Chapter 13, 14, 15 (Hypersensitivity Reactions) - Immunology

Type I, II, III, IV

What antibody is mediated for Type I?

IgE mediated

What antibody is mediated for Type II and Type III?

IgM or IgG

What’s different about Type IV hypersensitivity than the other hypersensitivities?

Helper T cell mediated (CD4+ TH1 and TH17 T cells) as well as CD8+ cytotoxic T cells; also delayed type.

What is Type I hypersensitivity?

Anaphylactic reactions

What are the other terms for Type I hypersensitivity?

Allergic or immediate hypersensitivity (due to quick time after exposure for clinical symptoms; <30 minutes)

What is Type II hypersensitivity?

Cytotoxic or cytolytic reactions

How long does it take for Type II hypersensitivity reaction to show clinical symptoms after exposure?

5-12 hours

How long does it take Type III reactions to show clinical symptoms after exposure?

3-8 hours

How long does it take Type IV reactions to show clinical symptoms after exposure?

Over a day

What is Type III hypersensitivity?

Immune complex reactions

What is Type IV hypersensitivity?

Delayed-type hypersensitivity reactions (due to Helper T cell mediation)

What are the three phases in hypersensitivity type I?

Sensitization phase, activation phase, and effector phase

What happens in the sensitization phase?

Cell processes antigen and produces antibody, then class switches to IgE which primes the antigen with soluble antibodies for subsequent exposures.

What happens in the activation phase of type I hypersensitivity reaction?

Fc portion of IgE connected to antigen binds to FceR1 molecules on mast cells or basophils, it cross-links (2 or more receptors bounded to Ag binds to the Fce receptors) and activates the cell to degranulate its inflammatory mediators.

What happens in the effector phase of type I hypersensitivity reaction?

Complex responses occur as a result of the mediators released by mast and basophils (histamine, heparin, cytokines, etc in early phase as preformed mediators) OR (late phase newly synthesized mediators; chronic activations with ECF-A, anaphylatoxins, prostaglandins, thromboxanes, and leukotrienes)

What are some other ways FceR1 can cross-link?

Anti-igE, lectin, chemical cross-linking (binding chemical to Fc portion of IgE bounded to FceR1), or anti-FceR1

What are some effects of chronic activations in the late phase of Type I?

Tissue damage (from more granules released) and activation and proliferation of B, T, and Macrophages that result in TH2 cytokine and antibody production, as well as macrophage phagocytosis

What exactly is atopy?

Immediate Type I hypersensitivity reaction WITH both an environmental trigger and strong family predisposition, due to elevated IgE and huge numbers of TH2 cells.

How can you prevent anaphylactic reactions?

Desensitizing body with injections of antigen.

How does desensitizing/blocking antibody work?

Dose with antigen to develop IgG —> IgG antibodies circulate blood and remove antigen (acts as blocking antibodies) BEFORE IgE activates mast cells

What are some clinical effects/results from type I hypersensitivity?

Asthma, allergic rhinitis, eczema, and anaphylaxis

How does Type II mechanics work?

Reactions are resulted from binding of antibody directly to an antigen on the surface of a cell.

What are the three different pathways under type II hypersensitivity reaction?

Complement mediated (through MAC = cell lysis OR opsonization through macrophage phagocytosis), ADCC through NK cells and KIR/Fc receptors that activate and degranulate perforin and granzymes from NK to target cell = lysis, OR Antibody mediated cellular dysfunction or (anti-receptor antibodies = inhibiting receptors and destroying them in the process)

What are some autoimmune diseases with Type II hypersensitivity component?

Myasthenia gravis, Inappropriate blood hemagglutinins (and also hemolytic disease disease of the newborn), rheumatic fever

What infections causes Type III problems?

Systemic lupus erythematosus, dengue fever, rheumatoid arthritis

What autoimmune diseases have a Type IV hypersensitivity component?

Multiple sclerosis, Type I insulin-dependent diabetes mellitus

What is the mechanism for Type III hypersensitivity?

IgM or IgG immune complexes accumulate in circulation or lodge in basement membranes of tissues and activate complement or NK to degranulate

What happens after the immune complexes lodge in a type III reaction?

Inflammatory cells bind to Fc portion of the antibody-antigen complex and degranulate inflammatory mediators or lytic enzymes as well as cytokines that destroy the basement membrane

What is a result of Type III reaction?

Damaged tissue (fibrinoid necrosis) with platelet aggregation and neutrophil lysosomal enzymes as well as complement proteins that interact with the complexes.

Major events leading to DTH reactions?

1. Activation of antigen-specific inflammatory TH1 and TH17 cells in sensitized individual (Sensitization stage)

2. Proinflammatory cytokines and macrophage activators (Elicitation stage)

3. Recruitment and activation of antigen-NONSPECIFIC inflammatory leukocytes

4. Resulting in accumulation of plasma and local tissue damage due to inflammatory cells (macrophages)