Immunity

the immune response

By Dr.Faiqa Ahmed
Lecturer YIPS
 Definition
“Immunity refers to protection against infections. The
immune system is the collection of cells and molecules
that are responsible for defending the body against the
countless pathogens that individuals encounter”

Immunodeficiency diseases: defects in immune system render

individual easy prey to infection and are cause of immunodeficiency
diseases.
Hypersensitivity diseases: when immune system is itself capable of
causing tissue injury and disease.
Antigen:
any invading agent like foreign proteins, organisms or toxins that can
produce an immune response is called antigen.
Antibody: (immunoglobulin)
The specific globulin protein formed in the blood plasma as a reaction to
antigen is called antibody. Blood contains three types of globulins alpha,
beta and gamma. Antibodies are gamma globulins
the term "immune response" refers to adaptive immunity.
Types of immunity
There are two types of immunity
1. Innate ( natural, non- specific immunity)
“is mediated by cells and proteins that are
always present (hence the term innate),
poised to react against infectious pathogens”
 refers to defense mechanisms that are present
even before infection and have evolved to
specifically recognize microbes and protect
multicellular organisms against infections”
 Innate immunity is the first line of defense,
because it is always ready to prevent and
eradicate infections
2. Acquired immunity (Adaptive
immunity)
 consists of mechanisms that are stimulated by
(adapt to) microbes and are capable of also
recognizing non-microbial substances, called
antigens.
 is normally silent and responds to the presence of
infectious agent by generating potent
mechanisms for neutrilizing and eliminating the
pathogens
Immune response is mediated by two specific cell
population including B- lymphocytes and T-
lymphocytes
Activation of B lymphocytes results in synthesis
and secretion of immunoglobulines
Second line of response
Innate and adaptive immunity. The principal mechanisms of
innate immunity and adaptive immunity are shown
 Types of immune response
Primary immune response
After the first exposure to particular antigen,
antigen is recognized , several days elapse
before enough immunoglobulin(antibody)is
produced to be detected as an increase in
serum immunoglobulin level.
IgM is the first immunoglobulin produced during
the primary response,
IgG comes later.
Secondary immune response
It follows repeat exposure to an antigen.
recognition occurs immediately and
production of serum immunoglobulin's occurs
rapidly.

Primary response Secondary response

Slow in action Rapid in action
Low in magnitude High in magnitude
Short lived Long lived
IgM IgG
 Innate immunity
The major components of innate immunity
are:
1. Epithelial barrier of skin, gastrointestinal
tract and respiratory tract (which prevent
microbe entry)
2. Phagocytic cells
3. Dendritic cells
4. Natural killer cells
5. Plasma protein such as complement
system

