoproteins controlling the proliferation and differentiation of committed
hematopoietic cells.

FIVE INFENTIFIED AND ISOLATED CSF

1. Granulocyte-Macrophage CSF (GM-CSF)
2. Granulocyte-CSF (G-CSF)
3. Macrophage-CSF (M-CSF)
4. IL-3
5. IL-7
 LECTURE IMMUNOLOGY
9 PEÑAMAYOR, DOLORES O’RIORDAN

AND SEROLOGY MEDTECH 3-YA-6

1ST SEMESTER | MIDTERM PERIOD

ANTIBODIES
PROPERTIES OF AN ANTIBODY
• Glycoprotein substances synthesized
by plasma cells in response to 1. Protein in nature
antigenic stimulation. 2. With high molecular weight
➢ Plasma cells are activated 3. Present in serum/plasma, saliva,
forms of B-cells or B semen, CSF and other body fluids
lymphocytes
CLASSIFICATION OF ANTIBODIES
➢ Plasma cells will be reproduce
only if there’s contact to ✓ IgG
the corresponding antigen ✓ IgA
• 2-14% carbohydrates ✓ Igm
• 86-98% proteins ✓ IgD
➢ The other term for antibodies ✓ IgE
is immunoglobulins ➢ Arranged in decreasing
➢ Immunoglobulins are part of concentration
gamma-globulin fraction of ➢ Most abundant is IgG and least
serum proteins is IgE
➢ Gamma-globulins are the
slowest moving serum proteins
➢ It is called antibody if you A. According to its sedimentation
know its antigenic constant
specificity, to where it
IMMUNOGLOBULIN SEDIMENTATION MOLECULAR
reacts COEFFICIENT WEIGHT
➢ If the antigenic specificity (IN
is not known, it is called DALTONS)
immunoglobulin IgG 7s 150,000
• Structurally all antibodies are Serum IgA 7s 160,000
immunoglobulins (gamma globulin) but Secretory IgA 9s; 11s; 13s 170,000 –
functionally, not all 385,000
immunoglobulins are antibodies. IgM 19s 900,000
• Immunoglobulins are considered to be IgD 7s 180,000
the humoral branch of the immune IgE 8s 190,000
response. ➢ Small s stand for sedimentation
coefficient, means svedverg unit
➢ The first immunoglobulin who will
settle first is the IgM which is the
biggest immunoglobulin with the
 highest sedimentation coefficient 2. Warm antibodies
and molecular weight ➢ Antibodies that react at
➢ While the least or the last who will 30-37 degree celcius
settle is the smallest ➢ Ex. IgG
➢ Monomer is the basic unit of ➢ It is needed to take note
antibody the class of immunoglobulin
➢ IgG is a monomer when selecting the
➢ Pentamer have 5 basic unit, appropriate incubation
➢ Dimer, Trimer, Pentamer is example temperature for certain
of polymers immunologic serologic blood
➢ Polymers are antibodies that is made banking test
up of more than 1 monomers
➢ IgG,Serum IgA, IgD, IgE are monomers C. According to occurrence
➢ IgM is pentamer 1. Natural antibodies
➢ Secretory IgA has a variety of ➢ These are the antibodies
types, can be form of monomer, dimer that are produced event
or trimer without exposure to
➢ Dimer is most common form in corresponding antigen
Secretory IgA ➢ Ex. ABO antibodies
• Anti-A
- Is found on all type B
Sedimentation Coefficient/constant
and O individuals
o Unit used to express the rate of - Has anti-B antibodies
sedimentation of Ig when they are but it doesn’t mean it
subjected to analytical ultra- was expose to type B
centrifugation. blodd kaya siya
nagproduce ng anti-B
B. According to temperature at which - Naturally, its automatic
they react that all type B and type
1. Cold antibodies O will produce anti-A
➢ Antibodies that react to a antibody even without
cold temperature exposure to the
➢ It react at 4 degree corresponding A antigen
celcius to room temperature • Anti-B
(24-27 degree celcius) - Is found on all type A
➢ Ex. IgM is a cold antibody and O individuals
➢ You don’t need to use - Has anti-A antibodies
water bath or incubator to but doesn’t mean it was
detect IgM expose to type A blood
➢ IgM can react even in room kaya siya nagproduce ng
temperature anti-A
 - Naturally, its automatic ➢ Ex. Antibodies
that all type A and anti againt covid 19
O it will produce anti-
B antibody even without E. According to its reaction with an
exposure to the antigen
corresponding B antigen • -in suffix for antibodies
2. Immune/ Acquired antibodies • -nogen suffix for antigens
➢ Antibodies that will only 1. Agglutinins
be produced if and only if ➢ They react in an
there is exposure to the agglutinogen
corresponding antigen ➢ Antibodies that
➢ Ex. Rh antibodies react with
• Rh positive (+) particulate/cellul
- If there is D antigen in ar antigen.
RBC 2. Precipitins
- It can’t produce anti-D ➢ Antibodies that
• Rh negative (–) react with soluble
- If there is NO D antigen antigen.
in the RBC ➢ For precipitation,
- It can produce anti-D the antibody
only if exposed to Rh + involve would be
blood precipitin
➢ Antigen involved
D. According to the species which would be
produce them precipitinogen
1. Isoantibodies/ Alloantibodies 3. Agglutinoids
- Antibodies produced in ➢ Agglutinins that
response to antigens of are modified by
other individual of the heat
same species. 4. Hemagglutinins
➢ To prevent the ➢ Antibodies that
patient from agglutinates RBCs
producing ➢ Blood typing is a
alloantibodies, agglutination of
cross-matching to RBCs
be done first ➢ All blood typing
prior transfusion procedures that
2. Heterophile antibodies will be performed
- Antibodies produced in are example of
response to antigens hemagglutination
coming from other reaction
species.
 ➢ In blood typing ➢ Involved during
procedure, anti- hypersensitivity reactions
sera serve as the 9. Antitoxins
hemagglutinin ▪ Neutralize harmful
➢ Hemagglutinogen effects of toxins
refers to the 10.Complement fixing
antigen that is antibodies
present on the ▪ Can activate the
RBCs complement system.
5. Lysins
➢ Antibody that F. According to their in vitro behavior
causes lysis of
1.Complete 2.Incompolete
cells
antibody (IgM) antibody
➢ Hemolysin - lyses (IgG)
RBC Synonyms Bivalent; Univalent;
➢ Leukocidin - lyses Saline acting blocking;
WBC or leukocytes coagglutinati
and also known as ng;
Panton Valentine conglutinatin
Factor found on g
Staphylococcus Response Thermolabile Thermostable
aureus to
➢ Reason why temperatur
Staphylococcus e
Ability to Cannot cross Can cross the
aureus is a
cross the placenta placenta
pyogenic organism,
placenta
can induce task
Occurrence Early in Late in
formation
immunization immunization
➢ Bacteriolysin - Reaction Saline acting Albumin
lyses bacteria acting
6. Opsonins ➢ The first one to appear after
➢ The one that coats primary infection is IgM
microbes ➢ IgG will appear late during
➢ Good example of infection or immunization\
opsonins would be
antibody or
immunoglobulins THE STRUCTURE OF IMMUNOGLOBULIN
7. Neutralizing antibodies Monomer - basic structural unit of an
➢ Antibodies that antibody
neutralize certain reactions

