The Lymphatic System (Fig. 16.6)
Fluid from capillaries enters space between tissue
cells (now interstitial fluid)
Interstitial fluid is picked up by lymphatic
capillaries and passed to lymphatic vessels (now lymph)
Lymph passes through lymph nodes with leukocytes
Lymph enters subclavian veins and returned to blood
Overview of the body’s defenses
A. First line of defense – nonspecific defense of keeping pathogens from entering tissues (nonspecific à protects against any pathogen)
Includes…
Mechanical factors (skin, mucus membranes)
Chemicals secreted
Normal microbiota
B. Second
line of defense – Nonspecific defense against pathogens in tissues
Includes…
Phagocytes
Inflammation
Fever
Antimicrobial substances
C. Third line
of defense – specific defense against pathogens in tissues
(specific à protect against specific pathogens)
Discuss in Chapter 17
Includes…
Lymphocytes
Antibodies
First line of defense à Keeping
pathogens from entering tissues
A. Mechanical
factors
1. Skin (Fig.
16.2)
Top layer of epidermal cells is dead and contains
keratin
à Rarely penetrated by microbes
2. Mucous
membranes
Top layer of cells is live à less protection than skin
3. Tears
Wash microbes from eye (Fig. 16.3)
4. Saliva
Wash microbes from mouth
5. Mucus and
cilia (Fig 16.4)
Mucus traps microbe, cilia moves mucus out of
respiratory passages
B. Chemical
factors
1. Sebum
Secreted by oil glands on skin
Inhibits growth of certain pathogens
2. Lysozyme
Enzyme that breaks down Gram Positive bacteria
Found in perspiration, tears, saliva
3. Gastric
Juice
HCl, enzymes
Destroys most bacteria and toxins
C. Normal
Microbiota
Normal flora outcompete pathogens
The second line of Defense à Nonspecific defense against pathogens in tissues
A.
Phagocytosis
1. Phagocytic
cells (certain types of leukocytes) (Fig. 16.5)
a.
Neutrophils –
First to site of infection
b. Monocytes
in blood à macrophages in
tissue (Fig. 16.7)
Predominant phagocytes as infection proceeds
c.
Eosinophils
Minor phagocyte
Usually attack parasites (helminths)
2. The
Mechanism of Phagocytosis (Fig. 16.8)
a. Chemotaxis
and adherence
Phagocytes attracted to site of infection and attach
to microbe or foreign material
b. Ingestion
Pseudopods engulf organism
c. Phagosome
formed
d.
Phagolysosome formed
Lysosome fuses with phagosome
e. Digestion
Enzymes kill microorganisms and digest
f. Residual
body formation
Contains indigestible material
g. Discharge
of wastes
Exocytosis of residual body
B.
Inflammation
Local
response of body to injury or infection
1. Four signs
and symptoms of inflammation (SHaRP)
a. Swelling
b. Heat
c. Redness
d. Pain
2. Functions
of inflammation
a. Destroy
injurious agent
b. Confining
or walling off injurious agent
c. Repair
damaged tissue
3. The
process of inflammation (Fig 16.9)
a. Tissue
damage occurs
b.
Vasodilation and increased permeability of blood vessels
c. Phagocyte
Migration and Phagocytosis
d. Tissue
repair
C. Fever
Systemic
response to injury or infection à Hypothalamus sets thermostat higher
(pyrogen – protein that causes fever)
Functions
1. High body
temp. intensifies effect of anti-viral proteins
2. Inhibit
growth of some microorganisms
3. Speed up
tissue repair
D.
Antimicrobial Substances
1. The
Complement System
Complement à Group of serum proteins that facilitate bacterial
lysis and Phagocytosis
Action of complement (Fig. 16.10)
a. Invading
microbe is bound by complement proteins (or other proteins) in blood
b. This
attracts other different complement proteins that either bind to microbe or
activate themselves
c. Outcomes
of binding/activation
(1) Inflammation
Attract phagocytes
(2) Cytolysis
Complement attacks the plasma mem. And causes lysis
(3) Opsonization
Bound complement protein signals a Phagocyte to
phagocytize the microbe
2.
