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Immune Defenses Against DiseaseChapter 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

Immune Defenses 2

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

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What are the types of Innate Immunity?

I. Non-induced mechanisms “Barriers to infection”

-- 1st line of defense

AnatomicalMechanical

Cilia and mucusSkin wounding

Immune Defenses 4

Innate Immunity…

II. Cellular responsesPhysiological, e.g., feverCellular , e.g., phagocytosisEnzymatic, e.g., complement

Receptor-mediatedBroadly specific -- recognize “danger signals”

-- molecules shared by many pathogens “PAMPs”

Responsespathogen killing (intra- & extra-cellular)activation of acquired immune responses

http://lpi.oregonstate.edu/infocenter/phagocytosis.html

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What are the cells of the Immune System?

Innategranulocytes

macrophages

Acquiredlymphocytes

‘Cytokines’ coordinate activities

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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

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What are 4 characteristics of theAdaptive Immune system?

SpecificityDiversityMemorySelf/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 regulationAttack infected cells

T-cell lymphocytes“T-cell receptor” (TCR) AG on MHC proteins

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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

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What is an antibody?

Functional regionsantigen 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

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How does the Humoral Systemrespond to an infection?

“Clonal Selection”

‘Naïve’ B-cells

Activation (AG selection) + TH cell stimulation

Plasma cells“Antibody” factories

Memory cellscreate acquired defense

(T-cell response is similar)

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Clinical Manifestation of Immunity

Primary vs Secondary responses

Differences in:lag timeAb Titermemory cells

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How do antibodies triggeran immune response?

Blocking of receptors

Toxin neutralization

Antigen clearing

Enhanced phagocytosis

Activation of complement

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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

Immune Defenses 15

How does the Cell-mediatedsystem 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

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

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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

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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

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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

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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

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How can microbes trigger Autoimmune disorders?

Examples Type I diabetes -- B-cells of pancreasRheumatoid arthritis -- cartilage of jointsMyasthenia Gravis -- acetylcholine receptorsMultiple sclerosis -- myelin sheath

Possible examples of “Molecular Mimicry”

Immune Defenses

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What causes Allergies

Two steps

SensitizationB-cells ----> IgE

mast cells

Triggeringmast cell activation

histamine

inflammation

Immune Defenses

IgE and Allergy