Transcript Ch. 43 immune system

• Chapter 43 ~
The Body’s Defenses
T CELLS.htm
Overview
• Three cooperative lines of defense
• Defense against pathogens from food, air, water as
well as cancerous cells
• Nonspecific: (innate)
– First Line: external
– Second Line: internal
• Inflammation signals its action has been activated
• Specific: Third Line (acquired)
– Immune System
– Simultaneous with Second Line of Defense
Lines of Defense
I NONSPECIFIC DEFENSES
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First Line of defense
• External
– Prevents entry of microbes
• Skin
– Physical barrier
• Mucous membranes-trap; ciliated epithelial cells
sweep out mucus and trapped particulate
– Trachea
• Secretions: Chemical defenses:
• Oil and sweat glands create a low pH (skin 3-5)
• Normal flora help maintain this low pH
• Saliva, tears, mucous secretions contain antimicrobial proteins– for
example lysozymes
• Stomach pH—exception is Hepatitis A virus
Second Line of Defense
• First line broken….
• 1.Phagocytic white blood cells (leukocytes)
• 2.Antimicrobial proteins
• 3. Natural Killer Cells
• 4. The Inflammatory response
1. Types of Phagocytic White Blood Cells
• Neutrophils
60-70% WBCs;
Enter infected cells
Attracted by chemicals released by infected cell
engulf and destroy microbes inside infected tissue.
Short life span—few days
• Monocytes
5% WBCs
Develop into macrophages
Large; Long lived, use pseudopodia
Digest microbe
Some migrate; some strategically fixed—such as spleen,
lymph nodes and tissue
• Eosinophils
1.5% WBCs; destroy large parasitic invaders (parasitic
worms)
Position themselves against invader-discharge enzymes
Other Nonspecific Defenses
• Natural killer (NK) cells
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Don’t attack microbe directly
destroy virus-infected body cells & abnormal cells
Not phagocytes
Attack-cause cell lysis
• 2. Antimicrobial Proteins
• 1. Complement Proteins—lysis results
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2. InterferonsProduced by virus-infected cells
Inhibit viral replication and activate natural killer cells
secreted by virus infected cells—limit cell-to-cell infection
Reproduced by recombinant DNA—being tested for treatment of
viral infections and cancer
The Inflammatory Response
• Occurs upon damage to tissue
– Physical injury
– Microorganism entry
3.The Inflammatory Response (localized)
• Tissue injury; release of chemical signals~
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most common is histamine (basophils & mast cells):
• Causing Vasodilation and increased permeability;
• Prostaglandins released from WBC and damaged tissues
– This increases blood flow to injury
– Enhances delivery of clotting elements &more phagocyte( cells
release chemokines attracts) :
• The Vasodilation and increased flow of blood causes
characteristic reddening.
4- Phagocytosis of pathogens~neutrophils arrive first, followed by
macrophages
Macrophages destroy as well as clean up (pus)
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Systemic Responses to more severe
infection
Meningitis, appendicitis
Fever & Pyrogens:
leukocyte-released molecules (pyrogens) increase body
temperature—sets body’s thermostat at higher temp.
High Temp: inhibits microbe growth; facilitate
phagocytosis; speed up tissue repair
Septic Shock
Overwhelming systemic response
High fever & low blood pressure
Most common cause of death in U.S. non-coronary critical care
units
II SPECIFIC IMMUNITY
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Specific Immunity—Acquired
Immunity
• Lymphocytes provide specific defense (special kinds of
leukocytes)
– B cells and T cells
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The Innate and acquired defenses interact---Helper T
cells coordinate.
• Antigen: a foreign molecule that elicits a response by lymphocytes (virus,
bacteria, fungus, protozoa, parasitic worms); usually a protein.
• Antibodies: circulating antigen-binding immunoglobulin, produced by B cells
• Antigen receptors: plasma membrane receptors on B and T cells
• Ended here Friday
APC- Antigen Presenting Cells
• Macrophages and B-Cells
• Display internalized antigens to Th cells.
• Lymphocyctes
• Develop from Pluripotent stem
cells
in bone marrow or liver of fetus.
• Display specificity for a particular
epitope (binding site) on an
antigen.
• Recognize self from non-self cells
• 2 main types:
– 1. B Cells
– 2. T Cells (thymus)
• B-Cells
--mature in bone marrow
– Secrete antibodies (immunoglobulins)
– Recognize intact antigens (on whole
microbes found while patrolling body
fluids—blood/lymph)
– Humoral Response
– Also have membrane antibodies on
surface
– APC-present antigens to Th, then they
are activated and proliferate
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T-Cells
• mature in thymus
• don’t secrete antibodies
• 2 types
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cytoxic (killer) -T Cells
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Function in Cell-Mediated Immunity
Infected cells, cancerous, foreign cells
Receptors for Class I MHC
CD8 protein enhances binding to Th cell for activation.
Helper T-Cells
• Usually needed to activate B Cells & their
proliferation
– T-Dependent antigens
Have receptors for class II MHC proteins
CD4 protein enhances Th cell binding to B-cell in the
humoral response.
