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2.D.

4 Immune System & Our


Chemical Defenses

Animals (& plants) have a variety


of chemical defenses against
infections that affect dynamic
homeostasis.

Immune
System

Nonspecific
Response
(Innate Response)

Plants

Invertebrate
s

Specific Response
(Acquired or Adaptive
Response)

Vertebrates

Vertebrates
Only

A pathogen is a biological agent such as


avirus, bacterium,prion, orfungus, that
causes a disease or infection in its host.

Plants, invertebrates and vertebrates


have multiple, nonspecific immune
responses to pathogens.

Example: Invertebrate immune systems


lack pathogen-specific defense responses.
Innate immunity in invertebrates consists
of the exoskeleton and the digestive
system and its associated microorganisms.

Immune cells called hemocytes


are found inside the hemolypmh
of insects. They engulf pathogens
via phagocytosis.

Vertebrate immune systems have


specific and nonspecific defense
mechanisms against pathogens.

Immune
System

Nonspecific
Response
(Innate
Response)

Specific
Response
(Acquired or
Adaptive
Response)

Nonspecific immunity, or innate


immunity, is present before any
exposure to pathogens and is
effective from the time of birth.

Innate immunity provides broad


defenses against infection. A
pathogen that successfully breaks
through an animals external
defenses soon encounters several
innate cellular and chemical
mechanisms that impede its attack
on the body.

3m

Intact skin and mucous membranes


form physical barriers that bar the
entry of microorganisms and viruses.
Certain cells of the mucous
membranes produce mucus, a
viscous fluid that traps microbes and
other particles.

In the trachea, ciliated epithelial


cells sweep mucus and any
entrapped microbes upward,
preventing the microbes from
entering the lungs.

Secretions of the skin and mucous


membranes provide an environment that
is often hostile to microbes. The skin has
a pH between 3 and 5, which is acidic
enough to prevent colonization of many
microbes. Also, lysozymes are enzymes
abundant in a number ofsecretions, such
astears,saliva,human milk, andmucus
that break down the cell walls of many
bacteria.

Internal cellular and chemical defenses


depend mainly on phagocytosis.
Phagocytes are types of white blood cells
that ingest invading microorganisms and
initiate the inflammatory response.

Macrophages, a specific type of


phagocyte, can be found
migrating through the body and
in various organs of the
lymphatic system.

Phagocytes such as macrophages


attach to their prey via surface
receptors and engulf them, forming

a vacuole that fuses with a lysosome.

Numerous antimicrobial proteins


function in innate defense by attacking
microbes directly of by impeding their
reproduction. They have been
demonstrated to kill Gram negative and
Gram positive bacteria, mycobacteria,
enveloped viruses, fungi, and even
transformed or cancerous cells.

About 30 antimicrobial proteins make up the


complement system. The complement
system can cause lysis of invading cells and
help trigger inflammation.

Interferons
(IFNs)
provide
innate
defense
against
viruses and

Inflammatory Response
In local inflammation, histamine and
other chemicals released from injured
cells promote changes in blood vessels
that allow more fluid, more
phagocytes, and antimicrobial proteins
to enter the tissues.

Inflammatory Response

Neutrophils
and
Neutrophils
and mast cells
Monocytes differentiate
phagocytize
pathogens
into macrophages
monocytes
migrate
to the

Natural killer (NK) cells patrol


the body and attack virus-infected
body cells and cancer cells. They
trigger apoptosis in the cells they
attack.

Specific immunity, also called


acquired immunity or adaptive
immunity, develops only after
exposure to inducing agents such as
microbes, toxins, or other foreign
substances.

Consists of lymphatic vessels and


the lymphoid organs
Lymph nodes - Red bone marrow (B-Cells) Thymus gland (T-Cells) - Lymphatic vessels
Tonsils Spleen

In acquired immunity,
lymphocytes (white blood cells)
provide specific defenses against
infection.

Lymphocytes arise from stem cells


in the bone marrow.

B cells mature in the Bone


marrow. T cells mature in the
Thymus.
Bone marrow
Lymphoid
stem cell

Thymus

T cell

B cell

Blood, lymph, and lymphoid tissues


(lymph nodes, spleen, and others)

An antigen is any foreign molecule


that is specifically recognized by
lymphocytes and elicits a response
from them. A lymphocyte recognizes
and binds to just a small, accessible
portion of the antigen called an
epitope.
Antigenbinding
sites

Antibody A

Antigen

Antibody B

Antibody C

Epitopes
(antigenic
determinants)

Vertebrates have two types of


specific immune responses: cell
mediated immunity and humoral
immunity.