8. Allergic antibodies
 • Proline
- Responsible for the
flexibility of the hinge.

Disulfide bonds

• Are chemical bonds essential for the

Only IgM and IgE has extra CH4 domain normal 3 dimensional structure of Ig
• 2 types of disulphide bonds:
✓ Interchain – connects light
chains and heavy chains
✓ Intrachain – connects domains
of the heavy chain
- connects domains of the
light chain

Domains
• Are globular regions on polypeptide
chain stabilized by intrachain
disulfide bonds
Tertrapeptide made up of: • Domains on the heavy chain
- VH, CH1, CH2, CH3, (CH4-- IgE)
1. Heavy chain
• Domains in the light chain
- With five principal antigenic
- VL, CL
types with their corresponding
Ig VL + VH bind with antigen
- gamma, alpha, mu, delta, CH1 binds with C4b
epsilon CH2 binds with C1g (if IgG)
2. Light CH3 binds with C1g (if IgM)
- with two antigenically defined binding site for T and
types B-cells, platelets, mast
• kappa cells, monocytes,
• lambda macrophages
CH2 + CH3 binds with NK cell,
Hinge region placental
syncitiotrophoblast and
• Flexible part of the antibody
neutrophils
located in the heavy chains. It is
more exposed to enzymes and
chemicals thus papain acts here to FUNCTIONS OF ANTIBODIES
produce Fab and Fc fragments. The
1. Binding with antigen
light chains are each linked to one-
2. Opsonization
half of a heavy chain by disulphide
3. Complement fixation and activation
bonds at the proximal end.
REGIONS ON POLYPEPTIDE CHAIN - cleaves after the hinge - lead
to 1 F(ab)2 + 1 Fc’
1. Variable
a. Amino acid sequence subject to
3. Reduction using mercaptoethylamine/
change
mercaptoethanolamine
b. Amino terminals (NH2)(positive)
• disrupts disulfide bonds - 2
c. Concerned with binding to antigen
HC + 2 LC

2. Constant
GENETICS OF IG:
a. Amino acid sequence is fixed and
unchanging • Genes coding for the synthesis of
b. carboxyl terminal heavy chains are located in C#14
(COOH)(negative) • Genes coding for the synthesis of
c. Concerned with binding to host kappa light chains are located in
tissue C#2
• Genes coding for the synthesis of
Polymer – Ig composed of more than a
lambda light chains are located in
single basic monomeric unit.
C#22
J chain – polypeptide chain which 1. V gene - variable
normally holds polymeric Ig 2. D gene - diversity
3. J gene - joining
Secretory component - a substance attached
4. C gene – constant
to polymeric Ig found on secretions.

