Week 7

WHAT ARE ANTIBODIES?

Antibodies/Immunoglobulins Antibodies are part of the human immune system.
Basically, they identify bad bacteria and viruses
STRUCTURAL PROPERTIES OF ANTIBODIES and track them down to fight back
 Antibody structure was described by Gerald  glycoprotein substance that is produced by B-
Edelman & Rodney Porter. lymphocyte in response to an antigen.
 Quaternary Proteins held together with non-  serum factors in blood formed in response to
covalent forces and disulphide bond. foreign substance exposure.
 Folded into compact globular subunit with
formation of balloon shaped loop at each
domain.
 Monomer – basic structural unit of an antibody.
 The Ig’s monomer is a “Y” shaped molecule the
consists of four polypeptide chains. (Two
Identical Heavy Chain & Two Identical Light
Chain)

Role of antibodies
 Serve as a physiological bridge between an
antigen present on a pathogen and the
cells/molecules that will destroy it.

STRUCTURAL PROPERTIES OF ANTIBODIES

I. Light Chain- 2
II. Heavy Chain- 2
III. Disulfide Bonds
IV. Regions
V. Hinge
VI. Domains
VII. Region

I. Light Chains
2 MAJOR CLASSES OF ANTIBODY LIGHT CHAINS
 Kappa or lambda
 Composed of 23,000 daltons and more than 200
amino acids.
 Common to all immunoglobulin classes.
 Two Types : Kappa (κ) (214 Amino Acids)
Lambda (λ) (213-216 Amino
Acids)
 Gene: Chromosome No. 2 (Kappa)
Chromosome No. 22 (Lambda)
 Region: Amino Terminal, Carboxy Terminal
 Determine the serological and physical chain of
an antibody
 C. INTRACHAIN BONDS
II. Heavy Chains
 Determine the serological and physical I. REGIONS VARIABLE
characteristics of the antibody.
 Each class performs different functions during the REGION (V)
immune response.  Shows a wide variety of amino acid sequence in the
 Gene: Chromosome Number 14 amino terminal portion of the molecule
 Types: IgG (γ) IgM (μ) IgA (α) IgD (δ) IgE (ε)
 Five classes: mu, delta, gamma, epsilon and alpha. Areas of high variability:
 Region: Amino Terminal, Carboxy Terminal I. Variable Region of Heavy Chain (VH)
II. Variable Region of Light Chains (LH)
Chain composition of 5 immunoglobulin classes
 IgG - gamma Hc - 3 Ch domains - subclasses gamma 1- II. DOMAINS
4
 Are globular regions on polypeptide chain stabilized
 IgM - mu Hc - 4 Ch domains - no subclasses
 IgA - alpha Hc - 3 Ch domains - subclasses alpha 1-2 by intrachain disulfide bonds.
 IgE - epsilon Hc - 4 Ch domains - no subclasses
 IgD - delta Hc - 3 Ch domains - no subclasses  Domains on the heavy chain:VH,CH1,CH2,
CH3, (CH4)
NOTES!!!!!! .
 Domains on light chain: VL, CL
 IgA, IgD, IgG heavy chains
CONTAINS a hinge region. III. HINGE REGION
 Portion of heavy chain between the CH1 and CH2
 IgE and IgM contain NO hinge domains.
region  In this region, inter-chain disulphide bonds form
between the arms of Fab fragments,
 High Flexible and allows movement of the Fab arms
in relation to others.
ISOTYPIC VARIATION
 Refers to the type of heavy chain that is unique to Fragmentation of Antibodies
each immunoglobulin class.  Degrade immunoglobulin molecules into
 Isotypes of immunoglobulins are: definable fragments to facilitate study of their
structure.
 IgG: have gamma chain
 IgA: have alpha chain Primary Agents for Fragmentation:
 IgM:have mu heavy chain o PAPAIN
 IgE: have epsilon heavy chain o PEPSIN
 IgD: have delta chain 1.2 CLASSES
1.3 PROPERTIES
1.4 FUNCTIONS
ALLOTYPIC VARIATION
 Its refers to the genetic variation in the constant 1. IgG
regions of immunoglobulin molecule.
2. IgA
 Certain genetic markers within the constant 3. IgM
regions of the heavy chain are different in one or 4. IgD
more 2 amino acids which then distinguish 5. IgE
individuals within a species.

IDIOTYPIC VARIATION
 refers to the diversity at the binding site and in
particular relates to the hypervariable segments of SUMMARY OF STRUCTURES OF ANTIBODIES
the antibody combining site (Paratope).

 Composed of four polypeptide chains: 2 identical heavy

III. DISULFIDE BONDS chains (with variable and constant regions) and 2
identical light chains (with variable and constant regions),
 Bonds that hold the four polypeptide chains in held together by intra/interchain disulfide covalent bonds.
normal immunoglobulin molecules.
 Forms the basis of division of each immunoglobulin  Hinge region gives flexibility, allowing arms to move.
into domains. It is also susceptible to proteolytic cleavage.
Types :
A. INTERCHAIN BONDS Occurs between:  Light chains are bound to a partner heavy chain by
B. HEAVY CHAINS (H-H) – Hinge Region disulfide bonds and non-covalent interactions.
HEAVY and LIGHT CHAINS (H-L) LIGHT
CHAINS (L-L)  Separated into antigen-binding regions (Fab) and
effector activity tail region (Fc).
ANTIBODIES:
IgG  Secretory IgA
 Predominant Ig among humans comprising 75- o a polymeric form stabilized a short polypeptide
80% of the total Ig pool chain. It is known as the “antiseptic paint” of
 Has 4 Major Subclasses: IgG1, IgG2, IgG3, mucous membranes. It can activate the
IgG4 bacteriolytic activity through the alternate
 Equally distributed in the different fluid pathway of complement system and only the
compartments with detectable amounts in CSF presence of lysozyme.
and urine
 Readily diffusible
 IgG antibodies response appears later than IgM IgD
in primary response but they form the major  Heat labile immunoglobulin.
antibody of the secondary immune response  Accounts for less than 1% of the total serum Ig.
 Maternal IgG is actively and selectively  Anti-idiotypic Antibody
transferred across the placenta to the fetus and  Precise biological action is not known but it may
imparts passive protection to the newborn for 6-9 play a role in antigen-triggered lymphocyte
months differentiation.
Functions of IgG:
(1) Provides immunity for the newborn
(2) Complement Fixation
(3) Opsonization IgE
(4) Neutralization of toxins
(5) Participation in agglutination  Heat labile immunoglobulin, least abundant Ig in
(6) Participation in precipitation** the serum accounting for only 0.002% of the
total serum Ig.
IgM  Synthesized locally by plasma cell present I the
 The largest of the immunoglobulin molecule, mucous membrane of the GI and respiratory
accounting for 5-10% of the total tracts.
immunoglobulin pool.  It is unable to fix the complement via the
 The earliest antibody to appear in the primary classical pathway.
immune response but it doesn’t persist for long.  It is homocystotropic due to its affinity for cells
 PRIMITIVE ANTIBODY / of the host species, particularly for tissue mast
MACROGLOBULIN cells and blood basophils.
 Star shaped in the free state; crab-like in antigen-  Associated with immediate hypersensitivity
antibody reaction. reactions & with immunity to certain helminthic
 Maternal IgM does not cross the placenta. parasites.
 Seen in Intravascular Hemolysis.  Also known as REAGINIC ANTIBODY/
 A powerful agglutinator of particulate antigen. NUISANCE ANTIBODY

Functions of IgM: NOTES!!!!!

