Objective (1-Gallucci) - Immunologically-mediated Disease

Obj. 1

Describe the most common immunological abnormalities.

A. Immunodeficiency Disorders: The congenital or acquired absence of one or more components of the immune system.

B. Cancer: A potential function of the immune system is to prevent the emergence of neoplastic disease and, if so, immunological defects may then promote tumor growth.

• On the other hand, cancer especially that of the immune system—may result in an immunocompromised host.

• Either way cancer often, if not always, involves an immunological abnormality.

C. Immunologically-mediated Disease:

• Autoimmune Disease: Tolerance of self is one of the central dogmas of immunology but there is no question that an immune response against self is involved in many diseases.

• Alloimmune Disease: An untoward immunological response to a foreign immunogen derived from another member of the same species.

  • It can be correctly argued that this is just a special case of allergy.

  • But alloimmune disease of newborn, blood transfusion, and tissue transplantation are specialized enough to merit separate consideration.

• Allergic Disease: An untoward immunological response to a foreign immunogen which is called an allergen to provide the appropriate negative connotation.

  • Since the immune system is supposed to respond to foreign immunogens it may be argued in some cases that there is no immunological abnormality involved.

Obj. 2

Summarize how basic immunological principles are related to immunopathology.

A. Specificity:

1. B and T cell responses are as specific to “abnormal” antigens as normal ones.

B. Diversity: Aka: Heterogeneity

1. “Abnormal” antigens are as diverse as “normal” ones, so it produces a diverse immune cell

C. Discrimination of Self:

1. Tolerance is not inherited but is an acquired, active, ongoing process

2. Autoimmunity may be viewed in its simplest form as loss of tolerance.

D. Immunologic Memory:

1. Unwanted responses are remembered and amplified just like the desired responses (ie.memory cells).

E. Termination of the Response:

1. Luckily, there we’ve adapted methods of inhibiting these responses…to varying degress of success.

2. Suppression of immune responsiveness by various mechanisms—including immunogen-induced apoptosis is as normal and essential as immune responsiveness

Obj. 3

Compare an ideal versus an actual immune response.

A. The ideal immune response would be

1. Directed only against immunogens capable of harming the host.

2. Completely effective in totally eradicating the offending immunogen.

3. Completely protective, with no tissue damage from either the immunogen nor the response.

B. In the actual immune response tissue damage or other adverse consequences may arise from several sources including:

1. Etiologic agent

a. Prior to the development of immunity and robust response to secondary infection.

b. A deficiency in the immune response that allows damage

2. Inflammatory and/or Immune Response to the Etiologic Agent

a. Many etiologic agents are apparently harmless (e.g., most common allergens including drugs) at least from the standpoint of requiring immunological protection.

b. Many infectious agents do less damage to the tissues than the immune response—ie. the inflammation that comes with the response.

3. Autoimmunity—immune response to self antigens

a. Many times a foreign antigen can look like a self antigen, possibly to disguise itself.

• For example see—rheumatic fever.

4. Iatrogenic—adverse response to therapy

a. Drugs to aid in defense can cause severe damage (more on this later).

C. Conclusion: It is not always easy to distinguish between protective immunity and immunologically-mediated disease because they are often part of the same process.

• In other words, normal immune responses work just like abnormal ones.

Obj. 4

List the parameters by which immunologically-mediated disease can be classified.

A. Source of Antigen: Autoimmune Alloimmune Allergy

B. Mechanism: Coombs and Gell (1963) Types I - IV

1. IgE-mediated

2. Cytotoxic

3. Immune Complex

4. Cell-mediated

C. Clinical: Mixture of above and other (e.g., organ system)