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1120
MCB 3020, Spring 2005
Concepts of Immunology
Concepts of Immunology I:
I.
II.
III.
IV.
The immune system
Nonspecific immunity
Specific immunity
Antibodies
1121
1122
I. The immune system
Cells, proteins, and supporting
systems that kill or inactivate
invaders and monitor every cell
in the body for cancer.
TB
1123
A. Main activities of the immune system
Kills or inactivates invaders
bacteria
viruses
toxins
Kills or affects host cells
cells infected with bacteria or viruses
cancer cells
transplanted tissues (rejection)
sometimes attacks self (autoimmunity)
contributes to allergies
TB
B. Recognition of nonself
1124
The immune system detects antigens
expressed by pathogens and cancer cells.
Antigens are "nonself" (foreign)
molecules that interact with specific
components of the immune system
usually > 10,000 molecular weight
proteins
many polysaccharides
certain teichoic acids
TB
C. Key components
1125
1. Blood cells
2. Lymphatic system
TB
1. Blood cells
a. erythrocytes: red blood cells
non-nucleated
b. platelets: clotting aids
non-nucleated
1126
c. leukocytes: white blood cells
nucleated (contain nucleus)
TB
c. Leukocytes (white blood cells)
i. Phagocytes
Neutrophils
Monocytes
Macrophages
ii. Lymphocytes
B-cells (antibody production)
T-cells (cell-mediated immunity)
Natural killer cells
TB
1127
Blood cells
red
blood
cell
1128
monocyte
neutrophil
(polymorphonuclear
leukocyte, PMN)
TB
Bone marrow stem cell
1129
common precursor to blood and lymph cells
Bone marrow stem cell
Myeloid precursor
Platelets
Lymphoid precursor
T-cell
Mast cell
PMN
B-cell
Monocyte
Macrophage
Plasma cell
Memory
cell
Blood fluids
1130
Blood
Remove cells and platelets
Plasma
(contains clotting proteins,
antibodies, etc.)
Remove clotted materials
Serum
(rich in antibodies)
2. Lymphatic
system
1131
Lymph nodes
Thymus
MALT,
(mucosalassociated
lymphoid
tissue)
Spleen
Bone
marrow
Picture
26
Lymphatic system
1132
Lymph
A pale watery fluid similar to blood,
but lacking red blood cells. It contains
immune proteins such as complement
and antibodies and well as leukocytes
(white blood cells) which are key cells
of the immune system.
TB
Lymphatic system
1133
Basic components
a. Vessels for lymph circulation
similar to veins
b. Primary lymphoid organs
Thymus
Site of T-cell maturation
Bone marrow
Site of B-cell maturation
c. Secondary lymphoid organs
TB
c. Secondary lymphoid organs
1134
Organs rich in immune cells that filter the
blood and lymph by trapping antigens and
also provide sites for immune cell maturation
• lymph nodes
• spleen
• MALT
(Mucosal Associated Lymphoid Tissue)
TB
• Lymph nodes
1135
Filter tissue fluids. Their size is somewhere
between a grain of sand and a bean.
Fluids from
tissue spaces
TB
Lymph node
Lymph vessels sites for antigen trapping and
immune cell maturation, rich in
T-cell, B-cells and macrophages
• Spleen
1136
Filters antigens from the blood. It is
about the size of a fist and is located on
the left side of the abdominal cavity.
spleen
splenic
vein
splenic
artery
TB
the interior of the spleen is rich in immune cells
• MALT
1137
(Mucosal Associated Lymphoid Tissue)
Collects antigens from the mucus membranes
such as the respiratory and gastrointestinal
tracts. It can be diffuse or as aggregated
follicles. It is rich in immune cells.
TB
Lymphatic pumping
1138
•Breathing and skeletal muscle contraction
pumps lymph.
•Valves prevent back flow
•Exercise increase lymph flow 10-15x
TB
1139
D. Circulation of immune system components
1. proteins
Watery fluids containing various proteins and small
molecules slowly leak out of the veins and into tissues.
Pressure build in the tissues and these protein-containing
fluids are taken up by lymph capillaries forming lymph.
Lymph moves through the lymphatic system and returns
to the bloodstream through either the thoracic duct or
the right lymphatic duct.
Each day about 50% of total blood proteins leak out of the
capillaries and return to blood vial lymphatic vessels.
TB
Lymphatic capillaries
1140
tissue cells
curved arrows
indicate fluid flow
blood
vessels
lymphatic capillary
TB
spaces between cells are called interstitial spaces
1141
2. Circulation of leukocytes (white blood cells)
Blood cells are made in the bone marrow and
released into the blood stream.
Leukocytes move from the blood to the spaces
between tissue cells by "extravasation".
Leukocytes then re-enter the lymphatic system
and return to the blood stream thought the
thoracic or right lymphatic ducts.
TB
Extravasation
1142
Movement of cells through blood vessel walls
tissue
white blood cell
vein interior
tissue
endothelial cells
TB
II. Nonspecific immunity
1143
Immunity effective against many
different invaders.
anatomical defenses
inflammation and fever
professional phagocytes
TB
A. Defenses of the skin
1144
dead skin
cells
epidermis
salt-skin associated
lymphoid tissue, SALT.
dermis
subcutaneous
tissue
TB
1145
• Viruses cannot replicate on the dead cells of
the outer skin.