(1) Surface receptor for antigens FUNCTION OF 5 IMMUNOGLOBULIN
(2) Complement Fixation CLASSES
(3) Opsonization  IgG - most abundant antibody in
(4) Neutralization of toxins blood circulation.
(5) Participation in agglutination***
 IgE - important in allergic
reactions.
IgA  IgA (exists as dimer or tetramer in
 Represent 15-20% of human serum Ig pool. humans) - protection at mucosal
 Found in serum in small amount but surfaces
predominant in sero-mucous secretions of the
respiratory tract, genito-urinary tract and GI  IgM (has 10 antigen-binding sites)
tracts/. - first line of defence.
 Found also in Saliva, sweat , tears, colostrum
and breastmilk.

Forms of IgA:

 Serum IgA
o can agglutinate motile infectious agents thus
promoting their phagocytosis but they cannot
activate the complement system
CLASSIFICATION OF ANTIBODIES Occurrence Early in Late in immunization
A. According to SEDIMENTATION CONSTANT immunization
B. According to TEMPERATURE Reaction Saline acting Albumin acting
C. According to OCCURRENCE
D. According to SPECIE WHICH PRODUCE THEM
E. According to IN VITRO BEHAVIOUR
II. THEORIES OF ANTIBODY PRODUCTION
A. ACCORDING TO SEDIMENTATION CONSTANT
Ehrlich’s Side Chain Theory
IG Sedimentation Molecular Weight
 1900
Constant (Daltons)  Paul Ehrilich proposed
IgG 7s 150,000  cells' surfaces possessed variety of side chains
Serum IgA 7s 160,000  when toxic subs blocked on of these side chains via
Secretory 9s 170,000 an accidental affinity, cell responded by making large
IgA number of particular side chain, some of which spill
out into blood & f(x) as circulating antibodies
IgM 19s 900,000
IgD 7s 180,000  Once antigen was introduced, it would select the
IgE 8s 190,000 cell with proper receptors. Combination would
take place and then receptors will break off and
B. ACCORDING TO TEMPERATURE enter the circulation as antibody molecules.
I. Cold Antibodies: IgM  New receptors will be formed in place of those
II. Warm Antibodies: IgG broken off and this process could be repeated.

The Template Theory

C. ACCORDING TO OCCURRENCE
 Antibody-producing cells are capable of
I. Natural Antibodies: IgM synthesizing a generalized type of antibody, and
II. Immune Antibodies: IgG when contact with an antigen occurs.
 The antigen serves as a mold or template and
D. ACCORDING TO SPECIE WHICH PRODUCE alters protein synthesis so that antibody with a
THEM specific fit is made.
 Autoantibodies- produce by the immune system  The “molded” antibody then enters the
against the self-antigens.
circulation, while the antigen remains behind to
direct further synthesis.
 Isoantibodies/Alloantibodies- formed in response to
antigen from individual of the same specie. Selective Theory
 Heteroantibodies- antibodies produce in response to  1955
antigen from another specie.  Niels Jerne proposed
 his natural selection theory of antibody formation, in
E. ACCORDING TO REACTION WITH ITS ANTIGEN which randomly diversified antibody molecules were
Agglutinins Antibodies involved in thought to replicate after binding to injected antigen
agglutination.
 Assumes that antibodies are synthesized in a
Precipitins Antibodies involved in precipitation. manner similar to that of other proteins.
Agglutinoids Agglutinins that are modified by  Instructions for their synthesis are provided by
heat. genetic elements in the nucleus of the cell rather
Hemagglutinins Antibodies involved in from the antigen.
hemagglutination.
Clonal Selection Theory
Lysins Antibodies capable of lysis.
 1957
Allergic Antibodies that reacts with allergens.  Talmage & Burnet proposed that . . .
Antibodies  two new theories of antibody production
substituted the Natural Selective Theory
F. ACCORDING TO IN VITRO BEHAVIOUR
Complete Incomplete Antibody the interaction of antigens (Ggl: toxin or
Antibody other foreign substance that induces an
immune response in the body, esp. the
Synonyms Bivalent; Univalent; Blocking;
production of antibodies.) with receptors on
Saline acting Coagglutinating; the cell surface stimulated antibody
conglutinating formation & replication of selected cells.
Reponse to Thermolabile Thermostable  after > 30 yrs, Cell Selection Theory & name given to
Temperature it by Burnet (Clonal Selection), have become part of
Ability to cross Cannot cross Can cross the placenta established dogma of immunology
placenta the placenta  This theory has been confirmed by numerous
experiments later & is current theory.
 Individual lymphocytes are genetically pre-
programmed to produce one type of
immunoglobulin, and that specific antigen finds
or selects those particular cells capable of
responding to it, causing these to proliferate.
 Repeated contact with the antigen would
continually increase a lymphocyte pool.
 WEEK8
CLASSICAL PATHWAY:
COMPLEMENT SYSTEM  -9 Individual Proteins
-C1, C2, C3, C4, C5, C6, C7, C8, C9

C1 Complex:
i. Major Proteins of the complement
-C1q+C1s+C1r.
ii. Function
-C1q has globular heads that bind to IgG and IgM
iii. Pathways of activation
iv. Biologic consequences of activation by the Fc region.
-Binding needs: two molecules of IgG + One
v. Regulation
molecule of IgM.
vi. Measurement of active components of the
-Ionic and hydrophobic bonds.
complement
-Conformation leads to release of C1s.
Complement System
C1s:
Characteristics: -Cleaves C4 and C2.
- Soluble and cell bounded protein -C4>C4a+C4b.
- Heat labile proteins -C2>C2a+C2b.
- Predominantly inactive molecule -*C4bC2a form complex on membrane= C3
- All are produce on Liver Convertase.
- Except: C1 Components (Intestinal Epithelial -C3 Converstase cleaves C3.*
Cell) -C3>C3a+C3b.
Factor D (Adipose Tissue) -C3b is the key molecule.
Functions of Complement system:
-Kill micro-organism, lysis (cells, bacteria, virus, yeasts).
-Induce inflammation.
-Increase phagocytosis by opsonization.
-Clearance of insoluable immune complexes.

Complement-mediated cytolysis:
 -Binding of C3b to microbe, activation of late
components of complement.
-Formation of membrane attack complex
(MAC).
-Osmotic lysis of microbe.

