IMMUNOLOGY: Immune Recognition and Response

@ciatokinesis | De La Salle University

the tendency of a species to dissociate

(separate) into smaller components
Immune Recognition and Response ● The lower the dissociation constant, the
● Cells of the immune system must higher the affinity
constantly recognize molecular signals
from the external environment Receptor Locations
● The immune cells use several different
receptors: ● Immune antigen receptors can be
○ Adaptive Immune Cells (B and T transmembrane, cytosolic or secreted:
cells) ○ Transmembrane
■ These use specific B-cell ■ Present in plasma
receptors (BCRs) and T-cell membrane or cell surface
receptors (TCRs) ■ The structure of the
○ Innate Immune Cells antibody will change
■ These use Pattern ○ Cytosolic
Recognition Receptors ■ Present in cytoplasm or
○ Lots of immune cells will express nucleus
cytokine receptors ○ Secreted
■ Cytokines are molecules ■ Secrete antibodies
that will elicit a response in ■ The structure of the
the immune cell antibody will change
● Most are monomeric
○ Monomeric = Single
Receptor-Ligand Interaction immunoglobulin
● This is the term used for multiple
noncovalent bonds between receptor and
Adaptive Immune System Receptors
ligand
○ Hydrogen bonds ● B-cell receptors
○ Ionic Bonds ○ Consists of a membrane bound
○ Van der Waals Interactions antibody + accessory membrane
○ Hydrophobic Interactions bound molecules
● They can be either of the two types of ○ Immunoglobulins can be either
interactions: secreted or membrane bound
○ Univalent ■ Membrane bound differs
■ Antibody binds to one from secreted in the
antigen carboxyl-terminal end
○ Bivalent ○ Associated with CD21, CD19, and
■ Antibody binds to two or CD81
more antigens ○ Only Transmembrane BCRs have a
■ Allows multiple concurrent cytoplasmic tail
receptor-ligand interactions ○ Has an extracellular spacer of 26
because it increases the amino acids
strength of binding between
antibody and antigen ● T-cell receptors
○ Produce the T-cell receptor (TCR)
○ T-cells are always membrane bound
Affinity
so they are expressed on surface of
● As an immune response progresses, cells T cells
that have been activated will produce and ○ TCR heterodimers are like
express more receptors immunoglobulins, therefore they
● The receptors have a higher affinity as the are classified under the
immune response progresses immunoglobulin family
● The affinity of receptor-ligand interactions ○ Resembles the fragment
can be measured by equilibrium dialysis or antigen-binding (Fab) portion of the
surface plasmon resonance antibody

Dissociation Constant (𝐾𝑑)

Downstream Signaling (BCR)
● Type of equilibrium constant that measure
● IDm Alpha and ID Bata are the ones
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 responsible for downstream signaling
Basic Structure of Antibodies
● Accessory membrane-bound molecules are
important because no downstream ● Antibodies are in serum
signaling will happen without them ○ Serum is the fluid phase that
remains after plasma is allowed to
clot
Antibodies and T-Cell Receptors
○ Antibodies are also found in other
● Both antibodies and T-Cell receptors secretions
recognize epitopes ○ If you want to detect something
● Immunologically active regions of from serum, you should use a
immunogen that bind to antigen-specific blood tube without any
antibodies or T-cell receptors anticoagulant
● Antibodies are heterodimers
○ Heterodimers
Epitopes
■ a protein composed of two
● The structure that binds to the antigen polypeptide chains differing
● Most antigens offer multiple epitopes in composition in the order,
● Antigenic determinants recognized by both number, or kind of their
B and T cells amino acid residues
○ T-cell epitopes ○ Composed of 2 light chains and 2
■ T cell epitopes from heavy chains
proteins derived from ■ The 2 light chains are
enzymatic digestion of around 22,00 daltons each
peptide and then ■ The 2 heavy chains are
association with MHC around 55,00 daltons each
■ T-cells can only recognize ○ The first 110 amino acids of the
peptides or proteins when animo-terminal end of heavy and
associated with major light chains vary depending on
histocompatibility complex antibody specificity
○ B-cell epitopes
■ Tend to be on the outside of
Light Chains
the antigen (Ex. hydrophilic
amino acids on a protein’s ● The constant part of the amino acid
sequences of light chains:
surface)
○ Kappa (κ)
■ A single B-cell will only
■ Humans have 60% Kappa
produce antibody specific ■ Mice have 5% Kappa
to single epitope ○ Lambda (λ)
■ 40% of human light chains
Antibodies (Abs) are Lambda
■ Mice have 95% Lambda
● Epitope binding proteins ● Light chains are for the specificity of an
○ Membrane bound on B-cells antibody
○ May be secreted in blood (Humoral
Immunity) Heavy Chains
■ process of adaptive
● The identity of an antibody depends on the
immunity manifested by the heavy chains
production of antibodies by ● There are 5 different heavy chain constant
B lymphocytes regions also known as “isotypes”
● Share structural features, bind to antigen, ○ IgM (µ)
and participate in a number of effector ■ Monomeric IgM expressed
functions on B cells
■ Pentameric when secreted
● Known collectively as Immunoglobulins ■ 1st class produced in
(Igs) primary response
● Antibodies do not kill anything; their job is ■ Activates complement
to serve as target markets for other ■ Very good at agglutination
immune system components ○ IgG (γ)
■ Most abundant in serum
■ 4 human subclasses