• Dead skin cells slough off taking adherent microbes
with them.
• Langerhans cells associated with the SALT
phagocytose and destroy incoming microbes
• The SALT initiates a specific immune response.
• Cuts, insect bits and burns can breach the defenses
of the skin.
TB
B. Defenses of the mucus membranes
1146
microbes trapped
in mucus
mucus
sloughed cell with
adherent microbe
MALT
deeper tissues
epithelial cells
TB
• Mucus which is made of a mixture of proteins 1147
and polysaccharides sloughs off taking
trapped microbes with it.
• Mucus also contains lysozyme.
• The MALT contains macrophages which engulf and
destroy bacteria.
• The MALT also initiates a specific immune response.
TB
C. Professional phagocytes
1148
• Cells that can engulf and kill microbes
• Most effective against extracellular
microbes.
1. neutrophils
2. monocytes
3. macrophages
TB
1149
1. Neutrophils (PMNs)
(polymorphonuclear leukocytes)
engulf and destroy invading bacteria
first line of defense against bacteria;
motile (circulating) cells
2. Monocytes
Circulating cells that migrate to
tissues and become macrophages.
TB
3. Macrophages
noncirculating cells
1150
engulf and kill bacteria and protozoa
clean up dead cells and cell debris
present antigens
produce cytokines
TB
a. Macrophage killing
1. engulfment
macrophage bacterium
1151
lysosomes
phagosome
1152
fusion
phagolysosome
1153
2. Digestion with lysosomal enzymes
lysozyme
proteases
lipases
nucleases
TB
3. Generation of oxidizing agents
1154
1O (singlet oxygen)
2
O2- (superoxide)
H2O2 (hydrogen peroxide)
HOCl (hypoclorous acid)
These reactive oxygen species are
generated within the phagolysosome
TB
D. Microbial defense mechanisms
against phagocytes
1155
carotenoids (quench singlet O2)
phenolic glycolipids
(scavenge reactive oxygen)
leukocidins (kill phagocytes)
capsules (polysacch. outside cell wall)
(prevent phagocyte adherence)
TB
III. Specific immunity
1156
Immunity effective against specific
pathogens
Involves antigen-specific leukocytes
(white blood cells)
B-lymphocytes (B-cells)
T-lymphocytes (T-cells)
TB
A. Properties of Specific Immunity
1157
specificity: recognizes specific target
memory: rapid immune response
in subsequent exposure to antigen
(basis for vaccination)
tolerance: usually doesn’t hurt self
TB
B. B-cells
• produce antibodies
1158
• involved in humoral immunity
• each B-cell makes only one type
of antibody
C. T-cells
• we'll talk about T-cells next time
• some kill abnormal host cells
• some regulate other immune cells
TB
B-cells
activation
several days
plasma cells
(short lived)
antibodies
1159
memory cells
(long-lived)
antigen
restimulation
several hours
plasma memory
cells
cells
TB
IV. Antibodies
1160
A. Importance
B. Major Classes
C. Structure
D. Digestion
E. Antigen binding
TB
Antibodies (immunoglobulins)
1161
Soluble immune system proteins
that bind specific antigens.
antigen
antibodies
TB
A. Importance of antibody binding
1162
1. inactivates toxins
2. marks invaders for attack by other
immune system components
3. aids phagocytosis
TB
B. Major classes
IgG
IgM
IgA
IgE
IgD
1163
Major circulating antibody
First to appear after infection
Major secretory antibody
Involved in allergic reactions
Function not well understood
TB
C. Structure
IgG
1164
antigen
binding
sites
disulfide
bonds
light chain
heavy chain
variable region = yellow (striped)
constant region = light blue (solid)
TB
D. Antibody structure: Fc and Fab fragments1165
IgG
papain
(a protease)
Fc fragment
Fab fragments
TB
Notes on IgG structure
1166
• Y-shaped molecule
• four polypeptide chains
• many disulfide bridges
• 2 light chains (short chains)
• 2 heavy chains
• *Bivalent: two antigen binding sites
TB
1167
Notes on IgG structure
• variable regions form the antigenbinding site and  define specificity
• constant regions are nearly identical
in most IgG molecules
• note the composition of Fab and Fc
Fc fragment
TB
Fab fragments
E. Antigen binding
1168
antigen
antibodies
epitope = antigenic determinant
the part of the antigen bound by the antibody
(can be as few as 4 to 5 amino acids)
TB
Study objectives
1169
1. What are the main functions of the immune system?
2. Know the cell types of the immune system and their functions.
Leukocytes (white blood cells) are a key components of the immune system.
Leukocytes include lymphocytes (B-cells and T-cells,) monocytes, neutrophils
and natural killer cells. B-cells make antibodies.
T-cells kill virus-infected cells and regulate other immune cells.
