A biological agent that causes disease or illness to its host.
Bacteria Escherichia coli
Examples Typical effects
honeymoon cystitis or urinary tract infection (UTI), peritonitis, food poisoning
Mycobacterium tuberculosis tuberculosis
toxic shock syndrome
• Every kind of cell, virus, and substance has a
unique molecular configuration that gives it an
Viruses Hepatitis liver disease
Influenza virus flu • An individual’s own cells can be recognized as
Herpes simplex virus herpes
Molluscum contagiosum rash “self” and ignored. The body can recognize
Protozoa Cryptosporidium cryptosporidiosis pathogens which are “not self”.
Giardia lamblia giardiasis
• An example of “not self” is an antigen. An
Fungi Pneumocystis jiroveci
antigen is any molecular configuration that
candidiasis triggers the formation of lymphocyte armies.
• The most important antigens are proteins on the
Prions BSE, vCJD
surface of pathogens and tumor cells.
Robert Koch (1843-1910)
Edward Jenner (1749-1823)
1. First to link a specific pathogen to a
1. Smallpox was common during the mid 18th specific disease.
century and it was known that milkmaids did
2. Injected blood from anthrax-infected
not get smallpox, but did get “cowpox”. animals into healthy animals.
2. Injected material from a cowpox sore into arm 3. Subject animals developed anthrax and
of healthy boy (his son). had bacteria in blood.
3. Six weeks later, injected material from 4. When these bacteria were grown in lab,
smallpox sores. then injected, they caused anthrax.
4. Boy remained healthy. 5. Showed that endospores could exist in
5. French called Jenner’s procedure vaccination, soil for extended periods and were
responsible for “spontaneous” out
which means “encowment”.
Louis Pasteur (1822-1895) Evolution of immune response
• Early simple organisms had phagocytes to help ingest food
1. Developed immunization particles.
procedures for other • Soon these phagocytes began engulfing other foreign bodies.
pathogens. • Lysozymes developed and assisted in breaking down cell
membranes of invaders.
2. Called them vaccinations in • Eventually cells and molecules began signaling one another about
Jenner’s honor. invaders, which would lead to attacks on them.
• Cytokines evolved in invertebrates and coordinated signaled
• About 450 million years ago the jawed fished developed white
blood cells called B and T lymphocytes, which could recognize
How does the body protect itself 1st Line of Defense
from all these potential invaders? 1. Barriers at Body Surfaces
• Intact skin – tough, impermeable, constantly
The 3 level security system: • Mucus membranes in respiratory tract, gut,
1. Barriers at body surfaces • Infection fighting chemicals in tears, saliva,
gastric fluid. Lysozymes in all three produce
2. Nonspecific responses enzymes that digest bacterial cells walls.
Urine and gastric fluid have low pH.
3. Immune responses • Harmless bacterial inhabitants that can
outcompete pathogenic visitors.
• Flushing effect of tears, saliva, urine.
2nd Line of Defense
2nd Line of Defense
2. Nonspecific Responses
What happens when a pathogen gets past our first line of defense and
enters our bodies?
Imagine a skin cut. 1. Fast acting WBCs
We get an inflammatory response: 2. Macrophages (phagocytic WBC)
• Redness 3. Complement proteins
• Swelling B. Organs with pathogen-killing functions
• Fever C. Cytotoxic cells with a range of targets
What causes these symptoms?
Inflammation Inflammation (continued)
1. Mast cells in connective tissue 3. Monocytes from stem cells become macrophages.
A. Synthesize and release histamine. A. Macrophages engulf, digest, and clean-up.
B. Trigger vasodilation (redness, warmth). B. Macrophages make chemotoxins, interleukins,
C. Increases permeability of capillaries and swelling. lactoferin, endogenous pyrogens.
2. Neutrophils, eosinophils, basophils arrive. C. Fever is good. Kills pathogens, helps to rest.
A. Neutrophils phagocytize bacteria. 4. Complement proteins (specific and nonspecific).
B. Eosinophils release enzymes that create holes A. Trigger cascading reactions.
in parasitic worm outer layer. B. Attack complexes punch holes in pathogens.
