Lesson 1 Inflammation And allergy Flashcards by Rutchen Bello

The acute inflammatory reaction has two main components:

(a) Innate non-immunological
(b) Acquired immunological

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Summary of vascular events

Initial vasoconstriction to limit the spread of injury.
Reflex dilatation of small arterioles (vasodilation)
This vasodilation results in increased blood flow.
Then the blood flow along these vessels slows down leading to stasis of the blood.
The pooling of blood in the area of inflammation results in increased permeability of the post-capillary venules.
Increased vascular permeability results in exudation.

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Complex dynamic response of tissue to damaging stimuli

Inflammation

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Due to this the vascular endothelial cells swell and retract so they no longer form a complete intact internal lining

Anoxia
Lack of nutrient supply

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One of the main protein to leak out

Fibrinogen

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Migration process that is caused by attraction of leukocytes to chemical substances produced in the site of tissue damage

Chemotaxis

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Cells involved in inflammation normally present only in tissues

Vascular endothelial cells
mast platelets
Tissue macrophages

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Cells involved in inflammation that gain access into the tissue from the blood

Platelets
Leukocytes

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Leukocytes are classified into

Polymorphonuclear (neutrophils, basophils, eosinophils
Mononuclear (monocytes and lymphocytes

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During inflammation the endothelial cells of the small arterioles are “activated” to secrete:

Nitric oxide
Prostacyclin
Endothelin,
plasminogen activator
platelet-activating factor (PAF)
Thromboxane A2,
angiotensin II,
Several cytokines,

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both of which induce vascular relaxation and inhibit platelet aggregation

Nitric oxide
Prostacyclin

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all of which cause vasoconstriction

Endothelin
Plasminogen activator
Platelet activity factor
Thromboxane A2
angiotensin ll
Several cytokines

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Function also involved in angiogenesis which occur in wound repair, chronic inflammation and cancer

Endothelial cells

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Adhere to vascular endothelium only when the endothelial cells are activated

Neutrophils
Other migrating blood cells

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Are characterized by having nuclei with varying shapes. Are found in circulating blood, but may migrates to sites of inflammation

Polymorphonuclear cells

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have capacities similar to those of the neutrophils and in addition, release a number of potent granules constituents that can damage multicellular parasites such as worms and mites.

Eosinophils

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constituents of eosinophils

eosinophils cationic protein
Peroxidase
Eosinophils major basic protein
Neurotoxin

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Are similar in many aspects to mast cells

Basophils

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morphologically similar to basophils, but are predominantly found in the tissues rather than in circulating blood.

Mast cell

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Contains surface receptors for both immunoglobulin E and for the complement component C3a and C5a

Mast cells

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Can be activated to secrete histamine (and other mediators) through stimulation of these receptors and by direct physical damage.

Mast cells

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Other substances released by mast cells include:

(a) Heparin or (heparan)
(b) Eosinophil chemotactic factor of anaphylaxis
(c) Neutrophil chemotactic factor
(d) ẞ-glucoronidase
(e) Neutral proteases
(f) Superoxide dismutase
(g) Peroxidases
(h) Leukotrienes,
(i) Prostaglandins
(j) Nerve growth factor, and
(k) Some interleukins.

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Other substances released by mast cells include:

(a) Heparin or (heparan)
(b) Eosinophil chemotactic factor of anaphylaxis
(c) Neutrophil chemotactic factor
(d) ẞ-glucoronidaseà
(e) Neutral proteases
(f) Superoxide dismutase
(g) Peroxidases
(h) Leukotrienes,
(i) Prostaglandins
(j) Nerve growth factor, and
(k) Some interleukins.

