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


• 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


• 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


• humoral & cellular responses are coordinated

– humoral response

• uses antibodies

–secreted by plasma cells

–target antigens in body fluids


• humoral & cellular responses are coordinated

– cellular response

• uses T cells

–attack body cells

»virus-infected or mutated


• 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


• 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


• 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


• 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


• 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


• 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


• 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


• 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


• 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


• 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)


• 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


• 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


• ~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


• 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


• 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


• 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


• AIDS treatments

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

chapter 19 natural defenses against disease

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