- Protect secretory IgA from acid

digestion in the stomach. IMMUNOGLOBULIN VARIABILITY
- Facilitated the transport of
1. Isotypic Variation (isotypes)
secretory IgA across mucosal
• Refers to the different heavy
surfaces
and light chain classes
2. Allotypic variation (allotypes)
• Refers to the genetic
Fragments of Ig:
variation within a species
• 2 Fab (antigen binding fragment) involving different alleles at
• 1 Fc (crystallizable fragment) a given locus (subclasses
within a class of Ig.)
3. Idiotypic variation (idiotypes)
ENZYME DIGESTION • Refers to the diversity at the
1. Cleavage with papain enzyme binding site and in particular
- cleaves before the hinge - relates to the hypervariable
lead to 2 Fab + 1 Fc segments of the antibody
2. Cleavage with pepsin enzyme combining site (paratope)
CHARACTERISTICS OF DIFFERENT TYPES OF 2. IgM
IMMUNOGLOBULINS a. The largest of the immunoglobulin
molecule, accounting for 5-10% of
1. IgG
the total immunoglobulin pool.
• Major antibody in secondary/
b. Star-shaped in the free state;
anamnestic immune response
crab-like in antigen-antibody
a. Predominant Ig among humans
reaction.
comprising 75-80% (70-75%)
c. The earliest antibody to appear
of the total Ig pool.
in the primary immune response
b. Has 4 major subclasses:
but it does not persist for long.
IgG1, IgG2, IgG3, IgG4
d. Maternal IgM does not cross the
c. Equally distributed in the
placenta.
different fluid
e. IgM detection in newborn is a
compartments with
useful indicator of intrauterine
detectable amounts in CSF
infection
and urine
f. A powerful agglutinator of a
d. Readily diffusible
particulate antigen
e. IgG antibody response
g. Functions of IgM:
appears later than IgM in
✓ Complement fixation
primary response but they
✓ Agglutination
form the major antibody of
✓ Opsonization
the secondary immune
✓ Neutralization of toxins
response.
✓ Surface receptor for
f. Maternal IgG is actively
antigens (on B-cells)*
and selectively transferred
across the placenta to the
fetus and imparts passive
protection to the newborn
for 6-9 months
g. Function of IgG:
✓ Provides immunity for
the newborn
✓ Complement fixation
3. IgA
IgG3, IgG1, IgG2 (IgG4
a. Represent 15-20% (10-15%) of
cannot activate the
human serum Ig pool.
complement via classical
b. Found in serum in small amounts
pathway
but predominant in sero-mucous
✓ Opsonization
secretions of He respiratory
✓ Neutralization of toxins
tract, genito-urinary tract and
and viruses
GI tracts. It is also found in
✓ Participation in
tears, sweat, saliva, colostrum
agglutination and
and breastmilk.
precipitation reactions
 c. Forms of IgA: c. Precise biological action
✓ Serum IgA (IgA1) is not known but it may
- can agglutinate motile play a role in antigen-
infectious agents thus triggered lymphocyte
promoting their differentiation.
phagocytosis but they 5. IgE
cannot activate the a. Heat labile immunoglobulin. Least
complement system abundant Ig in the serum
✓ Secretory IgA (IgA2) accounting for only 0.004%
- A polymeric form (0.02%) of the total serum Ig.
stabilized a short b. Synthesized locally by plasma
polypeptide chain. It is cell present in the mucous
known as the “antiseptic membrane of the Gi and
paint” of mucous respiratory tracts.
membranes. It can activate c. It is unable to fix the
the bacteriolytic activity complement via the classical
through the alternate pathway.
pathway of complement d. It is homocytotropic due to its
system and only in the affinity for cells of the host
presence of lysozyme species, particularly for tissue
mast cells and blood basophils.
e. Because of its ability to attach
to the human skin, it is
associated with immediate
hypersentivity reactions but
also, apparently, with immunity
to certain helminthic parasites.
f. Also known as reaginic antibody/
nuisance antibody
4. IgD
• Marker for mature B-cells
a. Heat labile immunoglobulin, THEORIES OF ANTIBODY PRODUCTION
accounts for less than 1% 1. Ehrlich’s Side Chain Theory
of the total serum Ig but • Certain cells has had specific
is known to be present in surface receptors for antigen
large quantities on the that were present before
membrane of many contact with antigen occurred.
circulating immunocompetent Once antigen was introduced,
B lymphocytes. it would select the cell with
b. Detectable by highly proper receptors, combination
sensitive assay requiring would take place and then
radio-labelled antisera receptors will break off and
 enter the circulation as immunoglobulin, and that
antibody molecules. New specific antigen finds or
receptors will be formed in selects those particular cells
place of those broken off and capable of responding to it,
this process could be causing these to proliferate.
repeated. Repeated contact with the
2. The Template Theory/ Instructive antigen would continually
Theory increase a lymphocyte pool
• Felix Haurowitz
• Antibody –producing cells are
capable of synthesizing a HYBRIDOMA TECHNOLOGY
generalized type of antibody,
• monoclonal antibodies
and when contact with an
1. Source of reagents
antigen occurs, the antigen
2. Source of drugs
serve as a mold or template
and alters protein synthesis Anti-A
so that antibody with a
Anti-B
specific fit is made. The
“molded” antibody then HCG – human chorionic gonadotropin
enters the circulation , while HAT medium (hypoxanthine aminopterine
the antigen remains behind to thymidine)
direct further synthesis
Myeloma cells - deficient in HGPRT
All antibodies inside the body are in (hypoxanthine guanine phosphoribosyl
standard form: unfolded gamma globulin transferase) and thymidine kinase
3. Selective Theory
• Replication → Transcription
→ Translation
• Assumes that antibodies are
synthesized in a manner
similar to that of other
proteins. Instructions for
their synthesis are provided
by genetic elements in the
nucleus of the cell rather
from the antigen
4. Clonal Selection Theory
• Niel Jerne and MacFarlane
Burnet
• Individual lymphocytes are
genetically pre-programmed to
produce one type of
 LECTURE IMMUNOLOGY
10 PEÑAMAYOR, DOLORES O’RIORDAN

AND SEROLOGY MEDTECH 3-YA-6

1ST SEMESTER | MIDTERM PERIOD

COMPLEMENT COMPONENT
PROTEINS OF THE COMPLEMENT SYSTEM
 Collective term designating a
complex series /mixtures of plasma
proteins that have functions of
zymogen.
 Group of non Ig circulating in the
blood in biologically inactive form.
 Zygomens (inactive forms of
complement proteins)  serine
proteases
 When these complement proteins are
activated from inactive forms or
zymogens they will have an enzymatic  Aside from the 9 major complement
activities they will function as components in the classical pathway,
serine proteases once they are the other proteins to this
activated complement system would include the
 Made or more than 30 proteins (alpha complement proteins involve in other
or beta globulins) pathway such as the alternative
 In contrast with to the gamma pathway and MBL pathway
globulins of antibodies, complements
are made of either alpha or beta PROTEINS OF THE COMPLEMENT SYSTEM-
globulins CONT’D
 The first 9 complement components
are regarded as the major complement
component
 C1-C9 are arranged chronologically,
but according to the activation in
classical pathway the sequence of
complement is C1, C4, C2, C3, C5,
C6, C7, C8, C9
Plus other regulatory and inhibitor 3. Disposal of wastes
complement proteins a. Clearance or removal of immune
complexes from tissues
 All the rest of complement proteins
include those other regulatory and
 Immune complex is the other term for
inhibitory complement proteins
Antigen-antibody complex
 These other regulatory and inhibitor
 When your antibody bind to its
complement proteins are important
corresponding antigen, you formed
because their function is to prevent
antibody-antigen complex or immune
the over activation and under
complex
activation of the complement system
 Spleen – organ involved in removing
 Under activation is not good because
immune complexes
it may lead to infections
 Complement must be present so that
 Over activation of complement system
the spleen can be remove the immune
may cause tissue damage
complex
 In other words, these other
 Process of removing immune complexes
regulatory and inhibitor complement
in the blood by the spleen is said
proteins will maintain balance or
to be complement dependent
homeostasis within the complement
 Meaning if walang complement, spleen
system
cannot be able to do its function

