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Immunology
Concept, Functions and Types
of Immunity
Concept, Functions and Types of Immunity
Introduction
Concept and functions of Immunity
Types of Immunity
Part I Concept and functions
of Immunity
I Concept of Immunity
1)Tranditional concept----Immunity refers to
protection against infectious diseases.
2)Modern concept---- Immunity is a function of
which an individual recognizes and excludes
antigenic foreign substances. It is normally
beneficial,but sometimes,it is injurious.
II Concept of Immunology
1) Tranditional concept----anti-infection immunity
to
different
types
of
pathogenic
microorganisms.
2)
Modern
concept----Immunology
is
an
independent
subject
about
composition,functions of immune system;
mechanism of immune response and the disease
associated with immunity.
III Functions of Immunity
Immune defense
Immune homeostasis
Immune surveillance
Functions and Manifestation of Immunity
Functions
Normal Manifestation
Abnormal Manifestation
Immune
Hypersensitivity
Defense
Immunodeficiency
Immune
Homeostasis
Immune
Surveillance
infection
Eliminate injured and senile cells
Tolerate to self components
Anti-infection
immune dismodulation
Autoimmune disease
destroy transformed cells
(anti-tumor )
Prevent from persistent infection
Tumor or
Persistent virus
Part II Types of Immunity
I. Innate Immunity
(or native immunity/ non-specific immunity
/congenital immunity)
II. Adaptive Immunity
(or acquired immunity/specific immunity)
I. Innate immunity
( natural immunity/ non-specific immunity )
Innate immunity:
Protection against infection that relies on
mechanisms that exist before infection,are
capable of a rapid response to microbes,and
react in essentially the same way to repeated
infections.
 Exists at birth
 Be the first line of defense against infection
Innate immunity
1. Characteristics
 Exists naturally
 Non–specific
 No immune memory (innate immunity can’t
be enhanced by the second stimulation of
the same antigen)
Immune memory: Exposure of the immune
system to a foreign antigen enhances its
ability to respond again to that antigen.
 Hereditable
 No racial difference
2. Composition
(1) Barriers
 Physical barrier : skin and mucosa
 Chemical barrier: antimicrobial substances in
secretion of skin and mucosa
 Biotic barrier: normal flora existing on the surface
of skin and mucosa
 Anatomic barrier
. blood- brain barrier
. blood- placental barrier
. blood- tymus barrier
(2) Humoral factors
 Complement
 Lysozyme
 Interferons(IFN)
 C-reactive protein
(3)Cells participating in innate immunity
 Phagocyte: endocytosis and phagocytosis
mononuclear phagocytes
----Monocytes,Macrophages (M Φ)----PRR
Neutrophils
 Nature killer cells (NK)—KAR/KIR,IgG
receptor
 Dentritic cells(DC)
 γδ T cells
 B1 cells
 Other cells participating in innate immunity
Fc
Macrophages
NK cells
Neutrophils
Macrophages
Macrophages excluding the
pathogen
Over view




What are the main types of white
blood cells?
Name the two main types of immunity?
What are the main distinctions between
these two categories?
What cells are involved in which aspects
of the immune system?
Lymphocytes



Many types; important in
both humoral and cellmediated immunity
B-cells produce
antibodies (APC cell)
T- cells



Cytotoxic T cells
Helper T cells
Memory cells
Lymphocytes

Natural Killer cells



Large granular lymphocytes (not B or T)
Kills tumor cells
Kills cells infected with certain viruses
(intracellular pathogens)
Monocytes/Macrophage

Phagocytosis and killing of
microorganisms




Activation of T cells and
initiation of immune
response
Monocyte is a young
macrophage in blood
There are tissue-specific
macrophages
APC cells
Dendritic Cells



Phagocytosis and killing
of microorganisms
Function as antigen
presenting cells (APC)
In the blood and
tissues – mature and
migrate to the lymph
nodes
Neutrophil

Granulocyte






Cytoplasmic granules
Polymorphonuclear
Phagocytosis
Short life span (hours)
Very important at “clearing” bacterial
infections
Innate Immunity
Eosinophils





