Chapter Abstract

The innate complexity of the immune system can contribute to various levels of malfunction that may result in serious deleterious effects. Some of the elements that defend the body can either directly, or indirectly result in damage to "self" as well as reject transplanted tissues and/or organs. Immune disorders such as hypersensitivity, autoimmune disease, and immunodeficiency obviously result in undesirable conditions. Disorders of the immune system are involved in asthma, anaphylaxis, rheumatoid arthritis, graft rejection, and possibly even some cancers. This chapter deals with representatives of immune disorders and some of the progress made in their identification and treatment.

Learning Objectives

• Explain the term immunopathology.
• Tell how the immune system might be described as a two-edged sword or a two-sided coin.
• Distinguish between Type I hypersensitivity, Type II hypersensitivity, Type III hypersensitivity, and Type IV hypersensitivity.
• Relate allergy to hypersensitivity.
• Explain what is meant by the term autoimmune disease.
• Explain how a condition of immunodeficiency can originate.

Lecture Outline - Specific Immunity

1. Disorders in Immunity

1. The immune system - good news and bad news

1. ordinarily defends the body against invaders
2. sometimes overactive or malfunctions - resulting in disease

1. Classification of immune reactions

1. type of lymphocytes
2. type / source of antigen
3. nature of pathology (damage) done by response

1. Types of Disorders

1. Hypersensitivity

1. TYPE I Hypersensitivity Immediate-type Hypersensitivity ("allergies")

1. immediate onset
2. allergens - classes

1. inhalants
2. ingestants
3. injectants
4. contactants

1. Mechanism

1. sensitization
2. IgE production, attachment to granulocytes (Mast cells / Basophils)
3. Allergen-IgE complex at cell surface triggers release of vasoactive amines (histamine, etc)

1. Effects

1. Localized effects

1. atopic allergy
2. allergic rhinitis
3. asthma
4. dermatitis
5. food allergy

1. systemic effects

1. vasodilatation (vasodilation)
2. bronchoconstriction
3. rash, labored breathing, prolific mucous, pain

1. Anaphylaxis

1. localized - atopic dermatitis

(a) skin-test ("patch-test), with selected allergens

2. generalized - anaphylaxis

1. anaphylactic shock
2. respiratory anaphylaxis
3. emergency response kits

1. Treatment of allergies

1. Antihistamine, to manage effects of histamine
2. desensitization, "allergy shots" regimen

1. TYPE II Hypersensitivity - Cytotoxic Hypersensitivity

1. destruction of "foreign" cells
2. mechanism - antibodies and complement lyse foreign cells
3. effects

1. blood transfusion reactions, blood typing, ABO system
2. hemolytic disease of newborn

1. Rh antigens
2. Sensitization
3. Prevention

1. TYPE III Hypersensitivity - Immune Complex Disorders

1. large quantities of soluble antigen (drugs, serum)
2. large Ag-Ab complex form, clog tissues and organs
3. examples, serum sickness (systemic); Arthus reaction (localized)

1. TYPE IV Hypersensitivity - Cell-mediated Hypersensitivity

1. delayed-type response
2. T-cells become activated, destroy tissue
3. Examples:

1. graft rejection - recipient T-cells target foreign antigens on donor

1. autograft - donor and recipient one in the same
2. isograft - between identical twins (some day…cloned organs!?!)
3. allograft - between individuals of the same species
4. xenograft - between different species

1. TB skin test
2. contact dermatitis - delayed response

1. Immunodeficiency

1. components of the immune system are absent

1. B-cells, T-cells, phagocytes, complement system
2. Primary (congenital) immunodeficiency

1. genetic basis, congenital

1. agammaglobulinemia - B-cell defect
2. athymic - thymus absent, or undeveloped
3. Severe Combined Immunodeficiency (SCID), T-cell and B-cell deficient or absent - fatal without bone marrow transplant

1. Secondary (acquired) immunodeficiency

1. result of damage after birth

1. infection, drugs, radiation, etc
2. HIV 1 thought to be most common cause

1. helper T-cells critical targets
2. deficiency leads to numerous opportunistic infections and cancer (Kaposi's Sarcoma)

1. some involve Type II and type III hypersensitivity conditions

1. immune tolerance of "self" antigens malfunctions
2. autoantibody and T-cells attach "self" tissues
3. effects may be systemic (Lupus Erythematosis)

1. SLE antibodies attack kidneys, lungs, skin, heart

1. effects may be localized

1. Rheumatoid arthritis

1. may attack endocrine system

1. Grave's Disease
2. Hashimoto's Thyroiditis
3. Diabetes mellitus Type I and Type II
4. Myasthenia gravis
5. Multiple Sclerosis

1. Cancer and the Immune System

1. cancer - neoplasm, characteristic over growth of normal tissue
2. some appear to be associated with malfunction of "immune surveillance"
3. Tumors

1. benign = localized, non-spreading
2. malignant = spreads from site of origin
3. carcinomas = from epithelial tissues
4. sarcomas = form connective tissues

1. can occur in most cell types (except mature, non-dividing cells)
2. appears to be associated with change of a normal gene to an oncogene

Define / describe each of the following as related to microbiology.

allergy allergen immunopathology autoimmunity IgE

immunodeficiency mast cell sensitizing dose allograft

provocative dose degranulation histamine

Type I Hypersensitivity Type II Hypersensitivity autograft

Type III Hypersensitivity Type I Hypersensitivity systemic anaphylaxis

serum sickness xenograft benign malignant

carcinoma sarcoma oncogene food allergy

1. Describe how knowledge of the immune system can be used to :

    a. protect the individual from specific diseases.

    b. protect a population form specific diseases.

    c. detect exposure to a specific pathogen

2. What is meant by "hypersensitivity"?

3. Describe the key characteristics of each of the following types of hypersensitivity:

    a. Type I hypersensitivity

    b. Type II hypersensitivity

    c. Type III hypersensitivity

    d. Type IV hypersensitivity

4. What is systemic anaphylaxis? Why is to so dangerous?

5. What is the relationship of IgE to allergic responses?

6. What is agammaglobulinemia? How is it acquired?

7. Differentiate between a carcinoma and a sarcoma.

8. Distinguish between benign and malignant forms of cancer.

9. What is serum sickness? How is it acquired? Why must it be considered during certain types

of passive immunization?