Inflammation/Lymphatics

module 2

What is an allergy?

What is an allergy?

Over-reaction of the immune system to a harmless antigen (allergens)

How are hypersensitivity reactions grouped?

Grouped into four types according to the effector mechanism responsible for producing the reaction

Type I

Binding of antigen to surface IgE, primarily on mast cells. Degranulation causes the release of inflammatory mediators

Type II

Small molecules binding to cell surface components modify the antigenicity of the molecule rendering them immunogenic. B cell response to the antigen destroys the cell

Type III

Soluble protein antigens bind to immunoglobulin forming immune complexes. These complexes deposit on small blood vessels triggering complement cascade and inflammation

Type IV

Antigen-specific effector T cell

Type 1 hypersensitivity - what is the antigen, what is the effector mechanism and reaction

Antigen = soluble antigen

Effector mechanism = mast cell degranulation

Reaction = Allergic rhinitis, asthma, systemic anaphylaxis

FceRI

Expressed constitutively on mast cells/basophils induced on activated eosinophils binds IgE in the absence of antigen

What are allergic reactions mediated by

H1 receptors on smooth muscle and endothelial cell

What are histamines derived from

histidines

What receptors do histamines bind to

H1, H2 and H3

What is the purpose of a histamine?

Increase permeability/edema, smooth muscle contraction

How is an invading parasite attacked and expelled from the host?

By breaking down the ECM proteins allowing invasion by leukocytes - enables the leukocytes to attack the parasite

What type of hypersensitivity is Asthma/allergic Rhinitis

Type I

What is Asthma/allergic rhinitis

Reaction to an inhaled allergen such as pollen, house dust mite, dander

What are 20% of the allergies in North America against?

Cysteine protease of D. pteronissimus

Wheal and flare

(a reaction) rash or hives (irregular, blanch raised areas with redness)

-Local urticarial reaction (hives!)

How does anaphylaxis present in felines?

Coughing, dyspnea (respiratory), vomiting and diarrhea (GI)

-Common sources of allergens = house dust mites, fleas

-Presentation = atopic dermatitis

Common allergies in equine

Sweet itch = allergy to culicoides (midge bite)

Heaves = respiratory manifestation of allergy to mold ex: aspergillum fumigates, alternaria tenuis

Sweet Itch

Equine

-Summer seasonal recurrent dermatitis - allergy to the saliva of biting insects such as culicoides (midge), sand flies and black flies

How does sweet itch manifest

Intense itching (pruitis) local hair loss (alopecia) and a thickening and ridging of the skin in the affected area

Heaves

Chronic obstructive pulmonary disease

-Respiratory manifestation of allergy to mold ex: aspergillum fumigates, alternaria tenuis

Type II hyper sensitivity antigen

Altered cell surface component

Type II hypersensitivity effector mechanisms

IgG binds to novel antigen which triggers the complement cascade

-FcR targets leukocytes

-IgG binds to cell surface receptor (autoimmunity)

Type II hypersensitivity reaction

Hemolytic anemia, autoimmunity

Haptenisation

The reaction of an antigenic compound (a hapten) with a carrier protein in order to stimulate an immune response.

-Drug modification of a protein antigen

-Penicillin derivatives - anemia

Neonatal isoerythrolysis

Ex: Foal's red blood cells are destroyed by antibodies in the mare's colostrum

Ex: Cats - kitten with blood group A or AB is born to a B mother

-All type B cats have high titer anti -A IgM

-Is rare in canines, spontaneously arising alloantibodies are infrequent

Clinical signs of neonatal isoerythrolysis in cats

Hemolytic anemia, jaundice, hemoglobinuria, weakness, lethargy

Hyperacute graft rejection

Immediate and rare

Preexisting antibody to the antigens of the graft

-Rhesus D reaction

What do A erythrocytes express on gangliosides

N-Glycolyl neuraminic acid

What do B erythrocytes express

N-acetyl neuraminic acid

AB erythrocytes express both ______ and _______

N-glycolyl neuraminic acid and N-acetyl neuraminic acid

Cats with B blood group lack the _____ enzyme that converts _____ to _______

Hydroxylase, acetyl to glycolyl

How to treat neonatal isoerythrolysis in cats

Blood type and prevent exposure to colostrum - Type A foster queen or milk replacement

Type III hypersensitivity antigen

Soluble antigen

Type III Hypersensitivity effector mechanisms

Immune complexes, complement, phagocytes

Type III hypersensitivity reaction

Arthus reaction (ex: to a tetanus vaccine), serum sickness (to drugs or antitoxins), Farmer's lung (hypersensitivity pneumonitis)

Type III hypersensitivity high dose antigen

vasculitis, nephritis, arthritis

Type III hypersensitivity Subcutaneous antigen

Arthus reaction

Type III hypersensitivity inhaled antigen

Famer's lung

What is an example of an infectious disease with an immune complex component and an example of one with autoimmune conditions?

