Immune BasicsImmune Basics

Peggy D. Peggy D. JohndrowJohndrow

20092009

Immune SystemImmune System

Body defense mechanismsBody defense mechanisms

Body DefensesBody Defenses

Skin, mucus membraneSkin, mucus membrane GI secretionsGI secretions Inflammatory responseInflammatory response Immune response - final defense!Immune response - final defense!

ReviewReview

Inflammatory ProcessInflammatory Process

Inflammatory Response

Any injury stimulates a response no matter what the cause

Inflammatory ProcessInflammatory Process

Response to injury or infection Adaptive mechanism either destroy or

dilute/weaken an injurious agent & prevent further injury

Promotes repair of damaged tissue Cardinal signs of inflammatory response: pain,

swelling, redness, heat, and impaired function Inflammatory agents categorized as physical agent,

chemical agent, or microorganism

5 Cardinal Symptoms 5 Cardinal Symptoms

R ed n essru b or

S w e llin gtu m or

P a ind o lo r

L oss o f F u n c tion

H eatC a lo r

Inflammatory ResponseInflammatory Response

Vascular Fluid Cellular

VasoconstrictThen Vasodilates

Moves intointerstitial spaceswithn 24 hours

WBC's go toaffected tissue

Release histamine,Kinins,hyperemia

Serous, thenprotein losses

Chemotaxis attractmore components

Blood flow slow,capillary dialtesand becomespermeable

Increasemovement intotissue of fluidincreases edema

WBC's move out eatand clean up forhealing. Dead cellsPUS

ImmunologyImmunology

Response to InvasionResponse to Invasion Phagocytic ResponsePhagocytic Response Humoral or Antibody Immune Humoral or Antibody Immune

ResponseResponse Cellular Immune ResponseCellular Immune Response

BloodBlood

Primary source of elements designed to Primary source of elements designed to provide protection against injurious provide protection against injurious agentsagents

Transports to site of injury through Transports to site of injury through vascular changes, concentrate material vascular changes, concentrate material at siteat site

Blood both fluid and cellularBlood both fluid and cellular

Cellular ComponentsCellular Components

Non specific response Non specific response granulocytes(PMN’s)granulocytes(PMN’s)

LymphocytesLymphocytes Monocytes* most Monocytes* most

important phagocytic important phagocytic activityactivity

ThrombocytesThrombocytes Phagocytic WBC’s key Phagocytic WBC’s key

nonspecificnonspecific

Granulocytes enzymes Granulocytes enzymes to digestto digest

Neutrophils most Neutrophils most numerous & responsivenumerous & responsive

Phagocytes constantly Phagocytes constantly available to move to the available to move to the site of injury via blood site of injury via blood streamstream

How do blood cells find injury to How do blood cells find injury to site?site?

Chemotaxis Chemotaxis Attracted to an area by chemicals Attracted to an area by chemicals

released during infection or injuryreleased during infection or injury Cellular response to injuryCellular response to injury Substance released called chemotactic Substance released called chemotactic

substancesubstance

Phagocytic Immune Phagocytic Immune ResponseResponse

Involves WBC’s (granulocytes and Involves WBC’s (granulocytes and macrophages)macrophages)

Special talentsSpecial talents

Ingest foreign proteinsIngest foreign proteins

Move to site where they engulf and Move to site where they engulf and destroy invading agentsdestroy invading agents

Humoral Immune Humoral Immune ResponseResponse

Sometimes called the antibody responseSometimes called the antibody response B lymphocytes transform themselves into plasma B lymphocytes transform themselves into plasma

cells that manufacture antibodies (stimulate the cells that manufacture antibodies (stimulate the production of antibodies)production of antibodies)

Antibodies transported in blood stream and attempt Antibodies transported in blood stream and attempt to disable invadersto disable invaders

Cellular Immune ResponseCellular Immune Response

Involves T lymphocytes which can turn Involves T lymphocytes which can turn into cytoxic or (killer) T cellsinto cytoxic or (killer) T cells

Attack pathogens directlyAttack pathogens directly

Antigen (Immunogens)Antigen (Immunogens)

Substance when introduced into a Substance when introduced into a person elicits formation of antibioties person elicits formation of antibioties (sensitized cells) (sensitized cells)

Must be recognized as foreign within Must be recognized as foreign within the bodythe body

ResponseResponse

Antigen stimulates the production of Antigen stimulates the production of antibodiesantibodies

Examples Examples small patch of protein on outer surface small patch of protein on outer surface

of microorganismof microorganism Single bacterium, Large molecule , toxinSingle bacterium, Large molecule , toxin Have markers on the surface which Have markers on the surface which

induce antibody productioninduce antibody production

Antibody Antibody (immunoglobulins)(immunoglobulins)

Contact with an antigen substance Contact with an antigen substance within the body produces a substances within the body produces a substances called an antibody. called an antibody.

