IMMUNOLOGY

NON SPECIFIC DEFENSEShttp://science.nhmccd.edu/biol/inflam.htmlhttp://www.blink.biz/immunoanimations/#http://www.biology.arizona.edu/immunology/tutorials/immunology/main.html

ROLE OF TOLL-LIKE RECEPTORS IN NONSPECIFIC

IMMUNITY

NONSPECIFIC DEFENSES AGAINST MICROBIAL

INFECTIONS

• PHYSICAL

• CHEMICAL

• CELLULAR

• PHYSIOLOGICAL

PHYSICAL BARRIERS

• SKIN

• MUCOUS MEMBRANES

• BULK FLOW OF FLUIDS

SKIN

• KERATIN MAKES IT IMPERMEABLE TO MICROBES AND WATER

• OUTER LAYERS DEAD --PREVENTS MANY VIRAL INFECTIONS

• Tsetse Fly • MOSQUITO

MUCOUS MEMBRANES

• MUCOUS TRAPS MICROBES AND DEBRIS

• BASEMENT MEMBRANE & LAMINA PROPIRA RESIST INVASION

• MUCOCILARY ESCALATOR PUMP

BULK FLOW OF FLUIDS

• GI TRACT

• URINARY TRACT

• TEARS

• SWEAT

CHEMICAL BARRIERS

• SEBUM

• LYSOZYME

• ACIDITY

• CRYPTINS

• IRON BINDING PROTEINS

• INTERFERON

• COMPLEMENT

LYSOZYME

• DEGRADES CELL WALLS OF BACTERIA

• FOUND IN SALIVA, MUCOUS, COLOSTRUM, TEARS AND OTHER SECRETIONS

ACIDITY

• ACIDS KILL OR PREVENT GROWTH OF MOST BACTERIA

• SKIN

• VAGINAL pH

• STOMACH pH

CRYPTINS

• PRODUCED BY PANETH CELLS IN GI TRACT

• LYSOZYME ALSO PRODUCED

PROTECT STEM CELLS OF GASTROINTESTINAL TRACT

FROM INFECTION

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

INTERFERON

• GLYCOPROTEINS

• PRODUCED IN RESPONSE TO VIRAL INFECTIONS

• INTERFERON ALPHA

• INTERFERON BETA

• INTERFERON GAMMA

ANTIVIRAL STATES

• BIND TO SPECIFIC SURFACE RECEPTORS

• http://www.uic.edu/depts/accc/seminars/flashintro/interferon.html

COMPLEMENT

• MORE THAN 20 GLYCOPROTEIN MOLECULES

• ACT TO REMOVE PATHOGENS

• PREVENTS AND LIMITS EXTRACELLULAR BACTERIAL INFECTIONS

• AUGMENTS OTHER DEFENSES

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

ALTERNATE PATHWAY

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

LECTIN PATHWAY

C3 COMPLEMENT IS SPLIT

• FORMS C3 a and C3b

• INITIATES ENZYME CASCADE

• LEADS TO MEMBRANE ATTACK COMPLEX, CHEMOTAXIS, OPSONIZATION, AND INFLAMATORY RESPONSE

FUNCTIONS OF THE COMPLEMENT SYSTEM

• TRIGGER INFLAMMATION

• CHEMOTAXIS ATTRACTS PHAGOCYTES

• OPSONIZIATION

• CYTOLYSIS

• REMOVAL OF IMMUNE COMPLEXES FROM THE BODY

INFLAMMATORY EFFECTS OF COMPLEMENT

• C5a ANAPHYLAXTOXIN

• C3a ANAPHYLAXTOXIN

• C4a ANAPHALAXTOXIN

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

C3a AND C4a DO SO ALSO BUT TO A LESSER DEGREE

OPSONIZATION BY COMPLEMENT C3b AND C4b

MEMBRANE ATTACK COMPLEX FORMATION BY C5b, C6,7,8,9

• MAKES PORES IN LIPID BILAYER

• OF HUMAN CELLS

• ENVELOPED VIRUSES

• GRAM NEGATIVE VIRUSES

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

CELLULAR BARRIERS

• NORMAL NATURAL FLORA

• PHAGOCYTOSIS

NORMAL HUMAN MICROBIOTA

• SKIN

• ORAL CAVITY

• GI TRACT

• UPPER RESPIRATORY TRACT

• VAGINAL TRACT

AREAS THAT NORMALLY ARE STERILE

• LOWER RESPIRATORY TRACT

• CENTRAL NERVOUS SYSTEM

• BLADDER

PROBLEMS THAT CAN OCCUR WHEN YOU LOSE YOUR NATURAL FLORA

• CANDIDA INFECTIONS

• PSEUDOMEMBRANOUS ENTEROCOLITIS

PSEUDOMEMBRANOUS ENTEROCOLITIS

SKIN

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

ORAL CAVITY

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

THROAT

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

INFLUENZAE

INTESTINES

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

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

GENITOURINARY

• GRAM NEGATIVE ROD SPECIES

• DIPHTHEROIDS• STAPH.