The vertebrate body is populated by


two main types of lymphocytes
which circulate through the blood:

B lymphocytes (B
cells)
T lymphocytes (T
cells)

The plasma membranes of both B cells


and T cells have about 100,000 antigen
receptors that all recognize the same
epitope.

B cell receptors bind to specific, intact antigens.


They are often called membrane antibodies or
membrane immunoglobulins.

Disulfide
bridge

Light
chain

Antigenbinding site

Antigenbinding
site

C C

Variable
regions
Constant
regions
Transmembrane
region

Heavy chains
B cell

Plasma
membrane

Cytoplasm of B cell
(a)
A B cell receptor consists of two identical heavy
chains and two identical light chains linked by
several disulfide bridges.

Each T cell receptor consists of two


different polypeptide chains.
AntigenBinding site
Variable
regions
V
Constant
regions

V
C

C
Transmembrane
region

Plasma
membrane

chain

chain

Disulfide bridge
Cytoplasm of T cell
(b)
A T cell receptor consists of one
chain and one chain linked by
a disulfide bridge.

T cell

T cells bind to small fragments of antigens


that are bound to normal cell-surface
proteins called MHC molecules. MHC
molecules are encoded by a family of
genes called the major
histocompatibility complex.

Infected cells produce MHC molecules


which bind to antigen fragments and then
are transported to the cell surface in a
process called antigen presentation. A
nearby T cell can then detect the antigen
fragment displayed on the cells surface.

Depending on their source


peptide, antigens are handled by
different classes of MHC
molecules.

Class I MHC molecules, found on


almost all nucleated cells of the
body, display peptide antigens to
cytotoxic T cells.
Infected cell
Antigen
fragment
1

1A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.

Class I MHC
molecule
T cell
receptor

(a) Cytotoxic T cell

2The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.

Class II MHC molecules, located mainly


on dendritic cells, macrophages, and B
cells, display antigens to helper T cells.
Antigenpresenting
cell

Microbe
1A fragment of
foreign protein
(antigen) inside the
cell associates with
an MHC molecule
and is transported
to the cell surface.

Antigen
fragment

1
2

2The combination of
MHC molecule and
antigen is recognized
by a T cell, alerting it
to the infection.

(b)

Class II MHC
molecule
T cell
receptor

Helper T cell

As B and T cells are maturing in the bone


and thymus, their antigen receptors are
tested for possible self-reactivity.
Lymphocytes bearing receptors for
antigens already present in the body are
destroyed by apoptosis or rendered
nonfunctional.

Humoral and cell-mediated immunity


defend against different types of
threats. Acquired immunity includes
two branches:
The humoral
immune response (B
Cells)
The cell-mediated
immune response (T
Cells)

The humoral
immune response
involves the
activation and clonal
selection of B cells,
resulting in the
production of
secreted
antibodies.
The cell-mediated
immune response
involves the
activation and clonal
selection of
cytotoxic T cells .

45

Cell Mediated Response

Helper T cells produce CD4, a


surface protein that enhances their
binding to class II MHC molecule
antigen complexes on antigenpresenting cells. Activation of the
helper T cell then occurs.

Activated helper T cells secrete


several different cytokines that
stimulate other lymphocytes.

The activated cytotoxic T cell secretes


proteins that destroy the infected
target cell
A1cytotoxic T cell binds to a
class I MHCantigen complex on a
target cell with the aid of
CD8. This interaction, along with
cytokines from helper T cells, leads
the activation of the cytotoxic cell.

2 activated T cell releases perforin


The
molecules, which form pores in the
target cell membrane, and proteolytic
enzymes, which enter the
totarget cell by endocytosis.

Cytotoxic T cell

The
3 enzymes initiate apoptosis within the
target cells, leading to fragmentation of the
nucleus, release of small apoptotic bodies,
and eventual cell death. The released
cytotoxic T cell can attack other target cells.

Released
cytotoxic
T cell

Perforin

Cancer
cell
Granzymes
1 TCR
Class I MHC
molecule

Target
cell

CD8
2

Peptide
antigen

Apoptotic
target cell

Pore

Cytotoxic
T cell

Humoral Response

Activation of B cells is aided by


cytokines and antigen binding to
helper T cells.