NK Cell Eosinophils Monocyte

Neutrophil Basophils &
Mast cells Macrophage
Phagocytes, dendritic cells and many other cells, such
as epithelial cells, express receptors that sense the
presence
of infectious agents and substances released from
dead cells. The microbial structures recognized by
these
receptors are called pathogen-associated molecular patterns;
 They are essential for the survival and infectivity of the
microbes (so the microbes cannot evade innate immune
recognition by mutating these molecules).
 The substances released from injured and necrotic cells are
called damage-associated molecular patterns. The cellular
receptors that recognize these molecules are often called
pattern recognition receptors.
It is estimated that innate immunity uses about 100 different
receptors to recognize 1000 molecular patterns.
The cellular receptors that recognize these molecules often
referred Pattern recognition receptors
 Receptors of Innate Immunity
Pattern recognition receptors are located in all
the cellular compartments where pathogens may
be present:
1. plasma membrane receptors detect
extracellular pathogens (Toll like receptors)
2. endosomal receptors detect ingested
microbes (NODlike receptor and
inflammasome), and
3. cytosolic receptors detect microbes in the
cytoplasm
Toll-like receptors (TLRs).
There are 10 TLRs in mammals
that recognize a wide range of microbial
molecules.
1. plasma membrane TLRs recognize bacterial
products such as lipopolysaccharide (LPS), and
2. endosomal TLRs recognize viral and bacterial
RNA and DNA
 Recognition of microbes by these receptors
activates transcription factors that stimulate the
production of several secreted and membrane
proteins, including mediators of inflammation,
anti-viral cytokines (interferons), and proteins
that promote lymphocyte activation and the
even more potent adaptive immune responses.
NOD-Like Receptors and the Inflammasome
are cytosolic receptors named after the
founding members NOD-1 and NOD-2.
They recognize a wide variety of substances,
including products of
1. necrotic cells (e.g., uric acid and released ATP),
2. Ion disturbances (e.g., loss of K+), and
3. some microbial products.
 Several of the NLRs activates an enzyme
(caspase-1) via inflammsome that cleaves a
precursor form of the cytokine interleukin-1 (IL-
1).
IL-1 is a mediator of inflammation that recruits
leukocytes and induces fever.
 The NLR-inflammasome pathway also
play a role in a number of chronic
disorders marked by inflammation.
 For example, recognition of urate
crystals by a class of NLRs underlies the
inflammation associated with gout.
 These receptors may detect and
respond to lipids and cholesterol crystals
that are deposited in abnormally large
amounts in tissues; the resulting
inflammation and atherosclerosis.
Other Receptors for Microbial Products
 C-type lectin receptors (CLRs) expressed on the plasma
membrane of macrophages and DCs detect fungal glycans
and elicit inflammatory reactions to fungi.
 cytosolic receptors detect the nucleic acids of viruses
that replicate in the cytoplasm of infected cells, and
stimulate the production of anti-viral cytokines.
 G protein–coupled receptors on neutrophils,
macrophages, and most other types of leukocytes
recognize short bacterial peptides containing N-
formylmethionyl residues. Because all bacterial proteins
and few mammalian proteins (only those synthesized
within mitochondria) are initiated by N-formylmethionine,
this receptor enables neutrophils to detect bacterial
proteins and stimulates chemotactic responses.
 Mannose receptors recognize microbial sugars (which
often contain terminal mannose residues, unlike
mammalian glycoproteins) and induce phagocytosis of the
Reaction of innate immunity
1. Inflammation
Cytokines and products of complement
activation, as well as other mediators, are
produced during innate immune reactions and
trigger the vascular and cellular components
of inflammation. The recruited leukocytes
destroy pathogens and ingest and eliminate
damaged cells

