Ch. 43 The Immune System

Objectives

LO 2.28 The student is able to use representations or models to analyze quantitatively and qualitatively the effects of disruptions to dynamic homeostasis in biological systems.LO 2.29 The student can create representations and models to describe immune responses.LO 2.30 The student can create representations or models to describe nonspecific immune defenses in plants and animals.LO 2.34 The student is able to describe the role of programmed cell death in development and differentiation, the reuse of molecules, and the maintenance of dynamic homeostasis.

Overview

• Innate Immunity – defenses are activated immediately upon infection; same response for all pathogens.

• Adaptive (Acquired) Immunity – defenses based on recognition of the pathogen.

Pathogens(such as bacteria,fungi, and viruses)

INNATE IMMUNITY(all animals)

• Rapid response

Recognition of traits sharedby broad ranges ofpathogens, using a smallset of receptors

•

Recognition of traits specific to particularpathogens, using a vastarray of receptors

•

• Slower response

Barrier defenses:

SkinMucous membranesSecretions

Internal defenses:

Phagocytic cellsNatural killer cellsAntimicrobial proteinsInflammatory response

Humoral response:

Antibodies defend againstinfection in body fluids.

Cell-mediated response:

Cytotoxic cells defendagainst infection in body cells.

ADAPTIVE IMMUNITY(vertebrates only)

Ch. 43.1 In Innate Immunity, Recognition and Response Rely on Traits Common to Groups of Pathogens

Invertebrates• Exoskeleton (chitin)• Chitin-based barriers and lysozymes

(break down bacterial walls) in intestines

• Hemocytes– Phagocytosis– Chemicals– Antimicrobial peptides (disrupt fungi

and bacterial plasma membranes)– Specialized recognition proteins

Pathogen

PHAGOCYTICCELL

VacuoleLysosomecontainingenzymes

Vertebrates• Barrier defenses

– Skin– Cilia: sweep mucus and any entrapped microbes

upward, preventing the microbes from entering the lungs

– Lysozymes in• Mucus – traps microbes• Saliva• Tears

– Acidic• Skin• Sweat• Stomach juices

• Cellular Innate Defenses– Phagocytosis after Toll-like receptor recognizes

pathogen• Neutrophils: circulate in blood• Macrophages: live in cells/organs (spleen)• Dendritic cells: tissue in contact with environment (skin)• Eosinophils: beneath mucosal surfaces; multicellular

pathogens.

– Natural Killer Cells: secrete chemical when they come in contact with a pathogen

• Antimicrobial Peptides and Proteins– Interferons

• Made by virally infected cells to warn surrounding cells.

• Inflammatory Response

– Histamine is released by mast cells in response to tissue damage• Trigger dilation and increased permeability of nearby capillaries• Increased blood flow delivers clotting factors to the injury (marks

beginning of repair process/blocks spread of microbes)– Cytokines from macrophages/neutrophils promote blood flow causing

redness and increased temp in the area.– Pus—the accumulation of dead phagocytic cells and fluid leaked from

capillaries

Pathogen Splinter

Mastcell

Macro-phage

Capillary

Redblood cells

Neutrophil

Signalingmolecules

Movementof fluid

Phagocytosis

43.2 In Adaptive Immunity, Receptors Provide Pathogen-Specific Recognition

• Pathogens have antigens that trigger lymphocytic responses.– B cells

• Binding of Y shaped antigen receptor on membrane to antigen causing it to secrete soluble receptors called antibodies.

– T cells• Single rod shaped antigen receptor only binds to already infected host cells that

display the antigen.Antibody

Antigenreceptor

B cell

Antigen Epitope

Pathogen(a) B cell antigen receptors and antibodies

Antibody C

Antibody BAntibody A

Antigen

(b) Antigen receptor specificity

Displayedantigenfragment

MHC molecule

Antigenfragment

Pathogen

Host cell

T cell

T cell antigenreceptor

(a) Antigen recognition by a T cell

Characteristics of Adaptive Immunity1. Immense diversity of lymphocytes and receptors.

– > 1 million different B cell antigen receptors; 10 million different T cell antigens; each cell carries a specific set of these

2. Self-tolerance.– Lymphocytes are tested; any with “self” receptors go through

apoptosis.

