Disturbances in Inflammatory and Immunologic Function

8/9/2019 Disturbances in Inflammatory and Immunologic Function

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DisturbancesIN

Inflammatory andImmunologicFUNCTIONING

by:

Joanne T. Tolentino, RN



Overview of Immune System

• Central and Peripheral Lymphoid SystemPrimary

Secondary

• Immune Function



• Defenses

A. Innate Immunity

Barriers

Defensive cells Chemical defenses

B. Adaptive Immunity Cell mediated immunity

Antibody mediated immunity



• Types of Immunity1. Active immunity

2. Passive immunity



We all get sick sometimes...but then we

get better.

What happens when we get sick?

Why do we get better?

THE IMMUNE SYSTEM



Immune/ Lymphatic

System

A collection of cells and proteinsthat 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 organnear 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





Adenoid

Tonsil

Lymphnodes

Spleen

Peyer’s patches(small intestine)

Appendix

Lymphaticvessels Lymph

nodeMasses of defensive cells

Bloodcapillary

Lymphatic

vessel

Tissue

cells

Interstitial fluid



Immunity

may be defined as the ability to

destroy pathogens or other

foreign material and to preventfurther cases of certain

infectious diseases.

YOUR ACTIVE IMMUNE



YOUR ACTIVE IMMUNE

DEFENSES

Innate Immunity- invariant (generalized)

- early, limited specificity- the first line of defense

Adaptive Immunity- variable (custom)

- later, highly specific

- ‘‘remembers’’ infection



INNATE IMMUNITY

Recognition of traitsshared by broad rangesof pathogens, using asmall set of receptors

•

•Rapid response

• Recognition of traitsspecific to particular pathogens, using a vastarray of receptors

•Slower response

ACQUIRED IMMUNITY

Pathogens(microorganisms

and viruses)

Barrier defenses:SkinMucous membranesSecretions

Internal defenses:

Phagocytic cellsAntimicrobial proteinsInflammatory responseNatural killer cells

Humoral response:Antibodies defend againstinfection in body fluids.

Cell-mediated response:Cytotoxic lymphocytes defendagainst infection in body cells.



INNATE IMMUNITY

Innate immunity consists of:

• Barriers

• Defensive cells

• Chemical defenses

When you were born, you brought with you several

mechanisms to prevent illness. This type of immunityis also called nonspecific immunity.



INNATE IMMUNITY

Barriers

• Physical

– skin – hair

– mucous

• Chemical

– sweat – tears

– saliva

– stomach acid

– urine

INNATE IMMUNITY

Barriers

• Physical

– skin – hair

– mucous

• Chemical

– sweat – tears

– saliva

– stomach acid

– urine



Defensive cells

• Phagocytes—macrophages, neutrophils,

eosinophils

• Langerhans cells and other dendritic cells

• Natural killer cells

• Basophils and mast cells



Macrophages engulf pathogens and dead cell remains

Neutrophils release chemicals that kill nearby bacteria• pus = neutrophils, tissue cells and dead

pathogens

Phagocytic cells include:



Phagocyte migration

Neutrophils and macrophages recognize

chemicals produced by bacteria in a cut or

scratch and migrate "toward the smell".

CELLS alive!



Macrophages

• WBCs that ingest bacteria, viruses, deadcells, dust

• most circulate in the blood, lymph andextracellular fluid

• Macrophages, both fixed and wandering,

have receptors for the pathogens humans arelikely 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

One way that neutrophils kill is by producing an anti-

bacterial compound called “superoxide anion“, a processcalled 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.

YEAST →

NEUTROPHIL

↓



•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 dividedinto two categories:

•vascular response

•cellular responses



Vascular Responseimmediate 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



Vascular and Surrounding Tissues at SteadyState

InflammationInflammation



InflammationInflammation



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







PhagocytosisPhagocytosis



PhagocytosisPhagocytosis



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 activatedquickly. 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 afocused 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 adaptiveimmunity, 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



RESPONSEForeign 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



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-

bindingsite

Antigen-

binding site

Antigen-

bindingsite

Disulfidebridge

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

Light

chain

Heavy chains

T cell

α chain β chain

Disulfide bridge

Cytoplasm of T cell

(b) T cell receptor

Cytoplasm of B cell

) B cell receptor

B cell

V

V

C

C

V

V

C C C C

VV

Antigen- Antigen-



gbindingsite

binding site

Disulfidebridge

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

Light

chain

Heavy chains

Cytoplasm of B cell

a) B cell receptor

B cell

V

V

C

C

V V

C C

Antigen-



bindingsite

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

T cell

α chain β chain

Disulfide bridge

Cytoplasm of T cell

(b) T cell receptor

C C

VV



•All antigen receptors on a singlelymphocyte 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 sites