2. Anti-viral defense:
 Type I interferons produced in response to viruses act
on infected and uninfected cells and activate enzymes
that degrade viral nucleic acids and inhibit viral
replication.
Adaptive Immunity
Humoral (antibody mediated) immunity
“mediated by soluble proteins called antibodies
that are produced by B lymphocytes” Body
develops circulating antibodies from B- lymphocytes
which are globulin molecules and are capable of
attacking the invading agents. It is active against
extracellular bacteria while its role against intracellular
bacteria , viruses is limited.
Cell mediated immunity
In this type body develops large number of T-
lymphocytes which are specifically activated against
foreign agents and ultimately destroy them.
Cellular immunity is required against viral, fungal,
parasitic infections
Cells and Tissues of the immune
system
Lymphocytes:
present in the circulation and in various lymphoid
organs. Although all lymphocytes are
morphologically similar, they actually consist of
several functionally and phenotypically distinct
populations
Lymphocytes develop from precursors in the
generative
(primary) lymphoid organs; T lymphocytes mature
in the thymus, whereas B lymphocytes mature in
the bone marrow.
Each T or B lymphocyte and its progeny, which
constitute a clone, express a single antigen
Mature T and B lymphocytes recirculate through peripheral
(secondary) lymphoid organs—the lymph nodes, spleen
and mucosal tissues—and reside in these organs and in
most tissues. Foreign antigens are concentrated in these
organs, where they bind to and activate the clones of
lymphocytes that express receptors for those antigens, a
process known as clonal selection.
All mature lymphocytes go through distinct phases during
their lives—
1) naïve lymphocytes: express antigen receptors but have
not responded to antigens and do not serve any functions
2) effector lymphocytes: are induced by lymphocyte
activation and perform the functions that eliminate
microbes; and
3) memory lymphocytes,induced during activation,
survive in a functionally silent state even after the
antigen is eliminated and respond rapidly upon
subsequent encounters with the antigen
 T Lymphocytes
 Thymus-derived T lymphocytes develop into the
effector cells of cellular immunity and “help” B cells
to produce antibodies against protei antigens.
 T cells constitute 60% to 70% of the lymphocytes in
peripheral blood and are the major lymphocyte population
in splenic periarteriolar sheaths and lymph node
interfollicular zones. T cells cannot recognize free or
circulating antigens;but sense only peptide fragments of
proteins displayed by molecules of the major
histocompatibility complex (MHC),.
 Because T cell antigen receptors have evolved to see MHC-
bound peptides on cell surfaces. The outcome of this
interaction varies dramatically depending on the type of T
cell that is involved and the identity of the other interacting
cell, ranging from the killing of virus-infected cells to the
activation of phagocytes or B lymphocytes that have
ingested protein antigens.
Recognition of peptide antigen
Peptide antigens presented by MHC molecules are
recognized
by the T-cell receptor (TCR),
“a heterodimer that in most T cells is composed of
disulfide-linked α and β protein chains.”
Each chain has a variable region that participates in
binding a particular peptide antigen and
a constant region that interacts with associated signaling
molecules.
 TCRs are noncovalently linked to a cluster of five
invariant polypeptide chains, the γ, δ, and ε proteins of
the CD3 molecular complex and two ζ chains.
 The CD3 proteins and ζ chains do not bind antigens;
instead, they are attached to the TCR and initiate
intracellular biochemical signals after TCR recognition
of antigen.
 CD4+ CD8+
expressed on distinct T- expressed on distinct T-
cell subsets and act as co- cell subsets and act as co-
receptors receptors

bind to class II MHC Bind to class l MHC

expressed on 50% to 60% 40% of T cells.

of T cells

Called as helper T cells CD8+ T cells also can

because they secrete secrete cytokines,
soluble molecules that but their most important
help B cells to produce role is to directly kill virus-
antibodies and also infected cells and tumor
help macrophages to cells; hence, they are
destroy phagocytosed called cytotoxic T
microbes. lymphocytes (CTLs)
CD28 cells Regulatory T NKT Cells
lymphocytes Γδ T cells

