• “Natural or native immunity”
• Consists of cellular and biochemical defenses
that are in place before infection and respond
rapidly to it.
• Able to distinguish self and non-self but lacks
the ability to differentiate between agents.
• Major Components
–Phagocytic Cells (Neutrophils and
–Natural Killer (NK) Cells
–Several types of Plasma Proteins
Toll-Like Receptors (TLR)
• The eyes of the immune
system, recognize and
bind with telltale
allowing the effector
cells of the immune
system to see the
pathogens as distinct
• Triggers phagocyte to
engulf and destroy
the infections agent
• Also triggers
Phagocytic cells to
• Acquired or specific immunity
• Distinguishes among the different, even
closely related molecules and microbes
–White Blood Cells (Lymphocytes T and B)
• Or Immunogens are substances foreign to
the host that can stimulate and immune
• Recognized by antibodies or immunoglobulins
secreted in response to antigens.
• Include components found in bacteria, fungi,
viruses, protozoa, and parasites
• Non-microbial elements such as plant pollens,
insect venom and transplanted organs.
• ANTIGENIC DETERMINANTS OR EPITOPES
– It is the unique molecular shape of an epitopes that is
recognized by a specific immunoglobulin receptor
found in the surface of the lymphocyte or by an
antigen-binding site .
• Single antigen may contain multiple antigenic
determinants, each stimulating a distinct clone of
lymphocytes to produce a unique type of antibody.
• Haptens are low molecular weight
substances (<10,000 Daltons).
• When combined with large protein molecules,
they function as antigens.
• HAPTEN –CARRIER COMPLEXES
– Allergic response to antibiotic Penicillin
TYPES OF ADAPTIVE IMMUNE
• HUMORAL IMMUNITY – mediated by B cells
and is the principal defense against
extracellular microbes and toxins.
• CELL-MEDIATED or CELLULAR IMMUNITY –
mediated by cytotoxic T cells and defends
against intracellular microbes.
• Has the unique ability to “Remember” the
pathogen and quickly produce a heightened
• T cells develop receptors that recognize the
viral peptides displayed in the surface of
infected cells and then signal destruction of
the infected cell.
• REGULATORY CELLS – assist is orchestrating
and controlling the immune response.
– Helper T lymphocytes
• EFFECTOR CELLS – the final stages of the
immune response are accomplished with the
elimination of antigens.
– Activated T Lymphocytes, Mononuclear
phagocytes and other leukocytes
CLUSTERS OF DIFFERENTIATION
• (CD) molecules aid in the function of immune
cells and serve to define functionally distinct
subset of cells such as CD4+ helper T cells and
CD8 + cytotoxic T cells
• Helped scientist to identify distinct subsets of
lymphocytes and study both the normal and
abnormal developmental processes displayed
by these cells.
COMPLEX MOLECULES (MHC)
• Key recognition molecules essential for
distinguishing self from non-self.
• Coded by closely linked genes on
chromosomes 6 were first identified
because of their role in organ and tissue
• Essential for correct cell-to-cell interaction
among immune and body cells.
CLASS I MHC
• Found on virtually all nucleated cells in the
• Involved in the recognition of intracellular
• Antigen peptides associate with class I
molecules in cells that are infected with
cellular pathogens (virus)
• MHC antigen complex communicates to
cytotoxic T cells that the cell must be
CLASS II MHC
• Found primarily on Phagocytic cells such as
macrophages, Dendritic cells and B
lymphocytes, that engulf extracellular antigen.
• Triggers helper T cells to multiply quickly and
direct other immune cells to respond to the
invading pathogen through the secretion of
• MHC proteins are called Human Leukocyte
Antigens (HLA) since they were first detected
on White Blood Cells.
• HUMAN Class I MHC – HLA A and HLA B HLA C
• Human Class II MHC – HLA DR, HLA DP, HLA-
• Combination of HLA genes usually is inherited
as a unit called haplotype.
• Each inherits one chromosome from each
parent and therefore having two HLA
• The identification or typing of HLA molecules
is important in tissue or organ transplantation,
forensics, paternity evaluations.
• The closer the matching of haplotypes, the
greater in probability of identical antigens and
the lower the chance of rejection.
• Migrate from the blood to various tissues
where they mature into the major tissue
phagocytes, the MACROPHAGES.
• Macrophages are the major scavenger cells of
the body. It can be fixed in a tissue or free to
migrate from an organ to lymphoid tissues.
• Macrophages are activated to engulf and
digest antigens that come in contact with their
• The Phagocytic killing of microorganisms help
to contain infectious agents until adaptive
immunity can be marshaled.
