01Intro and Innate Immunity

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Microbiology 532: Immunology

Dennis E. Lopatin, Ph.D.Dept. of Biologic and Materials Sciences

4209 Dental Building

Office Hours by Appointment

Phone: 647-3912

Electronic mail: [email protected]


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Helpful Hints

Readings in text are beneficial

I expect you to read the relevant chapters in Nester.

Understanding the concepts is not optional

Think, rather than memorize

Test questions are based on concepts Ask questions

Dont wait until the last minute to study

Check the website


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Lecture 1Immunology

Introduction & Innate immunity


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Why Does a Dentist Need to

Understand Immunology?

Many of the oral diseases have an immune component Periodontal disease Caries Sjgrens Syndrome

Current and future therapeutics affect the immunesystem and oral health

Systemic and Oral diseases are interrelated Cooperation with other health care professional requires

common language


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What is immunity?

Protection from infection, tumors, etc.

Innate immunity is always available

Adaptive immunity distinguishes self fromnon-self and involves immune systemeducation

Responses that may result in host tissue

damage


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Two types of immunity

Innate immunity (not antigen-specific) Anatomical barriers

Mechanical

Biochemical Non-specific (eg. Low pH in stomach)

Receptor-driven (eg. PAMP-recognition)

Adaptive immunity (antigen-specific) Receptor-driven

Pre-existing clones programmed to make a specific

immune response (humoral/cellular)


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Antigen

A substance (antigen) that is capable ofreactingwith the products of a specific immuneresponse, e.g., antibody or specific sensitized

T-lymphocytes.A self component may be considered an

antigen even though one does not generallymake immune responses against those

components.


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Characteristics of Adaptive Immunity

Immune response is highly specific for the antigen that triggeredit.

Receptors on surface of immune cells have same specificity as the

antibody/effector activity that will be generated Exposure to antigen creates an immunologic memory.

Due to clonal expansion and creation of a large pool of cells committed tothat antigen

Subsequent exposure to the same antigen results in a rapid and vigorous

response


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Cells

involvedin

immunity

platelets

megakaryocyteeosinophil

neutrophil

basophil

mast cell

commonmyeloidprogenitor

monocyte

macrophage

NaturalKiller cell

plasma cell

B Lymphocyte

T Lymphocyte

commonlymphoidprogenitor

Pluripotenthematopoieticstem cell


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BloodSerum or

Plasma

Leukocytes,

Platelets and RBC

Serum ProteinsMononuclear

Cells

Polymorphonuclear

leukocytes (orGranulocytes)

Immunoglobulins

ComplementClotting factors

Many others

Neutrophils

EosinophilsBasophils

Lymphocytes

(T cells, B cells& NK cells)

Monocytes

Where is that stuff?


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Lymphoid Organs

Primary or central lymphoid organs

bone marrow and thymus

where lymphocytes are generated

Secondary or peripheral lymphoid organs

where adaptive immune responses are initiated


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Distribution of Lymphoid Tissues


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Response to Initial Infection


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Stages of Response to Infection


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Courseof

TypicalAcute

Infection


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Skin

Stratified and cornified epithelium provides a

mechanical barrier

Indigenous microbiota competes with pathogens

Acid pH inhibits growth of disease producing

bacteria

Bactericidal long chain fatty acids in sebaceous

gland secretions


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Respiratory Tract

Upper Respiratory Tract

Nasal hairs induce turbulence

Mucous secretions trap particles

Mucous stream to the base of tongue where material is swallowed

Nasal secretions contain antimicrobial substances

Upper respiratory tract contains large resident flora

Lower Respiratory Tract

Particles trapped on mucous membranes of bronchi and bronchioles

Beating action of cilia causes mucociliary stream to flow up into the

pharynx where it is swallowed

90% of particles removed this way. Only smallest particles (


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Genitourinary Tract

Male No bacteria above urethrovesicular junction

Frequent flushing action of urine

Bactericidal substances from prostatic fluid

pH of urine

Bladder mucosal cells may be phagocytic

Urinary sIgA

Female (Vagina)

Large microbial population (lactobacilli)

Microorganisms produce low pH due to breakdown of glycogen

produced by mucosal cells


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Receptors

Almost all of biology occurs because recognition

Enzymatic action

Interactions between cells (cooperation/activation)

Communication between cells

Innate and adaptive immunity requires it


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Innate Immune Recognition

All multi-cellular organisms are able to recognizeand eliminate pathogens

Despite their extreme heterogeneity, pathogensshare highly conserved molecules, called

pathogen-associated molecular patterns(PAMPs)

Host cells do not share PAMPs with pathogens

PAMPs are recognized by innate immune

recognition receptors called pattern-recognitionmolecules/receptors (PRMs/PRRs)


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Typical PAMPs

Lipopolysaccharides

Peptidoglycans

Certain nucleotide sequences unique to bacteria

Other bacterial components


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Endogenous Signals Induced by PAMPs

Mediate inflammatory cytokinesAntigen-presenting cells recognize PAMPs

Same APC processes pathogens into specificpathogen-derived antigens and presents them withMHC encoded receptors to T-cells

T-cell responds only when presented with bothsignals

Different Effector Cytokines in Response to DifferentPathogens (Th1 vs. Th2)


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Antimicrobial Peptides/Defensins

Four hundred peptides described to date Defensins (3- 5-kD, four families in eukaryotes)

a-defensins (neutrophils and intestinal Paneth cells) b-defensins (epithelial cells)

Insect defensins Plant defensins

Defensins appear to act by binding to outer membraneof bacteria, resulting in increased membranepermeability.

May also play a role in inflammation and wound repair


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Complement System

Three pathways now known

Classical

Alternative

Lectin or MBL pathway (binding to mannose-containing carbohydrates)

Host cells have complement regulatory proteins

on their surface that protect them fromspontaneous activation of C3 molecules


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ll d


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Immune Cells and Innate Immunity

Phagocytes Neutrophils

Moncyte/macrophage

Eosinophils (to a lesser extent)

NK cells (large granular lymphocytes) Antibody-dependent cell-mediated cytotoxicity (ADCC)

Have two major functions Lysis of target cells

Production of cytokines (IFN-gand TNF-a)

Act against intracellular pathogens Herpesviruses

Leishmania

Listeria monocytogenes

Act against protozoa Toxoplasma

Trypanasoma


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Immune Cells and Innate Immunity (contd)

g/dT cells

Two types of T cell receptors One composed of aand bchains (basic T cell antigen receptor) One composed of gand dchains (minor population of T cells)

Two groups of g/dT cells One group found in lymphoid tissues One group located in paracellular space between epithelial cells

Recognizes unprocessed target antigen in absence of APC help

B-1 cells (minor fraction of B cells, do not require T-cell help) Mast cells

Located in serosa, under epithelial surfaces and adjacent to bloodvessels, nerves and glands

Capable of phagocytosis Process and present antigen using MHC class I or II receptors LPS can directly induce release of mast cell mediators

Complement (C3a and C5a) induce mast cells to release mediators Chemotaxis, complement activation, inflammation TNF-asecreted by mast cells results in neutrophil influx into infected site


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Summary of Innate Immunity

External and mechanical barriers

Receptors for pathogen motifs

Soluble antimicrobial proteins Pattern of cytokines produced influences

adaptive response

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