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Host-Microbe Interactions
http://www.cellsalive.com/mac.htm
Clinical and laboratory features of patients with an
inherited deficiency of neutrophil membrane
complement receptor type 3 (CR3) and the related
membrane antigens LFA-1 and p150,95. Ross GD.
Over the last 3 years a group of more than 20 patients has
been described worldwide who have a similar history of
recurrent bacterial infections and an inherited deficiency
of three related leukocyte membrane surface antigens
known as CR3, LFA-1 and p150,95 (function unknown).
It is believed that the patients with this disease have a
reduced or absent expression of all three antigen family
members on different WBC types. Neutrophils have a
reduced phagocytic response to bacteria and yeast as
well as a reduced ability to migrate into sites of infection.
• Adapted from J Clin Immunol. 1986 Mar;6(2):107-13.
The Complement System
• Activated in 3 ways
– Antibody-antigen (augments specific defense)
– Molecules that recognize bacterial sugar polymer
(mannan)
– “Random binding” to cell surfaces (C3b)
• Triggers a cascade
• 3 effects
Effects of complement system
1. Opsonization
2. Membrane Attack Complex (Lysis)
http://www.blackwellpublishing.com/trun/artw
ork/Animations/Overview/overview.html
3. Inflammation
trauma or infection
vasodilation
A) phagocytosis.
B) chemotaxis.
C) diapedesis.
D) cytoadherence.
FEVER
• Hypothalamus controls
body temp
• Pyrogens resets temp
set point
• Pyrogens: cytokines;
LPS
• Unfavourable for
bacterial replication
• Favourable for immune
response--phagocytosis;
lymphocyte replication
etc
Interferon and viral infections: a protective alerting system
Complement and immunoglobulins can coat the outer
surface of a microorganism, enhancing phagocytosis.
This process is called
A) chemotaxis.
B) fixation.
C) opsonization.
D) endotoxicity.
E) membrane attack complexing.
Host-Microbe Interactions
2. Infection
3. Disease
All of the following statements are true with regard
innate immunity EXCEPT:
A) amylase
B) lysozyme.
C) keratinase.
D) streptokinase.
E) peptidase.
First line of defense-
Chemical & Physical Barriers
Which of the following substances is produced by the
cells in our body and interferes with the multiplication of
viruses by stimulating the production of antiviral
proteins?
A) antivirase.
B) interferon.
C) inhibitase.
D) complement.
E) multiplicase.
Which of the following are mechanisms that protect
the respiratory system from infection?
A)1,2,5.
B)1,3.
C)1,2,3.
D)2,4.
E)1,2,3,4.
Normal Flora of Humans
What normal flora?
• A normal human has approximately 1013 body
cells and 1014 individual normal flora!
• microbes that grow on external and internal surfaces
of the body without producing obvious harmful
effects
• Transient microbial flora : only occasionally inhabit
the body.
• Symbiotic relationships: Commensal, Mutualistic,
Parasitic
Body sites that harbor
normal flora
Importance of the normal flora
• Prevent attachment of invading organisms
• Produce antimicrobial substances against
other microbes that are pathogens
• Stimulate immune system
– Cause the production of cross-reacting antibodies
• Significant nutritional source of vitamins
• Cause dental caries and gum disease
How do we acquire microflora?
• During birth & within first 12 hours after
delivery
• Breast-fed v bottle-fed
• Contact with people, environment, food.
• Eruption of teeth & introduction of solid food.
What leads to changes in the normal
flora?
• Antibiotic treatment
• Immunosuppression
• Diet
• Changes in physiology , e.g. estrogen-glycogen
effect
Normal Skin Flora
• 1000 to >1 million/ cm2
• Diphtheroids: G+ rods & cocci, e.g.
Corynebacterium & Proprionobacterium , e.g.
