IMMUNO-SERO LECTURE NOTES (2ND WEEK) o e.g.

Blood group antigen, capsular

polysaccharides of some m.o.
Nature of Antigen and the Major Histocompatibility
 A substance must be subject to antigen
Complex
processing, which involves enzymatic digestion
 Lymphocytes – are the key cells that are to create small peptides or pieces that can be
responsible for the specificity, diversity, and complexed to MHC molecules to present
memory that characterize adaptive immunity. responsive lymphocytes.
 Immunogen – triggers an immune response.
o Macromolecules capable of triggering an
adaptive immune response by inducing Epitopes, Hapten, and Adjuvants
formation of antibodies.
Epitopes
 Antigen – is any substance that reacts with an
antibody or sensitized T cells but may not be  Determinant site
able to evoke an immune response.  Molecular shapes or configurations that are
 ARE ALL IMMUNOGENS ANTIGEN? – YES recognized by B or T cells
Factors Influencing Immune Response  Linear epitope – amino acids following one
another on a single chain.
 Biological properties of an individual  Conformation epitope – folding of one chain or
o Age, overall health, dose, route of multiple chain.
inoculation, and genetic capacity  Anything that is capable of cross-linking surface
 Quantity of immunogen immunoglobulin is able to trigger B-cell
o Generally, the larger the amount of an activation.
immunogen, the greater immune  Immunogens must be degraded into small
response peptides by APC to be recognized by T cells.
 Site and route of exposure
Haptens
 Genetic predisposition
 Nonimmunogenic materials when combined with
Traits of Immunogens
a carrier create new antigenic determinants.
 Immunogenicity – is the ability of an  May be artificially joined to carrier molecules in
immunogen to stimulate a host response lab setting or occurs naturally with a host.
depending on the following characteristics:  Catechol (extracted from poison ivy)
o Macromolecular size
Adjuvants (just only in vaccine)
o Foreignness
o Chemical composition and molecular  A substance administered with an immunogen
complexity that increases the immune response in order to
o Ability to be processed and presented provide immunity to a particular disease.
with MHC molecules  Used to accelerate immune response and
 10 000 MW to be recognized by the immune increase the duration of protection, thus the
system. need for booster immunizations.
o Most active immunogens have a MW of  Aluminum salts.
>100 000 Daltons
 The greater the molecular weight, the more
potent the molecule is as an immunogen. Remember: Both haptens and adjuvants (for adjuvant –
 The more distant taxonomically the source of the it is commonly employed in vaccines) are artificially
immunogen is from the host, the more made.
successful it is as a stimulus.

Structure of Immunogens:
Relationship of Antigens to the Host
 Proteins and Polysaccharides are the most
effective immunogens.  Autoantigens – antigens that belongs to the
 Carbohydrates are less immunogenic than host.
protein because they are smaller and have o Does not evoke immune response
limited number of sugars available to create their  Alloantigen – from other members of the host’s
structures. species and are capable of eliciting an immune
response.
 o Important in tissue transplantation and
blood transfusion.
Class I MHC
 Heteroantigen – from other species such as
animals, plants and microorganisms.  Presented in all nucleated cells.
 Heterophilic antigen – heteroantigen that exist o Highest on lymphocytes and myeloid
in unrelated plants or animals but are either cells, low or undetected on liver
identical or closely related in structure (usually hepatocytes, neural cells, muscle cells,
employed in the laboratory. and sperm
 Loci: HLA-A, HLA-B, HLA-C
 A3 region binds to the CD8 (Cytotoxic T Cells.
Major Histocompatibility Complex  “Watchdogs” of viral, tumor, and certain parasitic
antigens that are synthesized within the cells.
 Genetic capability to mount an immune
response is linked to Human Leukocyte Class II MHC
Antigen (HLA).
 T cell activation will occur only when antigen  Found primarily on APCs (antigen presenting
is combined with MHC molecules on the cells)
surface of another cells. o B lymphocytes, monocytes,
macrophages, dendritic cells, and
thymic epithelium.
 HLA-DP, HLA-DQ, HLA-DR
 Binds to CD4 Helper T cells
 Helps mount an immune response to bacterial
infections.

Remember: (Class I MCH Rule of 8)

Class I and Class II MHC Peptide Interaction

Genes Coding for MHC Molecules (HLA Antigens)

 Most polymorphic system found in humans ‘

 Chromosome 6
 Divided into 3 classes: Class I (A, B, C), Class II
(D-region – several loci DR, DQ, DP), Class III
(C4A, C4B, C2 and B complement proteins,
TNF)
o Multiple alleles possible each loci
 Uniqueness of HLA antigens creates a major
problem in matching organ donors to recipients
– highly immunogenic.
 Class I and II MHC molecules’ main role is
Clinical Significance of MHC
antigen presentation.
 Inheritance of certain HLA antigens appears to
Genes Coding for MHC Molecules (HLA Antigens)
predispose a person to certain autoimmune
disease.