• Macrophages function early in the immune
response to amplify the inflammatory
response and initiate adaptive immunity.
• Directs these processes through the secretion
of CYTOKINES (e.g. tumor necrosis factor
[TNF], interleukin-1 [IL-1] that activates
lymphocytes and mediate the different
aspects of inflammatory process.
• Influence adaptive immunity as APC’s that
break down complex antigens into peptide
fragments for association with class II MHC
molecules. Macrophages present these
complexes to the helper T cells so that self-
non-self recognition and activation of the
immune response can occur.
• Shares the important task of presenting
processed antigen to T lymphocytes.
• Distinct star shaped cells with long extensions
of cytoplasmic membrane provide an
extensive surface rich in Class II MHC
molecules and other membrane molecules
important for initiation of adaptive immunity.
• Found in most tissues where antigen enters
the body and in the peripheral lymphoid
tissues where they function as potent APCs .
• Langerhans cells are specialized dendritic cells
in the skin. Follicular dendritic cells are found
in the lymph nodes.
• Function in the activation of other T cells and
B cells in the control of viral infections, in the
rejection of foreign tissue grafts and in
delayed hypersensitivity reactions.
• Collectively these immune responses are Cell-
• T cells regulates self-recognition and amplifies
the response of B and T lymphocytes.
• Arise from the bone marrow stem cells as pre-
T cells and migrate to the thymus for their
• The immature T lymphocytes undergo
rearrangement of the genes needed for
expression of a unique T-cell antigen receptor.
2 Types of T CELLS
• CD4+ helper T cells – serves as a master
regulator for the immune system
• CD8+ cytotoxic T cells
Subtypes T Helper Cells
• TH1 – differentiation pathway is the response to
microbes that infect or activate macrophages and
those that induce activation NK cells.
• TH2 – activated in response to allergens and
helminths (intestinal parasites) which causes
chronic T lymphocyte stimulation, often without
significant innate immune response or
• Can be identified by the presence of
membrane immunoglobulin that function as
the antigen receptor, class II MHC proteins,
complement receptors, and specific CD
• Function as APCs in hummoral response to
• The antibody responses to haptens- the
hapten specific B cell is responsible for
recognizing the hapten and the carrier-specific
helper T cells for stimulating the
differentiation of B cells into immunoglobulin-
producing plasma cells.
• Antibodies compromise a class of proteins
• Each immunoglobulin is composed of two
identical light (L) chains and two identical
heavy (H) chains to for a Y shaped molecule.
• Two forked ends that bind antigen is the Fab
• Tail of the molecule Fc fragment determines
the biologic properties that are characteristics
of a particular class of immunoglobulins.
• Gamma globulin.
• Most abundant in body fluids and enters
• Crosses the placenta and transfers immunity
from mother to fetus.
• Subtypes: IgG1, IgG2, IgG3 and IgG4
• Some have restrictions in their response to
–IgG2 is responsive to Streptococcus
pneumoniae, Haemophilus influenzae and
• Forms a polymer of five basic immunoglobulin
• First to appear in response to an antigen and
the first antibody made by a newborn
• Diagnostically useful, detects infection in the
infant by a specific pathogen.
• Secretory immunoglobulin, found in the saliva,
tears, colostrum, in the bronchial,
gastrointestinal, prostatic, and vaginal
• Primary defense against local infections in
• Found on the cell membranes of B
lymphocytes and serves as an antigen
receptor for initiating differentiation of B cells.
• Involved in inflammation, allergic responses
and combating parasitic infections.
• Binds to mast cells and basophils to release
NATURAL KILLER CELLS
• Lymphocytes that are functionally and
phenotopically distinct from T cells, B cells,
• An effector cell important in innate immunity
that can kill tumor cells, virus-infected cells or
• They are called “natural” because unlike
cytotoxic T cells, they do not recognize a
specific antigen before being activated.
• Believed to be one of the immune surveillance
for cancerous or virus infected cells.
• Present in large numbers in the central
and peripheral lymphoid organs.
• Central lymphoid organs: BONE
MARROW and THYMUS
• Peripheral lymphoid organs:
–Peyer’s patches in the intestine
–Mucosa-associated lymphoid tissues in the
respiratory, GIT and reproductive systems
• An elongated,
that is located in the
neck region above
• Generates mature
• A fully developed organ at birth weighing
• At puberty thymus begins regressing and is
replaced by adipose tissue.
• Some thymus tissue persists into old age.