Monocytes become tissue macrophages which phagocytose invading
microorganisms, foreign bodies, and damaged an old cells. Neutrophils
phagocytose and destroy invading bacteria. Natural killer cells kill virus
infected cells and some tumor cells.
3. Know what antigens and antibodies are.
4. Know the basic components of the lymph system and their functions.
The primary lymphoid organs are the bone marrow and the thymus. All blood
cells are made in the bone marrow. B-cells mature in the bone marrow and
T-cells mature in the thymus. The secondary lymphoid organs are the lymph
nodes, spleen and mucosal associated lymphoid tissue (MALT). The lymph
nodes filter tissue fluids. The spleen filters the blood and the MALT collects
antigens from the respiratory and gastrointestinal tracts.
5.
6.
7.
8.
How do immune proteins and cells get to infection sites?
1170
What is extravasation?
Describe the nonspecific defenses of the skin and mucus membranes.
Distinguish between nonspecific and specific immunity. What are the
processes involved in each?
9. Know the professional phagocytes and understand how they kill bacteria.
10. Know the reasons for phagocytic failure. Carotenoids and phenolic glycolipids
interfere with oxidative killing. Leukocidins kill phagocytes. Capsules make it
difficult for phagocytes to get a good hold on the microorganism.
11. Know the properties of specific immunity and know the details of
the functions of B-cells (this lecture) and T-cells (next lecture).
12. Know the major classes of antibodies and their main characteristics.
IgG is the major circulating antibody. IgM is the first to appear after infection,
IgA is the major secretory antibody, and IgE is involved in allergic reactions.
13. Know the DETAILS of IgG structure. What are the antigen-binding site,
heavy chain, light chain, variable region, constant region, Fc fragment,
Fab fragment, disulfide bonds?
14. What is an epitope (antigenic determinant)?
1171
MCB 3020, Spring 2004
Chapter 20:
Concepts of Immunology II
Concepts of Immlunology II:
V. Humoral immunity
VI. T-cells
VII. Histocompatibility proteins
VIII. Cytokines
IX. Cell-mediated immunity
X. Immune tolerance
1172
V. Humoral immunity
Immunity resulting from direct
interaction with antibodies
1173
A. B-cells
B. Antibody production
C. Complement
TB
A. B-cells
1174
1. functions
produce antibodies
responsible for immune memory
function as APCs
(antigen-presenting cells)
produce cytokines
TB
2. B cell structure
1175
membrane
bound
antibody
MHCII
protein
TB
1176
B. Antibody production
1. Primary and secondary responses
primary
secondary
antibody
titer
antigen
injection
IgG
IgM
1
(titer = concentration)
100
days
200
TB
2. B-cell activation
1177
APC-TH cell
cytokines
B-cell with antigen bound
clonal expansion
plasma cells
memory cells
antibodies
TB
C. Complement
1178
A series of serum proteins that
reacts in a sequential manner with
Ag-Ab complexes to amplify
their activity
TB
1. Components of complement
~20 serum proteins, C1-C9
1179
• C1-C9 = membrane attack complex
(MAC) lyses bacteria and viruses
• C3b aids phagocytosis
(opsonization = phagocytosis
promoted by complement)
• C5a attracts phagocytes
TB
2. Activation pathway
1180
a. Classical pathway
bacterium
C1
• C1 "cross-links" antibodies
• the remaining components
of complement bind or are
formed by proteases.
TB
1181
bacterium
C5a attracts
phagocytes
C5b -C9 MAC
cell
lysis
TB
b. Alternative pathway
bacterium
1182
• C3b binds directly and
aids in phagocytosis
(opsonization)
• subsequent steps are
similar to the classical
pathway
TB
VI. T-cells
A. structural features
B. uses
TCR
1183
CD4
T-helper cell
Roles
• kill abnormal host cells (eg. virus-infected, cancer)
• regulate other immune cells
A. Structural features of T-cells
important cell surface proteins
1184
1. T-cell receptor (TCR):
recognizes antigens presented
by other host cells
2. CD8 or CD4
proteins
TCR
CD4
T-helper cell
1. T-cell receptors (TCR)
Membrane proteins found on the
surface of T-cells
1185
TCR
Variable region
Constant region
T-cell
cell membrane
TB
T-cell receptors (TCRs) recognize
antigens presented by other
host cells
TCR
CD8
Tc-cell
CD4
TH-cell
1186
2. CD8 or CD4 surface proteins
1187
a. T-cells with CD8 surface proteins
i. Cytotoxic T-cells (TC)
Kill abnormal host cells
ii. Suppressor T-cells (TS)
regulate other immune cells
b. T-cells with CD4 surface proteins
1188
i. T-helper cells (TH)
activate other immune cells
(eg. stimulate B cells to make antibodies)
ii. T-delayed hypersensitivity (TD)
attract and activate nonspecific
cells like phagocytes
1189
B. Uses of T-cells
Antigen specific activation of T-cells
1. TCR + CD8
binds MHCI-presented antigens
important for recognition of cancer
cells or virus-infected cells
2. TCR + CD4
binds MHCII-presented antigens
(MHC = major histocompatability complex)
1190
Antigen specific activation of T-cells
1. TCR + CD8
binds to antigens ( ) presented by
MHCI proteins ( ) found on other cells
MHCI-Ag-TCR
CD8
1191
2. TCR + CD4
binds MHCII-presented antigens.
