inflammation 1

Innate and Acquired/Adaptive/Humoral Immunity

antibody-mediated

• activated by antigen (pathogen provoking response)

• synthesize antibodies

  • proteins - immunoglobulins in blood

  • antibodies inactivate invading pathogens

  • marks them for phagocytic destruction

• T cells recognize foreign markers, antigens, destroy and activate phagocytic cells

• high efficacy for virals

process barriers

• mast cell

  • engulf foreign substance

  • release histamine

• complement system

  • innate and aquired immunity

  • assist the body to clear pathogens w/ plasma proteins, activates inflammation,

    • acts as a first responder

      • marking (opsonins),

      • chemotaxis - attract immune cells to site

      • lysis - will combine to kill

innate secretions

• mucus, enzymes, stomach acid will destroy pathogenic material

Blood: facts and fx

fluid connective tissue

• cells, fibers (baby type = fibrinogen), fluid matrix

stroke

• absent blood flow = cellular necrosis

fx

• transport of nutrients (glucose, lipids), gases, hormones, electrolytes, drugs

• waste away from cell (lactic acid, creatinine, CO2)

• body temp regulation

  • hypothalamus → vasodilation = heat loss thru blood flow

• clotting

• osmotic pressure for fluid movement

  • created by plasma proteins

  • isotonic - equal water going in and out

  • hypertonic - too much water out of cell

  • hypotonic - too much water into cell

• protection thru WBCs

blood

• 45% RBCs

• 55% plasma

  • 92% water

  • 8% solutes (electrolytes, nutrients), plasma blood proteins

• <1% buffy coat

Plasma Blood Proteins: facts

made in liver

part of plasma, within the 10% solute part of plasma

• albumins, globulins, fibrinogen

carriers of substance

• will have affinity to specific ones

• PPB (plasma protein binding)

some are antibodies = immunoglobulins

Hematopoeisis

pluripotent stem cell

• myeloid stem cell (BEMN)

  • neutrophil (majority)

  • basophil (allergy)

  • eosinophil (allergy)tghj \.\/

  • monocyte

    • macrophage

  • RBCs

• lymphoid stem cell

  • T cell

  • B cell

  • NK cell

• mast cell stem cell

  • mast cell

WBCs: fx, types

Fx

• immune response

• chemotaxis

  • migration + mobility toward pathogen

• mobile

  • migrate out vessels, into tissues

types

• neutrophils

  • majority of WBCs (50-70%)

  • 1st to injury (w/in 90 min)

  • highly responsive to bacteria, neutralizes

  • engulfs 1-10 bacteria (digestive enzymes)

    • apoptose after

    • degranulates

      • release inflammatory mediators to bring in more WBCs

  • when the mature ones run out, immature neutrophils come = serious

• lymphocytes

  • more for viruses

• Eosinophils

  • more for allergens

• Non-specific markers

  • C-reactive protein CRP (pro-inflammatory protein)

    • for tissue inflam.

Inflammation: what and triggers

innate, non-specific

onset

• minutes

  • if acute inflammation, <10 days

triggers

• noxious stimuli (stuff not supposed to be there)

  • allergen (from allergy)

    • foods

  • pathogen (infection causing)

  • tissue injury

  • autoimmune disease

  • disease process - neoplasm ex

Inflammation: Mediators and Mast cell degranulation

noxious stimuli activates immune system

• inflammatory mediators release

  • histamine = vasodilation + permeability

  • prostaglandins = pain, fever, inflammation

  • cytokines = some are pro-inflam.

  • leukotrines = bronchoconstriction, permeability

  • bradykinin = pain, vasodilation

  • complement system

    • trigger inflammation, attract immune cells, cause mast cell degranulation, some direct kill bacteria

  • nitric oxide release

    • vasodilation

    • help immune cells reach site

mast cell degranulation

• mast cells r distributed throughout tissues

• caused by cross-linking

  • when one allergen binds to multiple IgE molecule at once (linking them tgt)

    • activation signal

• tiny sacs inside (granules) contain the mediators, w/ signal they release them

• causes

  • vasodilation = redness, heat

  • vascular permeability = edeme

  • cellular infiltration = pus

  • thrombosis = clots

  • stimulation of nerve endings = pain

Allergy: Type 1 Hypersensitivity Process + what reduces this process

• allergic rxn caused by IgE antibodies and mast cell degranulation

• sees allergen (harmless) and treats it like pathogen

1) First exposure (sensitization)

