Disturbances

IN
Inflammatory
and
Immunologic
FUNCTIONING

by:
Joanne T. Tolentino, RN
 Overview of Immune System

• Central and Peripheral Lymphoid System

Primary
Secondary

• Immune Function
• Defenses

A. Innate Immunity
 Barriers
 Defensive cells
 Chemical defenses

B. Adaptive Immunity
 Cell mediated immunity
 Antibody mediated immunity
• Types of Immunity
1. Active immunity
2. Passive immunity
 THE IMMUNE SYSTEM
We all get sick sometimes...but then we
get better.

What happens when we get sick?

Why do we get better?

 Immune/ Lymphatic
System

A collection of cells and proteins

that works together to protect
the body from harmful/
infectious micro organisms
 Parts of Lymphatic System
• Lymph—the tissue fluid that enters lymph
capillaries

• Lymph Vessels are found in most tissue

spaces; collect tissue fluid and proteins

• Lymphatic tissue consists mainly of

lymphocytes
• The immune system is localized
in several parts of the body
–immune cells develop in the
primary organs - bone
marrow and thymus
–immune responses occur in
the secondary organs
Primary Lymphatic Organs

• Thymus –
glandular organ
near the heart –
where T cells
learn their jobs
• Bone marrow – blood-
producing tissue
located inside certain
bones

– blood stem cells give rise

to all of the different types
of blood cells
Secondary Lymphatic Organs

• Lymph Nodes—encapsulated masses of

lymphatic tissue

• Lymph Nodules—small unencapsulated

masses of lymphatic tissue

• Spleen—located in the upper left

abdominal quadrant behind the stomach
 Interstitial fluid
Adenoid

Tonsil

Blood
Lymph capillary
nodes

Spleen Tissue Lymphatic

cells vessel
Peyer’s patches
(small intestine)
Appendix

Lymphatic
vessels Lymph Masses of
node defensive cells
Immunity

may be defined as the ability to

destroy pathogens or other
foreign material and to prevent
further cases of certain
infectious diseases.
 YOUR ACTIVE IMMUNE
DEFENSES

Adaptive Immunity
Innate Immunity - variable (custom)
- later, highly specific
- invariant (generalized)
- ‘‘remembers’’ infection
- early, limited specificity
- the first line of defense
 Pathogens
(microorganisms
and viruses)

INNATE IMMUNITY Barrier defenses:

Skin
• Recognition of traits Mucous membranes
shared by broad ranges Secretions
of pathogens, using a
small set of receptors
Internal defenses:
•Rapid response Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells

ACQUIRED IMMUNITY Humoral response:

Antibodies defend against
• Recognition of traits infection in body fluids.
specific to particular
pathogens, using a vast Cell-mediated response:
array of receptors Cytotoxic lymphocytes defend
against infection in body cells.
•Slower response
 INNATE IMMUNITY
When you were born, you brought with you several
mechanisms to prevent illness. This type of immunity
is also called nonspecific immunity.

Innate immunity consists of:

• Barriers

• Defensive cells

• Chemical defenses
 INNATE IMMUNITY
Barriers

• Physical • Chemical

– skin – sweat
– hair – tears
– mucous – saliva
– stomach acid
– urine
Defensive cells

• Phagocytes—macrophages, neutrophils,
eosinophils

• Langerhans cells and other dendritic cells

• Natural killer cells

• Basophils and mast cells

Phagocytic cells include:

Macrophages engulf pathogens and dead cell remains

Neutrophils release chemicals that kill nearby bacteria

• pus = neutrophils, tissue cells and dead
pathogens
 Phagocyte migration

CELLS alive!