VITAL FUNCTIONS
ROUTES OR PATHWAYS OF COMPLEMENT
1. Host defense mechanism ACTIVATION
a. Opsonization
A. Classical
b. Chemotaxis and leukocyte
 Proteins termed as components
activation
are symbolized by the letter C
c. Lysis of bacterial and
followed by a number
mammalian cells (entry solve
 3 stages:
of complement activation)
1. Initiation or
d. Stimulation of inflammatory
recognition
response (mediators of
2. Amplification or
inflammation)
Enzymatic activation
 Those mediators of
3. Membrane attack leading
inflammations are
to cell destruction
anaphylatoxin
 The major activator is immune
2. Interface between innate and
complex or antigen-antibody
adaptive immunity
complex
 augmentation of antibody
 In classical pathway there are
response
two types of activators,
 enhancement of immunologic
immunologic activators and
memory
non-immunologic activators.
 Between the two, the major
activator of classical pathway
is immunologic activators and
it refers to immune complex
 IgG4 cannot activate the
classical pathway

 When IgM or IgG3, IgG2, IgG1  activated (trimolecular

bind with their target complex:
antigen, they form immune  C1q, C1r, C1s) stabilized by
complexes then these immune calcium (hold the C1 sub
complexes will trigger the units)
start of activation of  When immune complex is form
classical pathway so that and send signal to C1 C1
immune complex formed will will be form or separate from
send signal to complement complex and C1q will be
component 1 or C1 activated
 Immune complex will send  When C1s is activated by
signal to complement signal of immune complex C1q, C1r, C1s
C1 1st complement that is will separate from each other
 C1q (initiation/ recognition  C5b678 combine with C9 it will
unit) will bind with CH2 (IgG) form C5b6789 which cause
or CH3 (IgM) cytolysis of cell or Ag also
 C1q will activate C1r and known as Membrane Attack
converted to C1r bar Complex (MAC)
 C1r bar (activated C1r) will
Anaphylatoxin
activate C1s
 C1s is activated it will be  C4a, C3a, C5a
C1s bar  mediators of inflammation
 C1s bar (activated C1s) will
Opsonin
cleave to C4 and C2
 C4 will cleave to C4a  C3b
(anaphylatoxin) & C4b and C2
Chemotaxin
will cleave to C2a & C2b
 C4b and C2a will form C4b2a  C5a
(C3 convertase) and stabilized MAC
by Magnesium
 C4ba or C3 convertase will  Membrane Attack Complex (C5b6789)
activate C3
 C3 will cleave to C3a (got to
plasma and become
anaphylatoxin) and C3b
(opsonin)
 C3b will combine with C4b2a
and will form C4b2a3b (C5
converatse)
 C4b2a3b (C5 converatse)
activate C5 and cleave to C5a
(anaphylatoxin & chemotaxin)
and C5b (will bind to cell or
Ag)
 C5b will combine with C6 and
C7 and form C5b67 (making Cb5
more stabilized or make C5b
binds more to cell or Ag)
 C5b will create pores on cell
or Ag
 C5b67 combine with C8 it will
form C5b678 which cause lysis
of enucleated cells but not
nucleated cells
 B. Alternative / Alternate / Bypass /
Primitive / Properdin

 normal serum proteins are termed as

factors and are symbolized by
letters essential in the initiation
of this:
1. Soluble C3 - upon contact with
water will initiate activation
2. Factor B – analogous to C2
3. Factor D – believed to be
similar C1s
4. Properdin – a gamma globulin
which when complexed with C3b
stabilizes the alternate
pathway C3 convertase

SOLUBLE C3

C3b(H20)/iC3

C3b -------------------Factor B

C3b B -----------------Factor D

Bb
C3bBb (stabilized by properdin)
(C3 convertase )

--------------C6, C7
-bind to the cell
- create pores

C5b67 --------C8, C9
  Properdin stabilized the C3  In this pathway, the interaction of
convertase MBL with a carbohydrate on the
 Soluble C3 release iC3/C3b surface of polysaccharide of
(H2O) (water discarded will lead microbes leads to the formation of
to C3b in circulation) favor the enzymatic complex that binds and
uptake of factor B (complement activates C4 and C2.
component that binds with C3b)
forming C3bB which will
cleaved by factor D forming Bb
and Ba (tick over – spontaneous
activation of other soluble C3 in
plasma) fragment Bb will
combine with C3bB forming C3bBb
(C3 convertase of alternative
pathway) which act upon on C3
and cleave into C3a
(anaphylatoxin) and C3b (opsonin)
C3b will combin with C3bBb  MBL: analogous to C1q
forming C3bBb3b (C5 convertase  MASP-1: similar to C1r
of alternative pathway) will  MASP-2: related to C1s
cleave C5 into C5a  MBL will be activated and activate
(anaphylatoxin) and C5b (will MASP-1 (MBL associated serine
bind to cell & create pores) proteases) then activate MASP-2
C6 and C7 bind to C5b forming and will cleave C4 then cleave
C5b67 and will binf to C8 and C9 into C4a (anaphylatoxin) & C4b and
forming C5b6789 (MAC) lysis C2 cleave into C2a & C2b C4b and
of the cells C2a bind forming C4b2a (C3
 Ba - Cause tick over (spontaneous convertase) which act upon C3
activation of C3) rest will be the same as classical
 C3bBb3b (C5 convertase)  C5 pathway activation
 C5b6789 (MAC) – causes lysis of
cell

