of 54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
1/54
Innate Immune Response
BIOL 2900
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
2/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
3/54
Overview of Innate Defenses
First line of defense are barriers that shield
interior of body from external surroundings
Anatomical barriers include skin and mucous
membranes Provide physical separation
Membranes bathed in antimicrobial secretions
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
4/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
5/54
Overview of Innate Defenses
Phagocytes are specialized cells that engulf
and digest microbes and cellular debris
Act as sentries
Alerted to signs of invasion
More phagocytes can be recruited from
bloodstream
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
6/54
Overview of Innate Defenses
Cells of immune system have elaboratecommunication system
Communication achieved through
productions of proteins Proteins act as chemical messengers Called cytokines
Cytokines from one cell defuse to another Bind to cytokine receptor on cell
Receptor transmits signal to cell interior
Induces changes in cellular activities
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
7/54
Inflammation is initiated by microbial
invasion or tissue damage
During inflammation, cells in blood vessels
undergo changes that allow certain
immune particles to leak out of the cell
Overview of Innate Defenses
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
8/54
First Line of Defense
Physical barriers Skin is most visible barrier
Covers majority of surfaces in obvious contact with
environment Mucous membranes barrier that lines digestive
tract, respiratory tract and genitourinary tract Mucous protect these surfaces from infections
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
9/54
Figure 15.3
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
10/54
Skin Provides the most difficult barrier to penetrate Composed of two main layers
Dermis Contains tightly woven fibrous connective tissues
Makes extremely tough
Epidermis
Composed of many layers of epithelial cellsAs cells reach surface, they become increasingly flat
Outermost sheets of cells embedded with keratin
Makes skin water-repellent
Outer layers slough off taking microbes with it
First Line of Defense
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
11/54
Mucous membranes Constantly bathed with mucus Helps wash surfaces
Some mucous membranes have mechanisms
to propel microorganisms and viruses to
areas where they can be eliminated
First Line of Defense
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
12/54
Antimicrobial substances Both skin and mucous membranes are protected by variety of
antimicrobial substances including Lysozyme
Enzymes that degrade peptioglycan
Found in tears, saliva, blood and phagocytes
Peroxidase
Found in saliva, body tissues and phagocytes
Breaks down hydrogen peroxide to produce reactive oxygen
Lactoferrin Sequesters iron from microorganisms
Iron essential for microbial growth
Found in saliva, some phagocytes, blood and tissue fluids
Defensins
Antimicrobial peptides inserted into microbial membrane
First Line of Defense
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
13/54
Normal flora Defined as microorganisms found growing on
body surfaces of healthy individuals
Not technically part of immune system However, provides significant protection
Protects through competitive exclusion Covers binding sites
Pathogens cant bind
Competes for nutrients
Nutrients unavailable for pathogens
First Line of Defense
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
14/54
Cells of the Immune System
Always found in normal blood Numbers increase during infection
Some cells play dual roles in both innate
and adaptive immunity Blood cell formation called hematopoiesis
Blood cells including immune cells originate
from hematopoietic stem cells in bone marrow Blood cells stimulated to differentiate by
colony-stimulating factor
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
15/54
General categories of blood cells Red blood cells (RBC) a.k.a erythrocytes
Carry oxygen in blood
Platelets Fragments of megakaryocytes
Important component in blood clotting
White blood cells (WBC) a.k.a leukocytes
Important in host defenses
Divided into four categories
Granulocytes - Mononuclear phagocytes
Dendritic cells - Lymphocytes
Cells of the Immune System
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
16/54
Cells of the Immune System
Granulocytes Contain cytoplasmic graduals
Divided into three types Neutrophils
Basophils
Eosinophils
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
17/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
18/54
Cells of the Immune System
Neutrophils Most abundant and important in innate response
Sometimes called polymorphonuclear neutrophilic
leukocytes (PMNs) Basophils
Involved in allergic reaction
Eosinophils Important in expelling parasitic worms
Active in allergic reactions
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
19/54
Cells of the Immune System
Mononulcear phagocytes Constitute collection of
phagocytic cells called
mononuclear phagocyte
system Include monocytes Circulate in blood
Macrophages differentiate
from monocytes
Present in most tissues
Abundant in liver,
spleen, lymph nodes,
lungs and peritoneal
cavity
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
20/54
In order for immune system to respond,
cells must communicate with environment
and with each other
Cell surface receptors are the eyes and
ears of the cell
Cytokines are the voice
Adhesion molecules act as the hands
Cell Communication
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
21/54
Phagocytosis
Process of phagocytosis Chemotaxis Cells recruited to infection
Recognition/attachment
Use receptors to bind invadingmicrobes
Engulfment Phagocyte engulfs invader
forming phagosome
Phagosome lysosomefusion Phagosome binds lysosome,
forming phagolysosome
Destruction and digestion Organism killed due to lack of
oxygen and decreased pH
Exocytosis Phagocyte expels material to
external environment
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
22/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
23/54
Phagocytosis Animation
http://www.sp.uconn.edu/~terry/Common/phago053.html
http://highered.mcgraw-hill.com/sites/0072495855/student_vi
http://www.sp.uconn.edu/~terry/Common/phago053.htmlhttp://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.htmlhttp://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__phagocytosis.htmlhttp://www.sp.uconn.edu/~terry/Common/phago053.html7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
24/54
Inflammation
Inflammation occurs in
response to tissue
damage
Four cardinal signs Heat
Pain
Redness
Swelling Loss of function
Fifth sign that can also be
present
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