Steps to complement activation:

1. Recognition.
2. Enzyme activation.
C3 is the central step in all complement
3. Expression of biological activity.
pathways. C4bC2aC3b form a complex
called C5 convertase. This cleaves C5 and
Activation Pathways: forms C5> C5a + C5b.
1. Classical Pathway: initiated by antigen-antibody VERY IMPORTANT
complex.
2. Alternate Pathway: activated by cell wall of NOTE!!!!!!!!
bacteria and yeast.
3. Lectin Pathway: initiated by lectins that bind C5b:
Mannose [MBL]. -Initiates the formation of Membrane attack complex
(MAC).
-C5b forms nucleus for formation of Mac.
QUESTION? -C6 binds to C5b.
What are the differences and similarities -C7 binds to C5bC6.
of the complement pathways? -C8 binds to C5C6C7.
 -Difference: unique proteins and -*C5bC6C7C8 complex serves as a receptor for C9.
enzymes for the 1st. -C9 polymerizes into poly-C9 tube.
-Similarities: results are the same. -Insert into membrane.
-Ions escape, water enters, osmotic cell lysis.*
 DEFICIENCIES OF COMPLEMENT
Classical Pathway Alternative Pathway COMPONENTS
C1q – binds to fc portion of B – binds C3b to form DEFICIENT ASSOCIATED DISEASE
IgG (CH2) & IgM (CH3) C3 convertase COMPONENT
C1r – activates C1s D – cleaves factor B C1 (1q,r,s) Lupuslike syndrome; recurrent
C1s – cleaves C4 and C2 into Bb in the infections
presence of C3 and C2 Lupuslike syndrome, recurrent
Mg ions infections, artherosclerosis
C3 – key component of each Properdin- stabilize Most common complement
pathway C3 convertase deficiency
C5 – initiates MAC C3 Glomerulonephritis
C6 – stabilizes and binds C5b Lectin pathway Most severe complement
C7 – has affinity to lipid MBL – binds to deficiency
component mannose Most commonly measured
C8 – expose hydrophobic MASP 2 – acts like C4 Lupuslike syndrome
region [pore formation] C1s C5-C8, Neisseria infections
C9 – accelerates cell lysis MASP 1,2,3 – bind to Properdin
form an activated C1 C9 No known disease association
like complex C1-INH Hereditary angioedema
DAF, MIRLs Paroxysmal nocturnal
C3a, C4a, C5a – Anaphylaxis; cause increased hemoglobinuria
vascular permeability, contraction of smooth Factor H or I Recurrent pyogenic infections
- muscle, and release of histamine from MBL Pneumococcal diseases, sepsis,
basophils Neisseria infection
C3b, C4b, C5b – Opsonization MASP-2 Pneumococcal infections
C5b6789- membrane attack complex

PLASMA COMPLEMENT REGULATORS LECTIN (PROTEIN THAT BIND TO

C1 inhibitor Dissociates C1r and C1s CARBOHYDRATES) PATHWAY:
from C1q
 -Mannose-binding lectin (MBL) binds
Factor I Cleaves C3b and Cb carbohydrate on the surface of bacteria.
Factor H Cofactor with I to -MBL associated serine proteases (MASP)
inactivae C3B; prevents cleaves C4 and -C4: C4> C4a + C4a.
binding of B to C3b C2: C2> C2a + C2a.
C4-binding protein / Acts as a cofactor with I -C4bC2a: (C3 convertase) form complex on
membrane cofactor to inactivate C4b membrane.
protein / CD46 -Rest is similar to the classical pathway.
CR1 / CD35 Acts as a cofactor with I -*C5b initiates the formation of
and binds C3b Membrane attack complex (MAC)*.
Decay accelerating Accelerates dissociation
Factor / CD55 of C3 convertase
Membrane inhibitor of Inhibits MAC through
reactive lysis MIRL / binding with CD8 to
CD59 prevent insertion of CD9
S protein / vitronectin Prevents attachment of
C5b67 complex to cell
membrane
ALTERNATE PATHWAY:
 -C3 hydrolyzed to C3b on bacteria and yeast.
-C3b binds to activator surface form nucleus
to complement cascade.
-C3b binds Factor B and forms
C3bFactorB complex.
-Factor D cleaves Factor B when it is bound
to C3B.
-Forms C3bBb=C3 convertase.
-Properdine binds to form a more stable
complex C3bBbP.
-C3bBb and C3bBbP cleave more C3 to C3b
so more C3 becomes available.
-Amplfication loop.
-C3b binds to C3bBb and forms
C3bBbC3b that cleaves C5. C5>C5a+C5b.
-C5b initiates the formation of Membrane
attack complex.
QUESTIONS!!!!!!!!
How does the complement system induce
inflammation?
 Anaphylatoxin: C3a,C4a,C5a.
 Pro-inflammation:
 Strongly chemotactic for neutrophils and
inflammatory cells.
 Degranulate mast cells to release
inflammation mediator, including
histamine.
 Vasodilation.
 Induce expression of adhesion molecules
to increase extravasation.
 Enhance production of inflammation
mediators.
How does the complement system induce
phagocytosis?
 Binding of complement components C3b
or inactivated C3b, (iC3b) and C4.
 Complement receptors (CR1-complement
receptor 1, CR3, CR4,) expressed on
natural killer cells, granulocytes,
 Facilitate phagocytosis by opsonization.
How does the complement system clear immune
complexes?
 Antigen-Antibody complexes get very
large.
 Complement binds to complex.
 Activate complement cascade.
 Complex binds to complement receptor,
CR3 on phagocytotic cells.
 Enhanced phagocytosis and destruction of
Ag:Ab complexes.
REGULATION OF THE CLASSICAL PATHWAY:
-C1 S activity inhibited by C1 receptor (C1 INH).
-C4bC2a dissociated by C4 binding protein.
-Decay accelerating factor blocks formation of C3
convertase.
REGULATION OF ALTERNATE PATHWAY:
-Factor H dissociation of C3 convertase (displaces Bb
from C3bBb).
-Factor I and membrane co-factor protein (co-factor
I) cleave and inactivate C3b to iC3B.
-Decay accelerating factor dissociates C3bBb.
 WEEK 9
Hypersensitivity Reactions Type III ( Immune a. 3-8 hrs
(Types I, II, III, IV) Complex) b. Antibodies & antigens
Hypersensitivity form complexes that
a. Time before cause damaging
Hypersensitivity
chemical signs inflammation
 Normal but exaggerated or uncontrolled immune
b. Characteristics c. Examples
response to an antigen that can produce
c. Examples *Arthus reaction
inflammation, cell destruction, or tissue injury.
* Serum sickness
Inflammatory response
 local, eliminates antigen without extensively
damaging the host’s tissue Type IV (Cell- a.24-48 hrs
mediated or delayed b. Antigens activate Tc
type) Hypersensitivity that kill target cells
a. Time before c. Examples
NOTES!!!!!!! chemical signs *Rejection of
What are the 4 types of hypersensitivity reactions: b. Characteristics transplanted tissues
Type I (Anaphylactic Reactions) c. Examples contact DERMATITIS
2. Type 2 (Cytotoxic Reactions) (Poision Ivy)
3. Type 3 (Immune Complex Reactions) * Chronic diseases
4. Type 4 (Cell-Mediated or Delayed-type (Tuberculosis)
Reactions)