Neutrophils and macrophages recognize

chemicals produced by bacteria in a cut or
scratch and migrate "toward the smell".
Macrophages

• WBCs that ingest bacteria, viruses, dead

cells, dust

• most circulate in the blood, lymph and

extracellular fluid

• Macrophages, both fixed and wandering,

have receptors for the pathogens humans are
likely to encounter
Macrophage and E. coli
 Macrophage ingesting yeast

This human macrophage, like the neutrophil, is a

professional "phagocyte" or eating cell (phago="eating",
cyte = "cell"). Here, it envelops cells of a yeast, Candida
albicans. After ingestion, the white cell must kill the
organisms by some means, such as the oxidative burst.
Neutrophils

• WBCs – are phagocytic, like

macrophages

• neutrophils also release toxic chemicals

that destroy everything in the area,
including the neutrophils themselves
 Neutrophil phagocytosing S. pyogenes,
the cause of strep throat

Human neutrophils are WBCs that arrive quickly at the site of

a bacterial infection and whose primary function is to eat and
kill bacteria. This neutrophil ingesting Streptococcus
pyogenes was imaged in gray scale with phase contrast optics
and colorized.
 Neutrophil killing yeast

NEUTROPHIL
↓
YEAST →

One way that neutrophils kill is by producing an anti-

bacterial compound called “superoxide anion“, a process
called oxidative burst. Here, an amoeboid human
neutrophil senses, moves toward and ingests an ovoid
yeast. In the next two panels, oxidation can be seen by
using a dye, and is colorized here.
•Langerhans cells and other dendritic cells
—activate lymphocytes

• Natural killer cells—destroy foreign cells by

rupturing their cell membranes

• Basophils and mast cells—produce

histamine and leukotrienes (inflammation)
Chemical defenses

• Interferon blocks viral reproduction

• Complement proteins lyse foreign cells,

attract WBCs, & contribute to inflammation

• Inflammation
 Types of Inflammation

• Acute inflammation

• Chronic inflammation
 Acute Inflammation

• the early (almost immediate) response

to injury

• It is nonspecific and may be evoked by

any injury short of one that is immediately
fatal.
 The Inflammatory Response

The cardinal signs of inflammation

Heat (calor)
redness (rubor)
swelling (tumor)
pain (dolor)
loss of function (functio laesa)
The manifestation of acute
inflammation can be divided
into two categories:

•vascular response

•cellular responses
Vascular Response
immediate vascular changes that occur
(vasodilation and increased capillary permeability)

Three Patterns of Response

1. immediate transient response

2. immediate sustained response

3. delayed hemodynamic response

Vascular and Surrounding Tissues at Steady
State
Inflammation
The Cellular Stage

•marked by movement of phagocytic white blood

cells (leukocytes) into the area of injury.

• two types of leukocytes participate in the acute

inflammatory response—the granulocytes and
monocytes.
The sequence of events in the cellular
response to inflammation includes:

(1) pavementing
(2) emigration
(3) chemotaxis
(4) phagocytosis
Phagocytosis involves three
distinct steps:

(1) adherence plus opsonization

(2) Engulfment
(3) intracellular killing
Phagocytosis
Inflammatory Mediators

•Histamine
•Plasma Proteases
•Prostaglandins
•Leukotrienes
•Platelet-Activating Factor
Chronic Inflammation

 is self perpetuating and may last for weeks,

months, or even years

it may develop during a recurrent or progressive

acute inflammatory process

characterized by an infiltration by mononuclear

cells (macrophages) and lymphocytes
Healing of a skin wound by primary
and secondary intention

(A) The inflammatory phase

(B) The proliferative phase
(C) Remodeling stage
• Your mom’s antibodies were effective for
just a short time at birth, but your innate
immune system can be activated
quickly. It is always your first line of
defense during an infection, but it can’t
always eliminate the germ.
• When this happens, your body initiates a
focused attack against the specific
pathogen that is causing the infection.
This attack may lead to long-term
protection against that pathogen.
• This type of immunity is called adaptive
immunity, the customized second line
of defense.
• Acquired immunity, or adaptive
immunity, develops after exposure to
agents such as microbes, toxins, or other
foreign substances
• It involves a very specific response to
pathogens
Acquired Immunity: An Overview
• B cells and T cells have receptor proteins
that can bind to foreign molecules
• Each individual lymphocyte is specialized
to recognize a specific type of molecule
 STARTING AN IMMUNE
RESPONSE
Foreign invaders - viruses, bacteria, allergens, toxins
and parasites - constantly bombard our body.

