chapter 19 natural defenses against disease
TRANSCRIPT
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