Type I ( Anaphylactic) a. Less then 30 minutes

Hypersensitivity immediate
a. Time before b. IgE binds to mast cells;
chemical signs this causes degranulation of
b. Characteristics the mast cell and release of
c. Examples histamine (reactive)
c. examples
*Anaphylactic shock from
drug injections & insect
venom
*allergic conditions (hay
fever, asthma)

Type 2 (Cytotoxic) a. 5-12 hours

Hypersensitivity b. Antigen causes formation of
a. Time before IgM & IgG antibodies that
chemical signs bind to the target cell; when
b. Characteristics combined with action of A quick mnemonic to use to remember
c. Examples complement destroys target these is ACID:
cell  Type I – Allergic
c. examples  Type II – Cytotoxic
* Transfusion reaction (IgM-  Type III – Immune
agglutination) complex deposition
*Rh incompatibility (IgG cross  Type IV – Delayed
placenta)
MNEMONICS 101
TYPE I HYPERSENSITIVITY
 cell bound antibody reacts with antigen to release
physiologically active substances.
 has the short time of lag, usually seconds to minutes,
between exposure to antigen and the onset of clinical
symptoms.
 the key reactant present in type I, or immediate
sensitivity reaction, is IgE.
 Antigens that trigger formation of IgE are called
atopic antigens, or allergens.
 Carl Wilhelm Prausnitz & Heinz Kustner.
(Passive Cutaneous Anaphylaxis)
TREATMENT OF IMMEDIATE
HYPERSENSITIVITY
 Avoidance of known allergens is the first line of
defense.
 Localized allergic reactions, such as hay fever,
hives, or rhinitis, can be treated easily with
antihistamines and decongestants.
 Asthma is often treated with a combination of
therapeutic reagents, including antihistamines
and bronchodilators, followed by inhaled
corticosteroids.
 Hyposensitization.
 Anti-IgE monoclonal antibody (Omalizumab)

TRIGGERING OF TYPE I REACTIONS BY IgE:

 The regulation of IgE production appears to be a
function of a subset of T cells called Type 2 T
Helper Cells (Th2)
 Allergic Immune Response (Microorganisms,
Allergens): Type 2 T Helper Cells (Th2)= IL-4, IL-5,
IL-9, IL-13

 IL-5 and IL-9: Eosinophils

 IL-4 and IL-9: Mast Cells
 IL-4, IL-9, and IL-13: Overproduction of Mucus
 IL-4, IL-13: Activate transcription of the epsilon
gene in B cells

type I Hypersensitivities
Type 1 Common Cause Signs and Symptoms
In Type 1 hypersensitivity reactions mast-cell Name
activation is induced by secretion of IgE Allergy- Inhalation of Constriction of bronchi,
antibodies. Initial exposure to the antigen causes induced allergens labored breathing,
the priming of Th2 cells, and their release of IL-4 asthma coughing, chills, body
causes the B cells to switch their production of aches
IgM to IgE antibodies which are antigen-specific. Anaphylaxis Systemic Hives, itching, swelling
The IgE antibodies bind to mast cells and reaction to of tongue and throat,
basophils, sensitising them to the antigen. allergens nausea, vomiting, low
blood pressure, shock
When the antigen enters the body again, it cross Hay fever Inhalation of Runny nose, watery
mold or eyes, sneezing
links the IgE bound to the sensitised cells, causing
pollen
the release of preformed mediators including
Hives Food or drug Raised, bumpy skin
histamine, leukotrienes and prostaglandins. This
(urticaria) allergens, rash with itching;
leads to widespread vasodilation,
insect stings bumps may converge
bronchoconstriction, and increased permeability
into large raised areas
of vascular endothelium.

The reaction can be divided into two stages –

immediate, in which release of pre-formed
mediators causes the immune response, and the
late-phase response 8-12 hours later, where
cytokines released in the immediate stage activate
basophils, eosinophils, and neutrophils even
though the antigen is no longer present.
TYPE II HYPERSENSITIVITY Common Type II Hypersensitivities
 Reactions are cytotoxic responses. Common Cause Signs and
 In these reactions, complement-fixing IgG or Name Symptoms
Hemolytic IgG from mother Anemia, edema,
IgM antibodies are directed against cellular or
disease of crosses the enlarged liver or
tissue antigens such as those found on the
the newborn placenta, spleen, hydrops
surface of white blood cells (WBCs) and (HDN) targeting the (fluid in body cavity),
platelets. fetus’ RBCs for leading to death of
destruction newborn in severe
Type 2 cases
Type 2 hypersensitivity reactions are Hemolytic IgG and IgM Fever, jaundice,
transfusion bind to antigens hypotension,
mediated by antibodies targeting reactions on transfused disseminated
antigens on cell surfaces. When cell (HTR) RBCs, targeting intravascular
surface antigens are presented to T donor RBCs for coagulation, possibly
destruction leading to kidney
cells, an immune response is started, failure and death
targeting the cells to which the
antigens are attached.

Antibodies binding to cells can NOTES!!!!!!!!!

activate the complement system,
leading to degranulation of
neutrophils, a release of oxygen
radicals, and eventual formation of
membrane attack complex – all of
which lead to destruction of the cell.
Parts of the complement activation can
also opsonise the target cell, marking it
for phagocytosis.
The destruction of host cells in this
way can lead to tissue-specific
damage. Type 2 hypersensitivity
reactions may occur in response to
host cells (i.e. autoimmune) or to non-
self cells, as occurs in blood
transfusion reactions.
Immune reactions categorized as type
II hypersensitivities, or cytotoxic
hypersensitivities, are mediated by IgG
and IgM antibodies binding to cell-
surface antigens or matrix-associated
antigens on basement membranes.
These antibodies can either activate
complement, resulting in an
inflammatory response and lysis of the
targeted cells, or they can be involved
in antibody-dependent cell-mediated
cytotoxicity (ADCC) with cytotoxic T
cells.