Antigen-bindingsites

Epitopes(antigenicdeterminants)

Antigen

Antibody B

Antibody CAntibody A

CC C

V

V

V

V

C

The Antigen Receptors of B Cells and



The Antigen Receptors of B Cells and

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 variesextensively from one B cell to another



• Secreted antibodies, or immunoglobulins, are structurally

similar to B cell receptors but lack transmembraneregions that anchor receptors in the plasma membrane



•Each T cell receptor consists of twodifferent 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 areencoded by a family of genes called the major

histocompatibility complex

The Role of the MHC



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 antigenfragment displayed on the cell’s surface

• Depending on their source, peptide antigens arehandled by different classes of MHC molecules

Fig. 43-11



Antigen

Top view: binding surfaceexposed to antigen receptors

Plasmamembrane of infected cell

Antigenlass I MHColecule



• Class I MHC molecules are found on almost

all nucleated cells of the body

• They display peptide antigens to cytotoxic Tcells

Fig. 43-12



fected cell

ntigenragment

lass I MHColecule

celleceptor

a)

Antigen

associateswith MHCmolecule

T cellrecognizescombination

Cytotoxic T cell (b) Helper T cell

T cellreceptor

Class II MHCmolecule

Antigenfragment

Antigen-presenting

cell

Microbe

1

11

2

22



• 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

G ti f L h t Di it b G



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. 43-13DNA of undifferentiated B cell

V V V V J J J J CJ I t



1

DNA of differentiated B cell

pre-mRNA

mRNA

Light-chain polypeptide

Variableregion

Constantregion

Translation

B cell

B cell receptor

RNA processing

Transcription

DNA deleted between randomly selected V and J

segments

Functional gene

V 37 V 38 V 39 V 40 J 1 J 2 J 3 J 4 C J 5 Intron

V 37 V 38 V 39 C J 5 Intron

V 39 C J 5 Intron

V 39 C J 5 Poly-A tailCap

C V

VV

VV

C C

C C

2

3

4



Origin of Self-Tolerance

• Antigen receptors are generated by randomrearrangement of DNA

• As lymphocytes mature in bone marrow or thethymus, 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



p y g y p y y

Selection

• In the body there are few lymphocytes with antigenreceptors 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-livedactivated effector cells and long-lived memory

cells

Fig. 43-14Antigen molecules



B cells thatdiffer inantigen

specificity

Antibodymolecules

Antigenreceptor

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

Secondary immune response toantigen A produces antibodies to A;

Primary immune responseto antigen A produces



Antibodiesto A

Antibodiesto B

g p ;

primary immune response to antigen

B produces antibodies to B.

g p

antibodies to A.

Antibody

con

centrat io

n

(arbitraryunit

s)

Exposureto antigen A

Exposure toantigens A and B

Time (days)

104

103

102

101

100

0 7 14 21 28 35 42 49 56

Acquired immunity defends against



infection of body cells and fluids

• Acquired immunity has two branches: the humoralimmune response and the cell-mediated immuneresponse

• Humoral immune response involves activationand clonal selection of B cells, resulting inproduction of secreted antibodies

•Cell-mediated immune response involvesactivation and clonal selection of cytotoxic T cells

• Helper T cells aid both responses

Fig. 43-16Humoral (antibody-mediated) immune response Cell-mediated immune response

Key



B cell

Plasma cells

Key

Stimulates

Gives rise to

+

+

++

+

+

+Memory B cells

Antigen (1st exposure)

Engulfed by

Antigen-

presenting cell

Memory

Helper T cells

Helper T cell Cytotoxic T cell

Memory

Cytotoxic T cells

Active

Cytotoxic T cells

Antigen (2nd exposure)

Secreted

antibodies

Defend against extra cellular pathogens by binding to antigens,thereby neutralizing pathogens or making them better targetsfor phagocytes and complement proteins.

Defend against intracellular pathogensand cancer by binding to and lysing theinfected cells or cancer cells.