Immune complex component = feline infectious peritonitis (FIP)

Autoimmune = Systemic lupus erythematosus (SLE)

Type IV hypersensitivity antigen

Cell associated antigen

Type IV hypersensitivity effector mechanism

macrophages, eosinophils, CTLs

Type IV hypersensitivity reaction

chronic asthma, allergic rhinitis, contact dermatitis, tuberculin reaction

Type IV hypersensitivity is synonymous with what kind of reaction? What does it consist of? Example?

Delayed-type hypersensitivity (DTH), occurs 1-3 days after antigen exposure

ex: tuberculin reaction = small amount of protein extract from m.tuberculuosis is infected subcutaneously - if immune M. tuberculosis proteins are processed, used to stimulate Th cells with then promote a local inflammatory response recruiting leukocytes at the site of injection

(other examples : nickel allergy, poison ivy)

Atopic dermatitis in canines and felines

Type I hypersensitivity reaction to allergens: dust mite (dermatophagoides pteronyssinus) , flour mite (dermatophagoides farinae) or saliva of flea (ctenocephalides felis)

Treatment for atopic dermatitis

Identify allergen, prevent further exposure to allergen

-Hyposensitization may be a good treatment for house dust mites

Immunodeficiency results from

A defect at any stage of the immune response

Are congenital immunodeficiencies rare?

Yes, many are X-linked and more common in males

Complement deficiency - C3 example

Autosomal recessive - single base pair deletion in the C3 gene

-Brittany spaniels had increased susceptibility to bacterial infection

Inherited IgA deficiency

secreted immunoglobulin resistant to proteolytic degradation

secretory component mediates transport across epithelial surfaces

high affinity receptor on monocytes and neutrophils

What condition in Irish setters is a deficiency of b-chain LFA-1 and what does it cause?

LAD (Leukocyte adhesion deficiency)

-There is an absence of a functional LFA molecule - prevents adhesion of granulocytes to the endothelium - no migration!

Secondary immunodeficiency following drug treatment

Corticosteriods - anti-inflammatory agent

Increased production of IkBa - binds transcription factor NFkB preventing it from entering the nucleus and enhancing cytokine gene expression

Cyclosporin A (secondary immunodeficiency following drug treatment)

Inhibits T cell activation by disrupting the transduction of signals from the T cell receptor

Cancer (secondary immunodeficiency following drug treatment)

Affects rapidly dividing cells in the gut and bone marrow - causes immunosuppression

-WBC count should be monitored

immunodeficiency in response to viral infection - Lentiviruses (FIV, HIV,)

T helper cell depletion

immunodeficiency in response to viral infection - FeLV

Thymic atrophy

immunodeficiency in response to viral infection - distemper, parvo

Transient lymphocytolysis

immunodeficiency in response to viral infection- parasite infection

Generalized immunosuppression

Neonatal isoerythrolysis - foals

Foal's red blood cells are destroyed by antibodies in the mare's colostrum

Inflammation

A complex, regulated yet non-specific response to physical/chemical injury or biological agent

tumor, rubor, calor, dolor, functio laesa

The signs of inflammation in spanish; swelling, redness, heat, pain, loss of function

What are some of the benefits of inflammation?

-Dilution/inactivation of pathogens and toxins

-Killing pathogens/foreign materials/Necrotic tissue/neoplastic cells

-Wound healing factors

-Restrict movement for healing

-Increase temp to induce vasodilation and inhibit replication of pathogens

What are some of the disadvantages of inflammation

-Collateral damage

-Excessive and/or prolonged inflammatory response can cause problems (IBD, Johne's disease, pemphigus, lupus, anaphylaxis, glomerulonephritis)

-Anti inflammatory meds

What suffix means inflammation?

-itis

Inflammation of the skin

Dermatitis

Inflammation of the kidney

Nephritis