• allergen enters

• Antigen-presenting cell (APC) engulf/marks allergen and present to

• T helper 2 cells, they tell B cell

• B cell makes IgE antibodies

• IgE binds to mast cell (armed - but takes 1-2 weeks)

2) Second exposure (actual allergic rxn)

• same allergen enters again

• binds to IgE by cross-linking = activation signal

• mast cell degranulates, releasing inflam. mediators

Reducing MOA

1) Allergen-IgG complex

• before being able to bind to IgE on mast cell

• allergen attaches to IgG

  • forms allergen-IgG complex

• binds to the FcyRllb (STOP) receptor

  • bc the IgG bind to the receptor, it blocks degranulation

    • for good: prevent overreaction since IgE response is powerful

      • can cause anaphylaxis and tissue dmg

    • both signals of IgE and IgG binding can happen (GO and STOP)

      • whichever side is has more conc. overrides the other

      • so more cross-linked IgE binding will override the STOP

IgE antibody

• represent long-term immunity, delayed food sensitivities (hours/days)

• most abundant

• tolerance/chronic response

IgG

• immediate, severe allergic rxns (minutes/hours)

• acute, or fatal allergies

Inflammation: Stages and s&s

1) Vascular

• vasodilation + increased vascular permeability

  • redness, heat, swelling

  • doors open for next stages

• start bc of chemical signals released by activated macrophages + mast cells (histamine + prostaglandins = mast cells)

2) Cellular/Leukocyte extravasation

• neutrophils, macrophages, NK cells (WBCs) move into the tissue

  • margination = WBCs move toward the doors, approach endothelial cells

  • transmigration = squeezing thru the door/blood vessel wall

  • chemotaxis = directed movement of cells toward chemical signal, cells r guided to exact location

    • chemokines are released at injury site, so higher at injury site, less further away

    • leukocytes detect chemokines

    • move toward high conc.

• bc of mast cell degranulation in stage 1

  • clotting begins

3&4) Signaling & Phagocytosis

• WBCs engulf and digest pathogen

• inflammatory mediators attract more WBCs, induce own synthesis

• phagocytosis of noxious stimulus = tissue healing

s&s

• swelling, redness, pain, pus

Inflammation: Histamine about and effects

primary mediatory

• sensory-stimulated inflammation (allergy)

stored

• in mast cells

• released when mast cell contacts w/ allergen

MOA

• histamine binds to H1 receptor, turns them on (agonist), causes effects

• Histamine 1 (H1) receptor

  • type of G-protein coupled receptor (GPCR)

    • found on smooth muscle, blood vessels, lungs, gut, CNS peripheral tissue

Effects

• capillary vasodilation = increase blood flow

• stimulation of nerve endings = pain

• bronchoconstriction

• tachycardia

• itching

• urticaria (hives)

Allergy: about, s&s, TX

various types

• most common: type 1 hypersensitivity (IgE modulated)

noxious stimuli

• allergen/triggering antigen

  • pollen, dust, peanuts, drugs

• within 15 min of exposure

s&s

• local → systemic → systemic life threatening (anaphylaxis)

TX

• depends on severity of response

Antihistamines: MOA

H1 inverse agonist - blocks histamine from binding + turns receptor off

• reduced allergic rxn

  • causes opposite effect (reducing what histamine does)

Antihistamines: 1st Gen MOA and drugs

MOA

• crosses BBB, blocks H1 receptor in brain (hypothalamus)

  • histamine = excitatory CNS neurotransmitter (causes wakefulness)

  • antihistamine = does opposite (causes drowsiness)

    • sedating

Drugs

• Diphenhydramine (Benadryl, Allerdryl)

  • Cream version = topical so no CNS effect/it’s non drowsy)

• Chlorpheniramine (ingredient in Benylin)

Antihistamines: 2nd Gen MOA and drugs

MOA

• no CNS distribution

  • blocks H1 receptors in body (blood vessels, skin, lungs, gut)

  • non drowsy

2nd gen

• fexofenadine (Allegra)

• loratadine (Claritin)

• cetirizine (Reactine)

  • fast melt tab

  • onset =10-20 min

  • duration of 24 hrs

• desloratadine (Aerius)

• olopatadine (Patanol)

  • eye drops