Transcript 11-Immunology

Immune Defenses Against Disease
Chapter 15 (innate immunity)
Chapter 16 (adaptive/acquired immunity)
Chapter 17 (passive vs active immunization – pp 505-512)
Health lies in the balance
your immune system achieves
in its response to different
antigens
Response vs Tolerance
Modulation of response
Immune Defenses
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What are the two main arms of
the immune defense system?
1. ‘Innate’ defenses against infection
(antigen-nonspecific)
‘Barriers’ to infection
Normal microbiota
Cellular / enzymatic responses
2. ‘Acquired’ defenses against infection
antigen-specific
humoral & cell-mediated systems
These systems interact in many ways
Immune Defenses
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What are the types of
Innate Immunity?
I. Non-induced mechanisms
“Barriers to infection”
-- 1st line of defense
Anatomical
Mechanical
Cilia and mucus
Skin wounding
Immune Defenses
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Innate Immunity…
II. Cellular responses
Physiological, e.g., fever
Cellular , e.g., phagocytosis
Enzymatic, e.g., complement
Receptor-mediated
Broadly specific
-- recognize “danger signals”
-- molecules shared by
many pathogens
“PAMPs”
Responses
pathogen killing (intra- & extra-cellular)
activation of acquired immune responses
http://lpi.oregonstate.edu/infocenter/phagocytosis.html
Immune Defenses
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What are the cells
of the Immune System?
Innate
granulocytes
macrophages
Acquired
lymphocytes
‘Cytokines’ coordinate activities
Immune Defenses
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Organs of the Immune system
Primary Lymphoid organs
Bone marrow
Thymus
Secondary lymphoid organs
Spleen
lymph nodes
etc.
B-cells and T-cells circulate
Immune Defenses
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What are 4 characteristics of the
Adaptive Immune system?
Specificity
Diversity
Memory
Self/nonself discrimination
What are the two branches?
Humoral Response:
Attack free antigens via antibodies
B-cell lymphocytes
“B-cell receptors” (BCR)
Cell-mediated Response:
Hormonal regulation
Attack infected cells
T-cell lymphocytes
“T-cell receptor” (TCR)
AG on MHC proteins
Immune Defenses
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Acquired Immune system recognizes antigens
…What is an antigen?
Complex macromolecules (e.g., proteins)
-- distinctive to a pathogen (+/-)
Perceived as “foreign”
-- ‘self ‘ vs ‘non-self’
B-cell antigens (antibodies)
-- on pathogen surface
T-cell antigens
-- from intracellular pathogens
Immune Defenses
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What is an epitope?
Actual part of the antigen recognized
By antibody or T-cell Receptor
Immune Defenses
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What is an antibody?
Functional regions
antigen binding sites
constant region
-- triggers response
hinge region
What are the 5 types of antibodies
and their functions?
IgG – primary serum Ig
IgA – secretory Ig
IgM – B-cell receptor
IgE – eukaryotic Ags
IgD – membrane associated
Immune Defenses
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How does the Humoral System
respond to an infection?
“Clonal Selection”
‘Naïve’ B-cells
Activation (AG selection)
+ TH cell stimulation
Plasma cells
“Antibody” factories
Memory cells
create acquired defense
(T-cell response is similar)
Immune Defenses
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Clinical Manifestation of Immunity
Primary vs Secondary responses
Differences in:
lag time
Ab Titer
memory cells
Immune Defenses
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How do antibodies trigger
an immune response?
Blocking of receptors
Toxin neutralization
Antigen clearing
Enhanced phagocytosis
Activation of complement
Immune Defenses
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T-Killer cell activation is
carefully regulated
“Professional” antigen
presenting cells
T-Helper cells
Tc (T-Killer) cells
-- attack infected body cells
-- trigger cell death
Thus, the need for
attenuated pathogen
vaccines!
Immune Defenses
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How does the Cell-mediated
system respond to infections?
MHC proteins
-- antigen “presentation”
Role of macrophages
T-Helper cells
-- release cytokines
-- interferons, interleukins, etc
Cytotoxic-T (T-Killer) cells
-- attack infected body cels
--trigger cell lysis, apoptosis
Killer-T cell activation
Killer-T cell video
Immune Defenses
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How can our bodies produce millions of
different types of B-cells and T-cells?
Each B- or T-cell can recognize
only a specific antigen
Antibody/TCR genes are
randomly “rearranged”
Why don’t B and T-cells act against “self”
antigens?
-- Cells “tested” in bone marrow and thymus
Immune Defenses
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How is MHC different?
-- 100s of different MHC among humans
-- We each possess only 12-18
-- inherited from parents
Cause predispositions
-- Disease susceptibility
-- Allergies
-- Autoimmune disorders
Is basis of Transplant Compatibility
Immune Defenses
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Types of tolerance
Central vs Peripheral
Types of peripheral tolerance
1. Missing signals, e.g.,
-- no TH help for B-cells or Tc cells
2. Treg cells
-- Immunosuppressive cytokines
3. Tolerogenic DC cells
-- induced by missing danger signals
Immune Defenses
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Overview of Acquire immune responses
Cell meditated
TH activated by AG presented on P-APC
-- cytokines needed for
TC and B-cell activation
TC activated by DC cells &
AG presented on infected cell
-- kill target cells
Humoral
B-cells activated by free AG
Ab bind to pathogens
-- induce phagocytosis
-- activates “complement”
-- etc
Immune Defenses
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Immunization
Passive Immunotherapy
maternal antibodies
anti-toxins
Active Immunotherapy
(i.e., vaccination)
Types of vaccines
dead cells
attenuated cells
molecular components
Vaccine production
Immune Defenses
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Autoimmune disorders
Examples
Type I diabetes
-- B-cells of pancreas
Rheumatoid arthritis
-- cartilage of joints
Myasthenia Gravis
-- acetylcholine receptors
Multiple sclerosis
-- myelin sheath
Immune Defenses
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How can microbes trigger
Autoimmune disorders?
Examples
Type I diabetes -- B-cells of pancreas
Rheumatoid arthritis -- cartilage of joints
Myasthenia Gravis -- acetylcholine receptors
Multiple sclerosis -- myelin sheath
Possible examples of “Molecular Mimicry”
Immune Defenses
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What causes Allergies
Two steps
Sensitization
B-cells ----> IgE
mast cells
Triggering
mast cell activation
histamine
inflammation
IgE and Allergy
Immune Defenses
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