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Category:Immunodeficiencies (view source)
Revision as of 13:37, 12 August 2010
, 13:37, 12 August 2010Created page with "Immunodeficiencies - Introduction ==Primary Immunodeficiency== *Primary immunodeficiencies may affect either the innate immune system o..."
[[Immunodeficiencies - Introduction]]
==Primary Immunodeficiency==
*Primary immunodeficiencies may affect either the [[Innate Immune System - WikiBlood|innate immune system]] or the [[Adaptive Immune System - WikiBlood|adaptive immune system]]
*They are categorised by either the type or the developmental stage of the cells involved
*Lymphoid cell disorders affect [[Lymphocytes#T cells|T cells]] or [[Lymphocytes#B cells|B cells]] (or both)
*Myeloid cell disorders affect phagocytic function
*The severity of the immunodeficiency depends on at which stage in development the problem occurs
**E.g. Defects early on in development will affect the entire immune system
*[[Lymphocytes#T cells|T cell]] deficiencies can affect both the cell-mediated and humoral response as [[Lymphocytes#T cells|T cells]] play a central role in the immune system
===Deficiencies of Innate Immunity===
[[Image:Grey Collie Syndrome.jpg|thumb|right|150px|Appearance of a puppy with Grey Collie syndrome - Copyright Michelle Tennis & Peggy Melton]]
====Canine Cyclic Haematopoiesis====
*Also called '''Grey Collie Syndrome'''
*Autosomal recessive
*Insertion mutation in AP3B1 gene
*Diluted grey coat colour, stunted growth, poor wound healing
*Neutropenia every 2 weeks which lasts 3-4 days due to cyclic production of cells from [[Bone Marrow - Anatomy & Physiology|bone marrow]]
*Animals are prone to recurrent infections, mainly from the respiratory and gastrointestinal tract
**E.g. pyrexia, [[Diarrhoea|diarrhoea]], gingivitis and arthritis
*Puppies can be distinguished from other litter mates by the diluted grey colouring
*Affected puppies show symptoms such as fever, joint pain and eye, skin and respiratory infections from 8 weeks of age
*Affected animals rarely live beyond 2-3 years with most puppies dying within a few weeks of birth
====Canine Leukocyte Adhesion Deficiency (CLAD)====
*Occurs in Irish Setters
*Missence mutation of -Cys-36-Ser- in CD18 molecule
**CD18 is required for [[Neutrophils|neutrophil]] migration and phagocytosis
*Recurrent bacterial infection
*Neutrophilia ([[Neutrophils|neutrophils]] remain in the blood and are unable to fight infection in the tissue)
====Bovine Leukocyte Adhesion Deficiency (BLAD)====
*Occurs in Holstein cattle
*Missence mutation of -Asp-128-Gly in CD18 molecule
*Recurrent infection, e.g. pneumonia
===Deficiencies of Adaptive Immunity===
====Equine Severe Combined Immune Deficiency (Equine SCID)====
*Autosomal recessive
*Occurs in 2-3% of Arabian foals
*Defect in DNA-dependent protein kinase gene
**Gene codes for a DNA repair enzyme involved in V(D)J recombination for antigen receptors of [[Lymphocytes|lymphocytes]] (e.g. Ig and TCR)
*No functional [[Lymphocytes#B cells|B cells]] or [[Lymphocytes#T cells|T cells]]
*Foals develop infections (usually around 8 weeks of age as maternal [[Immunoglobulins|antibody]] in [[Materno-Fetal Immunity - Introduction#Passive transfer via colostrum|colostrum]] wanes around this time)
*Foals usually die from bronchopneumonia
====Canine X-Linked Severe Combined Immune Deficiency (Canine SCID)====
*Affects Basset Hounds and Corgis
*X-linked recessive defect in the gene coding for the IL-2 receptor