EPIDERIMIS• STREPTOCOCCI• CANDIDA

LEUKOCYTES

• DEFEND AGAINST INVADERS

• LESS THAN 1% OF TOTAL BLOOD VOLUMES

• 5,000 TO 10,000 CELLS PER CUBIC MILLIMETER

• PART OF IMMUNE SYSTEM

GRANULOCYTES

• FORMED IN MYELOID TISSUES

• LOBED NUCLEI

• GRANULES IN CYTOPLASM

• CIRCULATE IN BLOOD FOR FEW HOURS BEFORE ENTERING TISSUES

NEUTROPHILS

• SMALL CYTOPLASMIC GRANULES

• LOOK PINK TO BLUE BLACK WITH WRIGHT’S STAIN

• LYSOSOMES AND SECRETORY VESICLES

• CALLED POLYMORPHONUCLEAR LEUKOCYTES

• MOST ABUNDANT--60-70% OF LEUKOCYTES

• PHAGOCYTIC CELLS

• INGEST BACTERIA AND OTHER FOREIGN STUFF

EOSINOPHILS

• COARSE REDDISH ORANGE GRANULES WHEN STAINED WITH WRIGHT’S STAIN

• LYSOSOMES

• DESTROY PARASITES AND PARTICIPATE IN SOME ALLERGIC REACTIONS

BASOPHILS

• LARGE REDDISH PURPLE TO BLUE BLACK GRANULES IN CYTOPLASM WHEN STAINED WITH WRIGHT’S

• SECRETORY VESICLES OF HISTAMINE AND HEPARIN

• FUNCTIONALLY SIMILAR TO MAST CELLS

• INFLAMMATORY RESPONSE & ALLERGIC RESPONSES

MAST CELLS

• RELEASE MEDIATORS OF INFLAMMATION

• ASSOCIATED WITH HYPERSENSITIVITY REACTIONS

AGRANULOCYTES

• NO PROMINENT GRANULES

• MONOCYTES

• LYMPHOCYTES

MONOCYTES

• FORMED FROM RED BONE MARROW

• AMOEBOID MOVEMENT

• IN TISSUES FORM MACROPHAGES

LYMPHOCYTES

• MOST FOUND IN LYMPHOID TISSUES

• NK CELLS (TYPE OF NULL CELL)