Kills Ab-coated parasites
through degranulation
Involved in allergic
inflammation
A granulocyte
Double Lobed nucleus
Orange granules contain toxic
compounds
Basophils


Might be “blood Mast
cells’
A cell-killing cells


Blue granules contain toxic
and inflammatory
compounds
Important in allergic
reactions
Antigen-presenting cells (APC)




Highly specialized
Process antigen and display peptide
fragments on cell surface
Involved in T-cell activation
Macrophages, dendritic cells and B-cells
Immune system divisions


Innate immunity
 First line of defense
Adaptive (acquired) immunity
 Takes time to develop
 Humoral immunity
(antibody–mediated
specific immunity)
 Cell-mediated immunity
(The aspect of the
adaptive immune response
where antigen-specific T
cell have a main role)


Active immunity
Passive or maternal
immunity


Injection of Immunoglobulin
Absorption of maternal
antibodies
Innate vs. adaptive immunity


Innate immunity
 First line of defense (present in all individuals at all
times)
 Immediate (0 – 4 hours)
 Non-specific
 Does not generate lasting protective immunity
Adaptive immune response (late: > 96 hours)
 Is initiated if innate immune response is not adequate
(> 4 days)
 Antigen-specific immunity
 Generates lasting protective immunity (e.g. Antibodies,
memory T-cells)
Immune system cells

Innate immunity
 Granulocytes
(i.e. neutrophils)
 Macrophages
 Dendritic cells
 Natural killer (NK)
cells

Adaptive
immunity
 Lymphocyte
B cells
 T cells




Cytotoxic T cells (CTLs)
Helper T cells (Th)
Memory cells
Innate immune system

The first line of defense:




Penetration of the epithelial surface of the body by
microorganism (e.g. bacteria)
Engulfment of microorganism by macrophages,
neutrophils, and dendritic cells
Release of cytokines and chemokines
Inflammation
Killing by granulocytes



Macrophages and neutrophils recognize pathogen by means of
cell-surface receptors
 Example: mannose receptor, CD14 receptor, scavenger
receptors, glucan receptor etc.
Binding of MØ/neutrophils with pathogen leads to phagocytosis
 Bound pathogen is surrounded by phagocyte membrane
 Internalized (phagosome)
 Killing of pathogen (Phagolysosome*)
 Oxidative burst (synthesis of hydrogen peroxide (H2O2)or
free oxygen radicals)
 Acidification
 Antimicrobial peptides (e.g. defensins)
* Phagolysosome = lysosome +phagosome
Phagocytosis
Lipid
mediators
Mannose
receptor
Lysosome
Phagosome
Scavenger
receptor
LPS receptor
(CD14)
The macrophage
expresses receptors for
many bacterial
constituents
Cytokines
Bacteria binding to
macrophage receptors
initiate the release of
cytokines and small lipid
mediators of inflammation
Phagolysosome
Macrophages engulf and
digest bacteria to which
they bind
Phagocytosis

(Immunology animation: Janeway)



http://www.blink.biz/immunoanimations/#
Immune response (IV)
9.1 - Phagocytosis
Humoral immune response

Cell-surface immunoglobulin
receptors (BCR) detect
extracellular pathogens


Once activated, secrete
immunoglobulins as soluble
antibodies
Antibodies


Variable region (2 identical
antigen-binding sites)
Constant region (determines
how antibody disposes of the
pathogen once it is bound)
V region; At binding
Fc region
Cell killing – NK cells




NK cells do not require prior
immunization or activation
They attach to ‘target’ cells
(ADCC)
Cytotoxic granules are
released onto surface of cell
Effector proteins penetrate
cell membrane and induce
programmed cell death
Inflammation
Inflammatory cells
migrate into tissue,
releasing inflammatory
mediators that cause
pain
Chemokines
Cytokines
Bacteria
trigger
macrophages
to release
cytokines and
chemokines
Proteins
Fluids
Vasodilation and
increased vascular
premeability cause
redness, heat, and
swelling
Cytokines


Low molecular weight, soluble proteins that are
produced in response to an antigen and function as
chemical messengers for regulating the innate and
adaptive immune system
Innate immune system