3. Once recognized, increasing the number of specific lymphocytes for an antigen.

– Active lymphocyte divides by mitosis making cloned effector cells (begin fighting immediately; B=plasma cells; T= helper T cells and cytotoxic T cells) and memory cells (long lived cells that activate if antigen enters the body again)

4. Stronger and quicker response to previously encountered antigens.

– Memory cells

43.3 Adaptive Immunity Defends Against Infection of Body Fluids and Body Cells

Cell-Mediated Immune Response (attacks infected body cells)• Active helper T cells secrete cytokines which activate cytotoxic T cells.• Cytotoxic T cells bind to infected host cells

– Secretes proteins that disrupt membrane integrity and trigger apoptosis.– Once destroyed, antibodies attach to antigens from within the host cell.

Antigen-presentingcell

Pathogen

Antigen fragment

Class II MHC molecule

Accessory protein

Antigen receptor

Helper T cell

Cytokines

Cell-mediatedimmunity

Cytotoxic T cell

2

1

Cytotoxic T cell

31 2

Accessoryprotein

Class I MHCmolecule

Infectedcell

Antigenreceptor

Antigenfragment

Perforin

Pore

Gran-zymes

ReleasedcytotoxicT cell

Dyinginfected cell

© 2011 Pearson Education, Inc.

Animation: Helper T Cells Right-click slide / select “Play”

© 2011 Pearson Education, Inc.

Animation: Cytotoxic T Cells Right-click slide / select “Play”

Humoral Immune Response (attacks pathogen)• Helper T cells activate B cells.• B cells divide into memory or plasma cells.• Plasma cells give secrete 2,000 antibodies/sec!• Antibodies:

– Prevent the pathogen from infecting cells (neutralization)– Increase phagocytosis due to easy recognition (opsonization)– Complement system of proteins opens a pore in the pathogen causing water

to rush in the pathogen to lyse.

Pathogen

31 2

Antigen-presentingcell Antigen

fragment

Class IIMHC

molecule

Antigenreceptor

Accessoryprotein

Helper T cell

B cell

Cytokines

Activatedhelper T cell

Memory B cells

Plasma cells Secretedantibodies

OpsonizationNeutralization

Antibody

VirusBacterium

Macrophage

Activation of complement system and poreformation

Complement proteins

Formation of membraneattack complex

Flow of waterand ions

Pore

AntigenForeigncell

Humoral (antibody-mediated) immune response Cell-mediated immune response

Antigen (1st exposure)

Engulfed by

Antigen-presenting cell

Helper T cell

Memoryhelper T cells

Antigen (2nd exposure)

B cell

Plasma cells

Secretedantibodies

Defend against extracellularpathogens

Memory B cellsMemory

cytotoxic T cellsActive

cytotoxic T cells

Defend against intracellularpathogens and cancer

Cytotoxic T cell

Key

Stimulates

Gives rise to

Active and Passive Immunization• Active (cell mediated and humoral responses)

– Can be induced by vaccinations – weakened, killed, or parts of pathogens to – to create memory cells and can lead to immunization.

• Passive (passed on from mother to child for first few months of life)– Injection of antibodies from an immune animal to

a non-immune animal.

Immune Rejection

• Cells from another person’s body can be recognized as foreign due to different carbohydrate found on the cell membranes, causing an immune response.– Blood groups (ABO)– Tissue and Organ Transplant

43.4 Disruptions in Immune System Function Can Elicit or Exacerbate Disease

• Allergies– Exaggerated responses to allergens.

• Autoimmune diseases– Immune system does not recognize “self-cells”

• Lupus• Arthritis• Diabetes• MS

Immunodeficiency Diseases

• Inborn immunodeficiency results from hereditary or developmental defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses

• Acquired immunodeficiency develops later in life and results from exposure to chemical and biological agents

• Acquired immunodeficiency syndrome (AIDS) is caused by a virus

Evolutionary Adaptations of Pathogens

Antigenic Variation• Changes its antigens so the host does not recognize it

– Ex: Flu

Latency• Inactive state which does not trigger an immune

response (lysogenic cycle).Attacking the Immune System Itself• HIV – attacks helper T cells preventing both cell

mediated and humoral responses to infections.

Cancer and Immunity

• The frequency of certain cancers increases when adaptive immunity is impaired– 20% of all human cancers involve viruses

• The immune system can act as a defense against viruses that cause cancer and cancer cells that harbor viruses

• In 2006, a vaccine was released that acts against human papillomavirus (HPV), a virus associated with cervical cancer.