Immune SystemImmune System

Chapter 43Chapter 43

Introduction to the Immune Introduction to the Immune SystemSystem

The human body must defend itself against The human body must defend itself against unwelcome intruders.unwelcome intruders.

It must also deal with abnormal body It must also deal with abnormal body cells, which, in some cases, may develop cells, which, in some cases, may develop into cancer.into cancer.

Two major kinds of defense have evolved Two major kinds of defense have evolved to counter such threats.to counter such threats.

Innate DefensesInnate Defenses Acquired DefensesAcquired Defenses

Overview of the Immune Overview of the Immune SystemSystem

External Barriers:External Barriers: intact skin epidermis intact skin epidermis Acid mantle of skinAcid mantle of skin Keratin Keratin Intact mucous membranes Intact mucous membranes Mucus Mucus Nasal hairsNasal hairs Cilia Cilia Gastric juice Gastric juice Acid mantle of vagina Acid mantle of vagina Lacrimal secretion Lacrimal secretion Urine Urine Oil (sebum) secretionsOil (sebum) secretions

Internal Cellular Defenses:Internal Cellular Defenses:

Phagocytic cellsPhagocytic cells

NeutrophilsNeutrophils MonocytesMonocytes EosinophilsEosinophils Dendritic cellsDendritic cells

Internal Cellular DefensesInternal Cellular Defenses

Phagocytic ResponsesPhagocytic Responses

PseudopodiaPseudopodia IngestionIngestion VacuoleVacuole Fuse with lysosomeFuse with lysosome DigestionDigestion ExocytosisExocytosis

Internal Cellular Defenses:Internal Cellular Defenses:

Natural Killer CellsNatural Killer Cells

Non-specificNon-specific PerforinsPerforins ApoptosisApoptosis

Natural Killer (NK) Cells (Cytotoxic Natural Killer (NK) Cells (Cytotoxic lymphocyte)lymphocyte)

Promote cells lysis by direct cell attack against Promote cells lysis by direct cell attack against virus-infected or cancerous body cells virus-infected or cancerous body cells

Referred to as null third population cells that are Referred to as null third population cells that are spontaneous non antigen recognizing. spontaneous non antigen recognizing.

Lack surface antigen receptors but recognize Lack surface antigen receptors but recognize certain surface sugars on infected or cancerous certain surface sugars on infected or cancerous cellscells

Release cytolytic chemicals (perforins) that attack Release cytolytic chemicals (perforins) that attack a targets cell's cell membrane and bore hole. a targets cell's cell membrane and bore hole. Granzymes are released and cellular enzymes Granzymes are released and cellular enzymes disrupted.disrupted.

Present in spleen, lymph nodes, red bone marrow, Present in spleen, lymph nodes, red bone marrow, and blood and blood

Inflammatory ResponseInflammatory Response

Inflammatory ResponseInflammatory Response

Cardinal signs of Cardinal signs of inflammationinflammation

redness, pain, heat redness, pain, heat and swelling and swelling

Local versus Local versus systemic systemic inflammationinflammation

Septic shockSeptic shock

InterferonsInterferons - proteins that diffuse to nearby cells, - proteins that diffuse to nearby cells, where they stimulate the synthesis of a protein where they stimulate the synthesis of a protein known as PKE, which then interferes with viral known as PKE, which then interferes with viral replication in those cells by blocking protein replication in those cells by blocking protein synthesis at the ribosomessynthesis at the ribosomes Gamma interferonGamma interferon - produced by lymphocytes, - produced by lymphocytes,

mobilizes and activates macrophages and NK mobilizes and activates macrophages and NK cells, stimulates synthesis and expression of cells, stimulates synthesis and expression of more class I and II MHC, and enhances activity of more class I and II MHC, and enhances activity of B cells and cytotoxic T cellsB cells and cytotoxic T cells

Alpha interferon Alpha interferon - produced by most - produced by most leukocytes, mobilizes and activates leukocytes, mobilizes and activates macrophages and NK cellsmacrophages and NK cells

Beta interferonBeta interferon - produced by fibroblasts, - produced by fibroblasts, mobilizes and activates macrophages and acts mobilizes and activates macrophages and acts to reduce inflammationto reduce inflammation

ComplementComplement - twenty plasma - twenty plasma proteins that amplify the proteins that amplify the inflammatory response, lyses inflammatory response, lyses microorganisms and enhances microorganisms and enhances phagocytosis by opsonization. Two phagocytosis by opsonization. Two pathways: classic and alternative.pathways: classic and alternative.

PyrogensPyrogens - secreted by macrophages - secreted by macrophages and signal the body to increase and signal the body to increase temperature; high body temperature temperature; high body temperature inhibits microbial multiplication and inhibits microbial multiplication and enhances body repair processes. enhances body repair processes.

Antigen (Ags)Antigen (Ags) Antigens are substances that can mobilize Antigens are substances that can mobilize

immune system and provoke a responseimmune system and provoke a response Are considered nonself Are considered nonself ii. Nonself Antigensii. Nonself Antigens Types:Types:

Complete antigen Complete antigen - functional - functional properties:properties: immunogenecity - stimulate B and T immunogenecity - stimulate B and T

cell formation and antibody cell formation and antibody production production

reactivity - react with B and T cells reactivity - react with B and T cells

Small antigensSmall antigens (peptide, nucleotide, hormones) - (peptide, nucleotide, hormones) - may bind to body's own biological molecules may bind to body's own biological molecules (proteins); antigen when bound to body's own (proteins); antigen when bound to body's own molecules may cause an immune response, this is molecules may cause an immune response, this is called an allergy. Small antigens are calledcalled an allergy. Small antigens are called haptens haptens (incomplete antigen) and alone are not (incomplete antigen) and alone are not immunogenic. immunogenic.