Macrophages and Dendritic cells




Tumor necrosis factor-alpha (TNF-)
Interleukin-1 (IL-1)
Interleukin-12 (IL-12)
Adaptive immune system

T-lymphocytes


Interleukin-2 (IL-2)
Interleukin-4 (IL-4)
II.Adaptive immunity
( acquired immunity/specific immunity)
Adaptive immunity:
The form of immunity that is mediated by
T or B lymphocytes and stimulated by
exposure to infectious agents.
 Take effects after innate immune response
 Be the second line of defense against
infection
1.Characteristics
 Specificity
 Acquired (set up after birth )
 Immune memory
(Adaptive immunity can be enhanced by the
second stimulation of the same antigen)
 Transferable
 Self-limitation
2.Composition
T cell : Cell-mediated immunity (CMI)
B cell : Humoral immunity(HI) or
antibody-mediated immunity
3.The process of immune
response
in adaptive immunity
Recognition of antigens
Activation,proliferation and
differenciation of T or B lymphocytes
Effector phase of immune response
----Elimination of antigens
Comparison of Adaptive and Innate
Immunity
Innate immunity
Adaptive immunity
Characteristics Exists naturally
Acquired by antigen stimulation after birth
Responds rapidly in the early
develops slowly
stage of infection
No antigen specificity
Has antigen specificity
No immune memory
Has immune memory
Participates in natural defence
Participates in specific immune response
Cells
Neutrophil,Phagocytes,NK cell et al.
T cell, B cell, APC
Molecules Complement.lysozyme,cytokines et al
Antibody,cytokines
Immunology Terms
• Antigen
– Any molecule that binds to immunoglobulin or T cell receptor
• Pathogen
– Microorganism that can cause disease
• Antibody (Ab)
– Secreted immunoglobulin
• Immunoglobulin (Ig)
– Antigen binding molecules of B cells
• Vaccination
– Deliberate induction of protective immunity to a pathogen
• Immunization
– The ability to resist infection
Types of Immunity
• Humoral immunity
– Immunity that is mediated by antibodies
– Can be transferred by to a non-immune
recipient by serum
• Cell Mediated Immunity
– Immune response in which antigen specific T
cells dominate
Cells of the Immune system
• Many cells of
the immune
system derived
from the bone
marrow
• Hematopoetic
stem cell
differentiation
The Pathway of Specific Immune Response
Step 1
Pathogens eaten by Macrophage
Step 2
Displays portion of Pathogen
on surface
Step 3
Pathogens
Helper-T cell recognizes
Pathogen
Activates B- Cell
Activates Cytotoxic
T- Cell
Memory T-Cell
Memory B-Cell
Antibodies
Kills Infected Cells
Cellular Immunity .vs. Antibody Immunity
Cellular Immunity
• Carried out by T-Cells
• Infected cells are killed by
Cytotoxic T –Cells.
Antibody or Humoral Immunity
• Carried out by B-cells
• Antibodies are produced
and dumped into blood
stream.
• Antibodies bind to
antigens and deactivate
them.
Immune Response Explained
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
Antigen infects cells.
Macrophage ingests antigen and displays portion on its surface.
Helper T- Cell recognizes antigen on the surface of the
macrophage and becomes active.
Active Helper T-Cell activates Cytotoxic T-Cells and B-Cells.
Cytotoxic T-Cells divide into Active Cytotoxic T-cells and Memory
T – Cells.
Active Cytotoxic T-Cells kill infected cells.
At the same time, B-Cells divide into Plasma Cells and Memory
B- Cells.
Plasma cells produce antibodies that deactivate pathogen.
Memory T and Memory B cells remain in the body to speed up the
response if the same antigen reappears.
Supressor T-Cells stop the immune response when all antigens
have been destroyed.
Immune Response Summary
Displays copy of antigen
on surface of cell
Antigen
Macrophage
Antibody Immunity
Helper T - Cell
Cellular Immunity
Active Cytotoxic T-Cell
Kills Infected Cells
Memory T- Cell
Active B - Cell
Plasma Cell
Antibodies
Deactivates Antigens
Memory B-Cell
Primary .vs. Secondary Immune Response
• Primary Immune Response
– This is a response to an invader the First time the
invader infects the body.
• No measurable immune response for first few days.
• Next 10 – 15 days antibody production grows steadily
• Secondary Immune Response
– A more rapid response to an invader the 2nd time it
invades the body.
• Antibody production increases dramatically and in a much
shorter time period..
Primary .vs. Secondary Immune Response
Passive .vs. Active Immunity
1.
Active Immunity
This is immunity where the body is “actively” producing antibodies
to fight infection.
Ex: You have a throat infection and you are actively creating
antibodies to fight it.
Vaccination:
An injection of a weakened strain of an
infectious microbe (pathogen) that causes the body to undergo
active immunity (produce antibodies).
2.
Passive Immunity
This is immunity where antibodies are given to a
person from the blood of another person or animal.
This immunity only lasts for a short period of time.
ex: Breastfeeding mothers pass antibodies to their
children through the milk.
Antibodies – structure, classes and function
Objectives
By the end of the session you should be able to:
• illustrate and describe the basic structure of antibodies in terms
of heavy and light chains
• explain the structure in relation to function of the molecules
• define the terms ‘isotype’, ‘allotype’ and ‘idiotype’
• describe the structure of each of the five main classes of
antibody
• describe the location and function of each class of antibody
• define the terms ‘affinity’ and avidity’ of antibodies
The fragment antigen binding (Fab fragment) is a
region on an antibody which binds to antigens. It is
composed of one constant and one variable domain of
each of the heavy and the light chain. These domains
shape the paratope—the antigen binding site—at the
amino terminal end of the monomer. The two variable
domains bind the epitope on their specific antigens.
An epitope, also know as antigenic determinant, is the
part of a macromolecule that is recognized by the
immune system, specifically by antibodies, B cells, or
T cells. The part of an antibody that recognizes the
epitope is called a paratope. Although epitopes are
usually thought to be derived from nonself proteins,
sequences derived from the host that can be
recognized are also classified as epitopes.
Antibody heterogeneity
Isotypes
Two light chain isotypes – k and l :
Five heavy chain isotypes - m,g,d, and e
Allotypes
Genetic markers- (rather like blood groups and usually the result of
minor amino acid differences) on immunoglobulins that segregated
within the species and inherited in Mendelian fashion eg. Km (on k
light chains) and Gm (on IgG heavy chains)
Idiotypes
Each antibody varies in its amino acid sequences in the variable
regions of both heavy and light chains to create different specificities
Ig class
Heavy chain
Light chain
IgM
m (mu)
k (kappa) or l (lambda)
IgG
g (gamma)
k (kappa) or l (lambda)
IgA
 (alpha)
k (kappa) or l (lambda)
IgE
e (epsilon)
k (kappa) or l (lambda)
IgD
d (delta)
k (kappa) or l (lambda)
Summary of different classes and subclasses of antibodies
Physical forces holding antibodies and antigen together
Affinity and avidity of antibodies
Affinity
The tightness with which the antigen binding site attaches to an
antigen determinant (epitope)
Avidity
The tightness of binding when several antigen binding sites
attach to several antigenic determinants
Immunoglobulin