↓ ↓ ↓ ↓ ↓
↓

The response to this assault is a carefully orchestrated and

controlled interaction between immune cells with the ultimate
goal to eliminate the invader by pathogen-specific mechanisms.
 Antigen Recognition by
Lymphocytes

• An antigen is any foreign molecule to

which a lymphocyte responds
• A single B cell or T cell has about
100,000 identical antigen receptors
 Antigen- Antigen- Antigen-
binding binding site binding
site site

V
V
Disulfide
bridge
C
Variable

V
regions V V

V
C C Constant C C
regions

C
Light
chain
Transmembrane
region

Plasma
membrane
Heavy chains α chain β chain
Disulfide bridge
B cell Cytoplasm of B cell Cytoplasm of T cell T cell

a) B cell receptor (b) T cell receptor

 Antigen- Antigen-
binding binding site
site

V
Disulfide

V
bridge

V
Variable

V
regions
Constant
C C

C
regions
Light
chain
Transmembrane
region

Plasma
membrane
Heavy chains

B cell Cytoplasm of B cell

(a) B cell receptor

 Antigen-
binding
site

Variable
regions V V
Constant
C C
regions

Transmembrane
region

Plasma
membrane
α chain β chain
Disulfide bridge
Cytoplasm of T cell T cell

(b) T cell receptor

• All antigen receptors on a single
lymphocyte recognize the same epitope,
or antigenic determinant, on an antigen

• B cells give rise to plasma cells, which

secrete proteins called antibodies or
immunoglobulins
 Antigen-
binding Epitopes
sites (antigenic
determinants)
Antigen-binding sites
V

Antibody A Antigen Antibody C

V

V
C

C C
C

Antibody B
The Antigen Receptors of B Cells and T
Cells
• B cell receptors bind to specific, intact antigens

• The B cell receptor consists of two identical heavy

chains and two identical light chains

• The tips of the chains form a constant (C) region,

and each chain contains a variable (V) region, so
named because its amino acid sequence varies
extensively from one B cell to another
• Secreted antibodies, or immunoglobulins, are structurally
similar to B cell receptors but lack transmembrane
regions that anchor receptors in the plasma membrane
• Each T cell receptor consists of two
different polypeptide chains
• The tips of the chain form a variable (V)
region; the rest is a constant (C) region
• T cells can bind to an antigen that is free
or on the surface of a pathogen
• T cells bind to antigen fragments presented on a host
cell
• These antigen fragments are bound to cell-surface
proteins called MHC molecules
• MHC molecules are so named because they are
encoded by a family of genes called the major
histocompatibility complex
 The Role of the MHC
• In infected cells, MHC molecules bind and
transport antigen fragments to the cell surface, a
process called antigen presentation

• A nearby T cell can then detect the antigen

fragment displayed on the cell’s surface

• Depending on their source, peptide antigens are

handled by different classes of MHC molecules
 Fig. 43-11

Top view: binding surface

exposed to antigen receptors

Antigen
Class I MHC Antigen
molecule

Plasma
membrane of
infected cell
• Class I MHC molecules are found on almost
all nucleated cells of the body

• They display peptide antigens to cytotoxic T

cells
 Fig. 43-12

nfected cell Microbe Antigen-

1 Antigen presenting
associates cell
with MHC
Antigen molecule
ragment Antigen
fragment
1
1
Class I MHC Class II MHC
molecule 2 molecule
2
T cell T cell
2 T cell receptor
eceptor
recognizes
combination