Type 2 is distinguished from Type 3

by the location of the antigens – in
Type 2, the antigens are cell bound,
whereas in Type 3 the antigens are
soluble.
TYPE III HYPERSENSITIVITY
 Reactions are immune complex reactions.
 IgG and IgM antibodies from soluble immune
complexes with antigens.
 These complexes may be deposited in extravascular
tissues, which results in infiltration by neutrophils
and local tissue damage.
 Complement is also activated and contributes to the
inflammatory response.
Type 3
Type III hypersensitivities are
immune-complex reactions that were
first characterized by Nicolas
Maurice Arthus (1862–1945) in
1903. To produce antibodies for
experimental procedures, Arthus
immunized rabbits by injecting them
with serum from horses.
However, while immunizing rabbits
repeatedly with horse serum, Arthus
noticed a previously unreported and
unexpected localized subcutaneous
hemorrhage with edema at the site of
injection. This reaction developed
within 3 to10 hours after injection.
This localized reaction to non-self
serum proteins was called an Arthus
reaction. An Arthus reaction occurs
when soluble antigens bind with IgG
in a ratio that results in the
accumulation of antigen-antibody
aggregates called immune
complexes.
SIDE NOTE!!!!!!!!!!!
A unique characteristic of type III
hypersensitivity is antibody excess (primarily
IgG), coupled with a relatively low concentration
of antigen, resulting in the formation of small
immune complexes that deposit on the surface of
the epithelial cells lining the inner lumen of small
blood vessels or on the surfaces of tissues. This
immune complex accumulation leads to a cascade
of inflammatory events that include the following:
1. IgG binding to antibody receptors
on localized mast cells, resulting in
mast-cell degranulation
2. Complement activation with
production of pro-inflammatory C3a
and C5a
3. Increased blood-vessel permeability
with chemotactic recruitment of
neutrophils and macrophages
Arthus -Localized Type
Reaction -Intradermal, inflammation
-Erythema, edema
-Peaks: 3-8 hours
-Necrotic lesion that may ulcerate
-Rare in humans
Serum -Generalized Type
Sickness -Due: Passive Immunization, Bee
Stings
-Symptoms: 7-21 days after exposure
-Headache, Fever, Nausea, Vomiting,
Join pain, Rashes, Lymphadenopathy
-Recovery: 7-30 days
TYPE IV HYPERSENSITIVITY
 Reactions are delayed-type hypersensitivity
ype IV Hypersensitivities
reactions.
Subcategory Antigen Effector Examples
 CD4-positive T lymphocytes react with the foreign
Mechanism
antigen and releases lymphokines, some which are
1 Soluble Activated Contact
chemoattractants that attract PMNs, monocytes, and
antigen macrophage dermatitis
macrophage.
s damage (e.g.,
 These cells release substances such as proteases,
tissue and exposure to
collagenases, cathepsins, and TNF, which mediate
promote latex) and
inflammation.
inflammator delayed-type
y response hypersensitivit
Type 4 y (e.g.,
Type IV hypersensitivities are not tuberculin
mediated by antibodies like the other reaction)
2 Soluble Eosinophil Chronic
three types of hypersensitivities. Rather, antigen recruitment asthma and
type IV hypersensitivities are regulated by and chronic
T cells and involve the action of effector activation allergic rhinitis
release
cells. These types of hypersensitivities cytokines
can be organized into three subcategories and pro-
inflammator
based on T-cell subtype, type of antigen, y chemicals
and the resulting effector mechanism. 3 Cell- CTL- Contact
associat mediated dermatitis
ed cytotoxicity (e.g., contact
antigen with poison
ivy) and
tissue-
transplant
rejection
SUMMARY/ NOTES!!!!

Type Type 1 Type 2 Type 3 Type 4

Reactant IgE IgG IgG T effector cells
Antigens Antibody binds to APC activates
Mast-cell embedded in host soluble antigen, forming Th1/CTL. T cells
activation cells cause a circulating immune activation
Mechanism releases complement complex lodges in a macrophages and
histamines and activation and vessel wall and causes a cause an
other mediators destruction by local inflammatory inflammatory
MAC. response. response.
Time course Minutes Days
Contact
Rheumatoid Arthritis,
Acute Transfusion Dermatitis,
Example Anaphylaxis Vasculitis,
Reaction Mantoux
Glomerulonephritis
tuberculin test
 WEEK10 TYPES OF AUTOIMMUNITY
1. Organic-Specific Diseases- autoimmune;
virtually any organ system that affected by
Autoimmunity autoimmune diseases.
2. Systemic Diseases- wide spread involvement
(tissue); cell mediated responses

AUTOIMMUNITY
 Is an expression of the immune response that
occurs when the body’s self tolerance system
fails.
 The body’s immune cells are no longer able to
recognize “self” and thus mount an immune
response against its own
 antigens.
 Many autoimmune diseases are
associated with specific Class II
human leukocyte antigens (HLA),
and determining an individual’s
HLA type can help predict the risk
of certain disease
 Self tolerance, central tolerance, peripheral
tolerance
 Autoimmunity is a condition characterized by a
specific humoral or cell-mediated immune (or
combination) response against the constituents of SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
the body's own tissues (self- or auto-antigens). “COLLAGEN DISEASES”
Lesions are a result of hypersensitivity reaction  Systemic lupus erythematosus (SLE), is the most
mechanisms. common type of lupus. SLE is an autoimmune
disease in which the immune system attacks its own
MECHANISMS: Autoantibodies form in response to tissues, causing widespread inflammation and tissue
many different immunogenic stimuli. damage in the affected organs. It can affect the
joints, skin, brain, lungs, kidneys, and blood vessels.
The autoimmune response may be triggered There is no cure for lupus, but medical interventions
by: and lifestyle changes can help control it.
1. Sequestered antigens- not seen in T cell  CAUSES: Idiopathic, Drug-induced.
(thymus) self-tolerance/do not circulate in
blood/ immunogenic tolerance  SYMPTOMS: Rash (Butterfly) or other skin
EXAMPLE: abnormalities, Myocarditis, Lymphadenopathy,
-myolobasic protein-blood brain barrier Glomerulonephritis, Serositis
-sperm  Avoid EXPOSURE TO SUNLIGHT
 DRUGS: Procainamide, Penitoin methyldopa,
2. Foreign antigens- cross reaction in self-
penicillin, sulfonamides
antigen/tissue.
 HYPERSENSTIVITY TYPE 3 (vasculitis,
3. Altered antigens- denatured. glomerulonephritis)
FACTORS: Physical, chemical, and biological  DIAGNOSIS:
changes. ANA Testing
The fluorescent Antinuclear Antibody Test (FANA)
4. Mutation of immunocompetent cells-
ANA Testing by Immunohistochemistry
responsive toward self-antigen.
A. The LE Cell Test
5. Dysfunction of T cells- lose ability to
regulate immune response
MEDIATORS: High vascular permeability,
local tissue damage.
 RHEUMATOID ARTHRITIS (RA)
 Rheumatoid arthritis is a chronic inflammatory
disorder that can affect more than just your
joints. In some people, the condition can damage
a wide variety of body systems, including the
skin, eyes, lungs, heart and blood vessels.

 An autoimmune disorder, rheumatoid arthritis

occurs when your immune system mistakenly
attacks your own body's tissues.