Element of adaptive immune mechanism
Better known as antibody
It recognize the foreign objects
How they work (examples)


Animation1
Animation2
Structure of immunoglobulin

Two identical
heavy (H) chains
and two identical
light (L) chains
combine to form
this Y-shaped
antibody molecule
Disulfide bonds



Bonds between two amino acids result of the SH
(sulfhydral) group of one amino acid covalently
bonding to the SH group of another amino acid
Stronger than hydrogen bonds
Eg. Hair proteins are held together by disulfide bonds
Heavy chains

The heavy chains
each have four
domains


Variable domains
(VH)
Constant domains
(CH1,2,3)
Light chain

The light chains
are constructed of
two domains


Variable (VL)
Constant (CL)
Structure of immunoglobulin



The fragment antigen
binding (Fab fragment)
The fragment crystallizable
region (Fc region)
Antibodies bind to antigens
by reversible, noncovalent
interactions, including
hydrogen bonds and
charge interactions
Antigen binding some pictures
Antigen binding some pictures
Structure of immunoglobulin

Functional
consequences:


(VH) and (VL) are
positioned to
stereochemically
react with antigen
The stem is good
for mediate
effector functions
Hinge


Two disulfide bonds in the
hinge region unite the two
heavy chains
The hinge allows the two
antigen-binding Fab regions
of each antibody molecule
to move
Conclusion


Changes in the antigen binding site
conformation are vital for antigen
recognition
Herewith the variety of antibody
conformation is vital for our health
Humoral Immune Response
Cellular Events




Antigen is “processed” by T
lymphocytes and macrophages.
Possess special receptors on surface.
Termed “antigen presenter cell” APC.
Antigen presented to B cell
Cellular Immune Response



Important in defending against: fungi,
parasites, bacteria.
Responsible for hypersensitivity,
transplant rejection, tumor
surveillance.
Thymus derived (T) lymphocytes
Cell Mediated Reaction



