8Hypersensitivity

Contact Hypersensitivity

Usually maximal at 48 hours Predominantly an epidermal reaction Langerhans cells are the antigen presenting cells

a dendritic antigen presenting cell carry antigen to lymph nodes draining skin nickel salts in jewellry picryl chloride acrylates p-Phenylene diamine in hair dyes chromates chemicals in rubber
Hemolytic Disease of the Newborn
first birth post partum subsequent
RhD negative mother
RhD positive red cells
B cell
anti-RhD
RhD positive fetus
anti-RhD
Lysis Of RBC’s

cavitation, caseation, general toxemia seen in TB

May progress to granulomatous reaction in unresolved infection
Granulomatous Hypersensitivity




lysis
Toxic Complex Hypersensitivity (Type III)
Diseases associated with immune complexes

Persistent infection

microbial antigens deposition of immune complexes in kidneys self antigens deposition of immune complexes in kidneys, joints, arteries and skin
B
Fuc
ABO Blood Group Reactivity
blood group genotypes antigens antibodies to (phenotype) ABO in serum A AA, AO A anti-B B BB, BO B anti-A AB AB A and B none O OO H anti-A/B
RhD positive fetus
Drug-Induced Reactions: Adherence to Blood Components
blood cell adsorbed drug or antigen drug metabolite antibody to drug
complement

Disease Models
Serum sickness Arthus reaction

Serum Sickned Hypersensitivity (Type IV / Delayed-Type)
Manifestations of T-Cell Mediated Hypersensitivity Allergic reactions to bacteria, viruses and fungi Contact dermatitis due to chemicals Rejection of tissue transplants
anaphylatoxins Chemotactic factors


Neutrophils attracted
difficult to phagocytize tissue-trapped complexes frustrated phagocytosis leads to tissue damage
Characteristics of Cytotoxic Hypersensitivity


Directed against cell surface or tissue antigen Characterized by complement cascade activation and various effector cells
ABO Blood Group Antigens
H
NAG Gal NAG Gal
A
NAG Gal NAcGA
Fuc
A antigen
Fuc
B antigen
Precursor oligosaccharide
H antigen
NAG
Gal
Gal
NAcGA (N-acetylgalactoseamine) Gal (galactose)
Clinically, the most important form of DTH, since it causes many of the pathological effects in diseases which involve T cellmediated immunity Maximal at 14 days Continual release of cytokines Leads to accumulation of large numbers of macrophages Granulomas can also arise from persistence of “indigestible” antigen such as talc (absence of lymphocytes in lesion)

Associated with hapten-induced eczema

Poison Ivy contact dermatitis
Tuberculin Hypersensitivity



Maximum at 48-72 hours Inflitration of lesion with mononuclear cells First described as a reaction to the lipoprotein antigen of tubercle bacillus Responsible for lesions associated with bacterial allergy

Autoimmunity


Extrinsic factors


environmental antigens deposition of immune complexes in lungs
Inflammatory Mechanisms in Type III

Complement activation

General Characteristics of DTH





An exaggerated interaction between antigen and normal CMI-mechanisms Requires prior priming to antigen Memory T-cells recognize antigen together with class II MHC molecules on antigen-presenting cells Blast transformation and proliferation Stimulated T-cells release soluble factors (cytokines) Cytokines
Epitheloid Cell Granuloma Formation




Large flattened cells with increased endoplasmic reticulum Multinucleate giant cells with little ER May see necrosis Damage due to killer T-cells recognizing antigen-coated macrophages, cytokineactivated macrophages Attempt by the body to wall-off site of persistent infection
Jones-Mote Hypersensitivity



Now referred to as “cutaneous basophil hypersensitivity” Basophils are prominent as secondary infiltrating cells. Basophilic infiltration of area under epidermis Induced by soluble (weak) antigens Transient dermal response Prominent in reactions to viral antigens, in contact reactions, skin allograft rejections, reactions to tumor cells and in some cases of hypersensitivity pneumonitis (allergic alveolitis)
macrophages/monocytes neutrophils NK cells

Examples of Type II Hypersensitivity