IMMUNOLOGY

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IMMUNOLOGY

• NON SPECIFIC DEFENSES
• http//science.nhmccd.edu/biol/inflam.html
• http//www.blink.biz/immunoanimations/
• http//www.biology.arizona.edu/immunology/tutorial
  s/immunology/main.html

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ROLE OF TOLL-LIKE RECEPTORS IN NONSPECIFIC
IMMUNITY
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NONSPECIFIC DEFENSES AGAINST MICROBIAL INFECTIONS

• PHYSICAL
• CHEMICAL
• CELLULAR
• PHYSIOLOGICAL

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PHYSICAL BARRIERS

• SKIN
• MUCOUS MEMBRANES
• BULK FLOW OF FLUIDS

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SKIN

• KERATIN MAKES IT IMPERMEABLE TO MICROBES AND
  WATER
• OUTER LAYERS DEAD --PREVENTS MANY VIRAL INFECTIONS

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• Tsetse Fly

• MOSQUITO

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MUCOUS MEMBRANES

• MUCOUS TRAPS MICROBES AND DEBRIS
• BASEMENT MEMBRANE LAMINA PROPIRA RESIST
  INVASION
• MUCOCILARY ESCALATOR PUMP

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BULK FLOW OF FLUIDS

• GI TRACT
• URINARY TRACT
• TEARS
• SWEAT

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CHEMICAL BARRIERS

• SEBUM
• LYSOZYME
• ACIDITY
• CRYPTINS
• IRON BINDING PROTEINS
• INTERFERON
• COMPLEMENT

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LYSOZYME

• DEGRADES CELL WALLS OF BACTERIA
• FOUND IN SALIVA, MUCOUS, COLOSTRUM, TEARS AND
  OTHER SECRETIONS

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ACIDITY

• ACIDS KILL OR PREVENT GROWTH OF MOST BACTERIA
• SKIN
• VAGINAL pH
• STOMACH pH

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CRYPTINS

• PRODUCED BY PANETH CELLS IN GI TRACT
• LYSOZYME ALSO PRODUCED

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PROTECT STEM CELLS OF GASTROINTESTINAL TRACT FROM
INFECTION
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IRON BINDING PROTEINS

• LACTOFERRIN TEARS, SEMEN, BREAST MILK,
  BILE AND NASOPHARYNGEAL, BRONCHIAL CERVICAL
  AND INTESTINAL MUCOSAL SECRETIONS.
• TRANSFERRIN SERUM, CEREBROSPINAL FLUID,
  SWEAT AND INTERCELLUAR SPACES OF TISSUES AND
  ORGANS

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INTERFERON

• GLYCOPROTEINS
• PRODUCED IN RESPONSE TO VIRAL INFECTIONS
• INTERFERON ALPHA
• INTERFERON BETA
• INTERFERON GAMMA

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ANTIVIRAL STATES

• BIND TO SPECIFIC SURFACE RECEPTORS
• http//www.uic.edu/depts/accc/seminars/flashintro/
  interferon.html

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COMPLEMENT

• MORE THAN 20 GLYCOPROTEIN MOLECULES
• ACT TO REMOVE PATHOGENS
• PREVENTS AND LIMITS EXTRACELLULAR BACTERIAL
  INFECTIONS
• AUGMENTS OTHER DEFENSES

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ALTERNATIVE PATHWAY

• NONSPECIFIC INTITIATION OF PATHWAY
• CENTRAL ACTIVATOR IS C3
• ACTIVATED BY LPS, TEICHOIC ACID, FUNGAL CELL WALL
  CARBOHYDRATES, OR VIRAL ENVELOPES, Ig A OR Ig E

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ALTERNATE PATHWAY
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LECTIN PATHWAY

• NEWEST PATHWAY DISCOVERED
• NONSPECIFIC
• MEDIATED BY MANNAN BINDING LECTIN OR MANNAN
  BINDING PROTEIN
• ULTIMATELY FORMS AN ENZYME THAT LEADS TO
  SPLITTING OF C3

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LECTIN PATHWAY
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C3 COMPLEMENT IS SPLIT

• FORMS C3 a and C3b
• INITIATES ENZYME CASCADE
• LEADS TO MEMBRANE ATTACK COMPLEX, CHEMOTAXIS,
  OPSONIZATION, AND INFLAMATORY RESPONSE

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FUNCTIONS OF THE COMPLEMENT SYSTEM

• TRIGGER INFLAMMATION
• CHEMOTAXIS ATTRACTS PHAGOCYTES
• OPSONIZIATION
• CYTOLYSIS
• REMOVAL OF IMMUNE COMPLEXES FROM THE BODY

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INFLAMMATORY EFFECTS OF COMPLEMENT