MHCII
CD4
Antigen-presenting
cell (APC)
TH or TD
VII. Histocompatability proteins
A. MHC proteins
B. MHC protein classes
and antigen presentation
1192
MHC refers to the
Major histocompatibility complex
1193
A genetic region that encodes
proteins including the MHC proteins
A. MHC proteins
1194
Membrane proteins on host cells that
present processed antigens to T-cells
Most important proteins in tissue
rejection.
B. MHC protein classes
1. Class 1 (MHCI)
1195
Found on all nucleated cells
Presents "endogenous" processed antigens
Binds to TCRs + CD8 (on Tc and Ts cells)
*Important for recognition of cancer cells or
virus-infected cells peptide antigen
MHCI
TB cell membrane
of nucleated cell
Endogenous antigen presentation
by MHCI proteins
1196
Cell membrane
proteolysis
peptide
antigens
*internal
protein
endoplasmic
reticulum
Any nucleated cell
TB
2. Class 2 (MHCII)
1197
Found on antigen-presenting cells (APCs)
Macrophages, B-cells, others
Presents "exogenous" antigens
Binds to TCRs + CD4 (TH and TD)
peptide antigen
MHCII
cell membrane
of APC
TB
1198
Exogenous antigen presentation by
MHCII proteins in antigen-presenting cells
cell membrane
foreign
protein
MHCII
peptides
proteolysis
TB
MHCII
phagolysosome
Ii (a blocking protein)
(antigen-presenting cell)
endoplasmic
reticulum
VIII. Cytokines
Proteins secreted by leukocytes
Act as immune system modulators
Usually for local communication
1199
Examples of cytokines
1200
1. Interleukin-1 (IL-1)
Produced by activated APCs
Stimulates TH cells and B-cells
2. IL-2
Produced by activated TH cells
Stimulates B, TC, and TH cells
TB
APC
IL-1
1201
TH-cell
CD4
IL-2
B, TH, and others
TB
When activated, some T-helper cells 1202
produce cytokines that help stimulate B-cells
APC-TH cell
cytokines
B-cell with antigen bound
clonal expansion
plasma cells
memory cells
Antibodies
3. Interferon-a (IFN-a)
produced by leukocytes
antiviral agent that acts on
normal cells
1203
4. Tumor necrosis factor-a (TNF-a)
produced by macrophages and
NK
(natural
killer cells)
cytotoxic
to tumor
cells
TB
IX. Cell-mediated immunity
Immunity mediated by TC, TD, or
natural killer (NK) cells.
1204
Antibody may play a secondary role.
Specific and nonspecific cells are involved.
Primarily designed to eliminate altered
self cells: cells infected with viruses or
intracellular bacteria, and cancer cells.
Key cell types involved in
cell-mediated immunity
A. TC cells
B. Natural killer cells (NK)
C. TD cells
1205
A. TC-cells
TC-cell
1206
TCR-Ag-MHCI
virus-infected cell,
tumor cell,
or tissue graft
CD8
Perforin:
Cell lysis
protein monomers that polymerize to form a pore
TB
B. Natural killer cells
NK cell
Perforin
1207
virus-infected cell,
tumor cell,
Cell lysis
Normal cells express a protein (MHCI)
that deactivates NK cells
TB
C. TD-cells
• have CD4 receptors
• T cell receptor (TCR) binds
MHCII-Ag on APCs
• produce cytokines that attract
and activate macrophages
• important in response to
intracellular pathogens like
Mycobacterium tuberculosis
1208
X. Immune Tolerance
Induced unresponsiveness
to certain antigens (e.g. "self")
A. T-cell tolerance
B. B-cell tolerance
1209
A. T-cell tolerance
1. Clonal deletion
1210
Immature T-cell
MHC
TCR
self-antigen
thymus
wall
Death
2. Clonal anergy
1211
Self-reactive lymphocytes become
unresponsive in the secondary
lymphoid organs.
Antigen binding in the absence of
co-stimulatory factors may result
in unresponsiveness.
B. B-cell tolerance
Similar to T-cell tolerance
1. Clonal deletion
2. Clonal anergy
1212
Study objectives: Understand all concepts and DETAILS presented in this lecture.
1213
1. Understand humoral immunity, the function and structure of B-cells,
primary and secondary response during antibody production.
Why is a booster shot needed for most vaccinations?
2. What is complement? Describe the complement activation pathways.
3. Describe the structure and function of T-cells. T-cells are involved in antigen
specific responses. T-cell receptors (TCRs) determine the antigen recognized
by T-cells. Each T-cell has a number of copies of one specific TCR. The TCR
variable region usually binds only one specific MHC-presented antigen.
4. Know that the CD4 co-receptor is required for TCR binding to
MHCII-presented antigen and know that the CD8 co-receptor is required
for TCR binding to MHCI-presented antigen.