• T CELLS

• B CELLS

• IMPORTANT COMPONENTS OF IMMUNE SYSTEM

DIFFERENTIAL COUNT

• DIAGNOSTIC TEST

• RELATIVE ABUNDANCE OF EACH TYPE OF LEUKOCYTE

PLATELETS

• SMALL CYTOPLASMIC FRAGMENTS

• MANY SECRETORY GRANULES

• 250,000 TO 400,000 PLATELETS PER CUBIC MILLIMETER

• FORMED FROM MEGAKARYOCYTES

MEGAKARYOCYTE

TYPES OF PHAGOCYTIC CELLS• NEUTROPHILS • MONOCYTES AND

MACROPHAGES

NEUTROPHILS

• MOST ABUNDANT PHAGOCYTIC CELLS

• LIVE FOR SEVERAL DAYS

• CONTINUALLY REPLENISHED BY BONE MARROW

MONOCYTES

• LARGER CELLS • ABLE TO MOVE

INTO TISSUES AND BECOME MACROPHAGES

MACROPHAGES

• LIVE FOR LONG PERIODS

• MAKE UP MONONUCLEAR PHAGOCYTE SYSTEM

FIXED MACROPHAGES

• MICROGLIA• KUPPFER CELLS• ALVEOLAR

MACROPHAGES•

MICROGLIA

KUPFFER CELLS

WANDERING MACROPHAGES

• MOVE FREELY THROUGH TISSUES

• MOVE IN RESPONSE TO CHEMOTACTIC SIGNALS

CELLS OF THE IMMUNE SYSTEM

DENDRITIC CELLS

DENDRITIC CELLS

• LANGERHANS CELLS

• INTERSTITIAL CELLS

• INTERDIGITATING CELLS

• CIRCULATING DENDRITIC CELLS BLOOD DENDRITIC CELLS VEILED CELLS

DENDRITIC CELLS

DENDRITIC CELL

DENDRITIC CELL EMBRACING T HELPER CELL

LANGERHAN’S CELL

LANGERHANS CELLS

INTERDIGITATING CELL

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

FOLLICULAR DENDRITIC CELLS

PHAGOCYTOSIS

• INGESTION OF CELLS, FLUIDS AND DEBRIS BY CELLS

• LEUKOCYTES

HOW PHAGOCYTES KILL

• PHAGOSOMES

• PHAGOSOME + LYSOSOMES

• PHAGOLYSOSOMES

OXYGEN DEPENDENT KILLING MECHANISMS

• RESPIRATORY BURST

• SUPEROXIDE ANION

• HYDROGEN PEROXIDE

• SINGLET OXYGEN

• HYDROXYL RADICAL

MYELOPEROXIDASE

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

REACTIVE NITROGEN INTERMEDIATES

• NITRIC OXIDE

• NITRITE

• NITRATE

NITRIC OXIDE

• MACROPHAGES PRODUCE IT– WHEN ACTIVATED BY INTERFERON

GAMMA– KILLS MICROBES AND TUMOR CELLS– INHIBITS ATP PRODUCTION

OXYGEN INDEPENDENT MECHANISMS

• LIPASES

• PHOSPHOLIPASES

• PROTEASES

• RNA ases

• DNA ases

LYSOZYME

• DEGRADES BACTERIAL PEPTIDOGLYCAN

DEFENSINS

• BIND TO BACTERIAL SURFACES TO FORM ION CHANNELS

CATHEPSIN

• ELASTASE ENZYMES

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

SYMPTOMS OF INFLAMMATORY RESPONSE• REDNESS

• HEAT

• SWELLING

• PAIN

REDNESS

• DUE TO DILATION OF BLOOD VESSELS

HEAT

• DUE TO CAPILLARY DILATION

SWELLING

• DUE TO INCREASED PERMEABILITY OF BLOOD VESSELS

PAIN

• DUE TO PRESSURE ON NERVES FROM SWELLING

• BRADYKININS

• PROSTAGLANDINS

EXTRAVASATION

• MARGINATION

• PAVEMENTING

• DIAPEDESIS

MARGINATION OF PMNs

PAVEMENTING

DIAPEDESIS

MAST CELLS

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

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

ACUTE VS CHRONIC INFLAMMATORY RESPONSE

ACUTE INFLAMMATORY RESPONSE

• LOCALIZED

• SYSTEMIC

LOCALIZED

• TUMOR

• RUBOR

• CALOR

• DOLOR

• LOSS OF FUNCTION

SYSTEMIC ACUTE PHASE RESPONSE

• INDUCTION OF FEVER

• INCREASED SYNTHESIS OF ACTH AND HYDROCORTISONE

• INCREASED PRODUCTION OF WBC

• PRODUCTION OF ACUTE PHASE PROTEINS

CHRONIC INFLAMMATORY RESPONSE

• FORMED DUE TO PERSISTANT ANTIGEN

• FIBROSIS OCCURS

• GRANULOMA

• MULTINUCLEATED GIANT CELLS

• EPITHELOID CELLS

CHRONIC INFLAMMATORY RESPONSE

CHRONIC INFLAMMATORY RESPONSE

• GRANULOMA

CHRONIC INFLAMMATORY RESPONSE

• MULTINUCLEATED GIANT CELLS

• EPITHELOID CELLS

FEVER

• NORMAL BODY TEMPERATURE 37 DEGREES CELCIUS

• ABNORMAL INCREASE IN BODY TEMPERATURE

• PYROGENS CAUSE INCREASE

PYROGENS

• LIPOPOLYSACCHARIDES

• NAG AND NAM OF PEPTIDOGLYCAN

• PYROGENIC EXOTOXINS

• INTERLEUKIN 1/ENDOGENOUS PYROGEN

TYPES OF FEVERS

• CONTINUOUS – TYPHOID FEVER

• INTERMITTENT OR SPIKING– STREPTOCOCCAL INFECTIONS

• PHARYNGITIS

• REMITTENT– MALARIA– RELAPSING FEVER

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

BENEFITS OF FEVER

• INCREASES THE RATE OF ENZYMATIC REACTIONS

• INTENSIFIES THE ACTION OF INTERFERON

• CAUSES REDUCTION OF BLOOD IRON CONCENTRATIONS