Anantibody, also known as


animmunoglobulin(Ig), is a large Yshapedproteinproduced byB-cellsthat is
used by theimmune systemto identify and
neutralize pathogens.

Each antibody is specific to a particular


antigen. Each tip of the "Y" of an antibody
contains aparatope that is specific for one
particularepitopeon an antigen, allowing these
two structures to bind together with precision.

The binding of antibodies to antigens


is also the basis of several antigen
disposal mechanisms. It further leads
to elimination of microbes by
phagocytosis and complementmediated lysis.

Antibody-mediated mechanisms of antigen


disposal:
Binding of antibodies to antigens
inactivates antigens by

Viral neutralization
Agglutination of
(blocks binding to host) antigen-bearing particles,
and opsonization (increases
such as microbes
phagocytosis)

Precipitation of
soluble antigens

Complement
proteins

Bacteria

Virus

Activation of complement system


and pore formation

MAC

Pore
Soluble
antigens

Bacterium

Enhances
Phagocytosis

Macrophage

Foreign cell

Leads to
Cell lysis

A primary immune response is the


response that occurs after a harmful
antigen has been encountered for the first
time.

In a primary immune response, the binding


of an antigen to a mature lymphocyte
induces the lymphocytes proliferation
and differentiation, a process called
clonal selection.

Clonal selection of B cells generates a


clone of short-lived activated
effector cells and a clone of longlived memory cells.
B cells that
differ in
antigen
specificity

Antigen molecules

Antigen
receptor

Antigen molecules
bind to the antigen
receptors of only one
of the three B cells
shown.

The selected B cell


proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.
Some proliferating cells
develop into long-lived
Antibody
memory cells that can
molecules
respond rapidly upon
subsequent exposure
to the same antigen. Clone of memory cells

Clone of plasma cells

Some proliferating
cells develop into
short-lived plasma
cells that secrete
antibodies specific
for the antigen.

The secondary immune response is a


much quicker and more effective response
that occurs after a previously encountered
antigen reappears.

In the secondary immune response,


memory cells facilitate a faster, more
efficient response.
Day 1: First
exposure to
antigen A

Primary
response to
antigen A
produces antibodies to A

Day 28:
Second exposure
to antigen A; first
exposure to
antigen B

Secondary response to antigen A produces antibodies


to A; primary response to antigen B produces antibodies to B

104
Antibody concentration
(arbitrary units)

103

102

Antibodies
to A

Antibodies
to B

101

100
0

14

21

28

35

Time (days)

42

49

56

Immunization
1. Vaccines

provide antigen
to which immune
system responds
2. Pathogens or
pathogen
products treated
to remove
virulence

Passive
Immunity

Occurs when an
individual is given
prepared antibodies
(immunoglobins) to
combat a disease
-Short-lived
-Newborns are
often passively
immune due to
mothers blood &
milk

Immunity Side Effects


Tissue Rejection
Antibodies and cytotoxic T cells bring
about destruction of foreign tissues in
the body
Immune system is correctly
distinguishing between self and
nonself

Autoimmune Diseases
Cytotoxic T cells or antibodies
mistakenly attack the bodys own
cells

Autoimmune Diseases result as an


attack on tissues by bodys own
antibodies and T cells. It is the bodies
INABILITY to distinguish self from non-self.

Type 1 Diabetes: an autoimmune


disease that results in the destruction of
insulin-producing cells of the pancreas.

Type 2 Diabetes: diet-related insulin


resistance brought on by too much
sugar in the diet and lack of exercise.

Autoimmune Diseases
Lupus - a chronic
inflammatory
disease that occurs
when your body's
immune system
attacks your own
tissues and organs
There are no
cures for
autoimmune
diseases but they

A summary of innate and acquired


immunity:
INNATE IMMUNITY
Rapid responses to a
broad range of microbes

External defenses

Invading
microbes
(pathogens)

ACQUIRED IMMUNITY
Slower responses to
specific microbes

Internal defenses

Skin

Phagocytic cells

Mucous membranes

Antimicrobial proteins

Secretions

Inflammatory response
Natural killer cells

Humoral response
(antibodies)
Cell-mediated response
(cytotoxic
lymphocytes)

Learning Objectives:
LO 2.29 The student can create
representations and models to
describe immune responses. [See SP
1.1, 1.2]
LO 2.30 The student can create
representations or models to
describe nonspecific immune
defenses in plants and animals.[See
SP 1.1, 1.2]

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