Function in both types of immune responses:
1. Humoral (free invaders in body fluids)
2. Cell-Mediated (infected, defective, foreign cell)
MHC
• Major histocompatability complex
– Glycoproteins embedded in plasma membranes.
– “self-markers”; Most polymorphic genes known
– 2 main classes:
• Class I MHC: located on all nucleated cells
• Class II MHC: specialized cells: macrophages & B cells.
• Function in antigen presentation-bind to antigen &
facilitate antigen binding to a T cell.
Clonal selection- page 905
Antigens interact with specific lymphocytes, inducing
immune responses and immunological memory
• Clonal selection: antigen-driven cloning of
lymphocytes
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Antigen binds to receptor
“Selected” cell proliferates.
2 “clones” of cells are produced.
1.Effector cells: short-lived cells
that combat the antigen.
• 2. Memory cells: long-lived cells
that bear receptors for the antigen.
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“Each antigen, by binding to specific receptors,
selectively activates a tiny fraction of cells from
the body’s diverse pool of lymphocytes; this
relatively small number of selected cells gives
rise to clones of thousands of cells, all specific
for and dedicated to eliminating the antigen.”
Induction of Immune Responses
• Primary immune response: lymphocyte proliferation and differentiation the
1st time the body is exposed to an antigen.takes 10-17 days for max response.
During this time, selected B- cells generate antibody producing
effector cells (clonal selection) called Plasma cells:
And Selected T-cells will produce effector T cells (no antibodies)
• Secondary immune response: immune response if the individual is exposed
to the same antigen at some later time~ Immunological memory
• Faster, more intense, longer than Primary
2 Types of immune responses
• Humoral immunity
• B cell activation
• Production of antibodies
• Microbes circulating in blood
and lymph (body fluids)
• Defend against free bacteria,
toxins, and viruses in body
fluids.
• Cell-mediated immunity
• Tc cell activation
• Binds to and/or lyses cells
• Defend against cells infected
with bacteria, viruses, fungi,
protozoa, and parasites;
nonself cells, cancer.
Helper T cells—bring on the calvary
• Function in both humoral (antibody production) & cell-mediated
immunity
• Activated by antigen presenting cells (APCs) bearing the class
MHCII molecule
• CD4 (Th surface protein), enhances activation, as does
Interlukin 1 (IL-1) .
• Once activated, it proliferates, clone forms, Interlukin II (IL-2)further
stimulates and helps activate B-cells and Tc
• Cytokines secreted (stimulate other lymphocytes):
a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells
b) interleukin-1 (IL-1): activates helper T cell to produce IL-2
Cell-mediated Immunity:cytotoxic T cells
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Destroy cells infected by intracellular pathogens and cancer cells
Infected cell displays antigen (pieces of pathogen) on its….
Class I MHC molecules
Activity enhanced by CD8 surface protein present on most cytotoxic T cells
(similar to CD4 and class II MHC)
• TC cell releases perforin, a protein that forms pores in the target cell
membrane; cell lysis and pathogen exposure to circulating antibodies
Antibody Structure & Function
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Globular serum proteins
Epitope: region on antigen surface recognized by antibodies
2 heavy chains and 2 light chains joined by disulfide bridges
2 Antigen-binding sites (variable region)
5 classes of Immunoglobins
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IgM: 1st to circulate; First to respond to
infection. indicates current infection; too
large to cross placenta
IgG: most abundant; crosses walls of
blood vessels and placenta; protects
against bacteria, viruses, & toxins; activates
complement
IgA: produced by cells in mucous
membranes; prevent attachment of
viruses/bacteria to epithelial surfaces; also
found in saliva, tears, and perspiration
IgD: do not activate complement and
cannot cross placenta; found on surfaces of
B cells; probably help differentiation of B
cells into plasma and memory cells
IgE: very large; small quantity; releases
histamines-allergic reaction
Abnormal immune function
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Allergies (anaphylactic shock): hypersensitive responses to environmental antigens
(allergens); causes dilation and blood vessel permeability (antihistamines);
epinephrine
Autoimmune disease: multiple sclerosis, lupus, rheumatoid arthritis, insulindependent diabetes mellitus
Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.
Antibody-mediated Antigen Disposal
• Neutralization (opsonization): antibody binds to and blocks antigen
activity
• Agglutination: antigen (and microbe) clumping
• Precipitation: cross-linking of soluble antigens (proteins)
• Complement fixation: activation of 20 serum proteins, through
cascading action, lyse viruses and pathogenic cells.
– MAC attack
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Immunity
in
Health
&
Disease
Active: naturally acquired : conferred
immunity by recovering from disease
• Active: artificially acquired:
immunization and vaccination;
produces a primary response & memory
• Passive immunity: transfer of immunity
(antibodies) from one individual to
another.
• Short term—weeks to months
natural: mother to fetus via breast milk
artificial: rabies antibodies
• ABO blood groups (antigen presence)
• Rh factor (blood cell antigen); Rh- mother
vs. an Rh+ fetus (inherited from father).
IgG
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