(a) Cytotoxic T cell (b) Helper T cell

• Class II MHC molecules are located mainly on dendritic cells,
macrophages, and B cells

• Dendritic cells, macrophages, and B cells are antigen-presenting

cells that display antigens to cytotoxic T cells and helper T cells
 Lymphocyte Development

• The acquired immune system has three

important properties:
– Receptor diversity
– A lack of reactivity against host cells
– Immunological memory
Generation of Lymphocyte Diversity by Gene
Rearrangement

• Differences in the variable region account for

specificity of antigen receptors

• The immunoglobulin (Ig) gene encodes one chain of

the B cell receptor

• Many different chains can be produced from the

same Ig chain gene by rearrangement of the DNA

• Rearranged DNA is transcribed and translated and

the antigen receptor formed
 Fig. 43-13
DNA of undifferentiated B cell
V37 V38 V39 V40 J1 J2 J3 J4 J5 Intron C

1 DNA deleted between randomly selected V and J

segments
DNA of differentiated B cell
V37 V38 V39 J5 Intron C

Functional gene

2 Transcription

pre-mRNA V39 J5 Intron C

3 RNA processing

B cell receptor
mRNA Cap V39 J5 C Poly-A tail
V V
V V
4 Translation
C C

C C
Light-chain polypeptide V C

Variable Constant
region region B cell
 Origin of Self-Tolerance
• Antigen receptors are generated by random
rearrangement of DNA

• As lymphocytes mature in bone marrow or the

thymus, they are tested for self-reactivity

• Lymphocytes with receptors specific for the body’s

own molecules are destroyed by apoptosis, or
rendered nonfunctional
 Amplifying Lymphocytes by Clonal
Selection
• In the body there are few lymphocytes with antigen
receptors for any particular epitope

• The binding of a mature lymphocyte to an antigen

induces the lymphocyte to divide rapidly

• This proliferation of lymphocytes is called clonal

selection

• Two types of clones are produced: short-lived

activated effector cells and long-lived memory
cells
Fig. 43-14
Antigen molecules

B cells that
differ in
antigen
specificity Antigen
receptor

Antibody
molecules

Clone of memory cells Clone of plasma cells

• The first exposure to a specific antigen represents the
primary immune response

• During this time, effector B cells called plasma cells are

generated, and T cells are activated to their effector forms

• In the secondary immune response, memory cells

facilitate a faster, more efficient response
Primary immune response Secondary immune response to
to antigen A produces antigen A produces antibodies to A;
antibodies to A. primary immune response to antigen
B produces antibodies to B.

104
Antibody concentration
(arbitrary units)

103
Antibodies
to A
102 Antibodies
to B

101

100
0 7 14 21 28 35 42 49 56

Exposure Exposure to
to antigen A antigens A and B
Time (days)
 Acquired immunity defends against
infection of body cells and fluids
• Acquired immunity has two branches: the humoral
immune response and the cell-mediated immune
response

• Humoral immune response involves activation

and clonal selection of B cells, resulting in
production of secreted antibodies
• Cell-mediated immune response involves
activation and clonal selection of cytotoxic T cells
• Helper T cells aid both responses
Fig. 43-16
Humoral (antibody-mediated) immune response Cell-mediated immune response

Key
Antigen (1st exposure)
+ Stimulates
Engulfed by Gives rise to

Antigen-
+ presenting cell +

B cell + Helper T cell Cytotoxic T cell

+

Memory
Helper T cells

+ + +

Antigen (2nd exposure)

+ Memory Active
Plasma cells Memory B cells Cytotoxic T cells Cytotoxic T cells

Secreted
antibodies

Defend against extra cellular pathogens by binding to antigens, Defend against intracellular pathogens
thereby neutralizing pathogens or making them better targets and cancer by binding to and lysing the
for phagocytes and complement proteins. infected cells or cancer cells.
 Humoral (antibody-mediated) immune response
Key Antigen (1st exposure)
+ Stimulates Engulfed by
Gives rise to
Antigen-
+ presenting cell

