Immunology 2 - Primary Immunodeficiency Flashcards
What factors make up specific immunity?
Antibodies
Cellular immunity
What factors make up non-specific immunity?
Complement
Phagocytes
What is the difference between primary and secondary immunodeficiency?
Primary - Congenital
Secondary - Acquired
Immunodeficiencies increase the risk of what?
Infection
Cancer
Autoimmunity
Primary immunodeficiencies are broadly caused by what?
Mostly mutations
Some by autoimmunity
Primary immunodeficiencies predispose patients to what?
Infections and tumours
Primary immunodeficiencies are caused by abnormalities in what?
Innate immune system
Stages of lymphocyte development
Responses of lymphocytes to antigen stimulation
Agammaglobulinaemias are caused by what?
X linked mutation
Autosomal recessive mutation
Agammaglobulinaemias cause what?
Decreased serum Ig
Decreased B-cell numbers
Generally, B cell deficiencies present how?
Increased Pyogenic bacteria Enteric bacteria Reduced serum IG Normal DTH reactions Absent follicles (germinal centres)
Generally, T cell deficiencies present how?
Pneumocystis jiroveci Viruses Atypical fungi Normal/reduced Ig Reduced DTH reaction Normal follicles
Repeated infections with encapsulated bacteria is a sign of what?
Defective antibody production
IgG and IgA deficiency presents how?
Pneumococcus
Haemophilius spp
Infections with staph, gram -ve, fungi are associated with what?
Reduced number/function of phagocytes
Complement defects predispose to what?
Neisseria meningitidis meningitis
T-cell defects predispose to what?
Infection with intracellular organisms (protozoa, viruses, intracellular bacteria), mycobacterium
Reactivated latent Herpes (Cold sores, shingles)
Recurrent Candida
How does the severity T-cell immunodeficiency lead to a variation in Mycobacterium Tuberculosis presentation?
Mild - invasion outside lungs
Severe - widespread, low virulence mycobacteria
What tumours are associated with low T-cell numbers?
(Herpesvirus-induced tumours)
Kaposi sarcoma
non-Hodgkin lymphoma
What are the causes of primary immunodeficiencies?
Mutations
Polymorphisms
Polygenic disorders
What are polygenic disorders?
Combined action of >1 gene
(can be) Caused by autoimmunity
Polygenic disorders of the immune system typically affect what?
Antibodies
How is Severe Combined Immunodeficiency treated?
Bone marrow transplant
Screening in newborns
What mutations are associated with SCID?
Some autosomal
Some X-linked
What is the function of Mannan-binding lectin?
Binds sugars in bacterial cell walls to activate complement
Polymorphismsin MBL increase risk of infections
What are the common Polygenic Immunodeficiencies?
Common variable immunodeficiency
IgA deficiency
Specific antibody deficiencies
How does Common variable immunodeficiency present?
1 in 20,000 young people Low total IgG (others variable) Recurrent resp infections GI, skin, neuro infections Autoimmunity Family history
How does Specific antibody deficiency present?
Recurrent pneumococcus or haemophilius infections IN SPITE of normal IgG
Don’t respond to polysaccharide antigens
Autoimmune polyendocrinopathy candidiasis ectodermal dysplasia causes what?
Frequent severe Candia infections
Other autoimmunity
Antibodies against IL-17
Autoantibodies against interferon y causes what?
Recurrent mycobacterial infections
How does Severe combined immunodeficiency present?
Defective T and B cells Recurrent Infection in first few weeks Diarrhoea FH neonatal death Very low lymphocytes
How does Antibody Deficiency present?
Chronic/recurrent bacterial respiratory infections later in life
How is Antibody Deficiency investigated?
IgG, A, M
Exclude secondary immunodeficiency
Specific Haemophilius/pneumococcus antibodies
Complement/neutrophil function
How are Primary immunodeficiencies treated?
Prophylactic antibiotics
Immunoglobulin replacement therapy
Stem cell transplantation
Gene therapy
How is SCID treated?
Avoid live vaccines
Prophylaxis against Pneumocystis jiroveci
Stem cell transplant
What are the requirements for gene therapy?
Mutation identified
Correcting mutation must improve condition/survival
Must not cause malignancy
Defective HLA genes lead to what?
MHC faults (leading to faulty antigen presentation)
What conditions are associated with loss of antibodies from the body?
Kidney, Liver and Gut disease