Helper T cells – turn on immune
response
Suppressor T cells – turn off immune
response
Cytotoxic T cells directly attack antigen
Cell Mediated Immunity
Basic Antibody Structure
Figure 21.12a, b
Antibody Structure
 Antibodies responding to different antigens have different V
regions but the C region is the same for all antibodies in a
given class
 C regions form the stem of the Y-shaped antibody and:
 Determine the class of the antibody
 Serve common functions in all antibodies
 Dictate the cells and chemicals that the antibody can bind to
 Determine how the antibody class will function in
elimination of antigens
Mechanisms of Antibody Diversity
 Plasma cells make over a billion different types of antibodies
 Each cell, however, only contains 100,000 genes that code
for these polypeptides
 To code for this many antibodies, somatic recombination
takes place
 Gene segments are shuffled and combined in different ways
by each B cell as it becomes immunocompetent
 Information of the newly assembled genes is expressed as B
cell receptors and as antibodies
Antibody Diversity
 Random mixing of gene segments makes unique
antibody genes that:
 Code for H and L chains
 Account for part of the variability in antibodies
 V gene segments, called hypervariable regions,
mutate and increase antibody variation
 Plasma cells can switch H chains, making two or
more classes with the same V region
Antibody Targets
 Antibodies themselves do not destroy antigen; they
inactivate and tag it for destruction
 All antibodies form an antigen-antibody (immune)
complex
 Defensive mechanisms used by antibodies are
neutralization, agglutination, precipitation, and
complement fixation
Complement Fixation and Activation
 Complement fixation is the main mechanism used against
cellular antigens
 Antibodies bound to cells change shape and expose
complement binding sites
 This triggers complement fixation and cell lysis
 Complement activation:
 Enhances the inflammatory response
 Uses a positive feedback cycle to promote phagocytosis
 Enlists more and more defensive elements
Other Mechanisms of Antibody Action
 Neutralization – antibodies bind to and block
specific sites on viruses or exotoxins, thus
preventing these antigens from binding to receptors
on tissue cells
Other Mechanisms of Antibody Action
 Agglutination – antibodies bind the same
determinant on more than one antigen
 Makes antigen-antibody complexes that are crosslinked into large lattices
 Cell-bound antigens are cross-linked, causing
clumping (agglutination)
 Precipitation – soluble molecules are cross-linked
into large insoluble complexes
Mechanisms of Antibody Action
Figure 21.13
Cell-Mediated Immune Response
 Since antibodies are useless against intracellular antigens,
cell-mediated immunity is needed
 Two major populations of T cells mediate cellular immunity
 CD4 cells (T4 cells) are primarily helper T cells (TH)
 CD8 cells (T8 cells) are cytotoxic T cells (TC) that destroy
cells harboring foreign antigens
 Other types of T cells are:
 Suppressor T cells (TS)
 Memory T cells
Major Types of T Cells
Figure 21.14
Importance of Humoral Response
 Soluble antibodies
 The simplest ammunition of the immune response
 Interact in extracellular environments such as body
secretions, tissue fluid, blood, and lymph
The Humoral Immune Response (HIR) is the aspect
of immunity that is mediated by secreted antibodies
(as opposed to cell-mediated immunity which involves
T lymphocytes) produced in the cells of the B
lymphocyte lineage (B cell). Secreted antibodies bind
to antigens on the surfaces of invading microbes
(such as viruses or bacteria), which flags them for
destruction.[1] Humoral immunity is called as such,
because it involves substances found in the humours,
or body fluids.
Importance of Cellular Response
 T cells recognize and respond only to processed
fragments of antigen displayed on the surface of
body cells
 T cells are best suited for cell-to-cell interactions,
and target:
 Cells infected with viruses, bacteria, or intracellular
parasites
 Abnormal or cancerous cells
 Cells of infused or transplanted foreign tissue
Antigen Recognition and MHC Restriction
 Immunocompetent T cells are activated when the V
regions of their surface receptors bind to a
recognized antigen
 T cells must simultaneously recognize:
 Nonself (the antigen)
 Self (a MHC protein of a body cell)
The major histocompatibility complex (MHC) is a large
genomic region or gene family found in most vertebrates. It is
the most gene-dense region of the mammalian genome and
plays an important role in the immune system, autoimmunity,
and reproductive success. The proteins encoded by the MHC
are expressed on the surface of cells in all jawed vertebrates,
and display both self antigens (peptide fragments from the
cell itself) and nonself antigens (e.g. fragments of invading
microorganisms) to a type of white blood cell called a T cell
that has the capacity to kill or co-ordinate the killing of
pathogens, infected or malfunctioning cells.
MHC Proteins
 Both types of MHC proteins are important to T cell
activation
 Class I MHC proteins
 Always recognized by CD8 T cells
 Display peptides from endogenous antigens
Class I MHC Proteins
 Endogenous antigens are:
 Degraded by proteases and enter the endoplasmic
reticulum
 Transported via TAP (transporter associated with
antigen processing)
 Loaded onto class I MHC molecules
 Displayed on the cell surface in association with a
class I MHC molecule
Class I MHC Proteins
Figure 21.15a
Class II MHC Proteins
 Class II MHC proteins are found only on mature B
cells, some T cells, and antigen-presenting cells
 A phagosome containing pathogens (with exogenous
antigens) merges with a lysosome
 Invariant protein prevents class II MHC proteins
from binding to peptides in the endoplasmic
reticulum
Class II MHC Proteins
 Class II MHC proteins migrate into the phagosomes
where the antigen is degraded and the invariant
chain is removed for peptide loading
 Loaded Class II MHC molecules then migrate to the
cell membrane and display antigenic peptide for
recognition by CD4 cells
Class II MHC Proteins
Figure 21.15b
Antigen Recognition
 Provides the key for the immune system to
recognize the presence of intracellular
microorganisms
 MHC proteins are ignored by T cells if they are
complexed with self protein fragments
Antigen Recognition
 If MHC proteins are complexed with endogenous or
exogenous antigenic peptides, they:
 Indicate the presence of intracellular infectious
microorganisms
 Act as antigen holders
 Form the self part of the self-antiself complexes
recognized by T cells
T Cell Activation: Step One – Antigen Binding
 T cell antigen receptors (TCRs):
 Bind to an antigen-MHC protein complex
 Have variable and constant regions consisting of
two chains (alpha and beta)
T Cell Activation: Step One – Antigen Binding
 MHC restriction – TH and TC bind to different
classes of MHC proteins
 TH cells bind to antigen linked to class II MHC
proteins
 Mobile APCs (Langerhans’ cells) quickly alert the
body to the presence of antigen by migrating to the
lymph nodes and presenting antigen
T Cell Activation: Step One – Antigen Binding
 TC cells are activated by antigen fragments
complexed with class I MHC proteins
 APCs produce co-stimulatory molecules that are
required for TC activation
 TCR that acts to recognize the self-antiself complex
is linked to multiple intracellular signaling pathways
 Other T cell surface proteins are involved in antigen
binding (e.g., CD4 and CD8 help maintain coupling
during antigen recognition)
T Cell Activation: Step One – Antigen Binding
Figure 21.16
T Cell Activation: Step Two – Co-stimulation
 Before a T cell can undergo clonal expansion, it
must recognize one or more co-stimulatory signals
 This recognition may require binding to other
surface receptors on an APC
 Macrophages produce surface B7 proteins when
nonspecific defenses are mobilized
 B7 binding with the CD28 receptor on the surface of
