Difference between revisions of "Autoimmune Diseases"

 
(4 intermediate revisions by 4 users not shown)
Line 1: Line 1:
{{review}}
+
#REDIRECT[[:Category:Autoimmune Diseases]]
 
 
{{toplink
 
|linkpage =WikiClinical
 
|linktext =WikiClinical
 
|maplink = WikiClinical Content Map
 
|pagetype = Clinical
 
|sublink1 = Immunology - WikiBlood
 
|subtext1 = IMMUNOLOGY
 
}}
 
<br>
 
==Introduction==
 
 
 
'''Autoimmune disease''' is defined as ''a disease state characterised by a specific antibody or cell mediated response against the body's own tissues ('self' antigens).
 
 
 
The breakdown of [[Immune Tolerance - WikiBlood|tolerance]] to self antigens and the failure to regulate pathological immune responses are both responsible for autoimmune diseases. It has been shown in mice that thymectomy causes autoimmune disease, and plays a very important role in the recognition of 'self'.
 
 
 
Particular individuals may be more susceptible to autoimmune diseases due to:
 
 
 
===Genetic factors===
 
 
 
Many autoimmune diseases have a familiar component and the Human Leucocyte Antigen (HLA) haplotype is the predominant genetic factor, however having a particular HLA haplotype does not automatically result in the development of an autoimmune disease.
 
 
 
* HLA-DR3/DR4 (MHC Class II):
 
1. Diabetes Mellitus
 
 
 
2. Rheumatoid Arthritis
 
 
 
* HLA-B27 (MHC Class I):
 
1. Ankylosing spondylitis
 
 
 
* TNF alpha
 
 
 
* CTLA-4
 
 
 
===Hormonal factors===
 
 
 
Testosterone is protective against Systemic Lupus Erythematosus (SLE) and thus it is not seen in males.
 
 
 
===Environmental factors===
 
 
 
'''''Infection'''''
 
 
 
1. Molecular mimicry
 
 
 
* Some bacteria and viruses  have antigens that resemble host-cell components and the body can then also initiate an immune response against itself.
 
 
 
2. Polyclonal activation
 
 
 
* T and B cells activation can occur as a result of an infection resulting in polyclonal activation. This can then cause autoreactive autoantibodies or mediate autoimmunity.
 
 
 
3. Inappropriate MHC expression
 
 
 
* Autoreactive T cells are activated because infection stimulates APC and upregulates MHC class II.
 
 
 
'''''Diet'''''
 
 
 
'''''Stress'''''
 
 
 
 
 
 
 
{| border="1" cellpadding="2"
 
!width="150"|
 
!width="150"|Antibody mediated
 
!width="50"|Antibody mediated
 
!width="200"|Cell mediated
 
|-
 
| '''Type of hypersensitivity''' || [[Type II Hypersensitivity - WikiBlood|Type II]] || [[Type III Hypersensitivity - WikiBlood|Type III]] || [[Type IV Hypersensitivity - WikiBlood|Type IV]]
 
|-
 
| '''Pathogenesis''' || Antibody to cell surface or matrix antigens  || Antibody to soluble self antigens || T cell and macrophage activation to self antigens
 
|-
 
| '''Examples of diseases''' || Immune mediated haemolytic anaemia (IMHA)  || Systemic Lupus Erythematosus (SLE) || Rheumatoid arthritis
 
|-
 
|  || Immune mediated thrombocytopaenia (IMTP)||                          || Diabetes Mellitus type 1
 
|-
 
|  || Myasthenia gravis  ||  || Hypothyroidism (lymphocytic throiditis)
 
|-
 
|  || Pemphigus Vulgaris  ||  || Hypoadrenocorticism (Addisons disease)
 
|-
 
|  || Bullous pemphigoid  ||  ||
 
|}
 
 
 
==Antibody mediated autoimmune diseases==
 
[[Image:Large.jpg|right|thumb|150px|Myasthenia gravis - From Immunity: The Immune Response in Infectious and Inflammatory Disease DeFranco, Locksley and Robertson New Science Press 1999-2007]]
 
 
 
===1. Immune Mediated Haemolytic Anaemia (IMHA)===
 
 
 
'''Pathogenesis:''' [[Type II Hypersensitivity - WikiBlood|Type II hypersensitivity]]
 
 
 
* Autoantibody attack on the red blood cells causing extravascular and intravascular lysis which causes anaemia.
 