• C5a ANAPHYLAXTOXIN
• C3a ANAPHYLAXTOXIN
• C4a ANAPHALAXTOXIN

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C5a

• CAUSES MAST CELLS TO DEGRANULATE
• RELEASING VASODILATORS
• HISTAMINE AND OTHER
• CAUSES BLOOD VESSELS TO DILATE AND BECOME MORE
  PERMEABLE
• INCREASES EPRESSION OF ADHESION MOLEUCLES ON BOTH
  LEUKOCYTES AND VASCULAR ENDOTHELIUM
• FACILITATES DIAPEDESIS
• STIMLULATES NEUTROPHILS TO RELEASE OXYGEN
  RADICALS
• INDUCES FEVER

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C3a AND C4a DO SO ALSO BUT TO A LESSER DEGREE
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OPSONIZATION BY COMPLEMENT C3b AND C4b
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MEMBRANE ATTACK COMPLEX FORMATION BY C5b, C6,7,8,9

• MAKES PORES IN LIPID BILAYER
• OF HUMAN CELLS
• ENVELOPED VIRUSES
• GRAM NEGATIVE VIRUSES

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REMOVAL OF IMMUNE COMPLEXES BY C3b AND C4b

• ATTACH TO RED BLOOD CELLS
• CARRY IMMUNE COMPLEXES TO SPLEEN AND LIVER WHERE
  THEY ARE REMOVED BY MACROPHAGES AND DESTROYED

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CELLULAR BARRIERS

• NORMAL NATURAL FLORA
• PHAGOCYTOSIS

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NORMAL HUMAN MICROBIOTA

• SKIN
• ORAL CAVITY
• GI TRACT
• UPPER RESPIRATORY TRACT
• VAGINAL TRACT

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AREAS THAT NORMALLY ARE STERILE

• LOWER RESPIRATORY TRACT
• CENTRAL NERVOUS SYSTEM
• BLADDER

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PROBLEMS THAT CAN OCCUR WHEN YOU LOSE YOUR
NATURAL FLORA

• CANDIDA INFECTIONS
• PSEUDOMEMBRANOUS ENTEROCOLITIS

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PSEUDOMEMBRANOUS ENTEROCOLITIS
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SKIN

• STAPH. AUREUS
• STAPH. EPIDERMIS
• DIPHTHERIA SPP.
• TORULOPSIS
• PROPRIONIBACTERIUM

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ORAL CAVITY

• STREP. MUTANS
• BACTERIODES
• FUSOBACTERIUM
• VIRDANS STREP.
• ACTINOMYCETES
• LACTOBACILLUS

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THROAT

• STREP. PYROGENS
• STREP. PNEUMONIAE
• VIRIDANS STREP.
• NESSERIA SPP.
• STAPH. EPIDERMIS
• HAEMOPHILUS INFLUENZAE

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INTESTINES

• BACTEROIDES
• FUSOBACTERIUM
• ENTEROCOCCUS
• ESCHERICHIA
• LACTOBACILLUS
• STAPH. AUREUS
• CLOSTRIDIUM
• BIFIDOBACTERIUM

• ENTEROBACTER
• KLEBSIELLA
• EUBACTERIUM
• STREPTOCOCCI
• PSEUDOMONAS
• SALMONELLA
• COLIFORMS

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GENITOURINARY

• GRAM NEGATIVE ROD SPECIES
• DIPHTHEROIDS
• STAPH. EPIDERIMIS
• STREPTOCOCCI
• CANDIDA

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LEUKOCYTES

• DEFEND AGAINST INVADERS
• LESS THAN 1 OF TOTAL BLOOD VOLUMES
• 5,000 TO 10,000 CELLS PER CUBIC MILLIMETER
• PART OF IMMUNE SYSTEM

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GRANULOCYTES

• FORMED IN MYELOID TISSUES
• LOBED NUCLEI
• GRANULES IN CYTOPLASM
• CIRCULATE IN BLOOD FOR FEW HOURS BEFORE ENTERING
  TISSUES

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NEUTROPHILS

• SMALL CYTOPLASMIC GRANULES
• LOOK PINK TO BLUE BLACK WITH WRIGHTS STAIN
• LYSOSOMES AND SECRETORY VESICLES
• CALLED POLYMORPHONUCLEAR LEUKOCYTES
• MOST ABUNDANT--60-70 OF LEUKOCYTES
• PHAGOCYTIC CELLS
• INGEST BACTERIA AND OTHER FOREIGN STUFF

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EOSINOPHILS

• COARSE REDDISH ORANGE GRANULES WHEN STAINED WITH
  WRIGHTS STAIN
• LYSOSOMES
• DESTROY PARASITES AND PARTICIPATE IN SOME
  ALLERGIC REACTIONS