5. Understand the function of the MHC proteins in the immune response.
6. Understand the pathways of endogenous and exogenous antigen presentation.
7. What are cytokines? Know the functions of IL-1, IL-2, IFN-a, and TNF-a.
8. Understand the roles of TC-cells, NK cells and TD-cells in cell-mediated
immunity.
9. Understand how B-cells are activated to produce antibodies.
10. Understand immune tolerance, clonal deletion and clonal anergy.
1214
MCB 3020, Spring 2004
Immunology III:
Chapter 20
Immunology III:
XI. Clonal selection theory
XII. Generation of antibody diversity
XIII. Polyclonal and monoclonal
antibodies
XIV. Antigen-antibody interactions
XV. Immune-related diseases
1215
XI. Clonal selection theory
1216
A theory that explains how the immune
system responds to the millions of
different foreign antigens in a highly
specific way
TB
Each animal generates perhaps
a billion different lymphocytes.
1217
Each lymphocyte recognizes a
particular antigen.
Lymphocytes become "activated"
when they encounter the particular
antigen that they recognize.
TB
Precursor cell
B1
B2
resting B-cells
B3 B4 B5 Bn that recognize
different antigens
antigen binding
and cytokine stimulation
B5
clonal expansion
differentiation
B5
B5
1218
B5
B5
one type of
antibody
TB
Typical case of clonal selection
1219
Millions of different B-cells
protein antigen
A few hundred B-cells are stimulated
A few hundred different antibodies
are produced.
Each antibody recognizes
a particular epitope
TB
Note: Antibody diversity exists
prior to antigen stimulation.
1220
TB
XII. Generation of antibody diversity
1221
A. General structure of IgG
B. Heavy chain variability
C. Developmental gene
rearrangements
D. Additional variability
E. Light chain variability
TB
A. General structure of IgG
diversity region
1222
variable
regions
joining regions
TB
B. IgG heavy chain variability
1223
~200 variable region segments (V)
~50 diversity regions (D)
4 joining segments (J)
5 constant regions (C)
TB
C. Developmental gene rearrangements1224
DNA of precursor cell (not to scale)
V
D
J
B-cell DNA
transcription
and splicing
mRNA
C
random gene rearrangement
translation
TB
D. Additional diversity
Imprecise joining of gene segments
1225
TB
E. light chain diversity
1226
Generated similarly to heavy chain
diversity.
TB
XIII. Polyclonal and monoclonal
antibodies
1227
A. Compared
B. Monoclonal antibody production
TB
A. polyclonal
monoclonal
1228
many antibodies
that recognize
many epitopes
one antibody
that recognizes
one epitope
various classes
one class
making specific
antibodies requires
purified antigen
specific antibody
can be made with
impure antigen
reproducibility
difficult
high reproducibility
TB
B. Monoclonal antibody production
1229
B-cells do not survive in culture
B-cell fused to myeloma cells
produce hybridomas which survive in
culture and produce antibody
Fusion is inefficient so a selection
for hybridomas is used.
TB
immunized mouse
antibody
producing
B-cells
1230
mutant myeloma cells
fusion
cell mixture
hybridomas
TB
1231
well containing selective medium
test supernatant for antibody of interest
dilute
retest for antibody of interest
TB
XIV. Antigen-antibody interactions
1232
A. Neutralization
B. Precipitation
C. Agglutination
D. Serological tests
TB
1233
A. Neutralization
toxin or
virus
inactive
toxin or
virus
(Antibodies block active part
TB
of toxin of virus.)
1234
B. Precipitation
soluble
antigen
precipitate
*Bivalency is important for precipitation
TB
1235
C. Agglutination
insoluble
antigen,
cell, etc.
TB
C. Serological tests
1236
1. Uses
2. Direct ELISA
(enzyme-linked immunosorbent assay)
3. Indirect ELISA
4. Radioimmunoassay (RIA)
Enzyme bound to antibody
TB
radioactive antibody
1. Uses
1237
Drug testing
Disease diagnosis
Pregnancy tests
Blood typing
Pathogens typing
TB
2. Direct ELISA (detects antigen)
antiviral
antibody
1238
microtiter well
add sample (blood)
antigen
(e.g. viral protein)
antiviral
antibody
covalently
linked
enzyme
TB
1239
wash, then add
substrate for
enzyme
measure colored product
TB
3. Indirect ELISA (detects antibody)
antigen
anti-IgG
1240
add serum, wash
enzyme
substrate
colored
product
TB
1241
4. Radioimmunoassay (RIA)
• Similar to ELISA except radiolabeled antibody is used in place
of enzyme-linked antibody
• Used for samples that contain
substances which inhibit
ELISA enzymes.