Disease Symptoms HLA Alleles

Ankylosing Inflammation of B27
spondylitis vertebrae of the
spine
Celiac Disease Diarrhea, weight DQ2, DQ8
loss, intolerance
of gluten
Rheumatoid Inflammation of DR4
Arthritis multiple joints
Type I DM Increase in DQ8, DQ2
 (Diabetes blood glucose  High concentration of proline and hydrophobic
Mellitus) because of residues.
destruction of o Proline allows flexibility
insulin-  High concentration of protein and hydrophobic
producing cells
residues
o Proline allows flexibility
Antibodies/Antibody  Gamma, delta, and alpha chains all have a
hinge region
 End product of B lymphocyte stimulation and
differentiation
 Also known as immunoglobulin Classes
 Glycoproteins in the serum portion of the blood
Immunoglobulin G (IgG)
o 86-98% polypeptide, 2-14%
carbohydrates  The predominant immunoglobulin in humans,
 Slowest moving proteins and appear primarily in 70-75% of total serum immunoglobulin
the gamma band in serum electrophoresis  Half life of 23 days
 Main humoral element of the adaptive immune  Has four major subclasses that differ mainly in
response. the number and position of the disulfide bridges
between the gamma chains.
o IgG3 has the largest hinge region and
Tetrapeptide Structure of Immunoglobulins the largest number of interchain
 Major functions include the following:
 All immunoglobulins are made of tetrapeptide o Providing immunity for the newborn
unit that consists of two large chains (heavy – H because IgG is the only antibody that
chain) and two smaller chains (light – L can cross the placenta
chains). o Fixing complements
 These chains are held together by noncovalent o Coating antigen for enhanced
forces and disulfide interchain bridges. phagocytosis (opsonization).
 Two regions (Fab – fragment antibody region – o Neutralizing toxins and viruses.
antibody binding, Fc – fragment crystallizable – o Participating in agglutination and
fragment antibody)
precipitation.
Light Chain
All sub classes are able to participate in the secondary
 Two main types: kappa and lambda chains immune response, and enhance response.
o Kappa – 200 amino acids
o Lambda – 220 amino acids
 Molecular weight of 23 000 Daltons Immunoglobulin M (IgM)
 The difference between the kappa and lambda
 Macroglobulin
chains lies in the amino acid substitution at a few
 Define monomeric units are held together by 3
locations along the chain.
or joining chain
o There is no functional differences
o Glycoprotein made in plasma cells that
between the two types and is found in all
contain several cysteine residues
immunoglobulins, but only one type is
o Serves as linkage points for disulfide
present in given molecule.
bonds between two adjacent monomers
 Bence-Jones Protein
o May initiate polymerization by stabilizing
Heavy Chain Fc so sulfhydryl groups so that cross-
linkage can occur
 Constant regions of the H chain are unique to o Also facilitate secretion at mucosal
each class and give each immunoglobulin type surfaces
its name.  Has 10 functional binding sites.
o Each represents an isotype – a unique

Hinge Region
Remember: IgM positive – first infection (meron)
 The segment of H chain located between the
CH1 and Ch2. IgG positive – contracted before, has an exposure to the
infection (gumaling)
IgG and IgM positive – means they have current  Reacts best at pH 7.2-7.4 (30-37C) in the
infections and has a prior dengue infection. presence of calcium and magnesium
 Most plasma complement proteins are
synthesized in the liver except:
Immunoglobulin A (IgA) o C1 complement (epithelial cells of the
 There are two sub-classes, designated IgA1 and intestines)
IgA2. o Factor D (adipose tissues)
o They differ in content by 22 amino acids,
13 of which are located in the hinge
region and are deleted in IgA2. The lack Complement Activation
of this region appears to make IgA1
more resistant to some bacterial  Considered as a cascade because numerous
proteinases that are able to cleave IgA1. proteins of the complement system are
o IgA2 is the most predominant form in sequentially activated.
secretions at mucosal surfaces.  Three pathways:
 Found at a dimer along the o Classical pathway
respiratory o Alternative pathway
o IgA1 mainly found in serum, anti- o Lectin pathway
inflammation agent  Lectin and alternative pathway are more
 Appear downgraded important on the first time of infection

Immunoglobulin D (IgD)

 Found on the surfaces of immunocompetent but Classical Pathway

unstimulated B lymphocytes.
 First pathway to be described
 Second immunoglobulin to appear
 Main antibody directed mechanism for triggering
 Plays a role in B cell activation, regulating B-cell
complement activation
maturation and differentiation
 Not all immunoglobulin are able to activate this
 More susceptible to proteolysis because of its
pathway:
unusually long hinge region.
o IgM, IgG1, IgG2, and IgG3
Immunoglobulin E (IgE) o IgM – most efficient
 Part of the adaptive immunity
 Very low concentration on serum  Few substances that can bind complement
 Activates mast cells and basophils directly to initiate to the cascade:
 Least abundant immunoglobulin o CRP
 Most heat-labile of all immunoglobulins o Several viruses
o Mycoplasma

Complement System Alternative pathway

 Complex series of more than 30 proteins that  Originally named as properdin pathway
play a major part in amplifying the inflammatory  Properdin was thought to be the main inhibitor of
response to destroy and clear foreign matters. the pathway
 Can lyse foreign cells, opsonize and tag the  Properdin stabilizes as key enzyme
invaders for clearance, and direct adaptive
Lectin pathway
immune system to the site of infection.
 Proinflammatory in its ability to increase vascular  Antibody independent means of activating
permeability, recruit monocytes and neutrophil. complement proteins.
 Mannose-binding lectin – adheres to mannose
Laboratory
found
 Heat labile – able to augment the effects of the
components of immune system
 Ref. temperature Classical Pathway
o Activity lasts 3-4 days
o Deteriorates at room temp 1-2 days a) Recognition unit
b) Activation unit
c) Membrane Attack Complex
Regulators of the Complement Cascade