Type of antigen determines immune Type of antigen determines immune responseresponse

Circulating antibodies are called Circulating antibodies are called globulins (blood stream), associated globulins (blood stream), associated with gamma globulin with gamma globulin

AntibodyAntibody

Once antibody produced released into Once antibody produced released into the blood streamthe blood stream

Carried to the attacking organismCarried to the attacking organism Combines with antigen like jigsaw Combines with antigen like jigsaw

puzzlepuzzle To render pathogen harmlessTo render pathogen harmless See Figure 46-3See Figure 46-3

Four Stages of Immune Four Stages of Immune ResponseResponse

Recognition StageRecognition Stage Proliferation StageProliferation Stage Response StageResponse Stage Effector StageEffector Stage

Recognition StageRecognition Stage

Lymph Nodes and lymphocytes survey Lymph Nodes and lymphocytes survey body through the blood streambody through the blood stream

When they encounter foreign material, When they encounter foreign material, macrophages either remove or imprint macrophages either remove or imprint structure(memory)structure(memory)

Body knows it’s own structure (self) Body knows it’s own structure (self) recognizes foreign markers (nonself)recognizes foreign markers (nonself)

Triggers second stage ProliferationTriggers second stage Proliferation

Proliferation StageProliferation Stage

Lymphocyte returns to lymph node with Lymphocyte returns to lymph node with the antigenic messagethe antigenic message

Stimulates T and B lymphocytes to Stimulates T and B lymphocytes to enlarge, divide, and proliferateenlarge, divide, and proliferate

T lymphocytes (cytoxic T killer)T lymphocytes (cytoxic T killer) B lymphocytes stimulate production and B lymphocytes stimulate production and

release of antibodiesrelease of antibodies

ResponseResponse

Changed lymphocytes function either in Changed lymphocytes function either in humoral or celluar fashionhumoral or celluar fashion

HumoralHumoral

B-lymphocytes stimulate the production B-lymphocytes stimulate the production of antibodiesof antibodies

Production of antibodies by B-Production of antibodies by B-lymphocytes in response to an antigen lymphocytes in response to an antigen begins the begins the Humoral ResponseHumoral Response

Humoral refers to the fact antibodies are Humoral refers to the fact antibodies are released into the bloodstream and released into the bloodstream and reside in the circulating plasmareside in the circulating plasma

CellularCellular

Sensitized cells return to lymph nodesSensitized cells return to lymph nodes They stimulate lymphocytes known as They stimulate lymphocytes known as

cytoxic cells (killer) T cellscytoxic cells (killer) T cells Attack microbes directlyAttack microbes directly

Effector StageEffector Stage

Either antibody or (killer) T cells reaches the Either antibody or (killer) T cells reaches the antigen on the surface of the foreign invaderantigen on the surface of the foreign invader

Coupling initiates series of events which Coupling initiates series of events which leads to total destruction of invading microbe leads to total destruction of invading microbe or neutralization of the toxinor neutralization of the toxin

Series of events involve antibodies, Series of events involve antibodies, complement, and action by (killer) T cellscomplement, and action by (killer) T cells

ComplementComplement

Primary role of complement is to provide Primary role of complement is to provide specific lysis of cell membranespecific lysis of cell membrane

Complement is a series of 11 proteinsComplement is a series of 11 proteins Complement works with antibioties which are Complement works with antibioties which are

already bound to rupture the cellalready bound to rupture the cell Serves to complete the action of an AntibodyServes to complete the action of an Antibody Antibody by itself can’t produce cell lysisAntibody by itself can’t produce cell lysis

ComplementComplement

Complement considered nonspecificComplement considered nonspecific Component of plasmaComponent of plasma No immune substance can activateNo immune substance can activate Not increased by immunizationsNot increased by immunizations