**IL-2 receptor is a receptor for the cytokine IL-2 which causes [[Lymphocytes#T cells|T cells]] to proliferate
*Causes lymphoid hypoplasia, stunted growth and increases the animal's susceptibility to infection
*Animal usually dies from pneumonia or sepsis as the level of maternal [[Immunoglobulins|antibody]] decreases
====Selective [[IgA]] deficiency of German Shepherd Dogs====
*Poorly understood
*Linked to other disease syndromes such as deep pyoderma, inflammatory bowel disease, anal furunculosis and disseminated aspergillosis
*[[Immunoglobulin A|[[IgA]]]] deficiency so more susceptible to mucosal disease
====Immunodeficiency of Weimaraners, Irish Wolfhounds and Miniature Dachshunds====
*Unknown aetiology
*Inherited defects
*Low levels of circulating [[Immunoglobulin M|IgM]] and [[Immunoglobulin G|IgG]]
*Impaired [[Neutrophils|neutrophil]] function
*Causes recurrent pyrexia and infections
**E.g. Rhinitis and bronchopneumonia in Irish Wolfhounds due to low [[Immunoglobulin A|[[IgA]]]]
**E.g. Pneumocytosis in Miniature Dachshunds due to low [[Immunoglobulin G|IgG]]
===Laboratory Examples of Severe Combined Deficiency===
[[Image:Nude Mouse.jpg|right|thumb|150px|Athymic Nude Mouse - Armin Kübelbeck 2008]]
*Severe Combined Immune Deficiency(SCID)
**No functional [[Lymphocytes#B cells|B cells]] or [[Lymphocytes#T cells|T cells]]
*Athymic nude mice (no [[Thymus - Anatomy & Physiology|thymus]])
**No functional [[Lymphocytes#T cells|T cells]]
**Cell-mediated immunodeficiency
*Knock-out mice
**E.g. Gene coding for CD4, CD8, IL-10 removed
==Secondary Immunodeficiency==
*There are many causes of secondary immunodeficiency
**Most deficiencies are not genetic
**Most are agent-induced, such as from X-ray radiation and immunosuppressive drugs
===Viral Causes===
====Feline Leukaemia Virus (FeLV)====
[[Image:FeLV Electron Micrograph.jpg|thumb|right|150px|FeLV Electron Micrograph [http://phil.cdc.gov/phil/home.asp Public Health Image Library] Image #5610]]
[[Image:Kinetics of FeLV 2.jpg|thumb|right|150px|Kinetics of FeLV - Copyright Dr Brian Catchpole BVetMed PhD MRCVS]]
*Oncogenic retrovirus
*Causes neoplasia (lymphoma), myelosuppression (anaemia) and immunosuppression (of [[Lymphocytes#T cells|T cells]])
*2 strains:
**FeLV-A
***Natural strain
**FeLV-B
***Formed through FeLV-A recombining with endogenous retroviral sequences in the feline genome
***Increases the risks of lymphoma
**FeLV-C
***Formed from the spontaneous mutation of FeLV-A
***Is more myelosuppressive
*Virus replicates in the oropharyngeal lymphoid tissue causing a viraemia (virus circulating in the bloodstream) which then spreads to the systemic lymphoid tissue
*Shed in saliva
*Passed by oronasal route, e.g. mutual grooming
*Kittens between 6 weeks and 6 months are most susceptible
*60% of cats will become immune to the disease and recover
*Cats that are persistently viraemic will progress to develop FeLV-associated diseases
*Some cats will become viraemic again if treated with corticosteroids or stressed if the infection lies dormant in the [[Bone Marrow - Anatomy & Physiology|bone marrow]]
*Diagnosis:
**ELISA
**Rapid-Immuno-Migration
**Western Blot
**Virus Isolation
**Immunofluorescence
**PCR
*Treatment:
**Antibiotics for secondary infection
**Anti-retroviral therapy
*For vaccinations see [[Vaccines - WikiBlood#Cat Vaccinations|here]]
====Feline Immunodeficiency Virus (FIV)====
*Lentivirus
*Subtypes A, B and D
*Causes increased susceptibility to infections and neoplasia
*Specifically destroys [[Lymphocytes#Helper CD4+|CD4+ T cells]]
*Virus is present in saliva, blood and other bodily fluids
