inflammation 1&2

• This lecture discusses Inflammation
• Inflammation 1 is by H. Schaefer

Immunity Basics

• Innate immunity is what one is born with, including physical barriers
• Adaptive immunity is acquired and known as 'humoral'
• Lymphocytes (B-cells, T-cells) are white blood cells involved in acquired immunity
• Antibodies are B-cell mediated
• An antigen activates the immune system
• The body synthesizes 'antibodies', proteins called 'immunoglobulins' (in blood)
• Antibodies inactivate invading pathogens and mark them for phagocytic destruction
• T-cells are involved in cell-mediated immunity
• They recognize foreign markers, antigens, and destroy them directly, and activate phagocytic cells
• T-cells have a high viral efficacy

Innate vs Adaptive Immunity

• Innate immunity includes physical, cellular, and process barriers
• Adaptive immunity includes B cells and T cells
• Physical barriers are the skin/mucous membranes
• Cellular barriers are phagocytes (e.g. macrophage, neutrophil), NK cells, and mast cells
• Process barriers encompasses inflammation
• Adaptive immunity's T cells provide memory and signaling
• Adaptive B cells produce antibodies (immunoglobulins) and memory

Physical Barriers

• Epithelial linings are physical Barriers
• They are found along digestive, respiratory, urinary, and reproductive tracts
• Cells provide a physical barrier
• Secretions (mucus, enzymes, stomach acid) often ensnare, destroy, or wash away pathogenic material
• Epithelial cells are tied together by tight junctions and supported by fibrous basement membrane

Blood Basics

• Blood is fluid connective tissue
• It contains cells, fibers (e.g. precursor 'fibrinogen'), fluid matrix
• The goal of blood flow is perfusion of organs
• Blood supplies nutrients to all cells (electrolytes)
• Even cells without direct flow rely on diffusion of these nutrients from areas with blood flow (e.g. cartilage)
• Cellular necrosis results when blood flow is absent (e.g. stroke)
• This is especially bad in the brain because the cells don't regenerate
• Functions of blood:
• Transport of nutrients (glucose, lipids,..), gasses, hormones, electrolytes
• Waste away from cells (e.g. lactic acid, creatinine, CO2, ...)
• Body temperature regulation (hypothalamus => vasodilation = heat loss through blood flow)
• Clotting
• Osmotic pressure – fluid movement (e.g. albumin, ...)
• Protection (immunity e.g. WBC)

Plasma vs Cells

• Plasma makes up 55% of whole blood volume
• It contains H20, solutes (e.g. electrolytes, nutrients), blood proteins
• H20: 92% of plasma
• Blood proteins are low if body's protein is low (e.g. malnutrition, starvation,..)
• E.g. Albumins, Globulins, Fibrinogen
• They are synthesized in the liver
• They are carriers of substances ('affinity' to specific ones), known as PPB
• E.g. Albumin
• Some are 'antibodies' - immunoglobulins
• Cells make up 45% of whole blood volume
• They contain red (RBC), white (WBC), Platelets
• They're synthesized via 'hemopoiesis' (hematopoiesis)

Hemopoiesis/Hematopoiesis

• Hemopoiesis occurs in bone marrow, from stem cells

Leukocytes

• Buffy coat: platelets and leukocytes = <1% of whole blood
• Erythrocytes = 45% of whole blood

WBCs (leukocytes)

• Synthesized from hematopoietic 'myeloid' stem cells: leukopoiesis
• The are an immune response
• They migrate and mobilize toward stimulus: 'chemotaxis'
• They migrate out of blood vessels, into tissues and flow toward the stimulus
• Neutrophils are involved in innate immunity
• They makeup 50-70% of all WBCs
• First to injury, within 90 minutes to injury site
• Highly responsive to e.g. bacteria
• They engulf & digest (digestive enzymes)
• Apoptose after engulfing 1-10 bacteria
• Release inflammatory mediators to aggregate more WBCs
• Includes Prostaglandins, leukotrienes, ...