T cells is a crucial co-stimulatory signal
 Other co-stimulatory signals include cytokines and
interleukin 1 and 2
T Cell Activation: Step Two – Co-stimulation
 Depending on receptor type, co-stimulators can
cause T cells to complete their activation or abort
activation
 Without co-stimulation, T cells:
 Become tolerant to that antigen
 Are unable to divide
 Do not secrete cytokines
T Cell Activation: Step Two – Co-stimulation
 T cells that are activated:
 Enlarge, proliferate, and form clones
 Differentiate and perform functions according to
their T cell class
T Cell Activation: Step Two – Co-stimulation
 Primary T cell response peaks within a week after
signal exposure
 T cells then undergo apoptosis between days 7 and
30
 Effector activity wanes as the amount of antigen
declines
 The disposal of activated effector cells is a
protective mechanism for the body
 Memory T cells remain and mediate secondary
responses to the same antigen
Cytokines
 Mediators involved in cellular immunity, including
hormonelike glycoproteins released by activated T
cells and macrophages
 Some are co-stimulators of T cells and T cell
proliferation
 Interleukin 1 (IL-1) released by macrophages costimulates bound T cells to:
 Release interleukin 2 (IL-2)
 Synthesize more IL-2 receptors
Cytokines
 IL-2 is a key growth factor, which sets up a positive
feedback cycle that encourages activated T cells to
divide
 It is used therapeutically to enhance the body’s
defenses against cancer
 Other cytokines amplify and regulate immune and
nonspecific responses
Cytokines
 Examples include:
 Perforin and lymphotoxin – cell toxins
 Gamma interferon – enhances the killing power of
macrophages
 Inflammatory factors
Helper T Cells (TH)
 Regulatory cells that play a central role in the
immune response
 Once primed by APC presentation of antigen, they:
 Chemically or directly stimulate proliferation of
other T cells
 Stimulate B cells that have already become bound
to antigen
 Without TH, there is no immune response
Helper T Cells (TH)
Figure 21.17a
Helper T Cell
 TH cells interact directly with B cells that have antigen
fragments on their surfaces bound to MHC II receptors
 TH cells stimulate B cells to divide more rapidly and begin
antibody formation
 B cells may be activated without TH cells by binding to T
cell–independent antigens
 Most antigens, however, require TH co-stimulation to
activate B cells
 Cytokines released by TH amplify nonspecific defenses
Helper T Cells
Figure 21.17b
Cytotoxic T Cell (Tc)
 TC cells, or killer T cells, are the only T cells that can
directly attack and kill other cells
 They circulate throughout the body in search of body cells
that display the antigen to which they have been sensitized
 Their targets include:
 Virus-infected cells
 Cells with intracellular bacteria or parasites
 Cancer cells
 Foreign cells from blood transfusions or transplants
Cytotoxic T Cells
 Bind to self-antiself complexes on all body cells
 Infected or abnormal cells can be destroyed as long
as appropriate antigen and co-stimulatory stimuli
(e.g., IL-2) are present
 Natural killer cells activate their killing machinery
when they bind to MICA receptor
 MICA receptor – MHC-related cell surface protein
in cancer cells, virus-infected cells, and cells of
transplanted organs
Mechanisms of Tc Action
 In some cases, TC cells:
 Bind to the target cell and release perforin into its
membrane
 In the presence of Ca2+ perforin causes cell lysis
by creating transmembrane pores
 Other TC cells induce cell death by:
 Secreting lymphotoxin, which fragments the target
cell’s DNA
 Secreting gamma interferon, which stimulates
phagocytosis by macrophages
Mechanisms of Tc Action
Figure 21.18a, b
Other T Cells
 Suppressor T cells (TS) – regulatory cells that
release cytokines, which suppress the activity of
both T cells and B cells
 Gamma delta T cells (Tgd) – 10% of all T cells
found in the intestines that are triggered by binding
to MICA receptors