Transcript CHAPTER 19 Natural Defenses Against Disease

Natural Defenses
Against Disease
Nonspecific Defenses
Table 18.1
Animal Defenses Against Pathogens
• most animals have defenses that are nonspecific, or innate
– physical barriers
– cellular, chemical, or coordinated defenses
a septic wound
mast
cells
release
histamine
and
chemotactic
agents
Figure 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 nonspecific, 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 cells
Figure 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 NFkB
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
determinants
Figure 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 memory
Figure 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
Myositis
Alopecia Areata Psoriasis
Diabetes
Behcet's Disease
Vitiligo
Vasculitis
Rheumatic Fever
Fibromyalgia
Sarcoidosis
Goodpasture Syndrome
Scleroderma
Graft Versus Host Disease
Graves' Disease
Guillain-Barre Syndrome
Multiple Sclerosis
Wegener's Granulomatosis
Myasthenia Gravis
Chronic Fatigue Syndrome
Pemphigus Vulgaris
Primary 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 immunoglobulin
Figure 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 classes
Figure 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
a
typical
T cell
receptor
Figure 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)
a
Class II
MHC protein presents
a processed antigen fragment to a
TH cell
Figure 18.15
antigen presentation & MHC recognition
Figure 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
cytokines
formation
of a
B cell
clone
and
antibodies
Figure 18.17
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 chains
Figure 18.19
heavy chain
dimer
produced
by recombined
DNA
Figure 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 between
viral 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 count
Figure 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