functions T cells that TCRs that are Some T cells

as the function to composed of γ expresses
and δ chains,
receptor suppress which are
markers of both
for immune similar but not T cells and NK
molecule responses identical to α cells, thts y they
s called are and β chains. called NKT cells
costimul Called Such γδ T
cells, which do recognize
ators Regulatory not express microbial
T CD4 or CD8, glycolipids and
lymphocyte recognize may play a role
s nonprotein
in defense
molecules
against some
infections
 Molecules:
The Peptide Display System of
Adaptive Immunity
 MHC molecules are fundamental to T-cell recognition of
antigens, and genetic variations in MHC molecules are
associated with many immunologic diseases;.
 The MHC was discovered on the basis of studies of graft
rejection and acceptance (tissue, or “histo,” compatibility).
 It is now known that the normal function of MHC
molecules is to display peptides for recognition by
CD4+ and CD8+ T lymphocytes. In each person.
 The human MHC, known as the human leukocyte antigen
(HLA) complex, consists of a cluster of genes on
chromosome 6.
 On the basis of their chemical structure, tissue
distribution, and function, MHC gene products fall into two
main categories:
Class 1 MHC Class ll MHC
expressed on all nucleated expression of class II MHC
cells and are molecules
 encoded by three closely is restricted to a few cell types,
linked loci, designated HLA-A, mainly APCs (dendritic cells),
HLA-B, and HLA-C macrophages, and B cells.
encoded by genes in the HLA-
D region, which contains three
subregions: DP,DQ, and DR.
Each molecules consists of a heterodimers of noncovalently
poly-morphic α chain linked α and β subunits
noncovalently with β2
microglobulin polypeptide
The extracellular portion of The extracellular portion of class II
the α chain contains a cleft MHC molecules contains a cleft for
where the binding of antigenic peptides
•the polymorphic residues are and a region that binds CD4.
•class II MHC molecules bind to
located and
peptides derived from
• foreign peptides bind to MHC extracellular proteins synthesized
molecules for presentation to outside the cell, for example, from
 B-Lymphocytes
B (bone marrow–derived) lymphocytes are the cells that
produce antibodies, the mediators of humoral
immunity.
B cells make up 10% to 20% of the circulating peripheral
lymphocyte population.
They also are present in bone marrow and in the follicles of
peripheral (secondary) lymphoid organs.
Recognition of Antigen:
B cells recognize antigen by means of membrane-bound
antibody of the immunoglobulin M (IgM) class, expressed on
the surface together with signaling molecules to form the B-
cell receptor (BCR) complex , B cells recognize and respond to
many more chemical structures, including soluble or cell-
associated proteins, lipids, polysaccharides, nucleic acids,
and small chemicals, without a requirement for the MHC.
B cells express several invariant molecules that are
responsible for signal transduction and B-cell
activation .Some are signaling molecules attached to the
BCR; another example is CD21 (also known as the type 2
complement receptor, or CR2), which recognizes a
After stimulation, B cells differentiate into plasma
cells, which secrete large amounts of antibodies.
There are five classes, or isotypes, of
immunoglobulins:
IgG, IgM, and IgA constitute more than 95% of
circulating antibodies.
IgE is present in the circulation at very low
concentrations and also is found attached to the
surfaces of tissue mast cells;
IgD is expressed on the surfaces of B cells but is
secreted at very
low levels
 B Cells

antibodies
Activation of B Cells by Antigen

antigen
Clonal Selection
 Clonal Selection

plasma cells memory cells

antibodies
Natural Killer Cells and Innate Lymphoid
Cells:

NK cells are lymphocytes that arise from the same common

lymphoid progenitor that gives rise to T lymphocytes and B
lymphocytes.
 NK cells are innate immune cells, as they are functional
without prior activation and do not express highly
variable and clonally distributed receptors for antigens
NK cells have two types of receptors—inhibitory and activating.
1. Inhibitory receptors recognize self class I MHC molecules,
which are expressed on all healthy cells, whereas
2. Activating receptors recognize molecules that are expressed
or upregulated on stressed or infected cells.

Normally, the effects of inhibitory receptors dominate over those

of activating receptors, preventing spontaneous activation of
the NK cells.
Infections (especially viral infections) and stress
are associated with reduced expression of class I
MHC molecules and increased expression of
proteins that engage activating receptors. The net
result is that the NK cells are activated and the
infected or stressed cells are killed and eliminated.

NK cells also secrete cytokines such as interferon-γ

(IFN-γ), which activates macrophages to destroy
ingested microbes, and thus NK cells provide early
defense against intracellular microbial infections
Innate lymphoid cells (ILCs)
 are populations of lymphocytes that lack TCRs but produce
cytokines similar to those that are made by T cells.

 They are classified into three groups, which produce

 IFN-γ by TH1 of T cells.
 IL-5, by TH2 T of Tcells.
 IL-17cytokines by TH17 of T cells.

