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Disorders Associated With The Immune System

 

Introduction

 

Hypersensitivity

  1. Altered Immune Reaction
  2. Allergy
  3. Allergen
  4. Classes
    1. Immediate, based on humoral immunity includes Types I, II, and III
    2. Delayed is based on cell-mediated immunity, Type IV

 

Type I (Anaphylactic) Reactions

  1. Anaphylaxis is the result of IgE antibodies binding to basophils and mast cells (tissue basophils).
  2. Stimulates the release of:
    1. Histamine
    2. Leukotrienes
    3. Prostaglandins
  3. Systemic anaphylaxis
    1. Anaphylactic shock
    2. Counteracted by epinephrine injection
  4. Localized reactions

a.    Allergic rhinitis (hay fever) - Itchy and teary eyes, congestion, coughing and sneezing

    1. Asthma – Wheezing and shortness of breath
    2. Hives
  1. Desensitization by repeated injection of antigen
  2. Blocking antibodies - IgG

 

Type II (Cytotoxic) Reactions

  1. Mediated by IgG or IgM and complement
  2. Antibodies are directed toward host (or foreign) cell antigens
  3. Complement fixation occurs and we know what that results in, don’t we Courtney?

 

The ABO Blood Group System

  1. A, B, both (AB), or neither (O)
  2. Incompatible blood transfusions – Donor red blood cells are lysed

 

The Rh Blood Group System

  1. Distribution – about 85% of humans are Rh+
  2. Rh positive – posses one of eight antigens in the Rh group
  3. C, D, and E are common with D being the most common by far
  4. Rh incompatibility results from Rh- people being exposed to Rh+ blood
  5. Hemolytic disease of newborn (erythroblastosis fetalis)

 

Drug-Induced Cytotoxic Reactions

  1. Drug acts as a hapten, coats platelets or cells, antibodies and complement bind and cells are lysed.
  2. Drug induced thrombocytopenic purpura
  3. Agranulocytosis
  4. Hemolytic anemia

 

Type III (Immune Complex) Reactions

  1. Antigens involved not part of host cells but soluble
  2. Bound by IgM or IgG antibodies, complexes precipitate and lodge in basement membranes
  3. Complement fixation leads to inflammation, cell lysis
  4. Glomerulonephritis
    1. Inflammation of the glomeruli
    2. Immune-complex disease
    3. Occurs as a sequel to a beta-hemolytic streptococcal infection (group A)
    4. Antigen-antibody complex causes inflammation and damage to the glomerular membrane
    5. Symptoms:

                                                    i.     Fever

                                                   ii.     High blood pressure

    1. Treatment:

                                                    i.     Antibiotics to control the infection early on

                                                   ii.     Antihypertensive drugs and diuretics

                                                 iii.     Dialysis

                                                 iv.     Kidney transplant

    1. Most patients recover completely
  1. Systemic lupus erythematosus
  2. Rheumatoid arthritis

 

 

Type IV (Cell-Mediated) Reactions

  1. T Cells involved (Delayed hypersensitivity -TDTH)
  2. Sensitized T cell secretes lymphokines in response to antigen
  3. Lymphokines attract macrophages and initiate tissue damage
  4. Examples
    1. Tuberculin skin test
    2. Allergic contact dermatitis

 

Autoimmune Diseases

  1. Loss of self-tolerance
  2. Type I autoimmunity – antibodies to infectious agents cross react with self cells
    1. Autoimmune hepatitis (Hepatitis C virus)
  3. Type II (cytotoxic) autoimmunity – antibodies bind to cell surface antigens without cell destruction
    1. Graves’ disease – thyroid stimulators
    2. Myasthenia gravis – antibodies bind to Ach receptors and block neuromuscular junction
  4. Type III (immune complex) autoimmunity – antibodies against self proteins cause immune complex deposition and complement fixation
    1. SLE
    2. RA
  5. Type IV (cell-mediated) autoimmunity – activation of cytotoxic T cells by infectious agents
    1. Multiple sclerosis
    2. Hashimoto’s thyroiditis
    3. Insulin-dependent diabetes mellitus

 