P.acnes (acne)
• facultatively anaerobic, coagulase negative
Staphylococci [carriers of coagulase positive S.
aureus in population]
• Yeasts
First line of defense (Non-specific resistance)
• Physical and Chemical Defenses
• Normal Flora
Second line of defense (Non-specific resistance)
• Phagocytosis
• Inflammation
• Fever
• Antimicrobial substances: Complement, Interferon
Third line of defense (Specific Resistance)
• B cells and T cells
• Antibodies and Humoral Response
• Cellular Mediated Immunity
Genetic Immunodeficiencies
Common Variable Hypogammaglobulinemia: Affecting both males and females and
occurring at any age, this disease is manifest by repeated pyrogenic infections. The
B cells fail to mature to plasma cells. Passive Ig is the common treatment.
(Immunoglobulin)
Fig. 16.06
Effects of Antigen-Antibody Interactions-2
Parasites; virally –
infected host cells
NK cells release perforins
and proteases (16.8)
How is the antibody response triggered?
1. T-cell dependent antigens 2. T-cell independent Ags
Memory
A plasma cell
Clonal Expansion
1. Negative selection
Fig. 16.11
Cellular Immunity
C
A. Recognition of virally-infected cell by cytotoxic T cell
results in apoptosis
B: Helper T-cell activation and interaction with B-cells
C. Helper T- cells can also
activate macrophages Fig. 16.19
Activated macrophage: a hungry beast!
•enlarged
•membrane becomes irregular
•increased number of _lysosomes, containing
antimicrobial substances________
•produce nitric oxide
Applications of Principles of Immunity
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IgG levels in fetus vs infant
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Can you put the types of vaccines listed into categories?
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Vaccines
• Induce artificial active immunity
• Preparation of living or inactivated microbe or
virus or their components.
• Adjuvants help to induce better response
• Effective vaccines should be safe, few side
effects, lasting protection, low cost, stable,
easy to administer
• Should induce appropriate specific response
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Attenuated immunizing vaccines
• Use modified live microbe/virus
• Induce infection & mild disease and solid long lasting immunity.
• Single dose can induce immunity
• Potential for spread to other people helps to develop HERD IMMUNITY
• Disadvantages: may cause disease, cannot use in pregnancy, require
refrigeration
• Examples: measles, mumps, rubella, Sabin polio vaccine, (Vaccinia ( for
smallpox))
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Inactivated Immunization
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Inactivated Immunization: Subunit
vaccines
• Use isolated antigens or antigen fragments: a
subunit of the total agent
– bacterial toxin (toxoid), protein subunit,
polysaccharide
– e.g vaccines against meningococci, pneumococci,
pertussis, H. influenza
– Recombinant vaccine, e.g. Hepatitis B. Require
several doses.
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Future developments & information
• HIV/AIDS, Malaria, cancer
• Use of DNA alone
• Further information: www.immunizationinfo.org
vaccine.chop.edu (Children’s Hospital of Philadelphia)
• Developing New Smallpox Vaccines, in EID, vol7, #6, 2001. On
line at www.cdc.gov/eid
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Serology
• Testing for the presence of a specific antigen
using specific antibody (antiserum)
• Examples: ELISA blood test for HIV,
home pregnancy test
http://www.sumanasinc.com/webcontent/anim
ations/content/ELISA.html
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Mechanisms of Pathogenicity
VIRULENCE FACTORS
bacterial products or structural components that contribute to pathogenicity
or disease
1. Motility
Advantage of living
in host cell:
Ready supply of nutrients
Protected environment
Mechanism of Invasion: Type III secretion system
Deliver proteins
directly from
bacterial cytoplasm
to human cell
cytoplasm
that polymerize
actin filaments.
Invasion of tissues possible too.
Low immunogenicity:
‘Teflon’ pathogens (spirochaetes)
few surface proteins
IgA protease
Viral evasion of cytotoxic T cell and NK cell attack
D. TOXINS: Virulence factors that damage the host.