33918519 disturbances in inflammatory and immunologic function

7/30/2019 33918519 Disturbances in Inflammatory and Immunologic Function

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Disturbances

IN

Inflammatoryand

Immunologic

FUNCTIONING

by:Joanne T. Tolentino, RN


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Overview of Immune System

Central and Peripheral Lymphoid SystemPrimary

Secondary

Immune Function


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Defenses

A. Innate Immunity

Barriers

Defensive cells Chemical defenses

B. Adaptive Immunity Cell mediated immunity

Antibody mediated immunity


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Types of Immunity1. Active immunity

2. Passive immunity


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We all get sick sometimes...but then we

get better.

What happens when we get sick?

Why do we get better?

THE IMMUNE SYSTEM


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Immune/ Lymphatic

System

A collection of cells and proteinsthat works together to protect

the body from harmful/infectious micro organisms


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Parts of Lymphatic System

Lymphthe 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


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The immune system is

localized in several parts of thebody

immune cells develop in the

primary organs -bone

marrow and thymus

immune responses occur inthe secondary organs


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Primary Lymphatic Organs

Thymus

glandular organnear the heart

where T cells

learn their jobs


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Secondary Lymphatic Organs

Lymph Nodesencapsulated masses of

lymphatic tissue

Lymph Nodulessmall unencapsulated

masses of lymphatic tissue

Spleenlocated in the upper left

abdominal quadrant behind the stomach


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Adenoid

Tonsil

Lymphnodes

Spleen

Peyers patches(small intestine)

Appendix

Lymphaticvessels Lymph

nodeMasses ofdefensive cells

Bloodcapillary

Lymphatic

vessel

Tissue

cells

Interstitial fluid


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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


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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


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INNATE IMMUNITY

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

Rapid response

Recognition of traitsspecific to particularpathogens, 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.


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INNATE IMMUNITY

Innate immunity consists of:

Barriers

Defensive cells

Chemical defenses

When you were born, you brought with you several

mechanisms to prevent illness. Thistype of immunityis also callednonspecificimmunity.


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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


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Defensive cells

Phagocytesmacrophages, neutrophils,

eosinophils

Langerhans cells and other dendritic cells

Natural killer cells

Basophils and mast cells


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Macrophagesengulf pathogens and dead cell remains

Neutrophilsrelease chemicals that kill nearby bacteria pus = neutrophils, tissue cells and dead

pathogens

Phagocytic cells include:


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Phagocytemigration

Neutrophils and macrophages recognize

chemicals produced by bacteria in a cut or

scratch and migrate "toward the smell".

CELLS alive!


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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


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Macrophage and E. coli


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Neutrophil phagocytosing S. pyogenes,

the cause of strep throat

Human neutrophils are WBCs that arrive quickly at the site ofa 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.


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Neutrophil killing yeast

One way that neutrophils kill is by producing an anti-

bacterial compound called superoxideanion, 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


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Langerhans cells and other dendritic cellsactivate lymphocytes

Natural killer cellsdestroy foreign cells by

rupturing their cell membranes

Basophils and mast cellsproduce

histamine and leukotrienes (inflammation)


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Chemical defenses

Interferon blocks viral reproduction

Complement proteins lyse foreign cells,attract WBCs, & contribute to inflammation

Inflammation


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Types of Inflammation

Acute inflammation

Chronic inflammation


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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.


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The Inflammatory Response

The cardinal signs of inflammation

Heat (calor)

redness (rubor)

swelling (tumor)

pain (dolor)

loss of function (functio laesa)


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The manifestation of acute

inflammation can be dividedinto two categories:

vascular response

cellular responses


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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


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Inflammation


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Inflammation


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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 responsethe granulocytes and

monocytes.


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The sequence of events in the cellular

response to inflammation includes:

(1) pavementing

(2) emigration(3) chemotaxis

(4) phagocytosis


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Phagocytosis involves three

distinct steps:

(1) adherence plus opsonization

(2) Engulfment

(3) intracellular killing


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Phagocytosis


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Phagocytosis


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Inflammatory Mediators

Histamine

Plasma Proteases

Prostaglandins

Leukotrienes

Platelet-Activating Factor


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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


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Healing of a skin wound by primary

and secondary intention

(A) The inflammatory phase

(B) The proliferative phase

(C) Remodeling stage


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Your moms 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 cant 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.


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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


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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


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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


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Antigen-

bindingsite

Antigen-

binding site

Antigen-

bindingsite

Disulfidebridge

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

Light

chain

Heavy chains

T cell

chain chainDisulfide bridge

Cytoplasm of T cell

(b) T cell receptor

Cytoplasm of B cell

(a) B cell receptor

B cell

C C C C

VV

Antigen- Antigen-


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gbindingsite

binding site

Disulfidebridge

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

Light

chain

Heavy chains

Cytoplasm of B cell

(a) B cell receptor

B cell

C C

Antigen-


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bindingsite

Variableregions

Constantregions

Transmembraneregion

Plasmamembrane

T cell

chain chainDisulfide bridge

Cytoplasm of T cell

(b) T cell receptor

C C

VV


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All antigen receptors on a single

lymphocyte recognize the same epitope,

orantigenic determinant, on an antigen

B cells give rise to plasma cells,which

secrete proteins called antibodies or

immunoglobulins


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Antigen-binding sites

Antigen-bindingsites

Epitopes(antigenicdeterminants)