 NK cells are related to group1 ILCs based on their production

of IFN-γ, a cytokine also made by TH1 cells. Because ILCs
mostly reside in tissues, they are thought to provide early
defense against infections in the tissues, before T cells are
activated and can migrate into tissues. ILCs also may be early
participants in inflammatory diseases.
Antigen presenting cells
Capture antigen and display to lympho

Dendritic Cells
Dendritic cells (DCs) are the most important
antigen presenting cells for initiating T-cell
responses against protein antigens.
 Several features of DCs account for their key role in
antigen capture and presentation.
• These cells are located at the right place to capture
antigens—under epithelia, the common site of entry of
microbes and foreign antigens, and in the interstitia of
all tissues, where antigens may be produced. DCs within
the epidermis are called Langerhans cells.
 DCs express many receptors for capturing and
responding to microbes (and other antigens), including
TLRs and C-type lectin receptors.
 In response to microbes, DCs are recruited to the T-cell zones
of lymphoid organs, where they are ideally positioned to
present antigens to T cells.
 DCs express high levels of MHC and other molecules needed
for antigen presentation and activation of T cells
Types of DCs.:
 plasmacytoid DCs because of their resemblance to plasma
cells. These cells are present in the blood and lymphoid
organs, and are major sources
of the anti-viral cytokine type I interferon, produced in
response to many viruses.
 follicular dendritic cell (FDC). Cell with dendritic
morphology is
present in the germinal centers of lymphoid follicles in the
spleen and lymph nodes and is called the follicular dendritic
cell (FDC). These cells bear Fc receptors for IgG and receptors
for C3b and can trap antigen bound to antibodies or
complement protein
 Other APCs
Macrophages:

ingest microbes and other particulate antigens

and display peptides for recognition by T-
lymphocytes.
These T cells in turn activate the macrophages
to kill the microbes, the central reaction of cel
lmediated immunity.
B cells present peptides to helper T cells and
receive signals that stimulate antibody
responses to protein antigens, critical steps in
humoral immune responses.
 Lymphoid Tissues
Primary/central Lymphoid Organ
The tissues of the immune system in which T
lymphocytes and B lymphocytes mature and
become competent to respond to antigens, e.g
thymus and bone marrow
Secondary /peripheral lymphoid organs,
in which adaptive immune responses to microbes
are initiated.
Major perpheral organs are discussed below:
 Peripheral Lymphoid Organs
The peripheral lymphoid organs are organized to concentrate
antigens, Most of the body’s lymphocytes are located in
these organs.
Lymph nodes
are encapsulated, highly organized collections of lymphoid
cells and innate immune cells that are located along
lymphatic channels throughout the body. As lymph passes
through lymph nodes, resident APCs are able to sample
antigens that are carried to the node in lymph derived from
the interstitial fluids of tissues.
In addition, DCs transport antigens from nearby epithelial
surfaces and tissues by migrating through lymphatic vessels
to the lymph nodes. Thus, antigens (e.g., of microbes that
enter through epithelia or colonize tissues) become
concentrated in draining lymph nodes
The spleen. Blood entering the spleen flows through a
network of sinusoids, which enables the trapping of
bloodborne antigens by resident DCs and
macrophages.

The cutaneous and mucosal lymphoid systems

are located
under the epithelia of the skin and the gastrointestinal
and respiratory tracts, respectively. They respond to
antigens that enter through breaches in the
epithelium.
 Pharyngeal tonsils and Peyer’s patches of the intestine
are two anatomically defined mucosal lymphoid
tissues.
Cytokines: Messenger Molecules of the
Immune System
Cytokines are secreted proteins that mediate immune
and inflammatory reactions. Molecularly defined
cytokines are called interleukins,
 The majority of these cytokines act on the cells that produce
them or on neighboring cells, but some (like IL-1) have
systemic effects.
Different cytokines contribute to specific types of immune
responses.
• In innate immune responses, cytokines are produced
rapidly after microbes and other stimuli are encountered, and
function to induce inflammation and inhibit virus replication.
 These cytokines include TNF, IL-1, IL-12, type I IFNs, IFN-γ,
and chemokines Their major sources are macrophages, DCs,
ILCs, and NK cells, but endothelial and epithelial cells also
can produce them.
In adaptive immune responses,
 cytokines are produced principally by CD4+ T lymphocytes
activated by antigen and other signals, and function to promote
lymphocyte proliferation and differentiation and activate effectors
cells.
 Mainly
IL-2, IL-4, IL-5, IL-17, and IFN-γ; Some cytokines serve
mainly to limit and terminate immune responses; these
include TGF-β and IL-10