CBC & differential

• CBC & differential includes immature neutrophils aka 'band neutrophils'
• Numbers (not tested, reference range is provided in lab results)
• Presence of electrolyte level are on the results
• The results will point the specific levels of WBCs, RBC, Hemoglobin, Hematocrit, Platelets, Neutrophils, Lymphs, Monocytes Eos, Basos,Neutrophils (Absolute), Lymphs (Absolute),Monocytes (Absolute),Eos (Absolute), Baso (Absolute),Immature Granulocytes,Immature Grans (Abs)

WBC Responders

• Neutrophils respond especially if bacteria is present
• Depletion of mature neutrophils causes immature neutrophil presence: bands
• Lymphocytes: WBC respond especially if viruses are present
• Eosinophils: WBC respond especially if allergens are present
• Non-specific markers e.g. C-reactive protein (pro-inflammatory protein) are present if tissue inflammation is present

Inflammation Summary

• Inflammation is an innate, non-specific response
• Onset: minutes (acute inflammation)
• Triggered by noxious stimulus in tissues
• Acute = <10 days, chronic > 10 days
• Noxious stimuli:
• Allergen (=> allergy)
• Pathogen (infection): bacteria, viruses, fungi, parasites,
• Tissue injury
• Autoimmune disease
• Disease process (e.g. neoplasm)

Noxious Stimuli

• Common include injuries and food
• Triggers can include, for example, pathogens, wheat, eggs, fish, tree nuts, shellfish, soy, peanuts, milk, and sesame

Mast Cell Degranulation

• Noxious stimulus results in inflammatory mediator release
• Mast cells are primary secretors
• => e.g. histamine & prostaglandin
• Other pro-inflammatory mediators include complement system, cytokines, and nitric oxide release (endothelial + more from WBCs)
• Prostaglandin gets released from mast cells and also tissues
• Effects of Mast Cell Degranulation
• Vasodilation (redness, heat)
• Vascular permeability (edema)
• Cellular infiltration (pus)
• Plasma causes, inflammation becomes pus
• Thrombosis (clots)
• local clots are manageable, Systemic clots can kill
• Stimulation of nerve endings (pain)
• Pressure on the nociceptors

Hypersensitivity

• Common type: Hypersensitivity type 1
• Mast cells distributed throughout tissues
• Activated by noxious stimuli

The 4 Stages of Reaction

• Vascular Stage: vasodilation and vascular permeability Increased (IM)
• Cellular Stage: WBC migration (Neutrophils, Macrophages and NK)
• Signaling : inflammatory attraction- more phagosytosis
• Phagosytosis: Noxious stimulus and tissue healing

Histamine

• Histamine is a primary mediator of sensory stimulated inflammation
• Triggered by eg allergy
• Histamine- stored among mast cells- release and contact with allergen
• Agonist to H1 -Receptors PNS & CNS systems Effects
• capillary vasodilation & permeability
• Stimulation of nerve endings = > PAIN Bronchoconstriction and Tachycardia
• Itching and hives
• Symptoms: range from mild to life threatening
• Allergic are progressive and will respond to this systemic Issue.

Hypersensitivity 'allergy'

• Most common type I hypersensitivity (IgE modulated)
• IgE are present on a mast cell
• Noxious stimuli: allergen (antigen that triggers the response)
• e.g. pollen, dust, animal dander, peanuts, drugs (e.g. morphine)
• Occurs within 15 minutes of exposure
• pathophysiology
• 1st exposure- allergen (antigen): WBC activation - TH2 signaling to B cells = specific antibodies (IgE type) synthesized & secreted to the tissues
• those IgE antibodies are present in tissues (high numbers) & attach to mast cells (approx. within 1-2 weeks)
• 2nd exposure – antigen distributes & attaches to the IgE, 'crosslinking it' => mast cell degranulates quickly & effectively => histamine etc.... secreted
• S&S: local -> systemic -> systemic life threatening (anaphylaxis)
• Tx: depends on severity of response