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BASOPHILS

• LARGE REDDISH PURPLE TO BLUE BLACK GRANULES IN
  CYTOPLASM WHEN STAINED WITH WRIGHTS
• SECRETORY VESICLES OF HISTAMINE AND HEPARIN
• FUNCTIONALLY SIMILAR TO MAST CELLS
• INFLAMMATORY RESPONSE ALLERGIC RESPONSES

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MAST CELLS

• RELEASE MEDIATORS OF INFLAMMATION
• ASSOCIATED WITH HYPERSENSITIVITY REACTIONS

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AGRANULOCYTES

• NO PROMINENT GRANULES
• MONOCYTES
• LYMPHOCYTES

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MONOCYTES

• FORMED FROM RED BONE MARROW
• AMOEBOID MOVEMENT
• IN TISSUES FORM MACROPHAGES

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LYMPHOCYTES

• MOST FOUND IN LYMPHOID TISSUES
• NK CELLS (TYPE OF NULL CELL)
• T CELLS
• B CELLS
• IMPORTANT COMPONENTS OF IMMUNE SYSTEM

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DIFFERENTIAL COUNT

• DIAGNOSTIC TEST
• RELATIVE ABUNDANCE OF EACH TYPE OF LEUKOCYTE

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PLATELETS

• SMALL CYTOPLASMIC FRAGMENTS
• MANY SECRETORY GRANULES
• 250,000 TO 400,000 PLATELETS PER CUBIC MILLIMETER
• FORMED FROM MEGAKARYOCYTES

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MEGAKARYOCYTE
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TYPES OF PHAGOCYTIC CELLS

• MONOCYTES AND MACROPHAGES

• NEUTROPHILS

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NEUTROPHILS

• MOST ABUNDANT PHAGOCYTIC CELLS
• LIVE FOR SEVERAL DAYS
• CONTINUALLY REPLENISHED BY BONE MARROW

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MONOCYTES

• LARGER CELLS
• ABLE TO MOVE INTO TISSUES AND BECOME MACROPHAGES

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MACROPHAGES

• LIVE FOR LONG PERIODS
• MAKE UP MONONUCLEAR PHAGOCYTE SYSTEM

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FIXED MACROPHAGES

• MICROGLIA
• KUPPFER CELLS
• ALVEOLAR MACROPHAGES

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MICROGLIA
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KUPFFER CELLS
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WANDERING MACROPHAGES

• MOVE FREELY THROUGH TISSUES
• MOVE IN RESPONSE TO CHEMOTACTIC SIGNALS

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CELLS OF THE IMMUNE SYSTEM

• DENDRITIC CELLS

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DENDRITIC CELLS

• LANGERHANS CELLS
• INTERSTITIAL CELLS
• INTERDIGITATING CELLS
• CIRCULATING DENDRITIC CELLS BLOOD DENDRITIC
  CELLS VEILED CELLS

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DENDRITIC CELLS
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DENDRITIC CELL
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DENDRITIC CELL EMBRACING T HELPER CELL
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LANGERHANS CELL
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LANGERHANS CELLS
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INTERDIGITATING CELL
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FOLLICULAR DENDRITIC CELLS

• NO MHC II MARKERS
• NOT ANTIGEN PRESENTING CELLS
• FOUND IN LYMPH NODES
• LOTS OF ANTIBODY AND COMPLEMENT BINDING SITES
• BELIEVED TO PLAY A ROLE IN MEMORY B CELL
  DEVELOPMENT

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FOLLICULAR DENDRITIC CELLS
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PHAGOCYTOSIS

• INGESTION OF CELLS, FLUIDS AND DEBRIS BY CELLS
• LEUKOCYTES

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HOW PHAGOCYTES KILL

• PHAGOSOMES
• PHAGOSOME LYSOSOMES
• PHAGOLYSOSOMES

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OXYGEN DEPENDENT KILLING MECHANISMS

• RESPIRATORY BURST
• SUPEROXIDE ANION
• HYDROGEN PEROXIDE
• SINGLET OXYGEN
• HYDROXYL RADICAL

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MYELOPEROXIDASE

• CONVERTS HYDROGEN PEROXIDE AND CHLORIDE IONS INTO
  HYPOCHLOUROUS ACID
• BLEACH

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REACTIVE NITROGEN INTERMEDIATES

• NITRIC OXIDE
• NITRITE
• NITRATE

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NITRIC OXIDE

• MACROPHAGES PRODUCE IT
• WHEN ACTIVATED BY INTERFERON GAMMA
• KILLS MICROBES AND TUMOR CELLS
• INHIBITS ATP PRODUCTION

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OXYGEN INDEPENDENT MECHANISMS