 Some cytokines stimulate hematopoietic and are called

colony stimulating factors because they stimulate formation
of blood cell colonies from bone marrow progenitors. Their
functions are to increase leukocyte numbers during immune
and inflammatory responses, and to replace leukocytes that
are consumed during such responses.
 They are produced by marrow stromal cells, T
lymphocytes,macrophages, and other cells. Examples include
GM-CSF and IL-7
 OVERVIEW OF LYMPHOCYTEACTIVATION
AND ADAPTIVEIMMUNE RESPONSES
Adaptive immune responses develop in
steps, consisting of:
1. antigen recognition;
2. activation,
3. proliferation and differentiation of specific
lymphocytes into effector and
4. memory cells;
5. elimination of the antigen; and
6. decline of the response,
7. with memory cells being the long-lived
survivors.
Capture and Display of Antigens
Microbes and other foreign antigens can enter the
body virtually anywhere.microbes and their
protein antigens in epithelia and other tissues are
captured by resident dendritic cells, which then
carry their antigenic cargo to draining lymph
nodes through which T cells constantly recirculate
 Here the antigens are processed and displayed
complexed with MHC molecules on the cell
surface, where the antigens are recognized by T
cells. Similarly, soluble antigens are captured and
concentrated in follicles in lymph nodes and the
spleen, where they may be recognized by B cells
via their antigen receptors.
Microbe activates innate immune cells expressing
pattern recognition receptors.
In case of vaccination (innate response is
stimulated)

 activate APC to express molecules called co-

stimulators and secrete cytokines

Stimulate the proliferation and differentiation of

T-Lymphocytes
 Cell-Mediated Immunity
Activation of T Lymphocytes and
Elimination of Intracellular Microbes
 Naïve T lymphocytes are activated
(by antigen &costimulators in peripheral lymphoid
organs),
 Then proliferate and differentiate into effector cells that
migrate to any site where the antigen (microbe) is
present. One of the earliest responses of CD4+ helper T
cells is secretion of the cytokine IL-2 and expression of
high-affinity receptors for IL-2.
 The functions of helper T cells are mediated by the
combined actions of CD40-ligand (CD40L) and
cytokines.
 When CD4+ helper T cells recognize antigens being
displayed by macrophages or B lymphocytes,
 the T cells express CD40L, which engages CD40 on
CD40 is a member of the TNF-receptor family, and CD40L is
a membrane protein homologous to TNF.
 Activated CD4+ T cells differentiate into effector cells
that secrete different sets of cytokines and perform
different functions.
1. TH1 subset secrete the cytokine IFN-γ, which is a potent
macrophage activator.
2. TH2 cells produce
a) IL-4, which stimulates B cells to differentiate into
IgE-secreting plasma cells;
b)IL-5, which activates eosinophils; and
c) ) IL-13, which activates mucosal epithelial cells to
secrete mucus, and induces the “alternative” pathway of
macrophage activation involved in tissue repair and fibrosis
Eosinophils bind to and kill IgE-coated pathogens such as
helminthic parasites
3. TH17 cells, signature cytokine of these cells is IL-
17 recruit neutrophils and monocytes, which
destroy some extracellular bacteria and fungi and
are involved in certain inflammatory disease

Activated CD8+ T lymphocytes differentiate into

CTLs that kill cytoplasmic microbes, thereby
eliminating/ hidden reservoirs of infection.
 The principal mechanism of killing by
CTLs depends on the perforin–granzyme system

Perforin and granzymes are stored in the granules of

CTLs and are rapidly released

CTLs engage their targets (cells bearing the

appropriate class I MHC–bound peptides).