Histamine Antagonists (antihistamines)

• 1st & 2nd generation
• 1st generation causes sedation vs 2nd gen. causes no sedation
• First generation: Lipophilic
• crosses BBB = CNS effects
• Includes histamine which is an excitatory CNS neurotransmitter, which causes wakefulness
• antagonism of CNS H1 = drowsiness
• Types include diphenhydramine (Benadryl, Allerdryl) and chlorpherinamine (ingredient in e.g. Benylin)
• Second generation:
• no CNS distribution i.e 'non-drowsy'
• Types include fexofenadine (Allegra), loratadine (Claritin), cetirizine (Reactine) e.g. fast melt tabs
• Onset: 10-20 min
• Duration: 24 hrs
• A 2nd gen antihistamine is desloratadine (Aerius)

Topical antihistamines

• For Localized symptoms
• e.g olopatadine, patanol eyerdrops
• Tery Eye includes: Counjunctivitus
• Types for the skin are:
• Benadry and cream

Scenarios for Antihistamine Use

• A patient that touches Planr: eg stinging needle.

• Symptoms includes localized: Urticaria (pruritus) no change sign. Colour is the telling sign. .localized allergy

• Tx: Benadry crm

• Patient comes to friend's house and they have a cat:

• Within 15 minutes they Have symptoms: Watery Eyes (ephiphora) Itchy allergy

• Runny nose( rhinorrea) and Pruitas Tx: 2nd general and monitor situation- as is progressive

• Cat allergy gets quickly worse and includes

• difficulty :breathing and tachardia are evident.

Allergy testing

• allergen administered via topical or superficial injection

Allergy de-sensitization

• Allergy and suppress immune system of it
• Dynamics : will have inhibitory effect to help body
• B cells can respond by slowly creating antibodies
• lgG also combine with no-fit mast cells Suppress the immune

When breaching chemical and physical barriers

• There will be localized inflammation or bacterial and cell influx
• Causes increase flow of the blood to stop cells and fluid to protect
• Chemical (protein ract)

Cont.

• Blood: clots and creates capillaries and will dilate histamine
• Leukocytes are phagocyting cell debris.

Inflammation in tissue injury

• Tissues and mast cells: will create cell with a non-allergen from prostaglandin
• The arachidonic conversion occurs to use in tissues
• This protective mechanism used. -Was first found in the prostate glands

COX Enzymes

• COX are required for prostaglandin synthesis
• There are only 2 types Cox 1 and Cox 2
• Predominate site injury.

COX

• Inbition drug class : Nsaids( non sterodia) Anti-inflammatories

. Selective Cox -2 inhibitors Drug: celcobix Rx needs it, black box to people that have high CV( cardio vascular system high risks For the most people Not First line therapy decreases pyrogenes, but As decrease inflammation Does so as: anti-infalmmatory

Non selective COX inhibitors

Acetylciciyic (Asprin)

• lbuprofen

Voltaren

Naprosex

.Indomethacin needs Rx

• Can lead to ulcers
• Cauthion : has reaction
• Can increase: somnolence can be an effectr

NSAIDS

A Patients: can be used for soft tissue injury and can use topical adjuncts like Voltarn Must see effects

3.8c Mike Slide

Can use corticotpoin

Paths= protection :

• Risk of stope the Negative loop. Cant stop drug- as there will be low dose
• Corticotopin/ harmone acth as needed

Glucortods Steriiodal Drugs

A homeroomes of the adrenaline with nuclear

• Can improve fasting

• Can stop and prevent production of C2 ox-

• Can sup[ress bad symptoms

Drugs and examples are ; Hydroortisones one.

• Predinsolon and Methyl
• Dexamethosone

Explore the role of immunity components like antibodies and T cells in acquired immunity. Understand blood functions such as waste removal, temperature regulation via the hypothalamus, and the importance of plasma components like albumin in maintaining osmotic pressure.