chapter 19 natural defenses against disease

Natural Defenses Against Disease

Nonspecific DefensesTable 18.1

Animal Defenses Against Pathogens

• most animals have defenses that are non-specific, or innate

– physical barriers

– cellular, chemical, or coordinated defenses

a septic wound

mastcells

release histamine

and chemotactic

agentsFigure 18.4

Nonspecific Defenses

• inflammatory response to injury

– activated mast cells release histamine

– blood capillaries dilate & leak

Nonspecific Defenses

• inflammatory response to injury

– activated mast cells release histamine

– blood capillaries dilate & leak

– complement proteins attract macrophages

– macrophages engulf bacteria & dead cells

Figure 18.3

Animal Defenses Against Pathogens

• most animals have defenses that are non-specific, or innate

• vertebrates (and perhaps other groups) possess defenses that are specific, or targeted

Defensive Cells and Proteins

• non-specific & specific defenses are mediated by

cells & proteins of the bloodstream & lymphatic system

defensive roles of white blood cellsFigure 18.2

organs and

vessels of the

lymphatic system

Figure 18.1

Circulatory & Lymphatic Systems

• defensive cells and molecules circulate in the blood

• some cells and molecules leave the blood and enter the lymphatic system

• cells and molecules of the blood and lymph monitor the body and respond to pathogens

cell signaling in defense

• defensive responses resemble other cellular responses

– the receptor, toll, binds a fragment of a bacterium or a fungus

– a transduction pathway phosphorylates NF-B

Figure 18.5

Targeted Defense: The Immune System

• immune system cells produce several protein types

– antibodies & T cell receptors bind foreign substances

– MHC (HLA) proteins help recognize foreign substances & activate defensive cells

– cytokines alter the behavior of other cells

Targeted Defense: The Immune System

• attacks antigens that evade the non-specific defenses

• four features of the immune response

– specificity

– ability to respond to great diversity of antigens

– ability to distinguish self from non-self

– memory

Targeted Defense: The Immune System

• capacity of the immune response

– can respond to millions of different targets

– each cell responds to only one specific target

• targets that elicit a response are antigens

– antigens bear antigenic determinants

antigens and antigenic determinantsFigure 18.6

Targeted Defense: The Immune System

• humoral & cellular responses are coordinated

– humoral response

• uses antibodies

–secreted by plasma cells

–target antigens in body fluids

Targeted Defense: The Immune System

• humoral & cellular responses are coordinated

– cellular response

• uses T cells

–attack body cells

»virus-infected or mutated

Targeted Defense: The Immune System

• clonal selection

– effector and memory cells are produced as T cell & B cell clones expand

• explains the rapid, specific, and diverse response

• explains immunological memory

clonal selection:a B cell is “selected”

resulting in a

clone of plasma cells producing

the selected antibody & memory cells

Figure 18.7

Targeted Defense: The Immune System

• natural & artificial immunity both depend on immunological memory

– vaccination or previous exposure prepares an aggressive anamnestic immune response

immunological memoryFigure 18.8

the anamnestic response

Targeted Defense: The Immune System

• natural & artificial immunity both depend on immunological memory

– vaccination or previous exposure prepares an aggressive anamnestic immune response

• memory cells are stimulated without illness

– vaccines use inactive toxins as antigens

• attenuated cells

• cloned proteins

Table 18.2

Targeted Defense: The Immune System

• tolerance of self results from clonal deletion of anti-self lymphocytes

– ~90% of B cells are deleted by apoptosis

– loss of tolerance results in autoimmune disease

Addison's Disease Meniere's MyositisAlopecia Areata Psoriasis DiabetesBehcet's Disease Vitiligo VasculitisRheumatic Fever Fibromyalgia SarcoidosisGoodpasture Syndrome SclerodermaGraft Versus Host Disease Graves' Disease Guillain-Barre Syndrome Multiple SclerosisWegener's Granulomatosis Myasthenia GravisChronic Fatigue Syndrome Pemphigus

VulgarisPrimary Biliary Cirrhosis Ankylosing Spondylitis Antiphospholipid Syndrome (APS)Crohn's Disease and Ulcerative Colitis