Reactivity (immune response) is dependent upon Reactivity (immune response) is dependent upon antigen structure; localized regions,antigen structure; localized regions, antigenic antigenic determinants determinants are where antibodies or B and T are where antibodies or B and T lymphocytes can bind. lymphocytes can bind.

iii. Self Antigensiii. Self Antigens Are not foreign or antigenic to us, but are strongly Are not foreign or antigenic to us, but are strongly

antigenic to other individualsantigenic to other individuals egs. blood transfusions and organ transplantsegs. blood transfusions and organ transplants

Major Histocompatibility Complex (MHC) Major Histocompatibility Complex (MHC) antigensantigens Found on all cells except RBCs Found on all cells except RBCs

Involved in tissue recognition (aids in Involved in tissue recognition (aids in transplantation recognition) transplantation recognition)

Two types of MHC antigens: MHC class I found on Two types of MHC antigens: MHC class I found on all body cells all body cells

MHC class II found on antigen present cells MHC class II found on antigen present cells Antigen Presentation Ingestion of the antigen Antigen Presentation Ingestion of the antigen Digestion of antigen into peptide fragments Digestion of antigen into peptide fragments Fusion of vesicles (peptide fragments with MHC-II Fusion of vesicles (peptide fragments with MHC-II

molecules) molecules) Binding of peptide fragments to MHC-II molecules Binding of peptide fragments to MHC-II molecules Insertion of antigen-MHC-II complex into plasma Insertion of antigen-MHC-II complex into plasma

membrane membrane

ACQUIRED IMMUNITYACQUIRED IMMUNITY

All cells have cell All cells have cell surface surface macromolecules macromolecules

Adaptive immunity Adaptive immunity is sensitive to is sensitive to specific infections specific infections

Antigens Antigens distinguish self distinguish self versus non-selfversus non-self

ACQUIRED IMMUNITYACQUIRED IMMUNITY

ACQUIRED IMMUNITYACQUIRED IMMUNITY

Humoral ImmunityHumoral Immunity

Also known as Also known as antibody-mediated antibody-mediated immunityimmunity

Utilizes B-Utilizes B-lymphocyteslymphocytes

Recognizes antigen Recognizes antigen directlydirectly

Made in the bone Made in the bone marrowmarrow

Clonal Selection and Clonal Selection and ProliferationProliferation

Antibody StructureAntibody Structure

Antibody ClassesAntibody Classes

Antibody ClassesAntibody Classes

Antibody FunctionsAntibody Functions

Cell-Mediated ImmunityCell-Mediated Immunity

Utilizes T-Utilizes T-lymphocyteslymphocytes

T-cells are made in T-cells are made in the bone marrow the bone marrow but mature in the but mature in the thymus gland.thymus gland.

Cannot recognize Cannot recognize antigens directlyantigens directly

Cell-Mediated ImmunityCell-Mediated Immunity

CLASS I MHC PROTEIN

CLASS II MHC PROTEIN

Helper T-Lymphocyte Helper T-Lymphocyte StimulationStimulation

Helper T-cells stimulate B-Helper T-cells stimulate B-cellscells

Cytotoxic T-Lymphocyte Cytotoxic T-Lymphocyte StimulationStimulation

Overview of Adaptive Overview of Adaptive ImmunityImmunity

Adaptive ImmunityAdaptive Immunity

Problems with the Immune Problems with the Immune SystemSystem

Blood Transfusion ReactionBlood Transfusion Reaction Tissue RejectionTissue Rejection AllergiesAllergies Autoimmune diseaseAutoimmune disease ImmunodeficienciesImmunodeficiencies

Blood Transfusion ReactionsBlood Transfusion Reactions

Rhesus FactorRhesus Factor

Blood Blood TypeType

Presence Presence of D of D Antigen?Antigen?

Type of Type of AntibodyAntibody??

ReceiveReceive??

Rh PositiveRh Positive

YesYes NoneNone + and -+ and -

Rh Rh NegativeNegative NoNo Anti-DAnti-D - only- only

Tissue Transplant and Tissue Transplant and RejectionRejection

AutograftAutograft IsograftIsograft AllograftAllograft XenograftXenograft

Allergies or Allergies or HypersensitivitiesHypersensitivities

Type IType I

Type IIType II

Type IIIType III

Type IVType IV

Autoimmune DiseasesAutoimmune Diseases

Multiple sclerosisMultiple sclerosis

Rheumatoid Rheumatoid arthritisarthritis

Systemic lupusSystemic lupus

Grave's diseaseGrave's disease

Type I diabetes Type I diabetes mellitusmellitus

Immunodeficiency DiseasesImmunodeficiency Diseases

Primary Primary ImmunodeficiencyImmunodeficiency

a.k.a. “inborn”a.k.a. “inborn” SCIDSCID

Secondary Secondary ImmunodeficiencyImmunodeficiency

a.k.a. “acquired”a.k.a. “acquired” DrugsDrugs Stress and Hodgkin’sStress and Hodgkin’s AIDSAIDS