C. Basophils secrete histamine for inflammation. 5. Clotting proteins
A. Blood clots form, prevent spread of invaders.
Immune Response Figure 34.3 from page
576 of your text
Inflammation Response (nonspecific target)
e Includes histamines
Fluid and plasma Neutrophils, macrophages
Bacteria in tissue proteins leak out and other phagocytes
damages cells of capillaries engulf invaders and debris.
(swelling and pain) Macrophage secretions also
kill targets, attract more
Mast cells release Complement phagocytes, induce fever
histamine, which proteins attack and call for T and B
triggers vasodilation bacterial lymphocyte proliferation.
and increased membranes and
capillary permeability clotting factors
(redness and warmth) wall off area.
The Roles of Phagocytes The Roles of Phagocytes
• Secrete enzymes inflammation
that make holes in
parasitic worms due to histamine
• Engulf and digest
all foreign objects
3rd Line of Defense Adaptive Immunity Cast
What happens when a pathogen gets past our first line of defense and •Naïve B cells Sentries
second line of defense (inflammation) and infection becomes
Adaptive Immunity: Two attack strategies: Release specific antibodies
•Effector B cells
1. B lymphocytes 1. Antibody-Mediated Response
2. T lymphocytes 2. Cell-Mediated Response
Ready for future attacks
4 features of adaptive immunity: •Memory B cells
1. B & T cells distinguish self from nonself entities.
2. Attack specific targets – not activated by tissue damage.
3. B & T cells have a remarkable number of different receptor to antigens.
4. Adaptive immunity has memory. •Antibodies Tag infected cells for destruction.
Adaptive Immunity Cast Adaptive Immunity Cast
T Lymphocytes Others
•Helper T cells Sentries & communicators •Antigen presenting cells Stimulate activation of B & T cells
•Cytotoxic T cells Attack infected cells •MHC Major Histocompatability Complex
proteins present antigens.
•Memory T cells •Interleukins Signaling molecules
Ready for future attacks
•NK T cells Natural Killer cells •Lymphatic system Rendezvous center for disposal.
Classes of Leukocytes (White Blood Cells)
Antigen Presenting Cells
Eosinophils Neutrophils form clonal NK cells
Monocytes Basophils phagocytes;
Macrophages, Naïve B cells and Dendritic cells
attack parasitic populations kills virus
worms of effector infected and
and memory tumor cells 1. When a pathogen enters the body various cells engulf and digest the
2. The broken up invader bits are processed and combined with MHC on
the surface of the presenting cell.
3. MHC – Major Histocompatibility Complex is a self recognition protein
Mast cells B lymphocytes T lymphocytes on the surface of cells. MHC binds to pieces of processed antigens and
Dendritic cells Macrophages (B-cell) (T-cell)
secrete presents them to T & B cells.
presents antigen presents histamines secrete five types secrete
to helper T-cells antigen to T of antibodies interleukins; kills
cells; repairs infected cells
presenting cell Two types of Adaptive Immunity
1. Antibody-Mediated Response – extracellular pathogens
• B Lymphocytes
2. Cell-Mediated Response – pathogens inside cells
• T Lymphocytes
Fig. 34.5, p. 578
B and T Cell Armies Clonal Selection of a B Cell
• B and T lymphocytes have receptors for millions antigen
of specific antigens. When they recognize an 1. Only the B cell with
antigen, they trigger immune responses. antigen-receptor that
• B and T cells undergo repeated cell division to matches antigen is
make an army to fight the pathogen. stimulated to divide
• The army is divided into subpopulations of
2. Mitosis yields many
effector and memory cells. Effector cells kill the
pathogen. Memory cells are reserved for future cells with that
battles if the pathogen attacks again. receptor
• Memory cells are key to immunization.
antigen (e.g., at surface
ANTIBODY-MEDIATED IMMUNE RESPONSE of body cell infected
by intracellular bacteria,
protozoans, or viruses; or unbound
at a tumor cell’s surface) antigen Antibody-Mediated Response
CELL-MEDIATED IMMUNE RESPONSE (in this case, a
Naïve B cell antibody molecule
binds, processes, of a naïve B cell)
and displays this Antigen-presenting
particular antigen. cell processes,
displays antigen. antigen-MHC complex
displayed at cell surface
Naïve helper T cell interacts processed
with antigen-presenting cell TCR
helper T cell
antigen-presenting B cell
Naïve cytotoxic T
cell interacts with unprocessed antigen
Activated helper T cell
secretes signals. Signals
simulate cell divisions cell division and differentiations produce
and differentiation. Huge armies of effector and memory B cells
populations of effector cells
and memory cells form.