Symptoms

Signs and symptoms of rheumatoid arthritis may

include:

 Tender, warm, swollen joints

 Joint stiffness that is usually worse in the
mornings and after inactivity
 Fatigue, fever and loss of appetite
Staining Associated Associated
Pattern Antibodies Diseases
Homogeneous nDNA, dsDNA, RA, SLE,
ssDNA DNP, Sjogren’s Rheumatoid arthritis can affect many nonjoint
histones syndrome structures, including:
Peripheral nDNA, dsDNA, Sjogren’s
DNP syndrome, SLE
 Skin
Speckled RNP, Sm Scleroderma, RA,
Sjogren’s  Eyes
syndrome, SLE  Lungs
Nucleolar Nucleolar RNA Scleroderma,  Heart
Sjogren’s  Kidneys
syndrome, SLE  Salivary glands
Anti- Centromeric Scleroderma  Nerve tissue
centromere chromatin  Bone marrow
 Blood vessels
TREATMENT
Fever And Arthritis Aspirin, Anti-
inflammatory Drug HASHIMOTO’S SYNDROME
Skin Manifestation Hydroxychloroquine or  “Chronic Autoimmune Thyroiditis”
Chloroquine, Topical  Sign and Symptoms: Goiter, Hypothyroidism
Steroids  Thyroid Autoantibodies:
Acute Fulminant Lupus, Corticosteroids  Anti-Thyroglobulin Antibodies
Lupus Nephritis, CNS  Anti-Thyroid Peroxidase Antibodies
Complications-Systemic  Treatment: Thyroid hormone replacement
therapy.