Roles of Celluar and Roles of Celluar and Humoral Immune ResponseHumoral Immune Response

Humoral (B Cells)Humoral (B Cells) Bacterial lysis Bacterial lysis AnaphylaxisAnaphylaxis Allergic hay fever and Allergic hay fever and

asthmaasthma Immune complex Immune complex

diseasedisease Bacterial and some viral Bacterial and some viral

infectionsinfections

Cellular (T Cells)Cellular (T Cells) Transplant RejectionTransplant Rejection Delayed hypersensitivity (TB Delayed hypersensitivity (TB

reaction)reaction) Viral, fungal, and parasiticViral, fungal, and parasitic Graft vs host diseaseGraft vs host disease Tumor surveillance or Tumor surveillance or

destructiondestruction Intracellular infectionsIntracellular infections infectionsinfections

B Cells and T CellsB Cells and T Cells

Both B & T Cells role is to recognize Both B & T Cells role is to recognize presence of antigen & initiate disposal presence of antigen & initiate disposal and recognize self Antigen triggers and recognize self Antigen triggers response of events that leads to full response of events that leads to full immunologic responseimmunologic response

Antigen triggers response of events that Antigen triggers response of events that leads to full immunologic responseleads to full immunologic response

HumorallyHumorally

Major immunity against the followingMajor immunity against the following Bacteria producing infection ie. Staph, strep, Bacteria producing infection ie. Staph, strep,

etc.etc. Bacterial endotoxins diptheria, botulinal, Bacterial endotoxins diptheria, botulinal,

tetanustetanus Viruses polio hepatitisViruses polio hepatitis Organism that enter body from mucosal Organism that enter body from mucosal

tissue ie. Colds, influenzatissue ie. Colds, influenza

Cellular ResponseCellular Response

Chronic bacterial infections ie. Syphilis, Chronic bacterial infections ie. Syphilis, TBTB

Viral infections ie. Measles, herpes, Viral infections ie. Measles, herpes, chicken poxchicken pox

Fungal InfectionsFungal Infections ParasiticParasitic Tissue TransplantsTissue Transplants

Humoral Immune Humoral Immune ResponseResponse

Production of antibodies by B lymphocytesProduction of antibodies by B lymphocytesEither by direct antibody formation or by Either by direct antibody formation or by stimulation from T Helper cellsstimulation from T Helper cells

B lymphocytes stored in the lymph NodesB lymphocytes stored in the lymph Nodes Antigenic message returns stimulating the B Antigenic message returns stimulating the B

lymphocytes with the memory to produce lymphocytes with the memory to produce more exaggerated rapid response in person more exaggerated rapid response in person who is repeatedly exposed to the same who is repeatedly exposed to the same antigenantigen

Fluid ResponseFluid Response

Portion of fluid uncoagulated blood is plasmaPortion of fluid uncoagulated blood is plasma Plasma transports circulating antibodies Plasma transports circulating antibodies

produced in a specific response to antigenic produced in a specific response to antigenic stimulationstimulation

Antibodies bind to antigens becoming sticky Antibodies bind to antigens becoming sticky and help WBC’s locate, engulf and destroyand help WBC’s locate, engulf and destroy

blood creates a coating effect: OPSONINSblood creates a coating effect: OPSONINS

Antibodies Antibodies (immunoglobulins)(immunoglobulins)

Portion of fluid uncoagulated blood is plasmaPortion of fluid uncoagulated blood is plasma Plasma transports circulating antibodies Plasma transports circulating antibodies

produced in a specific response to antigenic produced in a specific response to antigenic stimulationstimulation

Antibodies bind to antigens becoming sticky Antibodies bind to antigens becoming sticky and help WBC’s locate, engulf and destroyand help WBC’s locate, engulf and destroy

blood creates a sticky coating effect: blood creates a sticky coating effect: OPSONIZATIONSOPSONIZATIONS

Five Classes of Five Classes of ImmunoglobulinsImmunoglobulins

Produced within the body to protect Produced within the body to protect Each varies in structure and distribution Each varies in structure and distribution in the bodyin the body

Protective functionProtective function IgA, IgD, IgE, IgG, IgMIgA, IgD, IgE, IgG, IgM