Pre-T cells enter the
thymus as immature T cells
Thymic Hormones and
T cells mature and multiply
and acquires T-cell
Undergoes THYMIC SELECTION
95% of thymocytes die when they do not produce appropriate type of self-
Mature Immunocompetent T cells leave the thymus in 2-3 days and enters
the peripheral lymphoid tissues via blood stream
Surface markers that
distinguish among the
types of T cells and
antigens that distinguish
self from non-self
Only T cells able to
antigen and not
react to self antigens
are allowed to
• Small aggregates of the
lymphoid tissue located
along lymphatic vessels
throughout the body.
• Many lymph nodes are
in the axillae, groin,
along great vessels of
the neck, thorax, and
• Two Functions:
1. Remove foreign material from lymph
before it enters the bloodstream
2. Centers of proliferation of immune cells.
• Bean-shaped tissue surrounded by a
connective tissue capsule.
• Lymph enters the node through afferent
channels and leaves through efferent lymph
vessels located in the deep indentation of the
• Lymphocytes and macrophages flow slowly
through the node, allows trapping and
interaction of antigen and immune cells.
• This reticular meshwork serves as a surface
where macrophages can more easily
• Dendritic cells also permeates lymph nodes
and aid antigen presentation.
• A large ovoid secondary
lymphoid organ located
high in the left
• Filters antigens from
the blood and is
important in the
response of systemic
– RED PULP
• Supplied with arteries
and is the area where
senescent and injured
RBCs are removed
– WHITE PULP
• Contains concentrated
areas of B and T cells
clusters of lymphoid
tissues in the
membranes lining the
• In the Tonsils, Peyer’s
Patches in the intestine
and the appendix ,
organized structures are
• Immunity at the
mucosal layers helps to
pathogens and thus
protects the vulnerable
• Low molecular weight proteins made by cells
that affect the behavior of other cells.
• Made primarily by and act primarily on
immune cells, especially activated helper T
cells and macrophages.
• Name of cytokines were derived from
their biological properties.
–Interleukins (IL) – made of leukocytes and
act on leukocytes
–Interferons (IFNs) – were found to interfere
with virus multiplication
• Cytokines modulate reactions of the host to
foreign antigens and injurious agents by
regulating movement, proliferation and
differentiation of leukocytes and other cells.
• Actions of cytokines affects more than one cell
type and have more than one biologic effect.
E.g. INFN-γ –inhibits virus replication and a
potent activator of macrophages and NK cells.
• Cytokines have biologic activities that overlap
which maximizes the immune response and
protection against detrimental mutations in a
• Excessive Cytokine production may lead to
serious adverse effects associated with septic
shock, food poisoning and types of cancer.
• Cytokine secretion is brief and a self-limited
– This short half-life of cytokines ensures that
excessive immune responses and systemic activation
do not occur.
• Production of cytokines occurs in a cascade.
Some function as antagonists to inhibit biologic
effects of earlier cytokines.
– Functions as appropriate control of cytokine
synthesis and subsequently of the immune response.
Major Functional Groups
• Pro inflammatory – produces fever and acute
phase response and by activating phagocytes.
• Evident in local inflammation, systemic
inflammation, or even septic shock
• Maturation factors for hematopoesis of white
or red blood cells.
– IL -3, GM-CSF
• Recombinant CSF molecules are being use to
increase rates of bone marrow
• Function in adaptive immunity as intracellular
communication molecules among T cells, B
cells, macrophages and other immune cells
• IL 2 therapy for several malignancies has lead
to some clinical success.
• Humoral and cell-mediated
• Active and Passive Immunity
• Complement System
ACTIVE VS PASSIVE Immune Responses
• ACTIVE IMMUNITY – acquired through
immunization or having a disease
• Depends on the antigen by the person’s
• Long lasting, though requires a few days to
weeks after first exposure before the immune
response is sufficiently developed.
• IMMUNIZATION – the process of acquiring the
ability to respond to an antigen after
administration by vaccines.
• PASSIVE IMMUNITY – Transferred from
– Infant receiving antibodies from the mother
• Maternal IgG
– Infant is protected from 3 to 6 mos.
– Can be artificially provided by transfer of
antibodies produced by other people or animals
through injection of hyperimmune serum with
high concentrations of antibodies for a specific
• Produces short-term protection that lasts
weeks to months.
• Depends on the maturation of B lymphocytes
into the plasma cells which produce and
• Combination of antigen with antibody can
result in several effector responses:
– Precipitation of antigen-antibody complexes
– Agglutination or clumping of cells
– Neutralization of bacterial toxins and viruses
– Lysis and destruction of pathogens or cells
– Adherence of antigen to immune cells
– Facilitation of phagocytosis and complement
PRIMARY IMMUNE RESPONSE
• Occurs when an antigen is first introduced in
• There is a latent period or lag before the
antibody can detect the serum.