*Feral and outdoor cats (mostly tom cats) are most at risk
*Virus replicates in lymphoid tissue
*Can remain asymptomatic
*Causes pyrexia and lymphadenopathy
*Transmitted by biting
*Diagnosis:
**ELISA
**Rapid-Immuno-Migration
**Western Blot
**Virus Isolation
**Immunofluorescence
**PCR
*Treatment:
**Antibiotics for secondary infection
**Anti-retroviral therapy
*For vaccinations see [[Vaccines - WikiBlood#Cat Vaccinations|here]]
====Bovine Immunodeficiency Virus (BIV)====
*Lentivirus (non-oncogenic)
*Causes a persistent viral infection and lymphocytosis
*Immunocompromised cattle may develop secondary infections
*The transmission is not well known, but the following possibilities are being researched:
**Through milk
**Through infected semen (e.g.artificial insemination)
**Placental transfer
*Diagnosis:
**Western Blot
**PCR
===Toxic Causes===
*Poisons
===Iatrogenic Causes===
*Drugs
**Corticosteroids
**Cyclosporin
**Cytotoxic cancer therapy
===Other Causes===
*Malnutrition
*Chronic disease
*Stress
*Senescence
==Links==
'''Internal'''
*[[Viruses|Viruses - WikiBugs]]
*[[Innate Immune System - WikiBlood]]
*[[Adaptive Immune System - WikiBlood]]
'''External'''
*[http://www.bitoheavencollies.com/GrayCollie.html| Grey Collie Syndrome] ''Information on Canine Cyclic Haematopoeisis (Grey Collie Syndrome) including new research into treating the condition and a clinical example''
*[http://carcino.com.msu.edu//mouse.html| Nude Mice] ''Information on nude mice and their role in cancer research''
==[[Immunodeficiencies Flashcards - WikiBlood|Immunodeficiencies Flashcards]]==
==References==
'''Books'''
*Ivan Roitt: '''Essential Immunology,''' Ninth edition
*Goldsby, Kindt, & Osbourne '''KUBY Immunology,''' Fourth edition
'''Lecture Notes'''
*Dr Brian Catchpole BVetMed PhD MRCVS
'''Websites'''
*Michelle Tennis & Peggy Melton http://www.bitoheavencollies.com
*http://carcino.com.msu.edu/mouse.html
[[Category:Immunology]]
==Primary Immunodeficiency==
*Primary immunodeficiencies may affect either the [[Innate Immune System - WikiBlood|innate immune system]] or the [[Adaptive Immune System - WikiBlood|adaptive immune system]]
*They are categorised by either the type or the developmental stage of the cells involved
*Lymphoid cell disorders affect [[Lymphocytes#T cells|T cells]] or [[Lymphocytes#B cells|B cells]] (or both)
*Myeloid cell disorders affect phagocytic function
*The severity of the immunodeficiency depends on at which stage in development the problem occurs
**E.g. Defects early on in development will affect the entire immune system
*[[Lymphocytes#T cells|T cell]] deficiencies can affect both the cell-mediated and humoral response as [[Lymphocytes#T cells|T cells]] play a central role in the immune system
===Deficiencies of Innate Immunity===
[[Image:Grey Collie Syndrome.jpg|thumb|right|150px|Appearance of a puppy with Grey Collie syndrome - Copyright Michelle Tennis & Peggy Melton]]
====Canine Cyclic Haematopoiesis====
*Also called '''Grey Collie Syndrome'''
*Autosomal recessive
*Insertion mutation in AP3B1 gene
*Diluted grey coat colour, stunted growth, poor wound healing
*Neutropenia every 2 weeks which lasts 3-4 days due to cyclic production of cells from [[Bone Marrow - Anatomy & Physiology|bone marrow]]
*Animals are prone to recurrent infections, mainly from the respiratory and gastrointestinal tract
**E.g. pyrexia, [[Diarrhoea|diarrhoea]], gingivitis and arthritis
*Puppies can be distinguished from other litter mates by the diluted grey colouring
