Agents to Manipulate Immune Response pt 1

how are Helper T cells activated?

antigens presented on outside of macrophages

what cell do Helper T cells activate?

- Killer T cells, which kill any infected cell

- B cells - make antibodies

what happens to bacteria with antibodies attached?

proteins attach the bacteria and attach themselves to the antibodies and punch holes in pathogens

what eats pathogens tagged with antibodies?

macrophages

what is innate immunity?

Nonspecific protection against foreign substances, lacks memory and specificity

what is included with innate immunity?

- Skin

- gastric acid

- bronchial mucous

- phagocytes

- leukocytes

what can innate immunity recognize?

a few pathogen associated molecular patterns (PAMPs)

what does acquired immunity do?

Recognize and adapt to foreign bodies to maintain the effectiveness of the immune response and protect the human body

what does an antigen generate?

antibody, ANTIbody GENerator = allergen

what response types can occur due to antigen presence?

cell-mediated or humoral response

when is acquired immunity activated?

Activated when pathogen overwhelms innate immune response

what is acquired immunity typically initiated by?

lymphoid tissue

what is an examples of something that can give you acquired immunity?

vaccine

what do antigens release to initiate an immune response?

cytokines and chemokines

what symptoms can result due to a release of larger amounts of cytokines?

- Fever

- tachycardia

- organ failure

- shock

- death

what system does the inflammatory response activate?

adaptive system

what does the adaptive system activate?

humoral and cellular immunity

what happens to the immune system over time?

it diminishes

what are young children more prone to?

allergies

can reactions change from childhood to adulthood?

yes, patients may not have same reaction as an adult as they did as a child

are allergies inheritable?

tendency is inheritable - NOT THE ACTUAL ALLERGY

what cells is humoral immunity managed by?

lymphocytic B cells

what are antibodies?

large protein molecules released from the lymphocytes that bind with and help destroy an offending antigen by marking it for destruction

what does the shape of the antibodies chemical structure allow for?

allows interlocking which make antibodies specific for a particular antigen

what are the types of Immunoglobulins (Ig)?

- IgG

- IgA

- IgM

- IgD

- IgE

where are IgG most commonly found?

blood

where are IgA most commonly found?

tears, saliva, respiratory and GI tract

what does IgA defend?

gut and mucosa

where are IgM most commonly found?

blood

where are IgD most commonly found?

on lymphocytes

what does IgD regulate?

cell activation

where are IgE most commonly found?

skin

what is the predominant Ig for allergies?

IgE

what cell manages cellular immunity?

lymphocytic T cells

what cell is cellular immunity mainly performed by?

WBC

what do WBCs do during cellular immunity?

- destroy the invading agent

- direct and assist other cells in performing that function

what classification is used for hypersensitivity reactions?

Coombs & Gel Classification

what are the types of hypersensitivity reactions on Coombs & Gel?

- Type I: Anaphylactic (IgE mediated)

- Type 2: Cytotoxic

- Type 3: Immune Complex

- Type 4: Cell-mediated delayed

which hypersensitivty reaction is most severe?

Type I: Anaphylactic/IgE-mediated

what are the characteristics of Type I: Anaphylactic/IgE-mediated?

Allergen binds to IgE on basophils or mast cells, resulting in release of inflammatory mediators

how long does the typical onset for Type I reactions take?

30 min to

what are some drugs that can cause Type I reactions?

- Penicillin immediate reaction

- blood products

- polypeptide hormones

- vaccines

- dextran

what are characteristics of Type II reactions?

- Cell destruction occurs because of cell- associated antigen that initiates cytolysis by antigen-specific antibody (IgG or IgM)

- Most often involves blood elements

how long does the typical onset for Type II reactions take?

> 72 h to weeks

what are some drugs that can cause Type II reactions?

- Penicillin

- quinidine

- heparin

- phenylbutazone

- thiouracils

- sulfonamides

- methyldopa

what are characteristics of Type III reactions?

- Antigen-antibody complexes form and deposit on blood vessel walls and activate complement

- Result is a serum sickness like syndrome (RA, vasculitis)

how long does the typical onset for Type III reactions take?

> 72 h to weeks

what are some drugs that can cause Type III reactions?

- Penicillins

- sulfonamides

- minocycline

- hydantoins

what are characteristics of Type IV reactions?

Antigens cause activation of T lymphocytes, which release cytokines and recruit effector cells (e.g., macrophages, eosinophils)

how long does the typical onset for Type IV reactions take?

> 72 h

what are some drugs that can cause Type IV reactions?

- TB test

- maculopapular rash

- contact dermatitis (poison ivy)

- bullous & pustular exanthems

what is another name for seasonal allergic rhinitis?

"hay fever"

what is season rhinitis triggered by?

- specific allergens (trees, pollen)

what increases the risk of allergic rhinitis?

smoke exposure

what triggers persistent allergic rhinitis?

non-seasonal allergens (dust mites, mold, animal dander), year round

what are some other causes of allergic rhinitis?

- infection

- pregnancy

- exercise

- climate change

- other meds

what immunoglobulin mediates allergic rhinitis?

