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Immunity
Overview of Defense Mechanisms
• Defense mechanisms include
– Barriers
• Skin, stomach acid, tears, vomiting
– Nonspecific defense mechanisms
• Phagocytosis, inflammation
– Specific defense mechanisms
• Immune response
– antibodies
– T cells
Pathogens Cause Disease
• Disease-causing agents include
– Living organisms
• Bacteria
• Fungi
• Parasites
– Nonliving infectious “particles”
• Viruses
• Prions
Bacteria
• Characteristics
– Simple (no organelles)
– Single-celled
– Small
• Infections
– Pneumonia, tonsillitis, tuberculosis, botulism, toxic
shock syndrome, syphilis, Lyme disease, etc.
• Generally treated with antibiotics
Viruses
• Extremely small, much smaller than bacteria
• Not alive
– No cells
– Unable to reproduce outside of a host cell
– No metabolic activity
• Structure
– Contain DNA or RNA
– Surrounded by protein coat
• Diseases
– AIDS, hepatitis, encephalitis, rabies, influenza, colds,
warts, chicken pox
Prions
• Infectious proteins
• Normal brain proteins not folded correctly
• Misfolding becomes self-propagating
– fills and disables cell with protein debris
• Resist cooking, freezing, drying
• Diseases
– Bovine spongiform encephalitis (BSE, “mad cow
disease”)
– Creutzfeldt-Jakob disease (CJD)
Determining Health Risk
• Transmissibility
– Ease of passage between people
• Mode of transmission
– Respiratory, fecal–oral, body fluids
• Virulence
– How much damage is caused by infection
Lymphatic System
• Functions
– Maintenance of blood volume in cardiovascular system
– Transport of fats and fat-soluble material from digestive
system
– Filtration of foreign material to defend against infection
Lymphatic System: Components
• Lymphatic vessels transport
lymph
• Lymph nodes cleanse lymph
• Spleen cleanses blood
• Thymus gland facilitates
maturation of
T lymphocytes
• Tonsils and adenoids protect
throat
Keeping Pathogens Out: The First Line
of Defense
•
•
•
•
•
•
•
Skin
Tears and saliva – contain lysozyme (antibacterial enzyme)
Ear wax – entraps microorganisms
Mucus – entraps microorganisms
Stomach – highly acidic, inhibits microorganisms
Vagina – slightly acidic, inhibits some microorganisms
Vomiting, urination, and defecation – remove
microorganisms
• Resident bacteria – outcompete pathogens
Nonspecific Defenses
• Phagocytic cells: WBCs engulf invading pathogens
– Neutrophils, macrophages, eosinophils
• Inflammation
– Redness, warmth, swelling, pain
• Natural killer cells: type of lymphocyte; attacks tumor
cells and virus-infected cells
• Complement proteins: lyse invading bacteria
• Interferons: antiviral proteins
• Fever response
1
2
Activated complement
proteins form complexes of
proteins that create holes
in the bacterial cell wall.
3
Water and salts diffuse
into the bacterium
through the holes.
The bacterium swells
and eventually bursts.
Water
and
salts
Complement
proteins
Bacterium
Cell wall of
bacteria
Photomicrograph of
an intact bacterium
A bacterium after lysis by activated
complement proteins
Figure 9.8
Specific Defense Mechanisms
(The Immune Response)
• Characteristics
– Recognizes/targets specific pathogens or foreign
substances
– Has “memory”
• “remembers” initial exposure
• responds more quickly and aggressively on subsequent
exposures
• Able to distinguish between
– Self cells and foreign invaders
– Healthy cells and abnormal (tumor) cells
Immune Response Targets Antigens
• Antigen: substance that triggers immune response
– On outer surface of invading cell or virus
– MHC (major histocompatibility complex) proteins
• Self-antigens on human cell surfaces
• Enable immune system to distinguish “self” from “nonself”
Lymphocytes
• B lymphocytes: Antibody-mediated
immunity
– Antibodies: bind and neutralize specific
antigens
– Active against viruses and bacteria
• T lymphocytes: Cell-mediated
immunity
– Directly attack foreign cells
– Coordinate immune response
– Active against parasites, viruses, fungi,
intracellular bacteria, cancer cells, cells
with “nonself” MHC
Antibody-Mediated Immunity
• B cells activated when
they recognize an
antigen
• Divide into two cell
types
– Memory cells – store
information for future
responses
– Plasma cells – actively
secrete antibodies,
which will bind to
antigen
T Cells: Cell-Mediated Immunity
• T cells
– Originate in bone marrow
– Mature in thymus
• Types of T cells
– CD4 T cells
– Helper T cells and Memory T cells
– CD8 T cells
– Cytotoxic T cells
T Cells: Cell-Mediated Immunity
• Helper T cells
– Activate other immune system cells
– Are target of HIV infection
• Cytotoxic T cells
– Attack and destroy abnormal (tumor or viral-infected)
cells and foreign cells
• Memory T cells
– Reactivate during later exposures
Immune Memory Creates Immunity
• Primary immune response
