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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