GRAVE’S DISEASE
 Most common cause of Thyrotoxicosis
 Sign and Symptoms: Goiter, Hyperthyroidism
 Thyroid Autoantibodies:
 Anti-TSH Receptor Antibodies
 Treatment: Radioactive Iodine, Surgery,
Methimazole
Tumor Immunology
Oncology
 Branch of medicine devoted to the study of
treatment of tumors.
WHO (2017), cancer is the 2nd leading cause of
death globally.
 The term tumor is commonly used to
describe a proliferation of cells that produce
a mass rather than a reaction or
inflammatory condition.
 Tumor are neoplasms that are describes as
benign or malignant.
Tumors- epithelial in origin such as ectoderm,
endoderm, mesoderm.
Cancer is a collective term. Latin word
“cancum” means cram. To cure cancer from a
long term, we are targeting the stem cells
compartment. It must be eradicated.
Oncogenes- mutant forms of proto-oncogenes.
Tumor Suppressor Genes- type of gene that
encodes protein.
Tummor immunology
•Study of the relationship between the immune
system and cancer cells
Apoptosis - cell death
•Tumor (to swell) or neoplasm (new growth)
excessive cell growth and division, resulting in the
development of an abnormal cell mass called
Bening tumors
 •Composed of slowly growing cells that are
well differentiated and organized, similar to
the normal tissue from which they originated
 •-they are surrounded by a capsule, which
secures them in place and prevents them
from circulating to other parts of the body
Malignant tumors or cancer cells –
 •Disorganized masses that are rarely
encapsulated, allowing them to invade
neraby organs and destroy their normal
architecture
 •Can vary in their degree of differentiation,
from completely differentiated or mature to
completely undifferentiated tumors that tend
to grow more aggressively and have poorer
prognosis
Cancer - derives its name from this property of
invasiness
Metastasis
 Exhibited by malignant tumors or the ability
of cells to break away from the original
tumor mass and spread through the blood to
nearby or distant sites in the body
Carcinoma - 80% of cancers
 derived from the skin or epithelial
linings of internal organs or glands
Leukemias or lymphomas - 9%
 malignant white blood cells present in
the circulation or lymphatic system
Sarcomas - 1%
 derived from bone or soft tissues such
as fats, muscles, tendons, cartilage,
nerves and blood vessels
Carcinogesis
 initiated by exposure of the host to factors in
the environment that induce genetic changes
in the cell
 asbestos and ciegerrette smoke, radiation
such as ultraviolet rays from the sun and
ionizing radiation from x-rays and certain
viruses
Mutations
 environmental factors that create genetic
changes in the dna of our cells that affect the
body's mechanisms that normally control cell
growth
Proto-oncogenes
 are normal genes that have a positive
influence on cell proliferation and
development
 mutations can convert them to oncogene-like
genes, which have dna sequences similar to
those found in the oncognes of transforming
viruses
 genetic alterations: point mutations,
chromosomal translocations and gene
amplifications that activates it
Tumor supressor genes –
 cell division is normally inhibited
 gatekeeper: genes exert their effects by
controlling the entry of cells into the cell
cycle and preventing cells from completing
the cell cycle if they contain damaged dna
  caretaker genes: important in maintaining
genetic stability by recognizing and repairing
damaged dna in a cell
 if a mutation occurs in which the normal
function of a tumor suppressor gene is lost,
growth inhibitory signals are removed,
resulting in dysregulated cell growth and
genetic instability
Development of a cancerous tumor –
result from series of mutations in proto-oncogenes
and tumor supressor genes that accumulate over a
lifetime
Hanahan and weinberg cancerous cell
characteristics –
1.sustained signaling of proliferation
2.Resistnace to cell death
3.Ability to induce angiogenesis (development
of new bloos vessels to provide oxygen and
nutrients to the tumor)
4.immortality in terms of cell division
5.invasion of metastasis
6.Ability to avoid supressors of cell growth
7.Reprogramming of energy metabolism to
support malignant proliferation
8.Ability to evade destruction by the immune
system
9.genomic instability and mutations
10.inflammatory responses to promote tumor
growth
TUMOR-SPECIFIC ANTIGENS (TSAS)
 unique to the tumor of an individual patient or
shared by a limited number of patients with the
same type of tumor
 coded: by viral oncogenes or by host proto-
oncogenes or tumor supressor genes that have
undergone genetic mutations
 produced by mutations induced by carcinogenic
chemicals in radiation
 tumor cells that do not normally occur in the normal
cell in our body. They are induced tumors. It can be
characterized by T-cell.
 Significance of identifying the TAA:
 The importance is that they are the potential target of
your tumor immunotherapy.
ex: point mutations in key genes involved in cell
proliferation such as the tummor supressor gene p53
and the gene coding caspase 8 and enzyme
important for apoptosis
BCR/ABL gene
 example of tsas
 fusion protein that is produced in chronic
myelogenous leukemia (cml) cells
 this protein results of a reciprocal chromosome
translocation commonly known as the
philadelphia which involves the bcr (breakage
cluster region) on chromosome 9 and the c-abl
gene on chromosome 22
 c-abl is a cellular proto-oncogene that codes for
tyrosine kinase, key enzyme in cell signaling
pathways that promote cell division
 during the translocation the two chromosomes
break and exchange parts so that the c-abl gene
is combined with part of the bcr to produce a
hybrid gene that is constantly expressed
 bcr/abl gene rearrangements result in
uncontrolled cell proliferation and are found in
the majority of cml patients
Tsas also include
•protein antigens encoded by cancer-causing viruses
•these antigens can be found in the nucleus,
cytoplasm or plasma membrane of the associated
tumor cells
TUMOR-ASSOCIATED ANTIGENS (TAAS)
•expressed in normal cells as well as in tumors
 tumor cells: abnormally express these
protein or cabohydrate antigens in terms of
their concentration, location or stage
differentiation
 In the course of malignant transformation of a cell,
new antigens or tumor-associated antigens develop at
the cell surface and the host recognize malignant
cells as “non-self”.
 The quantity of TAA increases proportionally with a
tumor growth and decreases with effective
therapeutic response.
Virus – Induced TAA
1. Epstein- Barr Virus (EBV)
-Found in the cells of patient with Burkitt’s
lymphoma and nasopharyngeal carcinoma.
2. Hepatitis B
-Found in primary liver cancer.
3. Human Papilloma Viruses 16 & 18
-Found in cervical carcinoma.
4. Human T- cell Leukemia Virus
-Found in adult type of T-cell leukemia.
TNM System
 Most widely used cancer-staging system.
The T refers to the size and extent of the main tumor.
The main tumor is called primary tumor.
Example: T1-T2-T3-T4- size of the tumor.
 TX- refers to the primary/main tumor that cannot
be measured.
 T0- main tumor that cannot be found.
 The higher the number after the T, the larger the
tumor/the more it has grown in nearby tissues.
AGENCIES:
 IUCC- International Union Against Cancer
 AJCS- American Join Committee on Cancer
Staging
The N refers to the number of nearby lymph nodes that
contain the cancer.
Example: Regional lymph node:
N0-N1-N2-N3
NX- cancer in nearby lymph nodes that cannot be
measured.
 N0- there is no cancer in nearby lymph nodes.
 N1-N2-N3- number and location of the lymph
nodes that contain cancer condition.
 The higher the number after the N, the more
lymph nodes that contain the cancer.
The M refers to whether the cancer has metastasized.
This means that the cancer has spread from the primary
tumor to other parts of the body.
 M0/M1- distant metastasis/spread of the cancer
cells.
 MX- metastasis that cannot be measured
 M0- cancer that not yet spread from the body.
 M1- cancer that has spread to other parts of the
body.
Tumor markers
 defined as biological substances that are found
in increased amounts in the blood, body fluids or
tissues of patients withe specific type of cancer
 the concentration of tumor marker in the serum
depends on the degree of tumor proliferation, the
size of the tumor mass, the proteolytic activities
of the tumor or release of the marker from dying
tumor cells
 tumor markers can be proteins, carbohydrates,
oncofetal antigens, hormones, metabolites,
receptors or enzymes
Ideal tumor marker characteristics
I. be produced by the tumor itself or by the
patients body in response to the tumor
II. be secreted into biological fluid, where it can
be inexpensively and easily quantified
III. have a circulating half-life long enough to
permit its concentration to rise with
increasing tumor load
IV. increase to clinically significant levels above
the reference level while the disease is still
treatable
V. have a high sensitivity; it should easily
detect the majority of individuals in the
population who have particular cancer
VI. have high specificity; marker should be
absent from or present at background level
in all individuals without malignant disease
in question to minimize false-positive test
results
Oncofetal Antigens
 Alpha Feto Protein (AFP) - synthesized by fetal
liver cells. Most but not all hepatomas secret
large amounts of AFP. Its presence in serum is
not diagnostic of hepatoma but is merely
suggestive.
 Carcinoembryonic Antigen (CEA) - glycoprotein
found in glycocalyx of cells derived from
endoderm and present in gastro intestinal
carcinomas especially cancer of colon.
Laboratory Test for Tumor Markers
 Immunohistochemistry
 Cytogenetic Studies
 Nucleic Amplification Technique
 Fluorescent In Situ Hybridization
Immunotherapy
Active Immunotherapy- the goal of active
immunotherapy is to have the patient develop an immune
response that will help eliminate the tumor.
Passive Immunotherapy
1. Passive transfer of allogeneic cellular immunity
from one person to another to fight cancer.
2. Possible recipient rejection of foreign cells.
3. Graft-versus-host disease (GVHD)
4. Fragility of live cells, although research models
are being studied.
Tumor immunology
Tumor markers have four major clinical applications  increasing level of the marker after a return
to aggressive treatment may be needed
1. Screening: asymptomatic individuals
-ex: psa to screen men aged 50 for the
presence of prostate cancer
2. Diagnosis: -elevated psa suggests the
presence of prostate cancer
3. Prognosis: high concentration of a tumor
marker
4. Monitoring: to determine whether their
treatment is working and to check for
recurrence of their tumor
Screening for tumor markers
 detected by simple blood test
 false-negative results: misleading
reassurance
 false-positive results: patient anxiety
 effectiveness of tumor marker depends son
sensitivity and specificity of marker as well
as cancer's prevalence in the population
*ex: alpha-fetoprotein (afp) a tumor marker for
hepatocellular cacinoma only seeing in china
Differential diagnosis
 physicians distinguish between different
diseases with similar symptoms
 ct scan revealed the presence of a lung
nodule, histological examination of a lung
biopsy could help differentiate whether the
nodule was caused by cancer or another
disease process such as an infection
 follow-up staining of the biopsy for tumor
markers could help determine the neoplasm's
tissue origin
Prognosis
 high concentration of a tumor marker at the
time of diagnosis or increasing levels of a
tumor marker over time can indicate the
presence of an aggressive tumor that has
metastasized and required rigorous treatment
be used to determine the type of therapy
-ex: breast cancer, anti-her2 agents such as
trastuzumab work best in patients whose tumors
overexpress the her2 protein or gene
 antiendocrine therapies such as tamoxifen
are suitable for patients whose tumors
overexpress the estrogen receptor
Monitoring patient response to treatment using
tumor markers
 monitor known cancer patients to determine
whether their treatment is effective and to
check for recurrence of the tumor
 serum tumor marker often correlates with the
amount of tumor in the patient
 lab determines a baseline concentration of
the marker before treatment begins, followed
by serial measurements over time
 decrease in the concentration of a tumor
indicates that therapy has been effective in
shrinking tumor
 WEEK11 B. Selective IgA Deficiency
 Most common humoral antibody
IMMUNODEFICIENCY deficiency.
Immunodeficiency
 50-80% Asymptomatic.
 Recurrent sinopulmonary infections
most frequent manifestation.
 May have severe malabsorption
(chronic diarrhea).
 Isolated low IgA level.
 Increased risk of autoimmune
disorders.