Interferons
Antiviral proteins produced by host cell after viral
stimulation
Interfere with viral multiplication
Chapter
17 Specific Defenses of the Host: The Immune Response
Immunity
Specific
response to microorganisms or toxins
Response produces antibodies and specialized
lymphocytes
Two major branches of immune system (summary)
A. Humoral
immunity
B lymphocytes (B-cells) producing antibodies
B. Cell-mediated
immunity
T lymphocytes (T-cells) kill foreign cells directly
or indirectly
Antigens (Fig. 17.3)
Proteins or polysaccharides that provokes an immune
response
Contain antigenic determinants – chemically distinct
sites that immune system recognizes
Antibodies (immunoglobulins) (Fig. 17.5)
Special proteins that are soluble in body fluids
(“humors”)
B-cells contact antigen à form antibodies
Are monospecific – combine only with specific antigen
Structure
DRAW
Humoral immunity
A.
Characteristics of B cells
Specific à each B-cell can only recognize one type of antigen
Body has 100 million different B-cells that recognize
100 million different antigens
Body has only small population of each type to start
with
B. B- cell
activation (Fig 17.8)
1. A
particular B-cell binds with its particular antigen
2.
Proliferation occurs (B-cell reproduces)
3.
Differentiation occurs
B-cells change into Plasma cells (P-cells)
A few B-cells change into memory cells
4. P-cells
secrete antibodies (Ab) into circulation
5. P-cells
die off after couple of weeks
6. If later
exposure to same antigen à
Memory cells rapidly differentiate into
P-cells and proliferate and produce Ab
C. Results of
antigen-antibody binding (Fig 17.9)
1.
Agglutination
Causes clumping of bacteria
Enhances Phagocytosis
Reduces number of infectious units to deal with
2.
Opsonization
Ab coats Ag à enhances Phagocytosis
3.
Neutralization
Blocks adhesion sites of microorganisms
Blocks active sites of toxins
4. Activation
of complement
Causes cell lysis
5.
Inflammation
6.
Antibody-dependent cell- mediated cytotoxicity
Activate other non-specific immune cells to destroy
invaders
D. Primary
vs. secondary response to antigen exposure (Fig 17.10)
1. Primary
Slower and smaller increases in Ab conc. In blood
à disease
2. Secondary
Memory cells from primary exposure rapidly
differentiate into P-cells
à rapid and larger increases in Ab conc. In blood
à no disease
Cell-mediated Immunity
A.
Characteristics of T cells
Specific
Produced in the bone marrow, but mature in the Thymus
gland
Communicate with other immune cells via cytokines
(chemical messengers)
Have small population of each type to start with
Each type of T-cell can only recognize one type of
antigen
Antigen must be displayed on the surface of an APC
along with MHC
APC à antigen presenting cells
1.
macrophages (Fig. 17.15)
2. dendritic
cells (Fig. 17.12)
MHC à major histocompatibility complex
Identifying protein produced by all cells, unique to
individual
Used by immune system to distinguish self from
non-self
B. Main types
of T cells
1. Helper
T-cells (TH cells)
(a.k.a. CD4 cells)
Once activated, influence and direct activity of
other immune cells
a. Subtypes
(1) TH1
cells
Activate macrophages and cytotoxic T cells
(2) TH2
cells
Activate B-cells to produce antibodies
b. TH
activation (Fig. 13.13)
(1) APC
phagocytizes and processes antigen.
Antigen-MHC complex presented on surface
(2) TH
cell binds to complex on APC
(3) Cytokines
produced by both cells cause proliferation (clonal expansion) of TH
cells
(4) TH
clones produce cytokines that stimulate other immune cells
2. Cytotoxic
T cells (TC cells)
(a.k.a. CD8 cells)
Lyse virus infected host cells and cancer cells
TC activation (Cell-mediated cytotoxicity)
(Fig. 17.14)
a. TC
binds to Antigen-MHC complex in virus infected cell
b. TC
releases perforin à
infected cell membrane attacked
c. Infected
cell lyses
The duality of the immune system (Fig. 17.18)
à Tying together humoral and cell mediated immunity
Types of acquired immunity
A. Natural
active immunity
Follows exposure to an antigen as a result of natural
infection
Active à immune response activated
Ex: Contract
chickenpox as a child à
immune from then on
B. Artificial
active immunity
Follows exposure to a vaccine (harmless antigen that
is similar to pathogen)
Active à immune response activated
Ex: polio
vaccine
C. Natural
passive immunity
Fetus obtains maternal antibodies or newborns obtain
from breast milk
Temporarily protects newborns from infectious disease
Passive à newborn is not mounting an immune response
D. Artificial
passive immunity
Antibodies produced by immune individual are injected
into another recipient to provide temporary protection
Passive à patient is not mounting an immune response to toxin
Ex: Inject
horse with botulinum toxin
à horse produces antibodies to toxin
àBotulism patient gets horse antibodies
à toxin neutralized
à patient lives
Chapter
18 Practical Applications of Immunology
Vaccines
Suspension of organisms or fractions of organisms
that is used to induce immunity
Provokes a primary immune response forming antibodies
and memory cells
Later when encounter actual disease agent, produce
rapid, intense secondary response à no disease
Types of Vaccines
A. Attenuated
whole-agent vaccines
Living but attenuated (weakened) microbes
More closely mimic actual infection à more effective
However, there is a slight danger live microbes can
back mutate to a virulent form
Not recommended for immune compromised people
Ex: Sabin
polio vaccine
MMR
B.