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enter the area of inflammation at a later stage, several hours after the polymorphs. Like neutrophils, they also adhere to endothelium, and migrate into the tissue in response to specific chemotaxic substances (chemokines)

Monocytes

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aso knows as big eater

Macrophages

In the area of inflammation it engulf debris, dead cells and microorganisms

. macrophages

Involved primarily in blood coagulation, also play a role in inflammation. Also called thrombocytes, they generate thromboxane A₂ (TXA₂) and platelet-activating factor radicals, and pro-inflammatory cationic proteins. Platelet-derived growth factor contributes to the repair processes following tissue damage.

Platelets

During injury and inflammation , type C and Ad fibers generate what chemical mediators? That acts on receptors and stimulate the release of neuropeptides

kinin and serotonin

Transmit pain impulses to the central nervous system

Type C and Ad fibers

specialized lymphocytes that are active in non-immunological reactions. They kill target cells, such as virus-infected cells and cancer cells that lack the major histocompatibility complex (MHC) molecules.

Natural killer cells

normally present in normal cells inhibit NK cells by acting on the inhibitory receptors on the NK cells themselves.

Major histocompatibility complex

Components of exudate

Fluid, fibrin, neutrophils, macrophages lymphocytes

containing salts and high concentration of proteins including immunoglobulins

Fluid

a high molecular weight filamentous insoluble protein.

Fibrin

Types of exudates

Serous Fibrinous Purulent

The fluid in the acute inflammatory exudates carries what?

nutrients mediators immunoglobulins.

may dilute or buffer any locally produced toxins

Fluids and salts

can diffuse into the area of inflammation to support the macrophages.

Glucose and oxygen

is constantly circulating to the local lymph nodes and assists in later development of a specific immune response.

Fluid

in the exudates may act as opsonins

Immunoglobulins

Responsible for body production- the humoral immune response

B cells

Responsible cell-mediated immune reactions

T cells

specialized non-T and non-B lymphoid cells that are active in non-immune innate response

Natural killer cells

This phase involves the production of B cells and T cells from uncommitted lymphocytes

The Induction phase of immunological response

It present antigenic molecules to the lymphocytes

Antigen-presenting cells

engulf and process the antigen and present it to uncommitted CD4+T helper lymphocytes im association with MHC

Antigen presenting cells

develop interleukins-2

CD4 cells

A cytokine which act on the same CD4+ causing proliferation, producing clones of activated T cells called THO

interleukins-2

Give rise to two subsets of T helper cells TH 1 and Th 2 cells

Th0

Produced by some Th0

II-4

produced by APC

II-12

Controls cell-mediated responses

Th1 pathway

Secretes macrophages-activating cytokines and other cytokines

Th1

Activates CD8+T cells to become cytotoxic cells that kill virally infected host cells

Interferon-gamma

Derived from Th2 cells inhibits Th1 function

II-4

controls antibody or humoral mediated response

Th2 pathway

derived from Th1 inhibits TH2 function

IFN-y

This phase involves how the cells, which are produced in the induction phase, act to eliminate antigens. This action may be antibody-mediated or cell-mediated.

The effect phase of immunological response

Antibodies or immunoglobulins have two functions;

To recognize and interact with specific antigens To activate one or more, the host’s defense system

C3a

anaphylotoxin

C3b

Chemotactic factor and opsonin

act as an opsonin, greatly facilitates phagocytosis Can form a link between a parasite (e.g. worm) and eosinophils, which are then able to damage or kill the parasite.

antibody

antibody that can attach to mast cells and basophils to stimulate these cells to release histamine and other inflammatory mediators

IgE

is implicated in certain allergic reaction.

Histamine

The cytokine-producing T cells also activate macrophages also produce and release what?

cytokines toxic oxygen neutral proteases complement components, eicosanoids, fibroblast stimulating factor, pyrogens (fever-inducing substances) factor that activate coagulation cascades.

kill extracellular microorganisms

neutral protease

(fever-inducing substances)

pyrogens

The production of this cells during first exposure to antigen greatly accelerates and makes more effective the immunological response to subsequent exposure.