Antigen

Antibody B

Antibody CAntibody A

CC

The Antigen Receptors of B Cells and


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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 varies extensively from one B cell to

another


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Secreted antibodies, or immunoglobulins,

are structurally similar to B cell receptors

but lack transmembrane regions that

anchor receptors in the plasma

membrane


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Each T cell receptorconsists 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


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The Role of the MHC


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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 cells surface

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

Fig. 43-11


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Antigen

Top view: binding surfaceexposed to antigen receptors

Plasmamembrane ofinfected cell

AntigenClass I MHCmolecule


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Class I MHC molecules are found on almost

all nucleated cells of the body

They display peptide antigens to cytotoxic Tcells

Fig. 43-12


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Infected cell

Antigenfragment

Class I MHCmolecule

T cellreceptor

(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


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Fig. 43-13DNA of undifferentiated B cell

V V V V J J J J CJ Intron


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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 Vand J

segments

Functional gene

V37 V38 V39 V40 J1 J2 J3 J4 CJ5 Intron

V37 V38 V39 CJ5 Intron

V39 CJ5 Intron

V39 CJ5 Poly-A tailCap

CV

VV

VV

C C

C C

2

3

4


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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 bodysown molecules are destroyed by apoptosis, or

rendered nonfunctional


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Fig. 43-14Antigen molecules


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B cells thatdiffer inantigen

specificity

Antibodymolecules

Antigenreceptor

Clone of memory cells Clone of plasma cells


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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 cellsare 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


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Antibodiesto A

Antibodiesto B

g p ;

primary immune response to antigen

B produces antibodies to B.

g p

antibodies to A.

Antibody

concentration

(arbitraryunits)

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 againstf f f


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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


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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


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Stimulates

Gives rise to

+

MemoryHelper T cells

Antigen-presenting cell

Helper T cell

Engulfed by

+

+

+

+ +

+

Defend against extracellular pathogens

Memory

B cells

Antigen (2nd exposure)

Plasma cells

B cell

Secretedantibodies


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Helper T Cells: A Response to


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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


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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


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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


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Cytotoxic T cell

Perforin

Granzymes

TCRCD8

Class I MHCmolecule

Targetcell

Peptideantigen

Pore


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Cytotoxic T cell

Perforin

Granzymes

TCRCD8

Class I MHCmolecule

Targetcell

Peptideantigen

Pore

Released cytotoxic T cell

Dying target cell

B Cells: A Response to


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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


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Antigen-presenting cell Bacterium

Peptide

antigen

Class II MHC

molecule

TCR CD4

Helper T cell

B cell

Activated

helper T cell

Cytokines

+ Secreted

antibodymolecules

Clone of memory

B cells

Clone of plasma cells


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Antigen-presenting cell

Endoplasmicreticulum ofplasma cell

Secretedantibodymolecules

Bacterium

B cellPeptideantigen

Class II MHCmolecule

TCR CD4

Helper T cellActivated

helper T cell

Cytokines

Clone of memory

B cells

Clone of plasma cells

2 m

+

Antibody Classes


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Antibody Classes

The five major classes of antibodies, orimmunoglobulins, 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

Cl f I


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Distribution FunctionClass of Immuno-

globulin (Antibody)

IgG

(monomer)

Most abundant Igclass in blood;also present intissue fluids

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

tive in activation ofcomplement systemthan IgM

Only Ig class that

crosses placenta,thus conferringpassive immunityon fetus


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globulin (Antibody)

IgA

(dimer)

J chain

Secretory

component

Present insecretions suchas tears, saliva,mucus, andbreast milk

Provides localizeddefense of mucousmembranes bycross-linking andneutralization ofantigens

Presence in breast

milk conferspassive immunityon nursing infant


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DistributionClass of Immuno-

globulin (Antibody)

IgM

(pentamer)

J chain

First Ig classproduced afterinitial exposure toantigen; then itsconcentration inthe blood declines

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

Function


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globulin (Antibody)

IgE

(monomer)

Present in blood

at low concen-trations

Triggers release from

mast cells andbasophils of hista-mine and otherchemicals that causeallergic reactions


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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 ofB cells (clonalselection)

The Role of Antibodies in


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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


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Virus

Fig. 43-21b

Opsonization


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Bacterium

Macrophage

Activation of complement system and pore formation


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Complement proteins

Formation of

membrane

attack complex

Flow of waterand ions

Pore

Foreign

cell


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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


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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 amicrobe or part of a microbe elicits an immune

response to an immunological memory


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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 injectingantibodies into a nonimmune person

Fig. 43-22


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How does an immune


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How does an immune

response end?

The immune response will end when the antigen that

caused the response is no longer present


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Induction of an immune response to infection

requires several days or weeks

What can you do while youre waiting???????

Temporary protection against infection can beestablished by giving pre-formed antibody

THE IMMUNE SYSTEM IN


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THE IMMUNE SYSTEM IN

HEALTH AND DISEASE

How does your everyday life affectyour immune system?


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Exercise and stress

exercise has been shown to boost the immuneresponse moderate exercise increases the immune response in all age

groups

intensive exercise can stress the immune system

lack of sleep and exhaustion decrease immunefunction

psychological stress has also been found to decreaseimmune function


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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


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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


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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

33918519 disturbances in inflammatory and immunologic function

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