– During this lag the B cells are activated to
proliferate and differentiate into antibody-
secreting plasma cells and memory cells.
• Recovery from infectious diseases occur when
the primary response is at its peak.
• Occurs on the second or subsequent
exposures to the antigen.
• The rise in antibody occurs sooner and
reaches a higher level because of the available
– Booster immunization given in Infectious diseases
• Provides protection against viruses,
intracellular bacteria, and cancer cells.
• Actions of T lymphocytes and effector
• Phagocytes and Macrophages becomes
activated after exposure to T-cell cytokines,
• Helper T cells become activated after antigen
recognition and by induction with IL-12
• Activated helper T cells then synthesizes IL-2
• These molecules drive and the multiplication
of helper T cells which amplifies the response
• Further differentiation of helper T cells leads
to production of additional cytokines which
enhance the activity of cytotoxic T cells and
• Contact dermatitis due to poison ivy
sensitivity is an example of cell-mediated
hypersensitivity caused by hapten-carrier
THE COMPLEMENT SYSTEM
• Primary mediator of both innate and adaptive
immunity that enables the inflammatory
response, lyse foreign cells and increase
• Consist of group of proteins (C1 – C9) present
in the circulation and functionally inactive
• For a complement reaction to occur,
complement components must be activated in
• Each enzyme or molecule activated be one
step can generate multiple activated enzyme
molecules at the next step.
• Complement activation is inhibited by
proteins that are present on the normal host
cells, thus, its actions are limited to microbes
and other antigens that lack these inhibitory
3 Phases of the Complement System
1. INITIAL ACTIVATION PHASE
- 3 Pathways for recognizing microbes and
activating the complement system:
• ALTERNATIVE PATHWAY – activated on
microbial cell surfaces in the absence of
antibody and is a component of innate
• CLASSIC PATHWAY – activated by types of
antibodies bound to antigen and is part of
• LECTIN PATHWAY – activated by plasma lectin
that binds to mannose on microbes and
activates the classic system pathway in the
absence of an antibody.
2. EARLY STEP INFLAMMATORY RESPONSE
- The Activation of the complement protein C3
and its enzymatic cleavage into a large C3b and a
smaller C3b fragment.
-Smaller 3a acts stimulates inflammation by acting
as a chemoattractant for neutrophils
- Large 3b attach to microbes and acts as an
opsonin for phagocytosis
- Also acts as an enzyme to cleave C5 into 2
components C5a which produces
vasodilatation and increases vascular
permeability and C5b leads to late step
membrane attack responses
• LATE STEP MEMBRANE ATTACK
– C3b binds to other complement proteins to form
an enzyme that cleaves C5, generating C5a and
– C5a stimulates the influx of neutrophils, and the
vascular phase of acute inflammation.
– C5b initiates the formation of complex of
complement proteins C6, C7, C8 and C9 into
membrane attack protein or pore that allows
fluids and ions to enter and cause cell lysis.
• Immune system develops 5-6 weeks as the
fetal liver becomes active in hematopoesis.
• Middle of the first trimester – development of
primary lymph organs (i.e. thymus and bone
marrow) begins and secondary lymphoid
organs (i.e. spleen, lymph nodes, and mucosa-
associated lymphoid tissues) develop soon
• The thymus at birth is the largest lymphoid
tissue relative to body size and normally two
thirds of its mature weight which it achieves
during the first year of life.
MOTHER TO INFANT
• The largest amount of IgG crosses the
placenta during the last weeks of pregnancy
and is stored in fetal tissues.
• The infant begins producing IgM antibodies
shortly after birth in response to immense
antigenic stimulation of new environment
• At approximately 6 days the IgM rises sharply
ang continues to 1 year of age when the adult
level is achieved
• IgA is detected 13 days after birth. Adult levels
are reached between the 6th and 7th year.
• Maternal IgA also is transferred in the
colostrum or milk by breast-feeding.
In the Elderly
• Aging – characterized by the declining ability
to adapt to environmental stresses.
• Decline of the immune response:
– Decrease in the size of the thymus glands
– Slight decrease of proportion of T cells to other
lymphocytes and decrease in CD4+ and CD8+
• Increasing proportion of lymphocytes become
• The range of antigens that can be recognized
by B cells does not diminish. If anything
autoreactive B cell clones increases to the
extent, the B cells begin to recognize some
self-antigens as foreign antigens