Memory cells

are substances present in the body and act near the sites of their synthesis. They are sometimes called local hormones

Autocoids

Histamine is always present where?.

in damaged tissues decomposing tissue extract putrefying (decaying) ingesta rich in proteins

Non-mast-cell histamine is secreted by what in the stomach? .

histaminocytes

Non-mast-cell histamine is secreted by what in the in the brain?

histaminergic neurons

activates phospholipase C in the mast cell membrane, which catalyzes the breakdown of membrane phospholipids (specifically phosphatidyl inositol) resulting in the release of diacyglycerol (DAG) and inositol-1, 4, 5-triphosphate (ITP).

antigen-antibody complex

by some mechanism cause the release of calcium ions (Ca²⁺) from the intracellular stores (such as the endoplasmic reticulum), or allow calcium entry into the cytosol.

DAG and ITP

These drug-stimulated histamine release are not allergic in the nature since there is no involvement of an antibody.

amides, amidine, quaternary ammonium compounds, pyridinium compounds, piperidines, alkaloids, and antibiotic bases.

Triple response of histamine

Red spot Flare Wheal

is poorly absorbed from the gut, and is usually given inhalation as nebulized solution or powder.

Cromolyn sodium

is better absorbed than cromolyn sodium.

nedicromy

These xanthine derivatives are bronchodilators used in the management of attack of bronchospasm. They have positive chronotropic and inotropic effects, and mild diuretic effects.

Theophylline Aminophylline

enzyme that catalysis the breakdown of cyclic AMP. This action results in an increase (accumulation) of cyclic AMP, which attenuates the action of inflammation.

Phosphodiesterase

Drugs that inhibit microsomal cytochrome P450 enzymes which may increase the serum level and the likelihood of adverse effects:

Cimetidine Allopuritol Ciprofloxacin channel blockers Erythromycin Fluconazole Cimetidine

Inducers of cytochrome P450 that decrease the therapeutic effect of drugs:

Phenobarbital and Phenytoin

By acting on specific adrenergic receptors, it causes peripheral vasoconstriction, bronchodilation and cardiac stimulation; effects that counter histamine effects.

epinephrine

The classical or H1 antihistamines are not as widely used in animals as in people because of two reasons:

(a) antihistamines have varying effectiveness in animals, and (b) glucocorticoids (see Lesson 2) are available and more effective

The classical or H1 antihistamines are not as widely used in animals as in people because of two reasons:

(a) antihistamines have varying effectiveness in animals, and (b) glucocorticoids (see Lesson 2) are available and more effective

The antihistamines tend to be effective when used for treatment of type I anaphylaxis, including what?

urticarial atrophy

e a number of physiologic role. Inhibition of COX-1 is believed to underlie the most significant “side effects” of non-steroidal anti-inflammatory drugs (NSAIs: aspirin-like drugs)

constitutive enzyme

Mediates most inflammatory and are antagonized by the classical anti-histwmine

H1 agonist and selective antagonist

Histamine Mepyramine

Has a role in gastric acid secretion

H2 agonist and selective antagonist

Histamine Dimaprit Cimetidine

H3 agonist and selective antagonist

R methyl histamine Thloperamide

Prevent release of histamine by inhibiting the responses of sensitized cells basophils to specific antigen

Epinephrine Theophylline Cromolyn sodium

Physiologically antagonized histamine effect

Epinephrine Theophylline Aminophylline

Anti motion sickness caused marked sedation with anti cholinergic effect cream or gel available for topical application

Diphenhydramine

Cream for topical application

Hystapyrrodine

Specific for anti motion sickness

Meclizine

Long acting marked sedation prominent anti-motion sickness

Promethaine

Has weak alpha

Promethazine

Cause prominent sedation

Pyrilamine

Has no sedation action can cause potentially fatal cardiac arrhythmia

Terfenadine

A nontoxic metabolite of terfenadine

Fexofemadine

Sedation anti cholinergic effect

Trimepraine

Sedation with usual doses of ataxia and convulsion when overdose

Tripelennamine