• More expensive
TB
• Generates radioactive waste
XV. Immune-related Diseases
A. Delayed type hypersensitivity
B. Immediate type hypersensitivity
C. Autoimmune diseases
D. Superantigens
1242
TB
A. Delayed type hypersensitivity
1243
allergic skin reactions
poison ivy, cosmetics, TB test
meditated by T-cells
occurs after several hours
to a few days
TB
B. Immediate type hypersensitivity
allergies
pollen, dust, penicillin, etc.
anaphylactic response
sneezing, runny nose,
flushed skin,etc.
mediated by antibodies (IgE)
require prior sensitization
occurs almost immediately
1244
TB
C. Autoimmune diseases
1245
Usually slow progressive disorders
Rheumatoid arthritis
anti-cartilage antibody
Multiple Sclerosis
anti-nervous system antibodies
Reactivation of anergized lymphocytes
TB
D. Superantigens
Antigens that stimulate a large
fraction of T-cells.
Severe vomiting, shock
Staphylococcal exotoxins
Responsible for toxic shock syndrome
1246
TB
superantigen
1247
abnormal binding
to TCR
TH-cell
APC
CD4
excess cytokine
production
shock
TB
XV. Vaccination
1248
Toxoids (inactivated toxins)
Killed microbes
Live attenuated microbes
Synthetic peptides
Engineered organisms
TB
Study objectives
1249
1. Know how clonal selection theory answers this question: How does the
immune system respond to the millions of different foreign antigens
it encounters in a highly specific way?
It states that each animal generates perhaps a billion different lymphocytes.
Each lymphocyte is reactive to a particular antigen.
Lymphocytes that are reactive to antigens actually encountered are activated.
From this it is inferred that antibody diversity exists prior to antigen stimulation.
2. Know how antibody diversity is generated. Understand developmental gene
rearrangements, and imprecise joining.
3. Compare and contrast polyclonal and monoclonal antibodies.
4. Know how monoclonal antibodies are produced.
5. Understand neutralization, precipitation, and agglutination.
6. Understand, compare, and contrast: Direct ELISA, indirect ELISA, and RIA.
7. Know the details of the following immune diseases: delayed type
hypersensitivity, immediate type hypersensitivity, autoimmune diseases.
8. Know the role of the immune system in disease caused by superantigens.
9. What antigens or cells have been used to make vaccines?
1250
MCB 3020, Spring 2004
Chapter 23:
Microbial Diseases
Microbial Diseases:
1251
I. Sexually transmitted diseases
II. Air-transmitted bacterial diseases
III. Air-transmitted viral diseases
IV. Insect-transmitted diseases
I. Sexually transmitted diseases
A. STD facts
B. Typical symptoms
C. Neisseria gonorrhoeae
D. Treponema pallidum
E. Chlamydia trachomatis
F. Herpes simplex II
G. Papilloma virus
H. HIV
1252
TB
1253
A. STD facts
The CDC estimates 12 million
Americans / year will get an STD.
Some have serious complications
including sterility.
Many can be passed to babies at birth.
Most are curable.
All are preventable.
TB
B. Typical symptoms
1254
Painful urination
Genital blisters or sores
Penile or vaginal discharge
Often, no symptoms
TB
C. Neisseria gonorrhoeae
1255
1. Symptoms
In males:
painful urination
creamy or green pus-like
penile discharge
TB
In females:
no symptoms
painful urination
creamy or green pus-like
vaginal discharge
1256
TB
1257
2. Complications
Inflammation of the testicles that
can cause sterility
In women, its a leading cause of
pelvic inflammatory disease
(PID) which can cause sterility.
3. Treatment: cured by antibiotics
4. No acquired immunity
TB
1258
"Yet another excellent reason to use condoms"
TB
D. Treponema pallidum
1. Disease
Syphilis
1259
TB
1260
2. Symptoms
primary
chancre at infection site
secondary
skin rash
tertiary
skin, bone,cardiovascular ,CNS
3. Treatment: cured by antibiotics
TB
E. Chlamydia trachomatis
1261
1. Facts
Most common STD
~4 million cases / yr in US
usually no symptoms
sometimes urethritis
diagnosed by serological tests
TB
1262
2. Complications
In women, a leading cause of PID
and sterility.
In men, sterility (infrequent)
3. Treatment: cured by antibiotics
TB
Chlamydia infected fallopian tube
1263
Picture
37
TB
F. Herpes II
1. Facts
~20% of adults have genital herpes
often no symptoms
sometimes, genital blisters
0.1% of newborns acquire herpes
during birth.