Perforin binds to the plasma membrane of the target

cells and promotes the entry of granzymes,
proteases

that specifically cleave and thereby activate cellular

caspases ,which induce the apoptosis of target
Cytotoxic T Cell

perforin

pores in target cell

The central role in Helper T cells in an infected cell
 Humoral Immunity
Activation of B Lymphocytes and Elimination
of Extracellular Microbes

 Upon activation, B lymphocytes proliferate and then

differentiate into plasma cells that secrete different
classes of antibodies with distinct functions .
 There are two major pathways of B-cell activation.

T cell–independent.
Many polysaccharide and lipid antigens have
multiple identical antigenic determinants
(epitopes) that are able to simultaneously engage
and cross-link several antibody molecules on each
B cell and initiate the process of B-cell activation.
T cell–dependent.
Typical globular protein antigens are not able to bind
to multiple antigen receptors, and the full response
of B cells to protein antigens requires help from
CD4+ T cells.
B cells also act as APCs—they ingest protein
antigens, degrade them, and display peptides
bound to class II MHC molecules for recognition by
helper T cells. The helper T cells express CD40L
and secrete cytokines, which work together to
activate the Bcells
Some of the progeny of the expanded B-cell clones
differentiate into antibody-secreting plasma cells. Each
plasma cell secretes antibodies with the same specificity as
the cell surface antibodies (B-cell antigen receptors) that
first recognized the antigen. Polysaccharides and lipids
stimulate secretion mainly of IgM antibody.
Protein antigens, by virtue of CD40L- and cytokine-
mediated helper T-cell actions, induce the production of
antibodies of different
classes (IgG, IgA, IgE).
Production of functionally different antibodies, all
with the same specificity, relies on heavy-chain class
(isotype) switching, which increases the range of
functions that antibodies serve.
Some of the isotype-specific functions of antibodies include
opsonization and transplacental transfer of IgG, IgA
secretion into mucosal lumens, and binding of IgE to mast
cells.
 Antibody Molecule
antigen binding sites

antigen

light chains heavy chains

 Helper T cells also stimulate the production of
antibodies with higher affinity for the antigen.
This process, called affinity maturation,
improves the quality of the humoral immune
response.

Some activated B cells migrate into follicles

and form germinal centers( secondary
lymphoid organ where B cell proliferate), which
are the major sites of isotype switching and
affinity maturation. The helper T cells that
stimulate these processes in B lymphocytes
also migrate to and reside in the germinal
centers and are called follicular helper T (Tfh)
cell
The humoral immune response combats microbes in
numerous ways .
Antibodies bind to microbes and prevent them from infecting
cells, thereby neutralizing the microbes.
• IgG antibodies coat (opsonize) microbes and target them
for phagocytosis, since phagocytes (neutrophils and
macrophages) express receptors for the Fc tails of IgG
molecules.
• IgG and IgM activate the complement system by the
classical pathway, and complement products promote
phagocytosis and destruction of microbes.
• IgA is secreted in mucosal tissues and neutralizes
microbes in the lumens of the respiratory and
gastrointestinal tracts (and other mucosal tissues).
• IgG is actively transported across the placenta and
protects the newborn until the immune system becomes
mature. This is a form of passive immunity.
• IgE coats helminthic parasites and functions with mast
cells and eosinophils to kill them.
Decline of Immune Responses and
Immunologic Memory
 The majority of effector lymphocytes induced by an
infectious pathogen die by apoptosis after the pathogen is
eliminated, thus returning the immune system to its basal
resting state.

 The initial activation of lymphocytes generates long-lived

memory cells, which may survive for years after the
infection. Memory cells are an expanded pool of antigen-
specific lymphocytes (more numerous than the naïve cells
specific for any antigen that are present before encounter
with that antigen), and they respond faster and more
effectively when reexposed to the antigen than do naïve
cells.
 This is why the generation of memory cells is an important
goal of vaccination.
Question!!!!