25/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
26/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
27/54
Inflammation
The inflammatory process Initiation leads to a cascade of events Results in dilation of blood vessels, leakage of fluid from
vessels and migration of leukocytes and phagocytes
Leakage of phagocytes from blood vessels called diapedesis
Certain pro-inflammatory mediators cause the
diameter of blood vessels to increase Results in increased blood flow
Increased blood flow responsible for cardinal signs of inflammation
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
28/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
29/54
Inflammation
Outcomes of inflammation Intent is to limit damage and restore function Inflammation itself can cause considerable damage
Release of toxic products and enzymes from phagocytic cellsis responsible for tissue damage
If inflammation is limited to area of injury,damage is usually nominal
If inflammation results in delicate systems,consequences are more severe
Inflammation around brain and spinal cord can lead to
meningitis
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
30/54
Fever
One of the strongest indicators of infection Especially of bacterial infection
Important host defense mechanism Temperature regulation center of body responds
to fever-inducing substances called pyrogens Fever-inducing cytokines termed endogenous
pyrogens
Microbial products termed exogenous pyrogens
Resulting fever inhibits growth of pathogens by Elevating temperature above maximum growth
temperature Activating and speeding up other body defenses
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
31/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
32/54
Adaptive Immune Response
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
33/54
Strategy of Adaptive
Immune Response
First response to particular antigen called
primary response May take a week or more to develop
Immune system remembers pathogen on
subsequent exposure Termed secondary response
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
34/54
Nature of Antigens
Coined from compounds that elicit
antibody production Antibody generator
Includes an enormous variety of materials
Today, term used to describe any
compound that elicits an immune
responseAntigen that causes immune response
termed immunogen
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
35/54
Nature of Antibody
Protective outcomes ofantibody-antigen binding Neutralization Prevents toxin from interacting with
cell
Immobilization and preventionof adherence
Antibody bonding to cellular structures
to interfere with function
Agglutination and precipitation Clumping of bacterial cells by specific
antibody
Bacteria more easily phagocytized
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
36/54
Protective outcomes of
antibody-antigen binding Opsinization Coating of bacteria with antibody to
enhance phagocytosis
Complement activation Antibody bonding triggers classical
pathway
Antibody-dependent cellular
cytotoxicity Multiple antibodies bind a cell which
becomes target for certain cells
Nature of Antibody
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
37/54
Nature of Antibody
Ab divided into five
classes Class is based on
constant region of the
Ab
Classes include: IgG
IgA
IgM
IgD
IgE
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
38/54
Five classes of Ab IgM First Ab to respond to infection
5 13% of Ab in circulation
Only Ab that can be formed by the fetus
Nature of Antibody
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
39/54
Five classes of Ab IgG Dominant Ab in circulation
80 85% Ab in circulation
Only Ab that can cross the placenta
The antibody of memory!!!!!
IgA Found in secretions - Breast milk, mucous, tears and
saliva
10 - 13 % of Ab in circulation
Nature of Antibody
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
40/54
Five classes of Ab IgD
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
41/54
Applications of
Immune Responses
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
42/54
Principles of Immunization
Naturally acquired immunity is acquisition ofadaptive immunity through natural events
Immunization mimics these events by inducing
artificially acquired immunity Natural or artificial immunity can be divided into
Active immunity
Passive immunity
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
43/54
Principles of Immunization
Active immunity Results from immune response upon exposure to an
antigen
Active immunity can develop naturally Following illness
Or artificially After immunization
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
44/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
45/54
Principles of Immunization
Passive Immunity Occurs naturally during pregnancy IgG from mother crosses placenta
Infers protection to the baby
Occurs naturally as result of breast feeding IgA antibodies in breast milk given to child
Artificial passive immunity involves transfer of antibodiesproduced by another person or animal
Can be used to prevent disease before or after likely exposure
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
46/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
47/54
Vaccines and Immunization
Attenuated vaccines Weakened form of pathogen Generally unable to cause disease
Strain replicates in vaccine recipient Causes infection with undetectable or mild symptoms
Results in long lasting immunity
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
48/54
Vaccines and Immunization
Attenuated vaccines Advantages Single dose usually sufficient to
induce long-lasting immunity
Due to multiplication of microbe
in body
Continued stimulation of
immune system
Vaccine has added potential for
being spread
disease after immunization
could be spread to un-
immunized individuals
inadvertently
Disadvantages Have potential to cause
disease in
immunocompromised
individuals
Pregnant women should
also avoid immunization
with attenuated vaccine
Attenuated vaccines in
use include Sabin polio vaccine
MMR
Yellow fever
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
49/54
Inactivated vaccines Unable to replicate in vaccinated individual
Retains immunogenicity of infectious agent Immunogenic not pathogenic
Inactivated vaccines fall into two categories Whole agents
Contain killed organisms of inactivated virus
Cholera, plague, influenza and Salk polio are whole agents
Fragments
Portions of organisms or agents including toxins proteins and cell
wall components
Includes toxoids, protein subunit vaccines and polysaccharide
vaccines
Vaccines and Immunization
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
50/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
51/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
52/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
53/54
7/28/2019 Fv Lecture 5 - Host Defense Mechanisms, Immunity (1)
54/54
Table 17.5