C. Mannose Binding Lectin (MBL) pathway

 MBL is a member of the so-called

“Collectin family of molecules”
 Binds with mannose (component found
on cell wall of certain microbes)
 Structurally similar to C1q and it
functions as an opsonin.
 C3 is the central component of complement system

CLASSICAL ALTERNATIVE
Immunologic activators: major activator Immunologic activators: minor activator
- IgM, IgG3, IgG1, IgG2 bound to antigen - Aggregated IgA
- IMMUNE COMPLEX - In some instances IgG4 and IgE
- bacteria like E.coli, Klebsiella,
Mycoplasma
- Parasites like Trypanosoma &
Schistosoma

Non-immunologic activators: minor Non-immunologic activators: major

activator activator
Apoptotic cells, Staphylococcal Protein - Bacterial and plant polysaccharide,
A, CRP bound to ligand, certain viruses LPS, zymosan, inulin, cobra venom factor,
and gram-negative bacteria, DNA viruses and tumor cells, some parasites
like trypanosomes
- SHISTOSOMES
Possess a recognition unit (C1q) No recognition unit
- Requires presence of Calcium (calcium - Lack of dependence on Calcium
dependent pathway) - Activation immediately starts with C3
- Requires C1, C2 and C4 for its (bypass pathway)
activation
Part of Humoral Immunity Part of Natural Immunity

 IgM, IgG3, IgG1, IgG2 will bind to target antigen then it will form immune complex
and that immune complex will trigger the start of the classical pathway of
complement activation
 The other activator will be non-immunologic activators such as Apoptotic cells,
Staphylococcal Protein A, CRP bind to their target cells and sometimes may directly
activated the classical pathway even without the presence of antibodies like IgG3,
IgG1, IgG2
 But between these two, the major activator of classical are immune complexes
involving the IgG3, IgG1, and IgG2
MAIN SOURCES OF COMPLEMENT PROTEINS  Plasma: fluid phase inhibitors
 Cells: cell bound regulatory
 Hepatocytes, intestinal and
 On Plasma / “Fluid phase
urogenital epithelial cells, blood
inhibitor”
monocytes and macrophages.
Anaphylatoxin inhibitor
 Many complement molecule genes are
C1 inhibitor: dissociates C1r &
localized in the MHC (C4, C2)--- MHC
C1s from C1q
Class 3 genes
FACTOR I: cleaves C4 & C3
 Homeostatic maintenance of
FACTOR H
complement activation is mediated by
- Major inhibitor
regulatory proteins.
- Co-factor with Factor-I to
 Examples:
inactivate C3b
o On plasma: anaphylatoxin
- Competes with Factor-B in
inhibitor, C1 inhibitor, Factors H
binding site of C3b
and I, C4 binding protein, S
C4 BINDING PROTEIN
protein and S 4040.
- Inactivates C4b
o On cells: C3b/C4b receptor
- Co-factor with Factor-I to
(CR1), Decay accelerating factor
cleave C4
(CD55), membrane co-factor protein
S PROTEIN / VITRONECTIN
and CD 59 (MIRL).
- Prevents attachment of C5b678
o MIRL: membrane inhibitor of
complex to cell membrane
reactive lysis
 On Cells / “Cell bound regulator”
o Plasma: fluid phase inhibitors
- Protects cell from By-stander
o Cells: cell bound regulatory
lysis
DECAY ACCELERATING FACTOR (DAF) /
 Complements are proteins they are
CD55
manly made in hepatocyte
- Dissociates C3-convertase
 All are produced in the liver except
- Found on RBC
for:
MEMBRANE INHIBITOR OF REACTIVE
C1 = Intestinal cells
LYSIS (MIRL)
C7
- Inhibits Membrane Attack
Properdin
Complex (MAC
 Many complement components are
localized in the MHC:
Factor B
C2
C4
 Homeostatic maintenance of
complement activation is mediated by
Regulatory Proteins:
 MIRL: membrane inhibitor of reactive
lysis
 Inactivated serum – Serum sample
with destroyed complement proteins

IN VITRO DESTRUCTION OF COMPLEMENT

1. Addition of chelating agents (EDTA)

– can chelate calcium
2. HEAT Inactivation of serum - heat
serum at 56 degrees celcius for 30
minutes
3. Treatment with zymosan

DIAGNOSTIC EVALUATION OF COMPLEMENT

A. Serum/Plasma aasay of C3 and C4 by

nephelometry
B. C1 binding assay measures the
binding of immune complexes
containing IgG1, IgG2 or IgG3 and/or
IgM to C1q. It can be useful as a
prognostic tool at diagnosis and  Lupuslike syndrome – there is over
during remission of acute production immune complex
myelogenous leukemia.  Paroxysmal nocturnal hemoglobinuria
C. Hemolytic Plaque Assay - RBC are lysed when sleeping
AH50 ASSAY – determine
complement components involve in
alternative pathway COMPLEMENT FIXATION TEST
CH50 ASSAY – determine
 EXAMPLE OF SECONDARY
complement components involve in
IMMUNOLOGIC/SEROLOGIC TEST
classical pathway
 SAMPLE USED: INACTIVATED SERUM
 2 SYSTEMS:
 Amount of serum required to lyse the
1. TEST SYSTEM = ANTIGEN AND
50% of the RBC in the assay
ANTIBODY (one of which is
unknown)
2. INDICATOR SYSTEM = SHEEP RBC
COATED WITH HEMOLYSIN
EXTERNAL SOURCE OF COMPLEMENT: GUINEA PIG DIAGNOSTIC EVALUATION OF COMPLEMENT
SERUM
1. NEPHELOMETRY: Serum/Plasma Assay of C3
& C4