+

+ +

Key Antigen (1st exposure)

Humoral (antibody-mediated) immune response



Stimulates

Gives rise to

+

MemoryHelper T cells

Antigen-presenting cell

Helper T cell

Engulfed by

+

+

+

+ +

+

Defend against extracellular pathogens

Memory

B cells


Plasma cells

B cell

Secretedantibodies

Cell-mediated immune response

Antigen (1st exposure) Key



Defend against intracellular pathogens

ActiveCytotoxic T cells

MemoryCytotoxic T cells

MemoryHelper T cells

Antigen-presenting cell


Helper T cell

Engulfed by

g ( p )

Cytotoxic T cell

Stimulates

Gives rise to

+

+

+

+

+ +

+

Helper T Cells: A Response to



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-presentingcell

Peptide antigen

Cell-mediated

immunity

(attack on

infected cells)

Class II MHC molecule

CD4

TCR (T cell receptor)

Helper T cell

Humoral

immunity

(secretion of

antibodies by

plasma cells) Cytotoxic T cell

Cytokines

B cell

Bacterium

+

+ +

+

Cytotoxic T Cells: A Response



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 celland a cytotoxic T cell

• Binding to a class I MHC complex on an infectedcell activates a cytotoxic T cell and makes it an

active killer

• The activated cytotoxic T cell secretes proteinsthat destroy the infected target cell



Cytotoxic T cell

Perforin

Granzymes

TCRCD8

ass I MHClecule

rgetll

Peptideantigen



Cytotoxic T cell

Perforin

Granzymes

TCRCD8

ass I MHClecule

rgetll

Peptideantigen

Pore



Cytotoxic T cell

Perforin

Granzymes

TCRCD8

ass I MHClecule

rgetll

Peptideantigen

Pore

Released cytotoxic T cell

Dying target cell

B Cells: A Response to



p

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



ntigen-presenting cell Bacterium

Peptide

antigen

ass II MHC

lecule

TCR CD4

Helper T cell




Peptide

antigen

ass II MHC

lecule

TCR CD4

Helper T cell

B cell

Activated

helper T cell

Cytokines

+




Peptide

antigen

ass II MHC

lecule

TCR CD4

Helper T cell

B cell

Activated

helper T cell

Cytokines

+ Secreted

antibodymolecules

Clone of memory

B cells

Clone of plasma cells



tigen-presenting cell

Endoplasmicreticulum of plasma cell

Secretedantibodymolecules

Bacterium

B cellPeptideantigen

ass II MHClecule

TCR CD4

Helper T cellActivated

helper T cell

Cytokines

Clone of memory

B cells

Clone of plasma cells

2 µm

+

Antibody Classes



Antibody Classes

• The five major classes of antibodies, or immunoglobulins, differ in distribution and function

• Polyclonal antibodies are the products of manydifferent clones of B cells following exposure to a

microbial antigen

• Monoclonal antibodies are prepared from a

single clone of B cells grown in culture



Distribution FunctionClass of Immuno-

globulin (Antibody)

IgG

(monomer)

Most abundant Igclass in blood;also present intissue fluids

Promotes opsoniza-tion, neutralization,and cross-linking of antigens; less effec-

tive in activation of complement systemthan IgM

Only Ig class that

crosses placenta,thus conferringpassive immunityon fetus




globulin (Antibody)

IgA

(dimer)

J chain

Secretory

component

Present insecretions suchas tears, saliva,mucus, andbreast milk

Provides localizeddefense of mucousmembranes bycross-linking andneutralization of antigens

Presence in breast

milk conferspassive immunityon nursing infant



DistributionClass of Immuno-

globulin (Antibody)

IgM

(pentamer)

J chain

First Ig classproduced after initial exposure toantigen; then itsconcentration inthe blood declines

Promotes neutraliza-tion and cross-linking of antigens;very effective incomplement systemactivation

Function




globulin (Antibody)

IgE

(monomer)

Present in blood

at low concen-trations

Triggers release from

mast cells andbasophils of hista-mine and other chemicals that causeallergic reactions



Distribution FunctionClass of Immuno-globulin (Antibody)

IgD

(monomer)

Trans-membraneregion

Present primarilyon surface of

B cells that havenot been exposedto antigens

Acts as antigenreceptor in the

antigen-stimulatedproliferation anddifferentiation of B cells (clonalselection)

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

Virus

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

Active and Passive



Immunization

• Active immunity develops naturally in response to an

infection

• It can also develop following immunization, also calledvaccination

• 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



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 beestablished by giving pre-formed antibody

THE IMMUNE SYSTEM IN



THE IMMUNE SYSTEM IN

HEALTH AND DISEASE

How does your everyday life affectyour 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 B6aids in antibody synthesis

• but mega-dosing can be harmful, too!

Environment



Environment

• Chemicals

– dioxin

– pesticides

– solvents

• Sunlight

• Medication

• Viruses

• Bacteria

• Food

Exposure to certain things in their environment may

activate the immune systems of some people

Gender and the immune



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

Documents

Disturbances in Inflammatory and Immunologic Function