Effector B cell T cell touch-kills
secretes antibody infected body cell
molecules that bind or tumor cell.
antigen, promote Fig. 34.6, p. 579 Fig. 34.12, p. 583
its elimination effector B cell memory B cell
Antibody-Mediated Response Antibody Structure
1. Antibody consists of variable region
of heavy chain
antigen-binding site antigen-binding site
2. Certain parts of each variable region
chain are variable; light chain
impart antigen region of
Antibody-Mediated Response: B Cells Immunoglobulins
1. Antibodies: 5 main types = 1. Ig M 1. Ig A
• Secreted first • On mucous surfaces
2. Immunoglobulins “Igs”: protein products of gene shufflings
• Activate complement 2. Ig E
that take place as B cells mature and an immune response is
underway • Triggers inflammation
• Ig M 2. Ig G • Parasitic worms
• Ig G • Activate complement
3. Ig D
• Ig A proteins
• Function not understood
• Ig E • Neutralize toxins
• Cross placenta
• Ig D
• Secreted in milk
Immune Responses to Same Antigen
Generating Receptor Diversity first exposure
to the same antigen
1. Antibody-coding gene
recombines as B cell
2. Produces variable
transcripts that are translation
translated to produce
receptor portion of the
1. Similar process produces
variable T cell antigen
Figure 34.9 from page 581
of your text
1. Carried out by T cells.
2. Stimulated by antigen-
3. Main target is antigen- Cytotoxic T Helper T cell
presenting body cells (cells
with intracellular pathogens) Infected
or tumor cells.
Fig. 34.13, p. 584
HIV and AIDS
Lymphocyte Battlegrounds 1. HIV: Human Immunodeficiency Virus
• A retrovirus that attacks the body’s immune system
1. Lymph nodes filter antigens from body • Targets antigen-presenting macrophages and helper T-cells
fluids. and impairs their function
2. Macrophages, dendritic cells, B cell and T 2. AIDS: Acquired Immune Deficiency Syndrome
cells in nodes and spleen mount a • Is the result of a weakened immune system caused by the
defense. Then take antigens HIV infection
• Is the result of being HIV positive and having one or more
to the lymphatic system where
of the AIDS defining illnesses
they meet B & T cells.
• Characterized additionally by having a T cell count of 200
Fig. 34.10, p. 581
AIDS: The Immune System Compromised AIDS: The Immune System Compromised
1. Transmission: Bodily Fluids
• 5-10 year lag after infection • Blood
• Flu-like • Semen
• Vaginal Secretions
• Weight loss, fever, fatigue, night sweats • Breast Milk
• Enlarged lymph nodes 2. Treatment
• No known cure
• Opportunistic infections
• Difficult because of high mutation rates
• Pneumocystis carinii (pneumonia) 3. Prevention:
• Kaposi’s sarcoma (cancer of the • “Safe” sex
• No IV drug use
Life Cycle of HIV
HIV (Virus Particle)
HIV retrovirus and Helper T lymphocyte
Illustrations and content based on "Infection by Human Immunodeficiency Virus - CD4 Is Not Enough" by Levy, J.A. - The
New England Journal of Medicine, Vol 335, no 20, pages 1525-1527, Nov., 1996. Illustrations (c) Massachusetts Medical
HIV-1 interacts with the cell-surface receptor CD4 of Helper T cells,
and through conformational changes becomes more closely associated
with the cell through interactions with other cell-surface molecules, The CD4-binding site on HIV-1 gp120 interacts with the CD4
such as the chemokine receptors CXCR4 and CCR5. The likely steps in molecule on the cell surface.
HIV infection are as follows:
Conformational changes in both the viral envelope and the CD4 This second attachment brings the viral envelope closer to the
receptor permit the binding of gp120 to another cell-surface cell surface, allowing interaction between gp41 on the viral
receptor, such as CCR5. envelope and a fusion domain on the cell surface. HIV then
fuses with the cell.
Subsequently, the viral nucleoid enters into the cell, most likely by
means of other cellular events. Once this stage is achieved, the
cycle of viral replication begins.