B cell Helper T cell

+

Memory
Helper T cells

+ +
Antigen (2nd exposure)
Memory +
Plasma cells
B cells

Secreted
antibodies

Defend against extracellular pathogens

 Cell-mediated immune response
Antigen (1st exposure) Key
+ Stimulates
Engulfed by
Gives rise to
Antigen-
presenting cell
+

Helper T cell Cytotoxic T cell

+

Memory
Helper T cells

+ +
Antigen (2nd exposure)
Active
+ Cytotoxic T cells

Memory
Cytotoxic T cells

Defend against intracellular pathogens

 Helper T Cells: A Response to
Nearly All Antigens

• A surface protein called CD4 binds the class II

MHC molecule
• This binding keeps the helper T cell joined to the
antigen-presenting cell while activation occurs
• Activated helper T cells secrete cytokines that
stimulate other lymphocytes
 Antigen-
presenting Peptide antigen
cell
Bacterium

Class II MHC molecule

CD4
TCR (T cell receptor)
Helper T cell
Cytokines +
Humoral +
immunity Cell-mediated
(secretion of immunity
+ +
antibodies by (attack on
plasma cells) B cell Cytotoxic T cell infected cells)
 Cytotoxic T Cells: A Response
to Infected Cells
• Cytotoxic T cells are the effector cells in cell-
mediated immune response
• Cytotoxic T cells make CD8, a surface protein that
greatly enhances interaction between a target cell
and a cytotoxic T cell
• Binding to a class I MHC complex on an infected
cell activates a cytotoxic T cell and makes it an
active killer
• The activated cytotoxic T cell secretes proteins
that destroy the infected target cell
 Cytotoxic T cell

Perforin
Granzymes

CD8 TCR
lass I MHC
olecule

arget Peptide
ell antigen
 Cytotoxic T cell

Perforin
Granzymes

CD8 TCR
lass I MHC Pore
olecule

arget Peptide
ell antigen
 Released cytotoxic T cell
Cytotoxic T cell

Perforin
Granzymes

CD8 TCR Dying target cell

lass I MHC Pore
olecule

arget Peptide
ell antigen
 B Cells: A Response to
Extracellular Pathogens
• The humoral response is characterized by
secretion of antibodies by B cells
• Activation of B cells is aided by cytokines and
antigen binding to helper T cells
• Clonal selection of B cells generates antibody-
secreting plasma cells, the effector cells of
humoral immunity
Antigen-presenting cell Bacterium

Peptide
antigen

ass II MHC
olecule
TCR CD4

Helper T cell
Antigen-presenting cell Bacterium

Peptide B cell
antigen

ass II MHC
olecule +
TCR CD4 Cytokines

Activated
Helper T cell helper T cell
Antigen-presenting cell Bacterium

Peptide B cell
antigen

ass II MHC
olecule + Clone of plasma cells Secreted
antibody
TCR CD4 Cytokines molecules

Activated
Helper T cell helper T cell Clone of memory
B cells
ntigen-presenting cell Bacterium

Peptide B cell
antigen

ass II MHC
olecule + Clone of plasma cells Secreted
antibody
TCR CD4 Cytokines molecules
Endoplasmic
reticulum of
plasma cell
Activated
Helper T cell helper T cell Clone of memory
B cells

2 µm
 Antibody Classes
• The five major classes of antibodies, or
immunoglobulins, differ in distribution and function

• Polyclonal antibodies are the products of many

different clones of B cells following exposure to a
microbial antigen

• Monoclonal antibodies are prepared from a

single clone of B cells grown in culture
 Class of Immuno-
Distribution Function
globulin (Antibody)

IgG Most abundant Ig Promotes opsoniza-

(monomer) class in blood; tion, neutralization,
also present in and cross-linking of
tissue fluids antigens; less effec-
tive in activation of
complement system
than IgM

