30: Type IV Hypersensitivity

another name for type IV Hypersensitivity

delayed-type hypersensitivity / T cell mediated

cells involved in type IV hypersens

CD4+ T cells, CD8+ CTL

whats the diff between type IV and the other hypersensitivities

it is t cell mediated, others are antibody mediated

delayed hypersens rxns occur from interactions between

antigen, APCs, t cells, macrophages

are Abs as important in type IV

no, cell-mediated instead

whys type IV called delayed hypersens

due to delayed appearance of response and symptoms

whats the goal of type IV mechanism

elimination of intracellular pathogens and if not eliminated, tissue destruction and granuloma formation occurs

describe the basic mechanism of type IV soluble antigen

1. APC presents tissue antigen

2. signals CD4 T cell and cytokines

   1. leads to inflammation and tissue injury via neutrophil enzymes

describe the basic mechanism of type IV cell associated antigen

cell associated antigen presented to CD* CTLs resulting in cell death and tissue injury

clinical presentation of type IV rxns

induration, hard, raised lesions

erythema and vesicles, reddened skin and fluid filled vesicles

clinical examples of type IV hypersens

tuberculin reaction, contact dermatitis, stevens johnson syndrome

explain tuberculin reaction

after tuberculin is injected, its taken up by langerhans cells and migrate to lymph node. Here they are presented to memory T cells that generate Th1 effector cells who accumulate antigen around the antigen deposit with t cells.

in human and mice, tuberculin rxn tend to be predominated by

A/B t cells

sheep and cattle, tuberculin rxn tend to be predominated by

y WC1 T cells predominate

t or f: there are no B cells in the tuberculosis lesion

t

symptoms of tuberculosis

bad cough for 3 weeks, chest pain, coughing up blood, weakness, losing weight, no appetite, chills and fever, sweating at night

what is used to identify those suffering from TB

mycobacterial extract

symptoms of t-reaction

red hard swelling at injection site, starts after 12-24 hr, greatest intensity at 24-72 hrs. severe- tissue destruction and necrosis. lesions infiltrated w lymphocytes and macrophages.

human tuberculosis

mycobacterium tuberculosis

bovine tuberculosis

mycobacterium bovis (ZOONOTIC)

dog tuberculosis

mycobacterium canis

how does bovine TB spread

aerosol inhalation, ingestion of unpasteurized milk

wheres bovine tb occur

africa, asia, M.E

describe single intradermal TB test for cattle

-routine

-simple

-prone to false positives poor sensitivity

describe comparative TB test for cattle

-used when avain TB/johne’s disease is prev

-more specific than SID

-more complex than SID

describe short thermal TB test for cattle

-postpartum animals/infected animals

-high efficiency, time consuming

-anaphylaxis risk

describe stormont TB test for cattle

-postpartum/adv cases

-very sens and accurate

-3 visits req and may sensitize an animal

other skin tests for infectious diseases with cell immunity occurs

1. brucellin

2. mallein for glanders

3. histoplasmin

4. coccidioidin

5. toxoplasmosin

how long does allergic contact dermatitis occur after infection

48-72 hours

whats allergic contact derm

reactive chemical on skin triggers rxn by binding to PRRs like TLR4

describe the pathogenesis of allergic contact derm

1. -bind to skin proteins and act as hapten carriers to be recognized by skin macrophages (langerhans cells)

2. -present antigen to t cell in lymph node

3. -t cells produce IFN-Y and IL17 and activated cytotoxic t cells

4. -kill altered cells and see itching/sloughing of skin

how can allergic contact derm rxn get stronger

re-exposure over time

soruces of contact allergens in animals

insecticides, wood preserves, floor waxes, carpet dyes, paints, house plants, metals

how is allergic contact dermatitis diagnosed

-patch testing

-closed: suspected allergens attached to skin for 48-72 hrs and a pos rxn is erythema and vesiculation

open- solution of allergen is applied to skin and examined for 5 days

optimal therapy for allergic contact derm

identification and avoidance bc sensitization therapy not effective

steroids for acute and antibiotics for secondary

name the dermatitis: hairless areas, reactive chemicals, delayed response

allergic contact derm

name the dermatitis: mononuclear cell infiltration, vesiculation pathology.

allergic contact derm

name the dermatitis: hyperemia, urticaria, pruritus, face/nose/eyes/feet

atopic derm

name the dermatitis: foods/pollen/fleas, dx w intradermal testing w immediate response

atopic derm

name the dermatitis: mast cell and eosinophilic infiltration, edema. tx w steroids/antihistamine/hyposensitization

atopic derm

atopic derm is _____, type IV hypersens is_____

type I vs type IV

what kind of rxn is stevens johnson syndrome

mucocutaneous rxn

describe what stevens johnson syndrome is

t cell mediated hypersens to drugs (14 days after) usually antibiotics,sulfa drugs,NDAIDS

symptoms of steven johnson syndrome human

rash that blisters into vesicles, shed large areas of epidermis and develop skin ulcers (skin, lips, mouth, eyes, genitals)

symptoms of stevens johnson syndrome in dogs

dyspnea, fever, vomiting, weight loss. sloughing of skin over the nasal planum, footpads, oral/nasal/pharyngeal/conjunctival and preputial musosa

how do skin ulcers from stevens johnson syndrome occur

keratinocyte apoptosis. due to drugs/their metabolites binding to epidermal cells and triggering CD95L expression leading to CTL destruction

why is CD95L so bad for stevens johnson syndrome

triggers keratinocyte apoptosis leading to skin necrosis

summarize type IV

delayed

summarize III

immune complex

summarize II

antibody

summarize I

allergy/anaphylaxis

delayed hypersens rxns are mainly mediated by

t cells and macrophages

what is the slow developing inflamm response that occurs when reactive chemicals bind to skin cells and trigger t cell responses

allergic contact dermatitis