Inactivated whole-agent vaccines
Microbes that have been killed, usually by formalin
or phenol
Ex: Salk
polio vaccine
Influenza vaccine(Fig. 18.1)
Rabies vaccine
C. Toxoids
Inactivated toxins
Directed at toxins produced by pathogen
Require a series of injections followed by boosters
Ex:
Tetanus vaccine (DTaP)
Diphtheria vaccine (DTaP)
D. Subunit
vaccines
Use only antigenic fragments of microbe
1. Acellular
vaccines
Fragment separated from a disrupted bacterial cell
Ex: acellular
Pertussis vaccine (DTaP)
2.
Recombinant vaccines
Use genetic engineering to produce desired antigenic
fraction
Ex: Hepatitis
B vaccine
Viral gene for part of capsid inserted into yeast
à yeast produces protein that is used for vaccine
E. Conjugated
vaccines
Young children do not respond well to vaccines based
on capsular polysaccharides
So polysaccharides are combined with proteins, such
as the diphtheria toxoid, to enhance immune response
Ex: Haemophilus
influenzae type b vaccine (Hib)
Gives significant protection even at 2 months old
F. Nucleic
acid vaccines
Experimental
Plasmids of “naked” DNA that codes for antigen is
injected into body
Cells in body produce antigenic protein
Schedule
of childhood immunizations (Fig. 18.3)
Chapter 19 Disorders Associated with the Immune System
Acquired Immunodeficiency Syndrome (AIDS)
A.
Etiology: Human Immunodeficiency
Virus (HIV)
B.
Origin: ~1930 – monkeys
butchered for food in central Africa
à virus transferred to humans
1959 – earliest documented case (from saved blood
samples) in Congo
1983 – HIV identified as cause of AIDS
C. Structure
of HIV: (Fig. 19.12)
Enveloped virus with single stranded RNA genome
gp120 spikes in viral envelope bind to CD4 receptors
on T cells and macrophages
D. HIV
infection:
Infection can…
a. Remain
latent (Fig. 19.13a)
Provirus inactive
b. Be active
(Fig 19.13b
(1) Synthesis
of viral RNA and proteins
(2) Assembly
(3) Release –
by budding
E. Ways HIV evades
immune system:
1. Provirus
inside host cell is not accessible to antibodies
2. Virus can
infect by cell-cell fusion, not accessible to Ab
3. Virus
undergoes rapid antigenic changes
F. Stages of
HIV infection: (Fig. 19.15)
Category A
Asymptomatic or chronic swollen lymph nodes
Category B
Early indications of immune failure
à Chronic yeast infections, diarrhea, etc,
Category C
About 10 years from initial infection
Clinical AIDS à immune system failure
CD4 T cell population less than 200/mm3
Opportunistic infections
à Pneumocystis pneumonia, Kaposi's sarcoma, etc.
G.
Transmission:
1. Sexual
contact
2.
Transplacental infection of the fetus (in 20% of infected mothers)
3.
Blood-contaminated needles
H. AIDS
worldwide: (Fig. 19.16)
20 million deaths
40 million currently HIV infected
14, 000 new HIV infections per day
I. Prevention
1.
Discouraging sexual promiscuity
2. Condom use
3. Vaccines
under development, but many problems to solve
J. Treatment:
Combination of reverse transcriptase inhibitors and
protease inhibitors
Up to 40 pills a day on a complex and rigorous
schedule
NOT A CURE à Reduces viral load in blood but does not eliminate
latent virus
Chapter
20 Antimicrobial Drugs
Chemotherapeutics – chemical used in the treatment of
disease
A.
Antibiotics
Produced by microorganisms
Inhibits other microorganisms
Main sources
Bacteria à Streptomyces, Bacillus
Molds à Penicillium, Cephalosporium
Ex:
Penicillin (Fig. 20.1)
B. Synthetic
drugs
Produced in lab by mixing chemicals
Ex: Sulfa
drugs
The spectrum of Antimicrobial Activity (Table 20.2)
A. Narrow
spectrum
Only affect narrow range of microorganisms
Ex: only
affects Gram positive
B.