C. Bruton’s X-linked Agammaglobulinemia

 X-chromosome linked, affects males
almost exclusively.
 Lack of circulating B cells & deficiency
of antibody.
 Child clinically well for first 6 months of
life.
 Recurrent upper/lower respiratory tract
infections.
 Sepsis, meningitis, skin infections.
 Paucity of lymphoid tissue (tonsils,
Category Description adenoids).
1 Combined Immunodeficiencies  Treatment: IVIG, Antibiotic Therapy
2 Combined Immunodeficiencies with
Associated or Syndromic Features
3 Predominantly Antibody Deficiencies
4 Disease of Immune Dysregulation D. Common Variable Immunodeficiency
5 Congenital Defects of Phagocyte  B lymphocytes don’t differentiate into
Number, Function, or Both
plasma cells
6 Defects in Innate Immunity
7 Autoinflammatory Disorder  Recurrent sinopulmonary infections
8 Complement Deficiencies  Low IgG, IgA, IgM
9 Phenocopies of Primary  Treatment: IVIG
Immunodeficiencies
 Associated with autoimmune disease,
lymphoma
Humoral Immunodeficiency
(B Cells)
A. Transient Hypogammaglobinemia of
Infancy
 Slow to develop normal levels of
antibody
 Asymptomatic, minor infections
 Low levels of IgG, IgA (IgM usually
normal)
 IgG is the most affected of this
condition.
 Resolves by 3-6 y/o
CELLULAR
IMMUNODEFICIENCY
(T CELL)
DiGeorge Syndrome
 Developmental abnormalities of
the third and fourth pharyngeal
pouches that affects thymic
development.
 No T cells secondary to thymic
hypoplasia.
 “CATCH 22”
 Overwhelming infections with
viruses, fungi, bacteria
 Correct Hypocalcemia, Cardiac
Defects, Fetal Thymus
 Treatment: Transplant
COMBINED
IMMUNODEFICIENCY
SCID (Severe Combined Immunodeficiency)
 Defects in stem cell maturation
 Adenosine deaminase deficiency
(ADA toxic to T and B cells)
 Manifestations seen in first 3
months of life
 Recurrent, severe bacterial, viral,
fungal, and protozoan infections
(usually respiratory infections)
 Most have lymphopenia, decreased
IgG, IgA, and IgM
 Diagnosis made by analysis of T, B,
and NK cell subsets
 Treatment: isolation, treat
underlying infections, bone marrow
transplant
Wiskott-Aldrich Syndrome
 X-linked recessive
 TRIAD OF
IMMUNODEFICIENCY:
 Recurrent, Severe Infections,
Eczema, Thrombocytopenia
 Low levels of IgM
 Increased risk for hematologic
malignancy
 Treatment: Manage
Bleeding/Infections, BMT
Ataxia Telangiectasia
 Autosomal recessive deficiency in
DNA repair affecting T and B cells
 Progressive ataxia, telangiectasia,
variable immunodeficiency
(recurrent sinopulmonary
infections common)
 Increased risk of malignancy
(leukemia, lymphoma)
PHAGOCYTIC DISORDERS
Chronic Granulomatous Disease (CGD)
 Defective NADPH oxidase
 75% X-linked recessive, 25%
autosomal recessive
 Severe, recurrent staph aureus
infections of lymph nodes, and skin
(granulomas, heal slowly),
pneumonitis, osteo,
hepatosplenomegaly
 Nitroblue tetrazolium (NBT) test
 Treatment: antimicrobial
prophylaxis, IFN-gamma, BMT
 Leukocyte Adhesion Deficiency (LAD) IMMUNO-PROLIFERATIVE DISORDERS

 Deficient chemotaxis LEUKEMIAS: Malignant cells

 Recurrent soft tissue, skin,
respiratory infections, impaired
wound healing (typically no pus,
minimal inflammation)
 Delayed umbilical separation
 Increased WBC count
 Treatment: BMT
Complement System
Disorders
are primarily present in the
Bone marrow and peripheral
blood. LYMPHOMAS:
Malignant cells are in the
lymphoid tissues.
PLASMA CELL DYSCRASIAS: Involve Bone
Marrow, lymphoid organs and Non lymphoid
sites.
 Excess Accumulation of Cells:
(1) Rapid Proliferation
(2) Clonal Proliferation
(3) Chromosomal Mutations
 Malignant cells do not develop into mature
cells.

 Defects of early components (C1-C4) 1. LYMPHOMAS

associated with infections with Hodgkin’s Lymphoma, Non Hodgkin’s
encapsulated bacteria. Lymphoma
 Defects of late components (C5-C9) 2. LYMPHOBLASTIC LEUKEMIAS
associated with Neisseria infections. Acute Lymphoblastic Leukemia, Chronic
 Also associated with autoimmune-like Lymphoblastic Leukemia
conditions
3. PLASMA CELL DISCRASIA
 CH50 Functional Assay assesses entire Multiple Myeloma, Waldenström's
complement cascade Macroglobulinemia
 Treatment: treat infectious and
autoimmune sequelae
LYMPHOMAS
Solid tumor neoplasm of lymphoid tissue
categorized as Hodgkin or non-Hodgkin
lymphoma and defined by lymphocyte
morphology and the histologic features of the
lymph nodes.

LYMPHOBLASTIC LEUKEMIAS
Leukemias are generally classified as either
acute or chronic. Chronic leukemias are
usually slowly progressive and compatible with
extended survival. Acute leukemias are
generally much more rapidly progressive but
have a higher response rate to therapy.

PLASMA CELL DISCRASIA

Conditions are characterized by the
overproduction of a single immunoglobulin
component called a myeloma protein (M
protein), or paraprotein, by a clone of plasma
cells.

Hodgkin’s Lymphoma
A highly treatable and often curable
lymphoma that occurs both in young adults
and in the elderly. It is characterized by the
presence of ReedSternberg (RS) cells in
affected lymph nodes and lymphoid organs.
Non Hodgkin’s Lymphoma
The most common is diffuse large B-cell
lymphoma, which accounts for 30 to 40 percent
of NHL. The next most common type is
follicular lymphoma, characterized by a much
more aggressive course than diffuse large B-
cell lymphoma.

Acute Lymphoblastic Leukemia

Characterized by the presence of very poorly
differentiated precursor cells (blast cells) in the
bone marrow and peripheral blood. These cells
can also infiltrate soft tissues, leading to organ
dysfunction. ALL is usually seen in children,
between 2 and 10 years of age, and is the most
common form of leukemia in this age group.

Chronic Lymphoblastic Leukemia

The chronic lymphocytic
leukemias/lymphomas are a group of diseases
almost exclusively of B-cell origin

Multiple Myeloma
is a malignancy of mature plasma cells that
accounts for about 10 percent of all
hematologic cancers. It is the most serious and
common of the plasma cell dyscrasias. It is
usually diagnosed in persons between 40 and
70 years of age with a peak age of 67 years.

Waldenström's Macroglobulinemia
is a malignant proliferation of IgM-producing
lymphocytes and corresponds to
lymphoplasmacytoid lymphoma as defined by
the WHO.

REFERENCE:
 Turgeon, Mary Louise.
(2014). Immunology &
Serology in Laboratory
Medicine, (5th ed.). Missouri
: Elsevier.
 Stevens, Christine
Dorresteyn. (2010). Clinical
Immunology & Serology : A
Laboratory Perspective, 3rd
ed. Philadelphia ; F.A. Davis