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Immune System
Introduction• An animal must defend itself against
pathogens (organism or virus that causes a disease)
– Viruses
– Bacteria
– Fungi
– Parasites• Protozoa –heterotrophic protists (eukaryotes,
usually unicellular); giardia, trypanosoma, plasmodium (malaria)
• Worms (flatworms & roundworms)
– Prions
3 Types of Defense
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 43.1
Nonspecific: doesn’t distinguish one pathogen from another
Specific: recognition of a pathogen by lymphocytes; development of
immunity
1st Line of Defense:
Nonspecific
Skin, Mucous Membranes, Secretions
Physical barriers: skin & mucous membranes
• Mucus: viscous fluid secreted by cells of mucous
membranes, traps microbes and other particles
• Washing: tears, saliva, sweat
Chemical barriers:
• Stomach acid: kills most pathogens, but not all (ie.
giardia, hep A)
• Skin secretions: from sebaceous and sweat glands in
skin
– pH 3-5 to prevent colonization of microbes
– lysozymes: antimicrobial enzymes, digest cell walls of
bacteria
2nd Line of Defense:
Nonspecific
Inflammatory Response
& Phagocytosis
Tissue damage leads to:
• Inflammatory Response: enhanced blood
flow and vessel permeability
characteristic swelling, redness, and heat
of inflammation
• Phagocytosis: ingestion of pathogens by
phagocytes (leukocytes/WBCs)
Systemic Inflammatory Response
Severe tissue damage or infection
widespread response
– Rapid increase in leukocytes in the blood within a few hours after the initial events
– Fever can be triggered by toxins from pathogens or by pyrogens released by certain leukocytes
– Inhibits growth of some microbes, facilitating phagocytosis, and speeding up tissue repair
Septic shock: characterized by high fever and low blood pressure; most common cause of death in U.S. critical care units
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 43.5
1. Damaged cells release chem signals (histamine, prostaglandins)
2. Nearby capillaries dilate & become more permeable; fluid and
clotting agents move from the blood to the site
3. Chemokines & other chemotactic factors attract phagocytes from
the blood
4. Phagocytes consume pathogens & cell debris, producing pus
Localized Inflammatory Response
Blood Clotting: prevention of blood loss, pathogens from entering
Fig. 42.16
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Blood clotting steps1. Endothelium of blood vessel is damaged and connective
tissue is exposed to blood
2. Platelets (cell fragments) adhere to collagen fibers(glycoprotein in the extracellular matrix; nonelastic; does not tear easily) in connective tissue
3. Platelets and tissue release chemicals that makes nearby platelets sticky
4. Platelets form a ‘plug’ that provides emergency protection against blood loss
5. When vessel damage is more severe, a clot of fibrin reinforces this ‘plug’
Fibrinogen Fibrin
Fibrinogen: ‘inactive’ soluble plasma protein
Fibrin: ‘active’ insoluble plasma protein
clotting factors released from clumped platelets or
damaged cells + clotting factors in blood plasma
prothrombin thrombin
(inactive plasma protein) (an active enzyme)
thrombin catalyzes the conversion of
fibrinogen (soluble) fibrin (insoluble)
fibrin threads get woven into a ‘patch’
Red blood cells trapped in a clot of fibrin
http://media-2.web.britannica.com/eb-media/28/98328-004-5514AFAC.jpg
http://www.textbookofbacteriology.net/Phago.jpeg
Phagocytosis: ingestion of pathogens by
phagocytes (leukocytes/WBCs)
Phagocytes
1. Neutrophils
2. Monocytes
3. Eosinophils
Neutrophils
• 60%-70% of leukocytes (WBCs)
• damaged cells (by invading pathogens) release chemical
signals (cytokines) that attract neutrophils from the blood
• neutrophils enter infected tissue, engulfing and
destroying pathogens by
• self-destruct as they destroy foreign invaders
• avg life span = days
http://education.vetmed.vt.edu/Curriculum/VM8054/Labs/Lab6/IMAGES/Neutrophil%20Blood%20WITH%20LABEL%20copy.jpg
Monocytes
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin
Cummings
Fig. 43.3: phagocytosis by a macrophage
• 5% of WBCs
• more effective than neutrophils
• circulate in blood a few hours
• then migrate into tissues and develop into macrophages
macrophages: large, long-lived phagocytes
• avg. life span = months
(macrophages)
Locations of macrophages:- circulate in body: blood & lymph
- tissues: lung, liver, kidney,
connective tissue, brain,
lymph nodes, spleen
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 43.4a
Lymphatic system
Eosinophils
• 1.5% of WBCs
• large parasitic invaders (ie blood fluke, Schistosoma
mansoni)
• position themselves against external wall of a parasite,
discharge destructive enzymes from cytoplasmic
granules
http://www.funsci.com/fun3_en/blood/blood_09.gif
NOT Phagocytes: Natural Killer (NK) cells
(but part of the nonspecific response)
• destroy virus-infected body cells
• also attack abnormal body cells that could become
cancerous
• NOT phagocytic: mount an attack on the cell’s
membrane, causing the cell to lyse
A natural killer cell (NK cell, yellow)
of the immune cell attacking a cancer
cell (red).