– Occurs on first exposure to antigen
– Characteristics
• Lag time of 3–6 days for antibody production
• Peak at 10–12 days
• Secondary immune response
– Occurs on second and subsequent exposure to antigen
– Characteristics
• Lag time in hours
• Peak in days
Primary immune
response
Secondary immune
response
Antibody concentration (units/ml)
100
10
1
0.1
0
7
14
1st exposure
21
28
0
7
14
21
28
35
42
2nd exposure
Time (days after exposure)
Figure 9.16
Immunization
• Active immunization
– Intentionally expose to a form of antigen that doesn’t
produce disease
– Also known as vaccination
• Passive immunization
– Administer protective antibodies to an individual
– Passed from mother to baby
Antibiotics Combat Bacteria
• Antibiotics kill bacteria or inhibit their growth
• Antibiotics are selectively toxic for bacteria
– Target features unique to prokarotes
• Antibiotics are not effective against viruses
– Cold, flu, etc
Tissue Rejection: A Medical Challenge
• Tissue rejection – recipient’s immune system attacks
transplanted tissue/organ
• To minimize risk of rejection
– Must match ABO and other blood group antigens and
MHC antigens
– 75% MHC match is essential
– Immunosuppressive drugs – Prevent patient’s immune
system from attacking transplanted tissue
Allergies
• Allergies - Inappropriate
response to an allergen
– Allergen: any substance
(antigen) that causes an
allergic reaction
•
•
•
•
Pollen
Bee venom
Foods (nuts, seafood)
Oil from poison ivy plant
• Treatment of allergies
– Antihistamines
– Epinephrine injection
– Allergy shots
Autoimmune Disorders
• Inability of immune system to distinguish “self”
from “nonself”
• Autoantibodies and cytotoxic T cells target body’s
own tissues
• Examples
– Lupus erythematosis (LE or lupus)
• Inflamed connective tissue
– Rheumatoid arthritis
• Inflamed synovial membrane
Immune Deficiency: AIDS
• AIDS: Acquired Immune Deficiency Syndrome
• Caused by infection with HIV (Human
Immunodeficiency Virus)
• HIV targets helper T cells
• Transmission via body fluids (blood, semen, breast
milk, vaginal secretions)
Retrovirus
Single-stranded
DNA made from
RNA template
Viral RNA
Nucleus
Double-stranded
DNA
Proteins
Viral coat
Core of virus
Figure 9.21
AIDS Develops Slowly: Phase I
• Phase I
– May last a few weeks to a few years
– Brief period of flu-like symptoms
•
•
•
•
•
Swollen lymph nodes
Chills
Fever
Fatigue
Body aches
– Most people don’t exhibit recognizable symptoms
– Virus is multiplying, antibodies are made but are
ineffective for complete virus removal
AIDS Develops Slowly: Phase II
• Phase II
– Occurs within 6 months to 10 years
– Opportunistic infections present
– Helper T cells affected, numbers are decreasing
– If untreated, 95% will progress to next phase (AIDS)
AIDS Develops Slowly: Phase III (AIDS)
• Phase III: Clinical AIDS
– Helper T cells fall below 200 cells/mm3
– Opportunistic infections and cancers present
•
•
•
•
•
•
Tuberculosis
Pneumonia
Meningitis
Encephalitis
Kaposi’s sarcoma
Non-Hodgkins lymphoma
– If untreated, nearly always fatal
Phase I
Phase II
Phase III
Concentration of helper T cells in blood
(cells per mm3)
900
800
700
The time of transition
from Phase II to
Phase III is highly
variable between
individuals.
600
500
T cells
400
Antibodies
300
200
100
0
HIV in blood
0
1
2
3
4
Years after infection
5
6
7
Figure 9.22
The AIDS Epidemic: A Global Health
Issue
• Worldwide
– More than 33 million infected with HIV
– 25 million dead, so far
– Most infections in sub-Saharan Africa
– Increasing spread in Asia and India
• United States
– Just over 1 million infected with HIV
– 20,000 deaths/year
Risky Behaviors Increase Your
Chances of Getting AIDS
• Males (3/4 of new cases)
– Sex with other men
– Sharing needles during intravenous drug use
– Heterosexual sex with HIV-infected female
• Females (1/4 of new cases)
– Sex with HIV-infected male
– Sharing needles during intravenous drug use
Table 9.3
Sex Can Be Safer
•
•
•
•
Abstinence
Reduce number of sexual partners
Choose sexual partners with low-risk behavior
Avoid high-risk sexual practices
– Anal-genital sex is a high-risk practice
• Use latex or polyurethane condoms or barriers
• GET TESTED
New Treatments Offer Hope
• HIV Drugs
– Reverse transcriptase inhibitors: AZT
– Protease inhibitors: ritonavir, saquinavir
– Maraviroc: new drug
• Blocks entry of HIV into T cells
– Early treatment may delay or prevent clinical AIDS
• Vaccine
– Under development and testing
– Challenge: Virus mutates rapidly
80
AIDS Deaths
(thousands)
60
40
20
0
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2004
2006
2008
Year
a) Estimated number of deaths due to HIV/AIDS, 1990-2007.
Living with AIDS
(millions)
1.5
1.0
0.5
0
1990 1992
1994
1996
1998
2000
2002
Year
b) Estimated number of people living with HIV/AIDS, 1990-2007.
Figure 9.23