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Immunoglobulin synthesis,

properties and characteristics,


metabolisms and functions;
Humoral Immune Response
Reporters:

Ma. Exanil L. Plantig


Monica Angelique O. Ramos
Review
Innate Immunity VS Adaptive
Immunity
Innate Adaptive
immediate action requires days to develop
do not have long lasting
has immunologic memory
immunity
non-specific response highly specific
respond rapidly and
not enhanced on repeated
vigorously on 2nd exposure
exposure to antigen
to antigen exposure
Components: macrophage and Components: APC, T-cells,
granulocytes, NK cells, B-cells, antibodies and
complements, and chemicals complement.
Review
• Adaptive Immunity

– Two types:
• Humoral- antibody mediated
• Cellular- cell mediated
Immunoglobulin Classes
1. IgG IgG
Function/ Characteristic
– Predominant antibody in subclass
secondary responses IgG1 65% of the total IgG
– only antibody that can •against polysaccharide antigens
IgG2 •important defense against
cross placenta (primarily
encapsulated bacteria
IgG1 and IgG3) effective activator of the
• most abundant IgG3 complement due to its rigid hinge
region
immunoglobulin in
not effective activator of
newborns IgG4 complement due to its compact
structure
Immunoglobulin Classes
2. IgM
– main immunoglobulin produced early in the primary immune
response
– can be produced by a fetus with ongoing infection

– has highest binding capacity and cross linking among


immunoglobulins (10 identical antigen-binding sites)

– most efficient immunoglobulin in agglutination, complement


fixation, and other antigen-antibody reactions
Immunoglobulin Classes
3. IgA

– Main immunoglobulin for mucosal immunity.

– protect mucous membranes from attack by bacteria and viruses


– found in secretions such as milk, saliva, tears and other
secretions of respiratory, intestinal and genital tracts.
4. IgE

– Binds to receptor on the surface of mast cells, basophils, and


eosinophils.
• Bound IgE acts as a receptor for the antigen (allergen) that
stimulated its production
• Resulting antigen-antibidy complex triggers allergic responses of
the immediate (anaphylactic) type through the release of mediators
– May appear in external secretions
Immunoglobulin Classes
5. IgD

– Acts as antigen receptor when present on the surface of certain


B lymphocytes
• signals B cells to be activated

– Present only in trace amounts in serum

– Unconfirmed role
• It is found to bind to basophils and mast cells and activate these
cells to produce antimicrobial factors to participate in the respiratory
immune defense in humans.
Functions of Immunoglobulins
Antibody
Isotype-specific Effector Functions
Isotype
•Opsonization of antigens for phagocytosis by macrophages and
neutrophils
IgG •Activation of the classical pathway of complement
•Neonatal immunity: transfer of maternal antibody across the
placenta and gut
Activation of the classical pathway of complement antigen receptor
IgM
of naive B lymphocytes
•Mucosal Immunity: secretion of IgA into the lumens of the GIT and
respiratory tracts
IgA
•Activation of complement by the lectin pathway or by the
alternative pathway
•Mast cell degranulation (immediate hypersensitivity reactions)
IgE
•Immunity to parasites such as helminths and protozoa

IgD Ag receptor of naive B lymphocytes


Properties of Human Immunoglobulin
IgG IgA IgM IgE IgD
Molecular Weight
150 70-600 900 190 150
(daltons) (x1000)
Serum Concentration 7-18 0.8-4 0.4-2.5 <0.0005 <0.003
Serum half-life (days) 21 7 7 2 2
Activates complement Yes No Yes No No
Percentage of total <1
<1
immunoglobulins in 80% 10-15% 5-10%
serum (0.2%)
(0.002%)
Placental transfer to
+ - - - -
fetus
Immunoglobulin Class
Switching
• Initially, all B cells matched to an antigen carry
IgM specific for that antigen and produce IgM in
response exposure to antigen.
– Later, gene rearrangement permits elaboration of
antibosies of the same antigenic specificity but of
different immunoglobulin classes
Immunoglobulin Class
Switching
• In class switching, the same assembled variable gene
can sequentially associate with different constant genes
so that,

• Immunoglobulin produced later (IgG, IgA, IgE) has the


same specificity as the original IgM but different biologic
characteristics.