Broad-spectrum
Affects wide range
Ex: affects
Gram positive and negative
Classes of antimicrobials
A.
Bactericidal – kill microbes
B.
Bacteriostatic – prevent microbes from growing (but don’t kill)
The Actions of antibacterial drugs (Fig. 20.2)
A. Inhibition
of Cell Wall Synthesis
Prevent synthesis of intact peptidoglycan
Ex: Penicillin
G (Fig. 20.3)
Core of penicillin is Beta lactam ring (Fig. 20.6)
Source: Penicillium
(mold)
Spectrum:
Narrow (Gram +)
Uses:
staphylococci, streptococci, spirochetes
Ex:
Cephalosporins
Source: Cephalosporium
(mold)
Spectrum:
Broader (Gram +, some Gram - )
Advantages of semisynthetic penicillins over
Penicillin G
1.
Penicillinase resistance (Fig. 20.8)
2.
Broad-spectrum activity
3. Acid
resistance – survive stomach acids
B. Inhibition
of Protein synthesis
Eukaryotic cells have 80s ribosomes
Prokaryotic cells have 70s ribosomes
à good target à interfere with ribosomes à bad or no translation
Ex:
Tetracyclines
Source: Steptomyces
(bacteria)
Spectrum:
broad (Gram + and -)
Uses: UTI’s,
pneumonias, chlamydia, acne
C. Injury to
the plasma membrane
Change permeability of plasma membrane à lose important metabolites
Ex: Polymyxin
B
Source:
Bacillus (bacteria)
Spectrum:
narrow (Gram -)
Uses: topical
treatment of superficial infections
D. Inhibition
of Nucleic acid synthesis
Interfere with DNA replication and transcription
Ex: Rifampin
Source: Streptomyces
(bacteria)
Spectrum:
narrow (Mycobacterium)
Uses: Treat
TB and leprosy
E. Inhibition
of essential metabolite synthesis
Inhibits enzyme activity
Ex: Sulfa
drugs
Source:
Synthetic
Spectrum:
broad (Gram + and -)
Uses: certain
UTI’s
Action of antifungal drugs
Usually target ergosterol in plasma membrane (animals
have cholesterol instead)
Ex: Azoles
(miconazole, etc.)
Source:
Synthetic
Spectrum:
narrow (fungi)
Uses:
Athletes’ foot, vaginal yeast infections
Actions of Antiviral Drugs
A. Nucleoside
and nucleotide analogs
Substitute for regular nucleoside (sugar + phosphate)
or nucleotide (sugar + phosphate + base) and block viral replication
Ex: Acyclovir
(Fig. 20.16) à
treat genital and oral herpes
B. Enzyme
inhibitors
Inhibit enzymes used in viral cycle
Ex: Protease
inhibitors
Used to control HIV infections
Inhibits enzyme that cuts up proteins to make viral
capsid
C.
Interferons
Inhibits further spread of infection by having immune
system destroy virus-infected cell
Ex:
Alpha-interferon
Treat viral hepatitis infections
Tests to guide chemotherapy
A.
Disk-diffusion method (Fig. 20.17)
Used to determine whether a bacteria is sensitive or
resistant to an antibiotic
Procedure
1. Make
bacterial lawn
2. Place
antibiotic soaked paper disks
3. Incubate
4. Measure
zones of inhibition
Large zone à more sensitive to antibiotic
B. Broth
dilution tests (Fig. 16-15 handout)
Used to determine
1. Whether an
antibiotic is bactericidal or only bacteriostatic
2. Minimum
bactericidal concentration (MBC)
3. Minimum
bacteriostatic concentration (MIC)
Procedure
1. Make
dilution series of antibiotic
2. Add
bacteria
3. Incubate
4. Find most
minimum concentration that inhibits bacterial growth
Drug resistance
A. Causes of
resistance
1.
Indiscriminate use (Fig. 20.21)
Ex: Using
antibiotic to treat viral infection
2. Not
finishing the full drug regimen
Resistant strains survive
B. Mechanisms
of resistance
1.
Destruction or inactivation of drug
Ex: some
bacteria produce Beta-lactamase, which clips beta-lactam ring on penicillins
2. Prevention
of penetration to target site
Ex:
frequently seen in tetracycline resistance
à drug can’t get in cell to target site
3. Alteration
of the drugs target sites
Ex: change on
amino acid on ribosome
à anti-protein synthesis drugs won’t bind
4. Rapid
ejection
Ex: drug is
pumped out of cell before effective