*Affected puppies show symptoms such as fever, joint pain and eye, skin and respiratory infections from 8 weeks of age
*Affected animals rarely live beyond 2-3 years with most puppies dying within a few weeks of birth
====Canine Leukocyte Adhesion Deficiency (CLAD)====
*Occurs in Irish Setters
*Missence mutation of -Cys-36-Ser- in CD18 molecule
**CD18 is required for [[Neutrophils|neutrophil]] migration and phagocytosis
*Recurrent bacterial infection
*Neutrophilia ([[Neutrophils|neutrophils]] remain in the blood and are unable to fight infection in the tissue)
====Bovine Leukocyte Adhesion Deficiency (BLAD)====
*Occurs in Holstein cattle
*Missence mutation of -Asp-128-Gly in CD18 molecule
*Recurrent infection, e.g. pneumonia
===Deficiencies of Adaptive Immunity===
====Equine Severe Combined Immune Deficiency (Equine SCID)====
*Autosomal recessive
*Occurs in 2-3% of Arabian foals
*Defect in DNA-dependent protein kinase gene
**Gene codes for a DNA repair enzyme involved in V(D)J recombination for antigen receptors of [[Lymphocytes|lymphocytes]] (e.g. Ig and TCR)
*No functional [[Lymphocytes#B cells|B cells]] or [[Lymphocytes#T cells|T cells]]
*Foals develop infections (usually around 8 weeks of age as maternal [[Immunoglobulins|antibody]] in [[Materno-Fetal Immunity - Introduction#Passive transfer via colostrum|colostrum]] wanes around this time)
*Foals usually die from bronchopneumonia
====Canine X-Linked Severe Combined Immune Deficiency (Canine SCID)====
*Affects Basset Hounds and Corgis
*X-linked recessive defect in the gene coding for the IL-2 receptor
**IL-2 receptor is a receptor for the cytokine IL-2 which causes [[Lymphocytes#T cells|T cells]] to proliferate
*Causes lymphoid hypoplasia, stunted growth and increases the animal's susceptibility to infection
*Animal usually dies from pneumonia or sepsis as the level of maternal [[Immunoglobulins|antibody]] decreases
====Selective [[IgA]] deficiency of German Shepherd Dogs====
*Poorly understood
*Linked to other disease syndromes such as deep pyoderma, inflammatory bowel disease, anal furunculosis and disseminated aspergillosis
*[[Immunoglobulin A|[[IgA]]]] deficiency so more susceptible to mucosal disease
====Immunodeficiency of Weimaraners, Irish Wolfhounds and Miniature Dachshunds====
*Unknown aetiology
*Inherited defects
*Low levels of circulating [[Immunoglobulin M|IgM]] and [[Immunoglobulin G|IgG]]
*Impaired [[Neutrophils|neutrophil]] function
*Causes recurrent pyrexia and infections
**E.g. Rhinitis and bronchopneumonia in Irish Wolfhounds due to low [[Immunoglobulin A|[[IgA]]]]
**E.g. Pneumocytosis in Miniature Dachshunds due to low [[Immunoglobulin G|IgG]]
===Laboratory Examples of Severe Combined Deficiency===
[[Image:Nude Mouse.jpg|right|thumb|150px|Athymic Nude Mouse - Armin Kübelbeck 2008]]
*Severe Combined Immune Deficiency(SCID)
**No functional [[Lymphocytes#B cells|B cells]] or [[Lymphocytes#T cells|T cells]]
*Athymic nude mice (no [[Thymus - Anatomy & Physiology|thymus]])
**No functional [[Lymphocytes#T cells|T cells]]
**Cell-mediated immunodeficiency
*Knock-out mice
**E.g. Gene coding for CD4, CD8, IL-10 removed
==Secondary Immunodeficiency==
*There are many causes of secondary immunodeficiency
**Most deficiencies are not genetic
**Most are agent-induced, such as from X-ray radiation and immunosuppressive drugs
===Viral Causes===
====Feline Leukaemia Virus (FeLV)====
[[Image:FeLV Electron Micrograph.jpg|thumb|right|150px|FeLV Electron Micrograph [http://phil.cdc.gov/phil/home.asp Public Health Image Library] Image #5610]]