• Dependent on the cytokines released from T cells and


also happens after antigen stimulation
Antibody Responses
• Primary response
– Depends on the nature of antigens, dose of antigen

– First antibodies formed are IgM, followed by IgG, IgA or both

• Secondary response
– Presence of memory B-cells

– amount of IgM produced are similar to that produced after the


first contact.

– more IgG is produced and the levels persist much longer


Humoral Immunity
1. Antibody production
– antibodies/immunoglobulin are produced by B-cells and plasma cells
– make up about 20% of plasma proteins

– Main function: neutralization and elimination of infectious microbes and


microbial toxins through different mechanisms

• Opsonization and phagocytosis of antigens

• antibody-dependent cellular toxicity by the NK cell

• activation of complement cascade

• direct lysis of microbes

• inflammation
2. Defense against extracellular microbes and
microbial toxins
Neutralization of Microbes and
Their Toxins
• Most important effect of humoral immunity
• Many microbes have binding surface molecules that
attach to host membrane proteins or lipids.
• Influenza virus - haemagglutinin
• Gram negative bacteria – pili
• steric hindrance
Neutralization against Bacteria

1. Colonization of cell surface by bacteria


• Bind to surface via bacterial adhesins
• Some bacteria become internalized and propagate in internal
vesicles.
2. Antibodies attach to these adhesins, blocking colonization and uptake.
Neutralization against Viruses

1. Virus binds to receptors on cell surface.


• Receptor-mediated endocytosis of virus
• Acidification of endosome after endocytosis triggers fusion of
virus with cell and entry of viral DNA.
2. Antibody blocks binding to virus receptor and can also block fusion
event.
Neutralization against Microbial Toxins

1. Toxin binds to cellular receptors.


• Endocytosis of toxin-receptor complexes
• Dissociation of toxin to release active chain, which poisons
cell.
2. Antibody protects cell by blocking binding of toxin.
Neutralization

• The only antibody function mediated entirely by binding of


and does not require participation of immunoglobin
constant regions.
• Can be mediated by antibodies of any isotype in the
circulation (most abundant – IgG) or mucosal secretions
(IgA)
Vaccine-induced Humoral Immunity

Infectious Disease Vaccine Mechanism of Protective


Immunity
Polio Oral attenuated polio virus Neutralization by IgA
Tetanus, Diphtheria Toxoids Neutralization by IgG
Hepatitis A or B Recombinant viral envelope Neutralization by IgG
proteins
Pneumococcal Pneumonia, Conjugate Opsonization and
Haemophilus vaccines phagocytosis by IgM
composed of and IgG
bacterial capsule
OPSONIZATION AND
PHAGOCYTOSIS
• In innate immunity, ingestion can occur even without antibodies.
• In humoral immunity, antibodies are used to further stimulate the
recognition of the antigen.
• Efficiency of phagocytosis is markedly enhanced by opsonins (IgG and C3b)
• Fc receptor
• Found on the surface of phagocytes and NK cell
• Binds with the antibody
• Signals the phagocyte to be activated
MECHANISM

1. Opsonization of microbe
by IgG
2. Binding of opsonized
microbes to phagocyte Fc
receptors
3. Fc receptor signals activate
phagocyte
4. Phagocytosis of microbe
5. Killing of ingested microbe
INTRACELLULAR VS EXTRACELLULAR MODE OF ACTION

• Intracellular Microorganisms
1. Phagocyte activation
2. Production of phagocyte oxidase
3. Catalyses intracellular generation
• Extracellular Microorganisms
1. Activated leukocytes can secrete hydrolytic enzymes into
external milieu
2. Killing of extracellular microbes too large to be phagocytosed
ANTIBODY-DEPENDENT CELL-MEDIATED
CYTOTOXICITY
• The attachement of antibodies to viral proteins on the virus-infected
cell can lead to the interaction of the antibody-coated cells with a
killer cell, leading to lysis.
• Since antibodies are protective, strategies have been developed to
induce their production (Active Immunity) or to administer
preformed antibodies to the host (Passive Immunity).
Reference
• Brooks, G., Carroll, K., Butel, J. Jawetz, Melnick, & Adelberg’s
Medica Microbiology (26th edition). The McGraw-Hill Companies:
USA.
THANK YOU!
Mini Quiz
• Differentiate the five immunoglobulins by
its functions.