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 ■ Crosses the placenta
Hinge Regions
■ Involved in complement
activated ● γ (gamma), δ (delta), and α (alpha) heavy
■ Opsonin or promotes chains have extended peptide sequence
phagocytosis ● Hinge regions are rich in proline and
○ IgA (α) cysteine
■ Most abundant all over the ● Gives flexibility
body ○ Flexibility is important in making
■ Exists as a dimer sure there are no hindrances in
■ Can cross-link large binding to epitopes
antigens
■ Interacts better with
Innate Immune System Receptors
macrophages compared to
IgG ● Cytokines
○ IgD (δ) ● Innate Immune System receptors are the
■ Membrane bound on b cells PRRs or the Pattern Recognition Receptors
■ Signals the B-cells to be that recognize Pathogen Associated
activated Molecular Patterns or PAMPs
○ IgE (ε)
■ Involved in allergic Pattern Recognition Receptors
reactions
■ Involved in parasitic
infections
Isotype, Allotype, and Idiotype
● Isotype
○ Difference in classes (Ex. IgG, IgM,
IgE)
● Allotype
○ Difference in portions (Ex.
Difference between the IgG of one
person from another)
● Idiotype
○ Same class but different epitope
(Ex. Difference between IgG that’s
specific for staph and IgG specific
for strep)

Overall Structure of Immunoglobulin

● Primary
○ Sequence of amino acids
● Secondary
○ Folding into series of β pleated
sheets
○ Immunoglobulins
● Tertiary
○ Compact globular domains
○ Forms either light or heavy chain
● Quaternary
○ Adjacent light and heavy chains
interact and bind to form antibody
Hypervariable Regions
● Hypervariable regions are complementary
to the epitopes that they will bind to
● These allow light chains to detect even the
slightest variation in antibody
● Hypervariable regions are also known as
CDRs or Complementarity-determining
regions
Cytokines
● They are low-molecular weight regulatory
proteins or glycoproteins
● Cytokines are secreted by White Blood
Cells and various other cells
● Assist in regulating development of
immune effector cells
● Some cytokines possess direct effector
functions of their own
● Some cytokines are referred to as
Interleukins (IL)
Chemokines
● Chemokines are a subpopulation of
cytokines
● They mobilize immune cells from one area
to another
● They are a class of chemoattractants
Cytokine Action
● Cytokines mainly function by autocrine and
paracrine action

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 ○ Autocrine
■ form of signaling in which a
cell secretes a hormone or a
chemical substance that
binds to the receptors on
the same cell
■ Think of this as being
selfish
○ Paracrine
■ form of cell signaling in
● Cytokine families are based on structural
which the target cell is near studies
the signal-releasing cell ● All cytokine families have a molecular
■ Think of this as being mass less than 30kDa
generous to your neighbors ● All cytokine families have similarities and
● Cytokines bind to specific receptors few rarely act alone
● They trigger signal transduction pathways
that alter gene expression in target cells
● Exhibit pleiotropy, redundancy, synergy,
antagonism, and cascade induction
○ Pleiotropy
■ One cytokine can have
different effects in different
cells
○ Redundancy
■ Multiple cytokines can act in
the same cell for the same
outcome
○ Synergy
■ Two cytokines act together
for an effect that is stronger
than individual action
○ Antagonism
■ One cytokine can block the
action of another cytokine
○ Cascade induction
■ One cytokine acts on a
specific target cell and
leads to the release of one
or more other cytokines
which in turn persuades
other target cells to produce
and release more cytokines
Endocrine Action
● the signaling molecules are secreted by
specialized endocrine cells and carried
through the circulation to act on target
cells at distant body sites
● Very uncommon
● Cytokines function by only the autocrine
and paracrine actions because an
endocrine action would cause the whole
body to respond meaning the whole body
may be inflamed

Cytokine Families

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