http://www.bio-pro.de/imperia/md/images/artikelgebunden/stern/nk_tumor_338x319.jpg
3rd Line of Defense:
Specific Immunity
http://www.biooncology.com/bioonc/images/b-cell-lg.jpg
http://www.besthealth.com/besthealth/bodyguide/reftext/im
ages/tcell.jpg
T cell
B cell
Specific immunity: lymphocytes (leukocytes)
recognize and respond to particular foreign
bodies by generating selective immunity
responses throughout the body specificity
Antigens
Antigen: a foreign ‘invader’ (pathogens, transplanted
cells, cancer cells) that elicits a specific response by
lymphocytes (T cells & B cells)
– Each antigen has a particular molecular shape
– Stimulates B cells to secrete antibodies antibody
generator
Antigen receptors: membrane proteins on lymphocytes
responsible for recognizing antigens
B cell: immunoglobulins
T cell: T cell receptors
1. Lymphocytes
2 main types of lymphocytes:B lymphocytes (B cells)
T lymphocytes (T cells)
– both circulate throughout the blood and lymph
– concentrated in the spleen, lymph nodes, &
other lymphatic tissue
– specialize in recognizing different types of
antigens
– carry out specific defensive actions that
complement each other
All lymphocytes come from
stem cells
B cells
remain and mature in the
bone marrow
T cells
migrate from the bone marrow
& develop in the thymus
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 43.8
2. Immune Responses
Immunity
Antibodies: proteins produced by B cells that function as ‘effectors’ of an immune response; produced in humoral response/clonal selection; responsible for immunity
Challenge and response: immunity to a disease is only developed if the immune system is challenged by the disease
Types of Immunity
Humoral
bacteria, toxins, viruses
in
blood plasma & lymph
(body fluids)
B cells
Cell-Mediated
bacteria, viruses, fungi, protozoa, parasitic
worms, cancer
in
cells
T cells
http://library.thinkquest.org/03oct/01254/images/immune_map.jpg
Overview of immune response
Macrophage engulfs pathogen, presents antigen for
immune response
Cell Mediated
Cytotoxic (Killer)
T cells
• Cancer
• viruses
Helper
T cells
• produce cytokines
• phagocytosis
• inflammatory response
• B cells
• Memory T cells
http://library.thinkquest.org/03oct/00520/home.html
Humoral
B cell with antibodies
Helper T cell antigen
activated B cellproliferate
lots of activated B cells
plasma cells memory B cells
antibodies find/attach to pathogens phagocytosis
http://library.thinkquest.org/03oct/00520/home.html
Clonal Selection: antigen-driven cloning of
lymphocytes
Active vs Passive Immunity
Active immunity: immunological memory is
developed by the immune system when
exposed to an antigen
• Natural: the body actively produces antibodies
after being exposed to an infectious disease
• Artificial: vaccination (also called immunization)
= antigens transferred into an individual
Vaccination
• Vaccine: inactivated, killed, parts
(proteins), viable but weakened
(attenuated)
• No longer cause disease, but they can act
as antigens, stimulating an immune
response and immunological memory
• Examples: flu, yellow fever, hepatitis A & B
Immunological Memory in
Vaccination
Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings
Fig. 43.7
Active vs passive immunity (cont.)
Passive immunity: antibodies are transferred
from one individual to another; only temporary
b/c immune system has not developed
immunological memory
• Natural: antibodies are transferred from a
pregnant mother to her fetus (blood) and from a
nursing mother to an infant (breast milk)
• Artificial: antibodies from an animal already
immune to a disease are transferred via blood
transfusion or injection (ie snake antivenin)
Monoclonal Antibodies• antibodies specific for one antigen
• production
– Isolation & purification of an antigen
– Injection of antigen into healthy animal
– Immune system stimulated to form activated plasma cells which produce antibodies
– Plasma cells extracted and cultured with cancer cells
– Plasma/cancer cell hybridomas which survive for long periods of time and produce lots of antibodies
Monoclonal antibodies (cont.)
• diagnostic tests
– target antigen identification: antibodies detect
and mark antigens; signals are sent; Western
Blot, ELIZA
• colorimetric – enzymes
• chemiluminescent agents
• radioactive labels
• Fluorescent labels
– gonorrhea, HIV, Lyme disease
Monoclonal antibodies (cont.)
• Treatment
– cancer
• attach to cancer cell antigens, causes immune
response; Rituximab (B cell non-Hodgkin
lymphoma, CD20 antigen)
• Stops cancer cells from growing by blocking cell
surface protein activation
– autoimmune disorders (i.e. MS)
– delivery of medicine
Aquired ImmunoDeficiency Syndrome
• In U.S., late 1970s/early 1980s, increased rate
of Kaposi’s sarcoma & pneumonia in
homosexual men, hemopheliacs, blood
transfusion recipients, children of these gps
• Symptoms: opportunistic infections (pulmonary,
gastrointestinal), cancer (Kaposi’s sarcoma,
lymphoma), neurological disorders
(encephalopathy), fevers, sweats, weight loss
• Almost 100% mortality; most lethal pathogen
ever
Karposi’s Sarcoma is a symptom of
AIDS
Human ImmunoVirus
http://www.stanford.edu/group/virus/retro/2005gongishmail/hiv1.jpg
HIV (cont.)
• Retrovirus: RNA virus transcribes RNA into DNA; retro = backwards
• 2 major strains: HIV-1 & HIV-2
• Infects CD4 cell surface proteins on T helper cells, macrophages, some lymphocytes, some brain cells
• Transmission: via genital or colonic mucosa during sexual intercourse; blood to blood contact; breast milk
Did you know condoms (when used correctly) are 99% effective?!!
For HIV/AIDS,
you need to research:
• Global & local social implications
• Global & local economic implications
• Transmissions
• Prevention