Activates ComplementActivates Complement

IgG: protect against microorganism, toxins in IgG: protect against microorganism, toxins in blood and body fluids, Major immunoglobulin blood and body fluids, Major immunoglobulin in serum and body fluid. Crosses placenta. in serum and body fluid. Crosses placenta. Enhances phagocytosisEnhances phagocytosis

IgM: protects against microorganism in blood. IgM: protects against microorganism in blood. Confined to the vascular system. First to Confined to the vascular system. First to react to bacterial and viral infectionsreact to bacterial and viral infections

Does not Activate Does not Activate ComplementComplement

IgA: Appears in body fluids, protects mucous IgA: Appears in body fluids, protects mucous membranes from bacteria, virus, toxins in GI< membranes from bacteria, virus, toxins in GI< respiratory, genitourinary urinary system. respiratory, genitourinary urinary system. Prevents absorption of antigens from foodPrevents absorption of antigens from food

IgD: appears in small amounts in the serum, IgD: appears in small amounts in the serum, signal B cell differentiation, membrane of signal B cell differentiation, membrane of circulating B cellscirculating B cells

IgE: Appears in the serum, protects against IgE: Appears in the serum, protects against parasites, mediates allergic reactions and parasites, mediates allergic reactions and hypersensitivity reactions with membrane of mast hypersensitivity reactions with membrane of mast cell and basophilscell and basophils

Role of T LymphocytesRole of T Lymphocytes

T helper cells(T4 cells) activated on T helper cells(T4 cells) activated on recognition of antigens recognition of antigens

T4 helper cells stimulate the rest of the T4 helper cells stimulate the rest of the immune system by secreting cytokinesimmune system by secreting cytokines

T cytoxic cells (T killer cells) attack T cytoxic cells (T killer cells) attack antigens directly causing cell lysisantigens directly causing cell lysis

Role of T LymphocytesRole of T Lymphocytes

T suppressor cells that decrease B cells T suppressor cells that decrease B cells productionproduction

Keep immune response at a level Keep immune response at a level compatible with health ( sufficient to compatible with health ( sufficient to fight infection without attacking the fight infection without attacking the body’s healthy tissue)body’s healthy tissue)

T memory cells responsible for T memory cells responsible for recognizing antigensrecognizing antigens

InterferonInterferon

Group of proteins produced by variety Group of proteins produced by variety of cells with inflammatory processof cells with inflammatory process

In response to viral infectionIn response to viral infection Stimulates uninfected cells to Stimulates uninfected cells to

production alterations to protect production alterations to protect uninfected cells from viral multiplicationuninfected cells from viral multiplication

Antiviral actionAntiviral action

Role of InterferonRole of Interferon

Antiviral and antitumor propertiesAntiviral and antitumor properties Produced by T lymphocytes, B Produced by T lymphocytes, B

lymphocytes and macrophages in lymphocytes and macrophages in response to antigensresponse to antigens

Suppress antibody production and Suppress antibody production and celluar immunitycelluar immunity

Facilitate cytoxic roleFacilitate cytoxic role

Immune SystemImmune System

Ability to response while at the same Ability to response while at the same time response with a specific action that time response with a specific action that produces antibiodiesproduces antibiodies

Recognition and MemoryRecognition and Memory

Recognizes self antigenic make-up and Recognizes self antigenic make-up and doesn’t produce antibodies againstdoesn’t produce antibodies against

Called recognition of selfCalled recognition of self

REVIEWREVIEW

Two DivisionsTwo Divisions

Humoral mediated systemHumoral mediated system Cellular mediated systemCellular mediated system

T CellsT Cells

Phagocytic activity T killer cellsPhagocytic activity T killer cells Produce cells which control immune Produce cells which control immune

responseresponse T helper cells which help T helper cells which help

immunoglobulin production by B cells, immunoglobulin production by B cells, Stimulates B cells productionStimulates B cells production

B CellsB Cells

Produce immunogobulins in blood, Produce immunogobulins in blood, lymph, mucus and al body fluidslymph, mucus and al body fluids

Works in acute bacteria, biologic toxins Works in acute bacteria, biologic toxins tetanus, certain viral (cold, rabies, polio)tetanus, certain viral (cold, rabies, polio)

B Cells have immunoglobulins present B Cells have immunoglobulins present on surface cellson surface cells

“ “Lymphokines”Lymphokines”