2. C1 BINDING ASSAY

 Measures the binding of immune

complexes containing IgG1, IgG2,
IgG3, and/or IgM to C1q
 It can be useful prognostic tool @
diagnosis & during remission of
Acute Myelogenous Leukemia

3. HEMOLYTIC TITRATION ASSAY

 Use Ch50 for Class Pathway & AH50

for Alternative Pathway in order to
measure amount of serum required to
lyse
 50% of reagent red cell
 Unknown antigen present in patient 4. COMPLEMENT FIXATION TEST
serum during incubation there is
 Specimen: Inactivated serum
antigen-antibody complex
 Unknown: Antibody
 Unknown antigen is absent in patient
a. TEST SYSTEM
serum during incubation there is no
o Ag & Ab
antigen-antibody complex
o Sheep RBC coated with
1. Mix patient sample and reagent Hemolysis
 Reagent if unknown is Antigen: Known b. INDICATOR SYSTEM
Antibody
 Reagent if unknown is Antibody:
Known Antigen

2. Add GUINEA PIG SERUM as source of

complement

 GP serum will bind with immune

complex

Positive result – no hemolysis

Negative result – with hemolysis
 DEFICIENT ASSOCIATED DISEASE
COMPONENT
C1 - SLE-like syndrome
- recurrent infections
C2 - SLE-like syndrome
- recurrent infections
C4 - SLE-like syndrome
C3 - Glomerulonephritis
- severe recurrent
infections
Factor H / - recurrent Pyogenic
Factor I infections
C9 ** NO KNOWN DISEASE **
C1 Inhibitor - Hereditary Angioedema
C5-C8 - Neisseria infection
Properdin - Neisseria infection
MBL - Neisseria infections
- Pneumococcal disease
- Sepsis
MASP-2 - Pneumococcal disease
DAF - Paroxysmal Nocturnal
Hemoglobinuria
MIRL - Paroxysmal Nocturnal
Hemoglobinuria
ANAPHYLATOXIN C4a, C3a, C5a
OPSONIN C3b
CHEMOTAXIN C5a
PURFURATION C5b
LYTIC COMPONENT C8
IONS C1 = Calcium
C3-convertase = Magnesium
C3-CONVERTASE C4b2a = Classical Pathway
C3bBb = Alternative
Pathway
C5-CONVERTASE C4b2a3b = Classical
Pathway
C3bBb3b = Alternative
Pathway
 LECTURE IMMUNOLOGY
11 PEÑAMAYOR, DOLORES O’RIORDAN