Figure 18.9

B Cells: The Humoral Immune Response

• activated B cells

– form plasma cells

• synthesize & secrete specific antibodies

• antibodies, or immunoglobulins

– tetramers of four polypeptides

• two light chains & two heavy chains

• each with a constant & a variable region

components of an immunoglobulinFigure 18.10

B Cells: The Humoral Immune Response

• variable regions form antigen-binding sites

– determine the antibody’s specificity

• constant region determines destination and function

B Cells: The Humoral Immune Response• five immunoglobulin classes

– IgM: formed first; membrane receptor on B cells

– IgD: membrane receptor on B cells

– IgG: most abundant class; several functions

– IgE: inflammation & allergic reactions

– IgA: in various body secretions

five antibody classesFigure 18.3

B Cells: The Humoral Immune Response

• monoclonal antibodies

– identical & directed against a single antigenic determinant

• hybridomas

– produced by fusing B cells with myeloma cells

hybridoma production

Figure 18.12

Figure 18.14

T Cells: The Cellular Immune Response

• cellular immune response– directed against altered or antigen-infected

cells– TC cells attack & lyse virus-infected or

tumor cells– TH cells activate B cells & guide

development of other T cells and macrophages

– T cell receptors are analogous to immunoglobulins

atypical T cell

receptorFigure 18.13

T Cells: The Cellular Immune Response

• the major histocompatibility complex (MHC)

– encodes membrane proteins in macrophages, B cells, or body cells

– MHC proteins

• bind processed antigen

• present it to T cells (displayed on cell surface)

aClass II

MHC protein presents a processed antigen fragment to a

TH cellFigure 18.15

antigen presentation & MHC recognitionFigure 18.16

T Cells: The Cellular Immune Response

• activation of the humoral immune response

– class II MHC molecules

– T cell surface protein CD4

– cytokines

– effector phase results in active plasma cells

formation of a

B cell clone and

antibodiesFigure 18.17

cytokines

T Cells: The Cellular Immune Response

• cellular immune response

– class I MHC molecules

– TC cells

– CD8

– cytokines

– activate TC cells with appropriate specificity

preparation of a

cytotoxic T cell

Figure 18.17

T Cells: The Cellular Immune Response

• developing T cells are tested in the thymus

– must recognize self MHC molecules

• or fail to develop (anergy)

– must not bind to both self MHC & any of the body’s own antigens

• or die (clonal deletion - apoptosis)

T Cells: The Cellular Immune Response

• rejection of organ transplants is due to the genetic diversity of MHC molecules

– each individual (or pair of identical twins) has unique MHC proteins

– MHC proteins of one are treated as foreign by the immune system of others

The Genetic Basis of Antibody Diversity

• several gene families produce the diversity of antibodies & T cell receptors

• antibody heavy-chain genes

– constructed from one each of many V, D, J, & C segments

– V, D, and J segments combine by DNA rearrangement

– transcription & processing yields a mRNA

– other gene families produce light chains

heavy chain gene segments available for rearrangement

Figure 18.18

random combinations yield unique chainsFigure 18.19

heavy chain dimer

produced by recombined

DNAFigure 18.10

The Genetic Basis of Antibody Diversity

• possible antibodies as a result of these

– millions due to DNA recombinations

– tens to hundreds of thousands due to

• imprecise DNA rearrangements

• mutations

• random addition of terminal bases before DNA’s before are joined

– ~1011 possible different antibodies

The Genetic Basis of Antibody Diversity

• ~1011 possible different antibodies

– each B cell produces only one antibody

– millions of different B cells monitor blood, lymph, tissues for antigens that “fit”

• millions of different T cells produce unique receptors similarly from a different set of gene families

The Genetic Basis of Antibody Diversity

• plasma cells produce

– IgM first

– may switch to other classes of antibodies

• same antigen specificity

• different function

– accomplished by switching constant regions

switching from IgM to

IgG by switching

constant regions

Figure 18.20

Disorders of the Immune System

• allergies

– overreaction of the immune system to an antigen

• autoimmune diseases

– failure of self-recognition

– antiself B and T cells attack the body’s cells

inverse relationship betweenviral load & T cell concentration

Figure 18.21

Disorders of the Immune System

• immune deficiency disorders

– failure of some part of the immune system

• AIDS

–depletion of TH cells

–result of HIV infection

–when certain T cell clones are lost, their target pathogens are able to infect “opportunistically”

opportunistic infections vs. TH cell countFigure 18.22

Disorders of the Immune System

• HIV is a retrovirus

– inserts its genome into a chromosome of a macrophage or TH cell

– may lie dormant for years

– when transcription and translation occur, new viruses form

Disorders of the Immune System

• AIDS treatments

– steps in the reproductive cycle of HIV are possible targets for drugs