Reactions Related to the Human Leukocyte Antigen (HLA) Complex

  1. Histocompatibility antigens
  2. Tissue typing to prevent transplant rejection includes HLA and ABO matching

 

Reactions To Transplantation

  1. Graft rejection – tissue recognized as foreign may be attacked by cytotoxic T cells, macrophages, and antibodies
  2. Transplant into a privileged site (cornea, brain) or with privileged tissue (porcine heart valves) doesn’t cause rejection
  3. Pluripotent stem cells may differentiate into a variety of tissues that made be used for transplantation (like bone marrow)
  4. Types of transplants include:
    1. Autografts
    2. Isografts
    3. Allografts
    4. Xenografts
  5. Bone marrow can cause graft-versus-host disease
  6. Immunosuppressant drugs often required to prevent rejection

 

Immune Deficiencies

  1. Congenital or Acquired
  2. Congenial due to defective or absent genes
  3. Drugs, cancers, and infectious diseases can cause acquired immune deficiencies

 

The Immune System and Cancer

  1. Cancer cells have undergone transformation, divide uncontrollably, and posses tumor-associated antigens.
  2. Immunological surveillance – response of immune system to cancer cells
  3. Cytotoxic T cells and NK cells recognize and lyse cancerous cells.
  4. Cancer cells may escape immunosurveillance, may suppress T cells, or may grow faster than the immune system can respond.

 

Immunotherapy

  1. TNF and cytokines being tested as cancer treatments
  2. Immunotoxins – cytotoxins linked to monoclonal antibodies
  3. Vaccines using tumor antigens may work (Marek’s disease in poultry, melanoma in humans??)

 

Acquired Immunodeficiency Syndrome (AIDS)

The Origin Of AIDS

  1. Central Africa, mutated monkey virus, 1930’s
  2. Probably was contained in villages until the end of colonialism brought about urbanization and highway systems (travel and urban blight).
  3. First known case – patient died in 1959, preserved blood has anti-HIV antibodies

 

HIV Infection

  1. AIDS is the final stage of HIV infections
  2. HIV – retrovirus, ss RNA, reverse transcriptase, phospholipid envelpe with gp 120 spikes
  3. Spikes attach to CD4 receptors and coreceptors on host cells (helper T cells, macrophages, and dendritic cells).
  4. Viral RNA reverse transcribed to DNA, integrates into host chromosome and directs synthesis of new viruses or remains latent as a provirus.
  5. Evades immune system by latency, hiding in vacuoles, using cell-cell fusion, and by antigenic change.
  6. Genetically distinct groups of HIV are classified into clades.
  7. HIV infection is categorized by symptoms:
    1. Category A –asymptomatic
    2. Category B – selected symptoms
    3. Category C – AIDS indicator conditions, reported as AIDS
  8. Also categorized by CD4 T cell numbers: below 200/mm3 is reported as AIDS (true for Category A and B also).
  9. Progression from HIV infection to AIDS takes about 10 years.
  10. Life of AIDS patients can be prolonged by the proper treatemtn of opportunisitic infections.

 

Diagnostic Methods

  1. HIV antibodies detected by ELISA, antigens detected by Western blotting.
  2. Plasma viral load tests detect viral nucleic acid and are used to quantify HIV in blood.

 

HIV Transmission

  1. Sexual contact, breast milk, contaminated needles, transplacental infection, artificial insemination, and blood transfusion.
  2. Blood transfusions not likely source of infection in developed countries.

 

AIDS Worldwide

  1. U.S., Canada, western Europe, Australia, northern Africa, and parts of South America transmission has been by injecting drug use (IDU) and male-to-male sexual contact.  Heterosexual transmission is increasing.
  2. Sub-Saharan Africa transmission is primarily heterosexual contact.
  3. Eastern Europe and Asia – transmission is by IDU and heterosexual contact.

 

Prevention and Treatment of AIDS

  1. The use of condoms and sterile needles prevents the transmission of HIV.
  2. Vaccine development is difficult because the virus remains inside host cells.
  3. Current chemotherapeutic agents target the viral enzymes reverse transcriptase and protease.