Hypersensitivity Reactions

Diseases of theImmune System

Ch. 4 p (99 – 159)Feb. 28 /2016March 6 /2016

MHC
Collection of genes on chromosome 6 Three regions: class I, class II, class III Highly polymorphic! Gene products: class I molecules class II molecules class III molecules (and other stuff)
Major histocompatibility (MHC) complex

MHC MOLECULES (Gene Products)

MHC I; (All nucleated cells and platelets)MHC II; (APC’s, i.e., macs and dendritics, lymphs), MHC III; Complement System Proteins

class I MHC molecule

class II MHC molecule
class II MHC genes
class I MHC genes
class III MHC genes

MHC I

MHC II

IMMUNE SYSTEM DISORDERS

HYPERSENSITIVITY REACTIONS“AUTO”-IMMUNE DISEASESIMMUNE DEFICIENCY :PRIMARY (GENETIC)SECONDARY (ACQUIRED)

HYPERSENSITIVITY REACTIONS “HR” Type I (Immediate HR) Type II (Ab Mediated HR) Type III (Immune-Complex Mediated HR) Type IV (Cell-Mediated HR)

Type I hypersensitivity (Immediate HR)

Type I hypersensitivity
There are two forms of anaphylaxis: Systemic anaphylaxis: acute asthma, laryngeal edema, diarrhea, urticaria, and shock. e.g penicillin allergy and bee sting allergy. Local anaphylaxis (atopy): in10% of people hay fever, hives, asthma, etc. e.g food allergies and hay fever to pollen.

Type I hypersensitivity; Beneath the nasal mucosa at the left, eosinophils, plasma cells & lymphocytes

The acute laryngeal edema due to an anaphylactic reaction to penicillin

Variables that probably contribute to the strong TH2 responses to allergens include the route of entry, dose, and chronicity of antigen exposure, and the genetic makeup of the host



TYPE II HRANTIBODY MEDIATED IMMUNITY
Abs (IgG, IgM), attach to cell surfacesOpsonization, PhagocytosisComplement fixation, (cascade of C1q, C1r, C1s, C2, C3, C4, C5….. ), LYSIS of the cell membrane.Anti cell membrane receptorsThe Ags may be normal molecules intrinsic to cell membranes or in the ECM, or they may be adsorbed exogenous antigens (e.g., a drug metabolite)

Type II HR: Opsonization & Phagocytosis

Type II HR Inflammation:

Type II Hypersensitivity

Transfusion reactions: incompatible RBC's or serum is transfused. Autoimmune hemolytic anemia: antibody is made against one's own RBC's. Erythroblastosis fetalis: maternal IgG crosses the placenta and attaches to fetal RBC's. Goodpasture's syndrome: glomerular basement membrane antibody is present.

Idiopathic Autoimmune hemolytic anemia

This is the linear pattern of immunofluorescence with Ab to IgG in a patient with Goodpasture syndrome. The even linear pattern is produced because the Ab is directed against the entire glomerular BM (antiglomerular BM Ab).
Goodpasture syndrome

Type II HR; Ab-mediated cellular dysfunction (Antireceptor Abs)

Graves disease
Myasthenia gravis

Graves Disease

Myasthenia gravis

TYPE III HYPERSENSITIVITYIMMUNE COMPLEX MEDIATED

Ag/Ab“Complexes”Where do they go? (high hemodynamic Pr + Filtration function)Kidney (Glomerular BM),,,,,Pr UreaBlood Vessels,,,,,,, Peticheal hgeSkin,,,,,,, UrticariaJoints,,,,,, arthralgiaLNTissue damages,

Type III HR

The Ags; Exogenous, microbial pr, as in post strep.GN Or Endogenous,, nucleoproteins as in SLE
The Abs; IgG, IgM + Complement
Tissue damage: Ac inflammation, acute necrotizing vasculitis, Microthrombi & iscemic necrosis

TYPE III HR ,,,, Inflammatory Reaction

Platelet aggregation & activate Hageman factor
Microthrombi Ischemic necrosis
Tissue damage: Ac inflammation, acute necrotizing vasculitis
vasculitis, GN, arthritis, Petechial skin hges
The immune complexes activate;
1
2
Consumption of complement may result in decreased serum complement levels.
Pg, vasodilator, chemotactic, lysosomal enz digesting BM, collagen, elastin, & cartilage, ROS


Arthus reaction
Serum sickness
Serum sickness

Immune Complex-Mediated Vascular Inflammation (Vasculitis, ?HBV Ags)

Fibrinoid necrosis in Ar in polyarteritis nodosa. The wall of the artery shows a circumferential bright pink area of necrosis with protein deposition (Imm Complexes & inflammation ? Reversible
Lupus nephritis; Deposition of IgG, detected by immunofluorescence Chronic Unknown Ag
Arthus reaction, an area of tissue necrosis appears as a result of acute immune complex vasculitis

TYPE IV HYPERSENSITIVITYCELL-MEDIATED (T-CELL)DELAYED HYPERSENSITIVITY

Direct antigen  Cell contactGranuloma formationContact dermatitisTuberculin Skin Reaction

Mechanisms of T cell–mediated (type IV) HRcytokine-mediated inflammation, by CD4+ T cells, &Direct cell cytotoxicity, mediated by CD8+ T cells TH1 TH17
If the DCs produce IL-12, the naive T cells differentiate into TH1 type
If the APCs produce IL-1, IL-6, or IL-23 instead of IL-12, the CD4+ cells develop into TH17


Cytokine-mediated inflammation: CD4+ T ,,,,,,,TH1 and TH17 effector cells. Subsequent exposure to the Ag results in the secretion of cytokines. IFN-γ activates MQ,,,,,secrete cytokines IL-17 & other cytokines recruit WBC,,,,,InflammationT cell–mediated cytotoxicity: CD8+CD8+ T cells also secrete IFN-γ.


T cell–mediated cytotoxicity: CD8+Contact dermatitisGraft rejection GVH

ACUTE CELLULAR (T)

ACUTE HUMORAL
CHRONIC

Tuberculin Test

Cytokine-mediated inflammation: CD4+ T ,,,,,,,TH1 and TH17 effector cells

Sequence of events in the natural history of primary pulmonary tuberculosis

RENALTRANSPLANT REJECTION
HYPERACUTE (minutes) : AG/AB reaction of vascular endotheliumACUTE (days months): cellular (INTERSTITIAL infiltrate) and humoral (VASCULITIS)CHRONIC (months): slow vascular fibrosis

IgE

Atopy Anaphylaxis Asthma
Allergy (immediate)
I
IgM or IgG (Complement)
Autoimmune hemolytic anemia Thrombocytopenia Erythroblastosis fetalis Goodpasture's syndrome
Cytotoxic, antibody-dependent
II
IgG (Complement)
Serum sickness Arthus reaction (SLE)
Immune complex disease
III
T-cells
Contact dermatitis TB, Mantoux test Chronic transplant rejection Multiple sclerosis [3]
Delayed-type HR (DTH), cell-mediated immune memory response, antibody-independent
IV
IgM or IgG (Complement)
Grave's disease Myasthenia Gravis
Autoimmune disease, receptor mediated
V