Macrophages which has been activated Macrophages which has been activated releases stimulatory, soluble substance releases stimulatory, soluble substance called “Lymphokinescalled “Lymphokines

Soluble lymphokines attract microphage Soluble lymphokines attract microphage to site by chemotaxisto site by chemotaxis

ThymusThymus

Serves as control organ Serves as control organ

Reaches peak in childhood and Reaches peak in childhood and shrinks during pubertyshrinks during puberty

Lymph Nodes and SpleenLymph Nodes and Spleen

Primary site of localization of Primary site of localization of immune responseimmune response

Lymph Nodes and RES clear 80-Lymph Nodes and RES clear 80-90% Of antigen on a single pass90% Of antigen on a single pass

Cell MediatedCell Mediated

Involves Sensitized T Cell LymphocytesInvolves Sensitized T Cell Lymphocytes Go to site of antigen entranceGo to site of antigen entrance Protects against disease where Protects against disease where

circulating immunoglobulins can’t reachcirculating immunoglobulins can’t reach

Combined ResponseCombined Response

Most antigens provoke both typesMost antigens provoke both types 1st response T cells in the area of 1st response T cells in the area of

lymph nodes within 2 days, the B cells lymph nodes within 2 days, the B cells respond 3-5 daysrespond 3-5 days

T helper cells stimulate B cells with T helper cells stimulate B cells with increase number of immunoglobulinsincrease number of immunoglobulins

Health Assessment Health Assessment Important FactorsImportant Factors

AgeAge

People at extremes of lifespan People at extremes of lifespan more likely to develop problemsmore likely to develop problems

Elderly have T and B lymphocyte Elderly have T and B lymphocyte production impairmentproduction impairment

Autoimmune disease increase with Autoimmune disease increase with agingaging

WHY?WHY?

Change in body organ functionChange in body organ function

Environmental exposuresEnvironmental exposures

Nutritional StateNutritional State

Adequate nutrition is necessary for Adequate nutrition is necessary for optimal immune functionoptimal immune function

Autoimmune DisordersAutoimmune Disorders

Identify the presence of any pre-Identify the presence of any pre-existing autoimmune disease existing autoimmune disease

Related to estrogen and androgenRelated to estrogen and androgen Estrogen enhances immunityEstrogen enhances immunity Androgen tends to be Androgen tends to be

immunosuppressiveimmunosuppressive

Neoplastic DiseaseNeoplastic Disease

Immunosupression contributes to the Immunosupression contributes to the development of cancerdevelopment of cancer

Cancer itself is immunosuppressiveCancer itself is immunosuppressive Celluar Immunity Impaired or defective Celluar Immunity Impaired or defective

increases risk for cancerincreases risk for cancer Cancer outdistances the immune systemCancer outdistances the immune system Some surface antigens CEA, high alpha feta Some surface antigens CEA, high alpha feta

proteinsproteins

Chronic IllnessChronic Illness

Assess for history of Diabetes Mellitus, Assess for history of Diabetes Mellitus, Renal Disease, COPDRenal Disease, COPD

Chronic illness contribute to the Chronic illness contribute to the impairment of immune systemimpairment of immune system

Special ProblemsSpecial Problems

Burns, injuries, and illness alter the Burns, injuries, and illness alter the immune systemimmune system

Impaired skin integrity is the 1Impaired skin integrity is the 1stst line of line of defensedefense

Medications and Blood Medications and Blood TransfusionsTransfusions

Antibiotics, steroids, salicylates, Antibiotics, steroids, salicylates, nonsteroidal anti-inflammatory agents nonsteroidal anti-inflammatory agents and anesthetics can cause immune and anesthetics can cause immune suppressionsuppression

Multiple transfusions create previous Multiple transfusions create previous exposure to foreign antigens may be exposure to foreign antigens may be associated with abnormal immune associated with abnormal immune functionfunction

LifestyleLifestyle

ETOH consumptionETOH consumption Tobacco consumptionTobacco consumption Dietary intakeDietary intake Nutritional statusNutritional status Exposures Exposures

Physical ExamPhysical Exam

Skin and mucous membranesSkin and mucous membranes Lymph nodesLymph nodes Joints functionJoints function Body Systems:Body Systems:

CV, Resp, GI, GU, NeuroCV, Resp, GI, GU, Neuro