Only Ig class that

crosses placenta,
thus conferring
passive immunity
on fetus
 Class of Immuno-
Distribution Function
globulin (Antibody)

IgA Present in Provides localized

(dimer) secretions such defense of mucous
as tears, saliva, membranes by
mucus, and cross-linking and
J chain breast milk neutralization of
antigens

Presence in breast
milk confers
Secretory passive immunity
component on nursing infant
 Class of Immuno-
Distribution Function
globulin (Antibody)

IgM First Ig class Promotes neutraliza-

(pentamer) produced after tion and cross-
initial exposure to linking of antigens;
antigen; then its very effective in
concentration in complement system
the blood declines activation
J chain
 Class of Immuno-
Distribution Function
globulin (Antibody)

IgE Present in blood Triggers release from

(monomer) at low concen- mast cells and
trations basophils of hista-
mine and other
chemicals that cause
allergic reactions
 Class of Immuno-
Distribution Function
globulin (Antibody)

IgD Present primarily Acts as antigen

(monomer) on surface of receptor in the
B cells that have antigen-stimulated
not been exposed proliferation and
to antigens differentiation of
B cells (clonal
Trans- selection)
membrane
region
 The Role of Antibodies in
Immunity
• Neutralization occurs when a pathogen can no
longer infect a host because it is bound to an
antibody

• Opsonization occurs when antibodies bound to

antigens increase phagocytosis

• Antibodies together with proteins of the

complement system generate a membrane attack
complex and cell lysis
Viral neutralization

Virus
Fig. 43-21b

Opsonization
Bacterium

Macrophage
 Activation of complement system and pore formation

Complement proteins

Formation of
membrane
attack complex

Flow of water
and ions

Pore

Foreign
cell
Viral neutralization Opsonization Activation of complement system and pore formation
Bacterium
Complement proteins
Virus
Formation of
membrane
attack complex

Flow of water
Macrophage and ions

Pore

Foreign
cell
 Active and Passive
Immunization
• Active immunity develops naturally in response to an
infection

• It can also develop following immunization, also called

vaccination

• In immunization, a nonpathogenic form of a microbe or

part of a microbe elicits an immune response to an
immunological memory
• Passive immunity provides immediate, short-
term protection
• It is conferred naturally when IgG crosses the
placenta from mother to fetus or when IgA
passes from mother to infant in breast milk
• It can be conferred artificially by injecting
antibodies into a nonimmune person
Fig. 43-22
How does an immune
response end?

The immune response will end when the antigen that caused the response is no longer present
•
Induction of an immune response to infection
requires several days or weeks
What can you do while you’re waiting???????

• Temporary protection against infection can be

established by giving pre-formed antibody
THE IMMUNE SYSTEM IN
HEALTH AND DISEASE

How does your everyday life affect

your immune system?
 Exercise and stress
• exercise has been shown to boost the immune response
– moderate exercise increases the immune response in all age
groups
– intensive exercise can stress the immune system

• lack of sleep and exhaustion decrease immune function

• psychological stress has also been found to decrease

immune function
 Diet
• a well-balanced diet is essential for good immune
system health
– fats are very important in the production of WBCs, cytokines
and natural killer cells
– selenium, zinc, and copper are required in small amounts,
which you get if you eat a balanced diet
– vitamin E has been shown to boost antibody production in
the elderly
– vitamin B6 aids in antibody synthesis

• but mega-dosing can be harmful, too!

 Environment
Exposure to certain things in their environment may
activate the immune systems of some people

• Chemicals • Viruses
– dioxin
– pesticides
– solvents
• Bacteria
• Sunlight

• Medication • Food
 Gender and the immune
system
• women respond to antigens more strongly than men

• estrogen may affect the development or function of

immune cells

• may explain why more women develop autoimmune

diseases