AND SEROLOGY MEDTECH 3-YA-6

1ST SEMESTER | MIDTERM PERIOD

HYPERSENSITIVITY
Description of the four major
Heightened state of immune
hypersensitivity reactions
responsiveness.
It is an exaggerated response to an  Six Types of Hypersensitivity was
innocuous antigen that results in identified by Gell and Coombs
gross tissue changes that are 1. Type 1 Hypersensitivity
deleterious to the host. An immediate hypersensitivity,
 Type I, II, III immediate sudden allergic responses
hypersensitivity in terms of timing mediated by antibodies,
of appearance of symptoms, symptoms primarily IgE.
occur minutes or hours after the It involves secondary exposure
exposure to antigen to an offending allergen that
 Type IV delayed hypersensitivity bonds to mast cell-fixed IgE
These mediators caused the
HUMORAL MEDIATED CELL-MEDIATED symptoms of type 1
HYPERSENSITIVITY HYPERSENSITIVITY
hypersensitivity which are
REACTIONS REACTIONS
manifested within seconds to
Includes Types I, Include type IV
minutes after secondary
II, II and V reactions
reactions exposure.
Immune reactions Reactions are  Immune mediator: IgE
are observed delayed in time,  Effector cells: Basophil & Mast cell
minutes after usually after 24-  Mechanism: Cell bound Ab reacting
antigen exposure 48hrs with Ag to release physiologically
with its peak @ active substance
72hrs (days to  An immediate hypersensitivity or
weeks) sudden allergic responses mediated
Reactions are Reactions are by antibodies, primarily IgE
characterized by characterized by  Itinvolved secondary exposure to an
more fluid & significant cell offending allergen that bonds to
Erythema infiltration
mast cell fixed IgE
(Wheal & Flare with resultant
 The antigen cross-links two adjacent
reaction) induration
IgE molecules, leading to
degranulation of the mast cells,
with release of:
PRE-FORMED MEDIATOR NEWLY SYNTHESIZED HISTAMINE
MEDIATORS
 ERYTHEMA
a. HISTAMINE a. PROSTAGLANDIN
 WHEAL AND FLARE
- major component - enhances the
of mast cell action of Histamine  INCREASE IN MUCUS PRODUCTION
granules b. LEUKOTRIENE  INCREASE IN VASCULAR PERMEABILITY
- causes - has the same  INCREASE IN ACID PRODUCTION IN
↑ smooth muscle action as Histamine STOMACH
contraction but 1,000x more  URTICARIA
↑ vascular potent  INCREASE IN SMOOTH MUSCLE
permeability c. CYTOKINES CONTRACTION
↑ acid & mucous - such as IL-1, IL-
production 3, IL-4, IL-5, IL-6,
- leading to IL-9, IL-13, IL-14, ATOPY
Erythema, IL-16,
Corticaria, Wheal & TNF-α, GM-CSF  An inherited tendency to respond
Flare to naturally occurring inhaled
b. EOSINOPHIL and ingested allergens with
CHEMOTACTIC FACTOR continued production of IgE.
OF  Found in: HLA-DR2, DR4, DR7
ANAPHYLAXIS (ECF-A)
- attracts ATOPY
Eosinophil to the
 Ag that trigger formation of IgE are
area where Ag is
called as “Atopic Antigens or
- induces
Allergens”
expression of
eosinophil for C3b If not allergic/Normal/Non-allergic
c. NEUTROPHIL people...
CHEMOTACTIC FACTOR  Type-1 Helper cells(Th1) responses
(NCF) which suppresses the production of
d. TRYPTASE IgE
- cleaves Kininogen  IL-12, IL-18, & IFN-α(suppress
to generate production of IgE)
Bradykininwhich If allergic/ Allergic people …
prolongs the  Type-2 Helper cells (Th2) responses
effects of
which promotes the production of IgE
Histamine
 IL-4, IL-5, IL-9, & IL-13, IL-3
 These mediators caused the symptoms of
type 1 hypersensitivity which are
manifested within seconds to minutes
after secondary exposure.
ANAPHYLAXIS o Least expensive & more
specific
 Most common dangerous form of
CUTANEOUS / PRICK TESTING
type 1 HS
o Inject small amount of Ag to
Associated Diseases: the skin
o After 15mins, spot is examined
a. ALLERGIC RHINITIS
for Erythema, Wheal& Flare
 most common form of Atopy >3mm
 Signs & Symptoms: Nasal congestion, INTRADERMAL TEST
paroxysmal sneezing, itching of nose o 0.01 to 0.05 mL of test
& eyes solution is injected between
layers of skin
b. ANAPHYLAXIS
o After 15-20mins, site is
 most severe form of allergy inspected for Erythema, Wheal
 an acute reaction involving multiple &Flare (5-10 mm)
organs
In-Vitro Skin Tests:
 can die because of Anaphylactic
shock RADIOIMMUNOSORBENT TEST (RIST)
- Measures the total IgE
c. BRONCHIAL ASTHMA
RADIOALLERGOSORBENT TEST (RAST)
o recurrent airflow obstruction - Measure the Ag-specific IgE
with cough & mucous production
leading to
panting/breathlessness 2. Type 2 Hypersensitivity
d. Drug / Insect bites Reactions that produce cell
damage which is mediated by
e. Tropical Eosinophilia complement-fixing antibodies
Treatment: directed against cell surface
antigens.
 Avoidance of known Allergens Immune mediator: IgG &IgM
 Anti-histamine, Bronchodilators, Effector cells: RBC, WBC, &
Corticosteroids PLT
 Anti-IgE Mechanism: Free Ab reacting
 Immunotheraphy / Hypersensitization with Ag on the cell surface
/ Ag Desensitization: very small forming immune complex which
sensitizing Ag injected into patient activate complement system
with the idea of building up IgG Reactions that produce cell
instead of IgE damage which is mediated by
Diagnosis: complement-fixing antibodies
directed against cell surface
In-Vivo Skin Tests: antigens
Associated Diseases:  seen in: Chronic Lymphocytic
Leukemia, Non-Hodgkins Lymphoma,
a. TRANSFUSION REACTIONS
Myelodisplastic, SLE
 transfused incorrect/incompatible
blood type WARM AIHA
 activate complement system leading  reacts @ 37°c
to cell lysis  caused by drugs such as:
Penicillin, Acetaminophen,
b. IMMEDIATE / ACUTE HEMOLYTIC TRANSFUSION
Rifampin, Methyldopa, Sulfonamide,
REACTION (IHTR)
Procainamide
 IgM
f. IDIOPATHIC THROMBOCYTOPENIC PURPURA
 causes intravascular hemolysis of
(TTP)
RBC
 ABO blood group  patient produces Ab reacting to the
 Signs & Symptoms: fever, chills, platelet’s surface leading to tiny
low back pain, & hemoglobinuria hemorrhages/purpura
 caused by respiratory infections &
c. DELAYED HEMOLYTIC TRANSFUSION REACTION
drugs like Quinidine, Rifampin,
(DHTR)
Sulfonamide, Cephalothine,
 IgG Cligitoxin, Aspirin
 causes extravascular hemolyssi of
g. GOOD PASTEUR SYNDROME
RBC
 Rh blood group  Ab reacting in basement membrane of
 Signs & Symptoms: mild fever, the Lungs & Kidney
jaundice, anemia, shock
Diagnosis:
d. HEMOLYTIC DISEASE OF THE NEWBORN
 DIRECT ANTIGLOBULIN TEST / DIRECT
 ERYTHROBLASTOSIS FETALIS: severe form COOMB’S TEST (DAT)
of HDL o detects in-vivo sensitization
 mother is Rh(-) while baby is Rh(+) of RBC
 leakage of baby’s blood to  INDIRECT ANTIGLOBULIN TEST /
maternal immune system INDIRECT COOMB’S TEST (IAT)
 Rhogan/ Rh-Ig: contains anti-D o detects in-vitro sensitization
which can coat the baby’s RBC, of RBC
given @ 7th month & 3 days after o used in Ab screening &
delivery detection, cross-matching, &
blood-typing using known anti-
e. ACQUIRED IMMUNE HEMOLYTIC ANEMIA
sera
COLD AIHA
 reacts @ 30°c below
 common among patients who are 50-60
y/o and above & childer after
respiratory/viral infection
 3. Type 3 Hypersensitivity b. SERUM SICKNESS
Also called immune complex
 result of passive immunization with
mediated hypersensitivity.
animal serum, usually horse or
They are due to the deposition
bovine serum which are used to treat
of Ag-Ab complexes in tissues
such infections as Diptheria,
and blood vessels.
Tetanus, Gangrene
These complexes can destroy
the surrounding tissue c. SYSTEMIC LUPUS ERYTHEMATOUS (SLE)
directly or indirectly by
d. RHEUMATOID ARTHRITIS (RA)
attracting neutrophils to the
site of complex deposition
that release hydrolytic
4. Type IV Hypersensitivity
enzymes, causing local damage.
A hypersensitivity reaction
Immune mediator: IgG &IgM
mediated by sensitized T cells
Effector cells: Host tissue
releasing lymphokines,
Mechanism: Ab reacts with
attracting macrophage to the
soluble Ag to form complexes
site and activating them.
that ppt in the tissue
Once the macrophage arrives,
Due to the deposition of Ag-Ab
they begin to cause tissue
complexes in tissue & blood
damage that may develop into a
vessels
chronic granulomatous reaction
These complexes can destroy
if antigen persists.
the surrounding tissue
It is also called delayed type
directly or indirectly by
hypersensitivity since
attracting neutrophils to the
following secondary exposure
site of complex deposition
to the offending antigen, the
that release hydrolytic
manifestations of the
enzymes, causing local damage
interaction do not appear for
Soluble antigen is involve
more than 24 hours.
forming insoluble complex when
Immune mediator: T-cells
binds to Ab
Effector cells: Macrophages
Associated Diseases: Mechanism: Synthesizes T-cell
rather than Ab
a. ARTHUS REACTION
mediated by sensitized T-cells
 a necrotic dermal reaction releasing Lyphokines,
considered to be a local immune attracting macrophage to the
complex deposition phenomenon site & activating them
(involve blood vessels) Once the macrophage arrives,
 deposition of immune complex in they begin to cause tissue
small dermal blood vessel damage that may develop into a
Chronic granulomatous reaction
if Ag persist
TYPES OF CELL-MEDIATED OR TYPE IV VON PIRQUET TEST: scratch the skin
HYPERSENSITIVITY REACTIONS then introduce the Ag