IgE

symptoms associated with allergic reaction are treatable and can be accounted by the release of what?

histamine

what are some symptoms associated with allergic rxns and histamine release?

- Sneezing

- itchy nose/eyes

- watery rhinorrhea

what causes the inflammation associated with allergic rhinitis?

- mast cells

- cytokines

what causes the itching and sneezing associated with allergic rhinitis?

sensory nerves via efferent vagal pathways

what causes the vascular engorgement associated with allergic rhinitis?

substance P and calcitonin via sympathetic tone

what causes the rhinorrhea, itching, sneezing, and obstruction associated with allergic rhinitis?

histamine 1 and 2

what causes nasal obstruction associated with allergic rhinitis?

- kinins

- prostaglandins

- leukotrienes

what causes vasodilation, vascular permeability and nasal secretions associated with allergic rhinitis?

kinins

when does congestion peak after exposure?

12-24 hours

what releases histamine?

mast cells

what rapidly metabolizes histamine?

liver

what drugs stimulate the release of histamine?

- Beta-2 adrenergic receptors

- Cromolyn sodium

- Acetylcholine

- Some opioids

what do Beta-2 adrenergic receptors do to mast cells?

inhibit release from sensitized mast cell

what does Cromolyn sodium do to mast cells?

stabilizes mast cell membrane, decreasing antigen-triggered release

what does Acetylcholine do to mast cells?

increases histamine release from mast cells

what do some opioids cause mast cells to do?

release histamine (codeine)

where are H1 histamine receptors located in?

- brain

- smooth muscle

- heart

- endothelium

where are H2 histamine receptors located in?

- brain

- stomach

- smooth muscle

- heart

- mast cells

where are H3 histamine receptors located in?

brain

where are H4 histamine receptors located in?

- brain

- bone marrow

- blood elements

how does histamine affect the cardiovascular system?

- decrease BP

- increase HR

- increase force of contraction

- vasodilation of smaller vessels

how does histamine affect the respiratory system?

- bronchial constriction

- secretion stimulation

what intradermal reactions can histamine cause?

- flush (bright red/blue)

- flare ( larger area than flush)

- wheal (raised area of edema)

what are some pharmacologic treatments of allergic rhinitis?

- Antihistamines

- Intranasal corticosteroids

- Decongestants

- Analgesics

- Mast cell stabilizers

- Anticholinergics

- Leukotriene receptor

antagonists

what are some non-pharmacologic treatments of allergic rhinitis?

- minimize exposure to allergens (such as mold, animals, indoor allergens)

what is the MOA of antihistamines?

- Competitive antagonists to histamine (prevents histamine binding)

- 2nd generation may effect components of inflammatory response (1st gen less effects)

what are available routes of administration of antihistamines?

- oral

- ophthalmic

- intranasal

what is the PK of antihistamines?

- Rapid absorption, peak effect occurring in 1-2 hours

- Lipid solubility varies

- Duration of action varies

what activity of antihistamines cause a drying effect?

anticholinergic activity

what are examples of first generation antihistamines?

- Diphenhydramine (Benadryl) q 4-6h

- Chlorpheniramine (Chlor-

Trimeton) q 4-6h

- Meclizine (Antivert)

what are the actions of first generation antihistamines?

- Sedation (good BBB penetration)

- Anticholinergic action

- Adrenoceptor blocker

- Local anesthetic action (topical)

- Antihistamine effects

what should be avoided with first generation antihistamines?

alcohol - can exaggerate sedation

what are some side effects of first generation antihistamines?

- drowsy

- tremors

- blurry vision

what are some second generation antihistamines?

- Fexofenadine (Allegra) q 12-24h

- Loratadine (Claritin) q 24h

- Desloratadine (Clarinex) q 24h

- Cetirizine (Zyrtec) q 24h

- Levocetirizine (Xyzal)

- Azelastine (Astelin) NASAL

FORMULA

what is the action of second generation antihistamines?

- Less sedation (except Zyrtec & Xyzal)

- Longer half-life

what are examples of intranasal corticosteroids?

- Budesonide (Rhinocort)

- Fluticasone propionate (Flonase)

- Mometasone furoate (Nasonex)

what is the PK of intranasal corticosteroids?

- Rapid absorption through nasal mucosa

- No drug interactions (no systemic absorption)

what is the MOA of intranasal corticosteroids?

Inhibit mast cells, eosinophils, basophils, lymphocytes, macrophages, and eicosanoids, which contribute to inflammation

how long does it take for an adequate response to intranasal corticosteroids?

~2 weeks

what are some adverse effects of intranasal corticosteroids?

- sneezing

- stinging

- headache

- epistaxis

what are examples of decongestants (alpha-agonists)?

- Phenylephrine (Sudafed PE, Neo-Synephrine)

- Oxymetazoline (Afrin)

- Pseudoephedrine (Sudafed)

what is the MOA of decongestants (alpha-agonists)?

vasoconstriction in the superficial nasal mucosa vessels, decreasing swelling of the nasal mucosa

what is the PK of decongestants (alpha-agonists)?

vary in onset and duration of action