2. Treatment: antiviral drugs (no cure)
1264
TB
G. Genital warts (papilloma virus)
1. Facts
1265
~15% of adults have genital warts
warts on genitals and perianal region
can be difficult to detect
infants can be infected during birth
increases the risk of cervical cancer
2. Treatment: antiviral drugs and/or removal
of warts with lasers or chemicals. Repeated
treatments are usually needed (no cure). TB
H. HIV (AIDS)
• No cure
• Almost always fatal
• Treatment can delay the disease
for many years
• HIV invades CD4+ cells, including TH
• For viral attachment, the HIV
envelope protein binds to the CD4
TB
protein
1266
II. Air-transmitted bacterial diseases 1267
A. Streptococcus pyogenes
B. Streptococcus pneumonia
C. Staphylococcus aureus
D. Corynebacterium diphtheria
E. Bordetella pertussis
F. Mycobacterium tuberculosis
(Please memorize this list)
TB
Air transmission
1268
Picture
27
TB
A. Streptococcus pyogenes
1. diseases
1269
a. Strep throat
~ 50% of all severe sore throats
b. Scarlet fever
sore throat with rash and diarrhea
c. Necrotizing fasciitis (flesh eating)
d. Rheumatic fever
delayed autoimmune disease
involving joints and the heart TB
2. virulence factors
hemolysins
erythrogenic toxin (scarlet fever)
superantigens (flesh eating)
1270
3. Treatment
Penicillin and erythromycin
TB
Streptococcus pyogenes
1271
Picture
28
TB
Scarlet fever patient
1272
Picture
29
Picture
30
Flesh-eating bacteria
Young boy with a red rash
on the face and body
Infected leg
TB
B. Streptococcus pneumonia
1. Diseases
major cause of pneumonia
major cause of ear infections
2. Virulence factors
capsule
3. Treatment
penicillin and erythromycin
1273
TB
Streptococcus pneumonia
1274
Picture
33
capsule
TB
C. Staphylococcus aureus
1275
1. Diseases
skin infections
food poisoning
toxic shock syndrome
TB
2. Virulence factors (many)
hemolysins (skin infections)
enterotoxin (food poisoning)
superantigens (toxic shock)
1276
3. Treatment
penicillin and erythromycin
TB
Impetigo
Picture
34
1277
Infant with
facial sores
Staphylococcal skin infection
TB
1278
D. Corynebacterium diphtheriae
1. Disease
diphtheria (severe sore throat)
2. Virulence factor
diphtheria toxin (phage encoded)
3. Treatment
antibiotics and antitoxin
4. Prevention
vaccine (DPT)
TB
Diphtheria patient
Picture
35
psuedomembrane at
the back of the throat
1279
TB
E. Bordetella pertussis
1280
1. Disease
whooping cough
severe respiratory infection of
infants <1 year of age.
2. Treatment: antibiotics
3. Prevention: vaccine (DPT)
TB
F. Mycobacterium tuberculosis
1. Disease
tuberculosis lung infection
1281
2. Virulence factor
mycolic acids
TB
1282
3. Pathology
Primary infection
usually inapparent
sometimes severe
Post-primary infection
usually chronic and spread slowly
4. Treatment: isoniazid
TB
Normal
Tuberculosis
1283
X-ray of
infected
and normal
lungs
Picture
36
Tubercles: aggregates of
activated macrophages
TB
III. Air-transmitted viral diseases
1284
A. Rhinoviruses
B. Influenza virus
C. Measles
D. Mumps
E. Rubella (German measles)
F. Chicken pox
(Please memorize this list)
TB
IV. Insect-transmitted diseases
1285
A. Rickettsias
B. Lyme disease
C. Malaria
D. The Plague
(Please memorize this list)
TB
Study objectives
1286
1. Memorize the lists of sexually transmitted diseases, air-transmitted bacterial
diseases, air-transmitted viral diseases, and insect-transmitted diseases.
2. Memorize the details about the microbial pathogens, diseases, and treatments
presented in class.
More info on various diseases:
http://www.cdc.gov/ncidod/diseases/index.htm
More info on STD's
http://www.cdc.gov/nchstp/dstd/disease_info.htm
TB
STD PREVENTION
1287
Abstinence from both genital and oral sex is the only way to be 100% sure
that you are protected from sexually transmitted infections.
If you are sexually active, you can lower your risk by following these guidelines:
Use condoms. Condoms do not provide perfect protection, they do
provide the best protection available. Condoms should be used for vaginal,
anal, and oral intercourse.
Form a monogamous relationship in which both you and your partner are
faithful to each other at all times. Do not engage in sexual intimacy until both
of you have been tested.
Limit your number of partners. Your risk of acquiring STD's increases as your
number of partners increases.
Regular check-ups. STD testing should be part of your regular exam. Do not
wait for symptoms to appear. You should see your health care provider regularly
if you or your partner have other sexual contacts.
DO NOT BECOME SEXUALLY INTIMATE WHEN DRINKING ALCOHOL
OR USING OTHER DRUGS. Drugs reduce your ability to make sensible
decisions.
TB
1288
MCB 3020, Spring 2004
Chapter 23:
Microbial Diseases II
Major Microbial Diseases II:
III. Air-transmitted viral diseases
IV. Insect-transmitted diseases
V. Food-transmitted disease
VI. Water-transmitted diseases
1289
III. Air-transmitted viral diseases
A. Rhinoviruses
B. Influenza virus
C. Measles
D. Mumps
E. Rubella (German measles)
F. Chicken pox
(Please memorize this list)
1290
A. Rhinoviruses
1. disease
The common cold
1291
>100 serotypes
of rhinoviruses
several other
types of viruses
also cause colds
1292
B. Influenza virus
1. Diseases
The flu
Symptoms often include achiness,
high fever, vomiting and/or diarrhea
secondary infection by bacteria
can kill weakened people
1293
2. Rapid mutation of influenza
antigenic shift:
the exchange of genome
segments during co-infection.
antigenic drift:
accumulated mutations
3. treatment
Vaccines are partially effective
C. Measles
1294
Disease: Rash, fever, and cough
Prevention: Vaccine (MMR)
D. Mumps
Disease: inflamation of the
salivary glands.