[[Image:Kinetics of FeLV 2.jpg|thumb|right|150px|Kinetics of FeLV - Copyright Dr Brian Catchpole BVetMed PhD MRCVS]]
*Oncogenic retrovirus
*Causes neoplasia (lymphoma), myelosuppression (anaemia) and immunosuppression (of [[Lymphocytes#T cells|T cells]])
*2 strains:
**FeLV-A
***Natural strain
**FeLV-B
***Formed through FeLV-A recombining with endogenous retroviral sequences in the feline genome
***Increases the risks of lymphoma
**FeLV-C
***Formed from the spontaneous mutation of FeLV-A
***Is more myelosuppressive
*Virus replicates in the oropharyngeal lymphoid tissue causing a viraemia (virus circulating in the bloodstream) which then spreads to the systemic lymphoid tissue
*Shed in saliva
*Passed by oronasal route, e.g. mutual grooming
*Kittens between 6 weeks and 6 months are most susceptible
*60% of cats will become immune to the disease and recover
*Cats that are persistently viraemic will progress to develop FeLV-associated diseases
*Some cats will become viraemic again if treated with corticosteroids or stressed if the infection lies dormant in the [[Bone Marrow - Anatomy & Physiology|bone marrow]]
*Diagnosis:
**ELISA
**Rapid-Immuno-Migration
**Western Blot
**Virus Isolation
**Immunofluorescence
**PCR
*Treatment:
**Antibiotics for secondary infection
**Anti-retroviral therapy
*For vaccinations see [[Vaccines - WikiBlood#Cat Vaccinations|here]]
====Feline Immunodeficiency Virus (FIV)====
*Lentivirus
*Subtypes A, B and D
*Causes increased susceptibility to infections and neoplasia
*Specifically destroys [[Lymphocytes#Helper CD4+|CD4+ T cells]]
*Virus is present in saliva, blood and other bodily fluids
*Feral and outdoor cats (mostly tom cats) are most at risk
*Virus replicates in lymphoid tissue
*Can remain asymptomatic
*Causes pyrexia and lymphadenopathy
*Transmitted by biting
*Diagnosis:
**ELISA
**Rapid-Immuno-Migration
**Western Blot
**Virus Isolation
**Immunofluorescence
**PCR
*Treatment:
**Antibiotics for secondary infection
**Anti-retroviral therapy
*For vaccinations see [[Vaccines - WikiBlood#Cat Vaccinations|here]]
====Bovine Immunodeficiency Virus (BIV)====
*Lentivirus (non-oncogenic)
*Causes a persistent viral infection and lymphocytosis
*Immunocompromised cattle may develop secondary infections
*The transmission is not well known, but the following possibilities are being researched:
**Through milk
**Through infected semen (e.g.artificial insemination)
**Placental transfer
*Diagnosis:
**Western Blot
**PCR
===Toxic Causes===
*Poisons
===Iatrogenic Causes===
*Drugs
**Corticosteroids
**Cyclosporin
**Cytotoxic cancer therapy
===Other Causes===
*Malnutrition
*Chronic disease
*Stress
*Senescence
==Links==
'''Internal'''
*[[Viruses|Viruses - WikiBugs]]
*[[Innate Immune System - WikiBlood]]
*[[Adaptive Immune System - WikiBlood]]
'''External'''
*[http://www.bitoheavencollies.com/GrayCollie.html| Grey Collie Syndrome] ''Information on Canine Cyclic Haematopoeisis (Grey Collie Syndrome) including new research into treating the condition and a clinical example''
*[http://carcino.com.msu.edu//mouse.html| Nude Mice] ''Information on nude mice and their role in cancer research''
==[[Immunodeficiencies Flashcards - WikiBlood|Immunodeficiencies Flashcards]]==
==References==
'''Books'''
*Ivan Roitt: '''Essential Immunology,''' Ninth edition
*Goldsby, Kindt, & Osbourne '''KUBY Immunology,''' Fourth edition
'''Lecture Notes'''
*Dr Brian Catchpole BVetMed PhD MRCVS
'''Websites'''
*Michelle Tennis & Peggy Melton http://www.bitoheavencollies.com
*http://carcino.com.msu.edu/mouse.html
[[Category:Immunology]]