* The in saline autoagglutination test and the coombes test is used to diagnose the disorder.
 
 
 
===2. Immune Mediated Thrombocytopaenia (IMTP) ===
 
 
 
'''Pathogenesis:''' [[Type II Hypersensitivity - WikiBlood|Type II hypersensitivity]]
 
 
 
* There is an immunological attack on the platelets which reduces the ability for clotting.
 
* A reduced platelet count and detection of anti-platelet antibodies in the serum are used for diagnosis of this disorder.
 
 
 
===3. Myasthenia gravis===
 
 
 
'''Pathogenesis:''' [[Type II Hypersensitivity - WikiBlood|Type II hypersensitivity]]
 
 
 
===4. Bullous Pemphigoid===
 
 
 
'''Pathogenesis:''' [[Type II Hypersensitivity - WikiBlood|Type II hypersensitivity]]
 
 
 
===5. Pemphigus Vulgaris===
 
 
 
'''Pathogenesis:''' [[Type II Hypersensitivity - WikiBlood|Type II hypersensitivity]]
 
 
 
===6. Systemic Lupus Erythematosus (SLE)/Multi-systemic immune mediated disease===
 
 
 
'''Pathogenesis:''' [[Type III Hypersensitivity - WikiBlood|Type III hypersensitivity]]
 
 
 
==Cell mediated autoimmune diseases==
 
[[Image:Rheumatoid Arthritis Type IV hypersensitivity.jpg|right|thumb|150px|Rheumatoid Arthritis-Brian Catchpole RVC 2008]]
 
[[Image:Diabetes Mellitus Type IV hypersensitivity.jpg|right|thumb|150px|Diabetes Mellitus-Brian Catchpole RVC 2008]]
 
 
 
===1. Rheumatoid arthritis===
 
 
 
'''Pathogenesis:'''
 
 
 
* [[Type IV Hypersensitivity - WikiBlood|Type IV hypersensitivity]]: CD4 Th-1 cell mediated.
 
* Macrophages phagocytose self antigens and can present peptides on their MHC Class II molecules. The autoreactive TH-1 cells release IFN-gamma which activates macrophages to release prostaglandins, MMP enzymes and TNF-alpha (pro-inflammatory mediator), see diagram. These cytokines cause inflammation and tissue destruction.
 
 
 
===2. Diabetes Mellitus type I===
 
'''Pathogenesis:'''
 
 
 
* [[Type IV Hypersensitivity - WikiBlood|Type IV hypersensitivity]]
 
* The CTLs think that all the beta cells in the pancreas are infected by a virus, as it wrongly detects a self antigen presented by the MHC class I on the surface of the cell as foreign.
 
* Autoreactive CD8+ CTLs are inadvertently activated destroying the beta cells thus preventing the secretion of insulin and causing diabetes type 1 (see diagram).
 
 
 
===3. Hypothyroidism (lymphocytic throiditis)===
 
 
 
'''Pathogenesis:''' [[Type IV Hypersensitivity - WikiBlood|Type IV hypersensitivity]]
 
 
 
* T cell mediated
 
 
 
===4. Hypoadrenocorticism (Addisons disease)===
 
 
 
'''Pathogenesis:''' [[Type IV Hypersensitivity - WikiBlood|Type IV hypersensitivity]]
 
 
 
==References==
 

Latest revision as of 14:40, 11 August 2010