Prevention: vaccine (MMR)
1295
E. Rubella (German measles)
Disease: mild rash and cough
Infection of pregnant women can
cause birth defects
Prevention: vaccine (MMR)
1296
F. Chicken pox
Disease: mild fever and rash
Shingles: Reactivation of the
chicken pox virus resulting in
painful eruptions.
Prevention: vaccination
1297
IV. Insect-transmitted diseases
A. Rickettsias
B. Lyme disease
C. Malaria
D. The Plague
1298
1299
A. Rickettsias
Obligate intracellular parasites
"fever-rash" diseases
1300
1. Rickettsia rickettsia
Rocky mountain spotted fever
spread by ticks
2. Rickettsia prowazekii
Typhus fever
spread by body louse
3. Treatment: cured by antibiotics
B. Lyme disease
1301
~15,000 cases / yr in US
1. Cause
Borrelia burgdorferi
2. Symptoms
Flu-like symptoms, arthritis
Erythema migrans in 75% of cases
erythema migrans
Picture
38
1302
1303
3. Transmission
Spread by bites from infected ticks
Ticks usually found in grassy areas
4. Prevention:
Insect repellant and protective clothing
5. Treatment:
Cured by antibiotics if diagnosed early
1304
Ixodes dammini (deer tick)
Picture
40
Ixodes
drinking blood
nymph
Picture
38
pin
1305
C. Malaria
1. Cause
4 species of Plasmodium (protozoan)
2. Symptoms
Flu-like symptoms
Intermittent high fever
3. Transmission
Spread by bites from infected
Anopheles mosquitoes
4. Prevention
Mosquito control
Mosquito repellents
Antimalaria drugs
Consult your physician before
travelling to tropical and
subtropical regions.
5. Treatment: anitmalaria drugs
1306
1307
Red blood cells
infected with
Plasmodium
(malaria)
Picture
41
D. The plague
1. Facts
1308
~20 cases / yr in US
2. Cause
Yersinia pestis
3. Symptoms
painful swollen lymph nodes,
pneumonia, septicemia (invasion of
bloodstream by virulent microorganisms)
4. Transmission
bites by infected rat flea
and airborne by diseased people
1309
5. Treatment: cured by antibiotics
6. Prevention: No rats, no fleas, no plague
Bubo: painful swollen lymph node
1310
Picture
42
V. Food-transmitted disease
A. Food poisoning
1311
1. Symptoms
Diarrhea, vomiting, bloody stool
2. Transmission
Bacterial contamination of food
3. Common causes
1312
Salmonella enterica
Campylobacter
Staphylococcus aureus (enterotoxin A)
Clostridium perfringens
Clostridium botulinum
Shigella dysenteriae
E. coli O157:H7 ("burger bug")
4. Prevention: proper food handling
5. Treatment: sometimes, antibiotics
Food-poisoning examples
Shigella dysenteriae
1313
• Causes bacillary dysentery (Shigellosis)
• Bloody diarrhea, ulceration, mucous and pus
secretion, fever, vomiting
• Also causes hemolytic uremic syndrome
(red blood cell destruction and kidney failure)
• Produces a potent enterotoxin (Shigatoxin)
• Found in salad bars, bagged lettuce, and
vegetables
Food-poisoning examples
Escherichia coli O157:H7
1314
• Enterohemorrhagic Escherichia coli (EHEC)
are potent foodborne pathogens
• E. coli O157:H7 produces a shiga-like
verotoxin
• Toxin can lead to severe bloody diarrhea
• Hemolytic uremic syndrome
• Sources: ground beef, apple cider
1315
B. Ulcers
1. Most common cause
Helicobacter pylori (HP)
2. Symptoms
Burning sensation between
breastbone and belly button
3. Treatment
HP ulcers can be cured by
antibiotics
1316
4. Urease production protects organism
from stomach acid with cloud of ammonia
Picture
43
Helicobacter pylori infection of stomach lining
VI. Water-transmitted diseases
A. Symptoms
1317
diarrhea, vomiting, bloody stool
B. Causes of water-transmitted diseases
1318
1. Bacteria
• Vibrio cholerae (cholera)
• Salmonella typhi (typhoid fever)
2. Enteric Viruses
• Hepatitis A
• Rotavirus (common cause of infantile diarrhea)
• Norwalk agent
3. Protozoans (single-celled eukaryotes)
• Cryptosporidium parvus (cryptosporidiosis)
• Giardia lamblia (giardiasis)
• Entamoeba histolytica (amoebic dysentary)
C. Transmission
Fecal contamination of water
D. Treatment
For some bacterial infections,
antibiotics
1319
Study objectives
1. Memorize all the details about the microbial pathogens, diseases, and
treatments presented in class.
More info on various diseases:
http://www.cdc.gov/ncidod/diseases/index.htm
More info on STD's
http://www.cdc.gov/nchstp/dstd/disease_info.htm
1320