a. Delayed type hypersensitivity

- Effector cells are Tdth cells that HUMORAL MEDIATED HUMORAL MEDIATED
recruit other cells such as HYPERSENSITIVITY HYPERSENSITIVITY
macrophages. REACTIONS REACTIONS
b. Cell-mediated Cytotoxic reactions  Includes  Include type
Types I, II, IV reactions
- Effector cells are T cytotoxic
II and V  Reactions are
cells.
reactions delayed in
Associated Diseases:
 Immune time
a. PULMONARY TUBERCULOSIS reactions are  Reactions are
b. LEPROSY observed characterized
c. HYPERSENSITIVITY PNEUMONITIS / minutes after by
HUMIDIFIER LUNG DISEASE / FARMER’S LUNG / antigen significant
PIGEON BREEDER Exposure cell
DISEASE  Inflammatory infiltration
 allergic disease of the Lung reactions are with
Parenchyma characterized resultant
d. CONTACT DERMATITIS by more fluid induration
and eryhtema
 causes Vesicular papules, a fluid-
(Wheal and
filled lesions
Flare
Diagnosis:
reaction)
TUBERCULIN SKIN TEST
 uses purified tiltrate from the cell
wall of Mycobecterium tuberculosis
 purified protein derivative is
infected under the skin & reaction
is read @ 48-72hrs (+) individual
has been previously exposed to
MTB/other related organisms
PATCH TEST
 non-absorbent adhesive patch
containing the suspected allergen is
applied on the patient’s back read
@ 48hrs (+) redness with
papules/tiny blisters
MANTOUX TEST
 0.1 mg of Ag is injected
intradermally then check reaction
after 48-72hrs (+) redness >5mm
VOLMER TEST: almost the same as
Patch test
 TYPE COMMON DISEASES ANTIGENS MEDIATORS
I - Anaphylactic  Allergic  Plant pollen, IgE, mast cells
or immediate rhinitis, house dust
urticaria, hives mites, foods When there is
(e.g. fish, allergen in
eggs, environment mast
 Bronchial asthma chocolate) cell and basophils
 Fungal or mold will be activated
spores, animal IgE bind with
danders, antigens Epsi
animal hair portion will bind
 Drugs or insect
bites w/
 Penicillin, baso and mast cell
antiseptics, and trigger release
anesthetics, of granules
bee sting wasp
 Tropical
eosinophilia
 Parasites
(WUCHERERIA
BANCROFTI)
 Loeffler’s
syndrome
 Chitin on
larva of
Ascaris
lumbricoides
II - Cytotoxic  HEMOLYTIC  Antigens on IgG, IgM,
Transfusion RBCs Complement (IgA)
reactions (HTR)

 Hemolytic  Antigens on
Disease of the RBCs
Newborn

 Acquired immune  Penicillin,

hemolytic anemia quinidine
coating RBC
 Idiopathic  Ags on surface
thrombocytopenic of platelets
purpura

 Good Pasteur  Ags on

Syndrome basement
membrane of
the
 glomeruli of
the kidney

III - Immune  SLE (SYSTEMIC  Nuclear IgG, IgM, IgA,

Complex LUPUS material complement
ERYTHEMATOSUS)

 RA (RHEUMATOID  IgG
ARTHRITIS)

 Arthus-like  Aspergillus
reaction fumigatus

 Serum sickness  Horse serum

IV - Delayed or  PTB  M.  Activated T

tuberculin tuberculosis cytotoxic
cells
 Leprosy  M. leprae Macrophages

 Contact  Dyes, metals,

dermatitis cathecol,
rubber  Lymphocytes

V - Anti-receptor  Grave’s disease  TSH receptor IgG but complement

or stimulatory of acinar fixing
cells
 Myasthenia  acetylcholine
gravis
VI -  Gram negative  LPS- bacteria
Miscellaneous endotoxic shock

 PNH (paroxysmal  Defective RBC

nocturnal membrane
hemoglobinuria
 DIAGNOSIS OF HYPERSENSITIVITY
REACTIONS
1. TYPE 1
 In vivo skin tests (cutaneous
and intradermal testing)
 RIST (radioimmunosorbent test)
- measures total IgE
 RAST (radioallergosorbent
test) - measures allergen
specific IgE
2. TYPE 2
 DAT (Direct Antiglobulin Test)
3. TYPE 3
 Immunoassays and certain
agglutination reactions
4. TYPE 4
 Tuberculin Test/ Mantoux test
(skin test for TB)  inject
PPD (purified protein
derivative) to skin read
result after 72hrs