• LIPASES
• PHOSPHOLIPASES
• PROTEASES
• RNA ases
• DNA ases

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LYSOZYME

• DEGRADES BACTERIAL PEPTIDOGLYCAN

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DEFENSINS

• BIND TO BACTERIAL SURFACES TO FORM ION CHANNELS

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CATHEPSIN

• ELASTASE ENZYMES

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INFLAMMATORY RESPONSE

• GENERALIZED RESPONSE TO INFECTION OR TISSUE
  DAMAGE
• KILLS FOREIGN INVADERS
• KEEPS MICROBES LOCALIZED
• STOPS SPREAD OF INFECTION
• REMOVES CELL DEBRIS
• SETS STAGE FOR REPAIR

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SYMPTOMS OF INFLAMMATORY RESPONSE

• REDNESS
• HEAT
• SWELLING
• PAIN

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REDNESS

• DUE TO DILATION OF BLOOD VESSELS

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HEAT

• DUE TO CAPILLARY DILATION

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(No Transcript)
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SWELLING

• DUE TO INCREASED PERMEABILITY OF BLOOD VESSELS

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PAIN

• DUE TO PRESSURE ON NERVES FROM SWELLING
• BRADYKININS
• PROSTAGLANDINS

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EXTRAVASATION

• MARGINATION
• PAVEMENTING
• DIAPEDESIS

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MARGINATION OF PMNs
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PAVEMENTING
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DIAPEDESIS
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MAST CELLS
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MEDIATORS OF THE INFLAMMATORY RESPONSE

• CHEMOKINES
• KININS BRADYKININ
• CLOTTING SYSTEM
• FIBRINOLYTIC SYSTEM
• COMPLEMENT SYSTEM

• PLATELET ACTIVATING FACTOR
• PROSTAGLANDINS
• THROMBOXANES
• LEUKOTRIENES
• IL-1 AND 6
• TNF ALPHA
• IFN-GAMMA

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REPAIR

• IF STROMA (CONNECTIVE TISSUE FRAMEWORK) MAKES
  REPAIR YOU WILL HAVE SCAR TISSUE
• IF PARENCHYMA (FUNCTIONAL TISSUE) MAKES REPAIR
  YOU WILL STILL HAVE FUNCTIONING TISSUE

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ACUTE VS CHRONIC INFLAMMATORY RESPONSE
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ACUTE INFLAMMATORY RESPONSE

• LOCALIZED
• SYSTEMIC

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LOCALIZED

• TUMOR
• RUBOR
• CALOR
• DOLOR
• LOSS OF FUNCTION

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SYSTEMIC ACUTE PHASE RESPONSE

• INDUCTION OF FEVER
• INCREASED SYNTHESIS OF ACTH AND HYDROCORTISONE
• INCREASED PRODUCTION OF WBC
• PRODUCTION OF ACUTE PHASE PROTEINS

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CHRONIC INFLAMMATORY RESPONSE

• FORMED DUE TO PERSISTANT ANTIGEN
• FIBROSIS OCCURS
• GRANULOMA
• MULTINUCLEATED GIANT CELLS
• EPITHELOID CELLS

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CHRONIC INFLAMMATORY RESPONSE
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CHRONIC INFLAMMATORY RESPONSE

• GRANULOMA

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CHRONIC INFLAMMATORY RESPONSE

• MULTINUCLEATED GIANT CELLS
• EPITHELOID CELLS

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FEVER

• NORMAL BODY TEMPERATURE 37 DEGREES CELCIUS
• ABNORMAL INCREASE IN BODY TEMPERATURE
• PYROGENS CAUSE INCREASE

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PYROGENS

• LIPOPOLYSACCHARIDES
• NAG AND NAM OF PEPTIDOGLYCAN
• PYROGENIC EXOTOXINS
• INTERLEUKIN 1/ENDOGENOUS PYROGEN

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TYPES OF FEVERS

• CONTINUOUS
• TYPHOID FEVER
• INTERMITTENT OR SPIKING
• STREPTOCOCCAL INFECTIONS
• PHARYNGITIS
• REMITTENT
• MALARIA
• RELAPSING FEVER

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BENEFITS OF FEVER

• INCREASES PHAGOCYTOSIS
• INCREASE ENZYMATIC REACTIONS
• INTENSIFY ACTION OF INTERFERON
• REDUCES BLOOD IRON CONCENTRATION

• INCREASES BACTERIAL NEED FOR IRON
• SCREWS UP BACTERIAL ENZYME SYSTEMS

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BENEFITS OF FEVER

• INCREASES THE RATE OF ENZYMATIC REACTIONS
• INTENSIFIES THE ACTION OF INTERFERON
• CAUSES REDUCTION OF BLOOD IRON CONCENTRATIONS