immune diseases and immunodeficiences

autoimmune diseases

body is attacked by its own specific adaptive immune response

• causes are unknown

  • genetics

  • environmental factors

  • infections

immunology of autoimmune diseases

• immune tolerance/self tolerance is lost

• develop hypersensitivity against own cells

• mediated by autoantibodies or autoimmune T cells

• tissue damage occur due to activated CD8 cells, antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells and complement activation

• self-reacting B cells and T cells

organ-specific autoimmune diseases

• celiac disease

• hyperthyroidism (graves disease)

• type I diabetes

• addison disease

systemic autoimmune diseases

• multiple sclerosis

• rheumatoid arthritis

• systemic lupus erythematosus (SLE)/lupus

type I diabetes

• targets insulin-producing pancreatic beta-cells

• autoreactive CD4 and CD8 T cells (IV hypersensitivity)

• leads to reduced production of insulin resulting in elevated blood glucose levels

systemic lupus erythematosus (SLE)

• autoimmune complexes against nuclear antigens (antigen-antibody complexes)

• type III hypersensitivity reaction leading to deposition of autoimmune complexes in blood vessels in different types

multiple sclerosis (MS)

• primarily targeting the CNS

• impaired nerve impulses

• motor, sensory as well as cognitive functions are impaired

• muscle weakness, difficulty in speech and vision and lead to paralysis

• T cell mediated (type IV hypersensitivity)

• leads to inflammation and antibody production as well

immunodeficiency

compromised immune response due to components of immune system are absent or functionally defective

• 2 general categories:

  • primary immunodeficiency: present at birth; usually have genetic basis

  • secondary diseases: acquired after birth; caused by natural or artificial agents

primary immunodeficiencies

• pre-T cell

  • DiGeorge syndrome

  • adenosine deaminase deficiency (ADA)

    • recurrent fungal, viral infections

• pre-B cell

  • congenital agammaglobulinemia

  • hypogammaglobulinemia

    • recurrent bacterial infections

DiGeorge syndrome

• defective development of thymus and parathyroid glands

• mainly a defect in chromosome 22

• T cell deficiency

• symptoms:

  • cleft palate

  • cyanosis

  • abnormal facial features

  • learning difficulties

severe combines immunodeficiency disease (SCID)

• collection of syndromes caused by genetic defect that knocks out B and T cell-mediated immunity, multiple forms of SCIDs exist

• involve deficiency in both B and T cells

• in general, all patients extremely susceptible to all types of infection

• treatments:

  • maintain patients in aseptic environments

  • total replacement of lymphoid cells using bose marrow or stem cells

  • gene therapy

acquired immunodeficiency syndrome (AIDS)

• caused by human immunodeficiency virus (HIV) targeting CD4 cells of immune system

• HIV infection eventually results in death of CD4 cells, monocytes, macrophages and other Ag-presenting cells

• depletion of immune cells, particularly T cells, results in impairment of immune systmem, making patient susceptible to opportunistic infections and certain cancers

AIDS steps

1. HIV fuses to host-cell surface

2. HIV RNA, reverse transcriptase, integrase, and other viral proteins enter host cell

3. viral DNA formed by reverse transcription

4. viral DNA transported across nucleus and integrates into host DNA

5. new viral RNA used as genomic RNA and to make viral proteins

6. new viral RNA and proteins move to cell surface and a new, immaturem HIV forms

7. virus matures when protease releases proteins that form the mature HIV

antiviral drugs: treatment of HIV infections

• fusion inhibitors

• reverse transcriptase inhibitors

• protease inhibitors

• integrae inhibitors

fusion inhibitors

prevent binding of HIV to host cell co-receptor, inhibit the merging of viral envelope with host cell membrane

ex. enfuviritide

reverse transcriptase inhibitors

• competitive nucleoside analog inhibitors (AZT) and non-nucleoside noncompetitive inhibitors (etravirine)

• bind reverse transcriptase and inhibit conversion of RNA to DNA

protease inhibitors

block processing of viral proteins and prevent viral maturation

ex. ritonavir

integrase inhibitors

block activity of HIV integrase (recombination of viral DNA into host cell chromosome)

ex. raltegravir