immunology Flashcards
WHAT IS autoimmunity?
The presence of immune response against self-tissue/cells
What is the pathogenesis of autoimmune disease?
Genetic susceptibility
(Irritating event)
Breakdown of self-tolerance-loss of immune regulation and generation of auto reactive T and B cells
This leads to autoimmune phenomena and disease
What are monogenic disorders
single gene defect causing autoimmune disease - very rare
What is IPEX syndrome
presents in early childhood
Characterised by overwhelming systemic immunity
in harmless autoimmunity there is…
low titres of auto-antibodies or auto-reactive T cells
in harmful autoimmunity there is…
high titres of auto-antibodies or auto-reactive T cells
most autoimmune diseases result from complex genetic interplay between..
HLA genes
Genes determining sex
Other immune response genes
What does IPEX syndrome stand for?
Immune dysregulation
Polyendocrinopathy
Enteropathy
X-linked inheritance syndrome
What is the pathogenesis of IPEX syndrome
Pathogenesis- mutation in FOXP3 gene which is essential for development of regulatory T cells
What are the symptoms of IPEX syndrome?
Symptoms include- severe infections, intractable d, eczema, very early onset insulin onset diabetes and autoimmune manifestations
What is the treatment of IPEX syndrome?
Treatment
cure- Haematopoetic stem cel transplantation (HSCT)
supportive care- immunosuppressive drugs plus total parental nutrition
What gives rise to hugely diverse B cells and T cell populations (allowing for recognition of millions of different antigens)
Random rearrangement of TCR a and b chain gene segments (or Ig heavy and light chain gene segments) occurs in developing T cells and B cells
What are the two specific tolerance mechanisms required
Removal of self-reactive lymphocytes in primary lymphoid tissues (central tolerance)
Inactivation of self-reactive lymphocytes that escape central tolerance (peripheral tolerance) e.g. Regulatory T cells
What percentage of regulatory T cells make up the normal CD4+ T cell population
5-10%
_ _____ __ express Class 1 MHC on the cell surface
all nucleated cells
________ __ also express Class 11 on the cell surface
Specialised APC
What is Molecular mimicry?
cross-reactivity between antigens expressed by pathogen and self
What type of hypersensitivity reaction is SLE?
type III
What type of hypersensitivity reaction is RA?
type IV
What type of hypersensitivity is blood transfusions?
Type II
What is SLE
rare type 111 hypersensitivity disease increased risk of CVD peak age of onset in 2nd and 3rd decades high female preponderance genetic predisposition
What is the pathogenesis of SLE?
Infection –> ROS production
UV radiation
mutations in C1q(C2,C4)
Mutations in Mac-1
B cell activation–> production of auto-antibodies
A person has SLE if any 4 out of these 11 features are present serially or simultaneously
SOAP BRAIN MD
Serositis
Oral Ulcers
Arthritis
Photosensitivity
Blood (Haematological disorder) Renal disorder ANA disorder Immunological disorder Neurological disorder
Malar rash
DIscoid rash
Where is ANA highly useful in diagnosis?
SLE
Mixed CTD
Autoimmune hepatitis
What is anti-dsDNA, anti-Sm present in?
SLE
What are anti-Ro and anti-La associated with?
Sjogren’s syndrome
What is Scl-70 and anti U3-RNP found in?
SS
What is jo-1 found in?
PM
Type III hypersensitivity reactions:management
Limit sun exposure
analgesia
hydrochloroquinine
Decrease inflammation- corticosteroids ( prednisone)
Decrease production of auto-antibodies (Immunosuppresive agents and inhibit B cell proliferation)
What is the major susceptibility halotype in most ethnic groups in RA
HLA-DR4
What are the two pro-inflammatory cytokines involved in the pathogenesis of RA
TNFa
IL-1
What pro-inflammatory cytokine plays a critical role within the joint in RA
IL-6
What is RF?
A rheumatoid factor is an auto-antibody directed against the common (Fc) region of human IgG
(only 70% of patients with RA are +ve for RF at the time of diagnosis
What makes ACPA particularly wonderful in the diagnosis of RA?
Highly specific for RA, occurring in many patients before clinical onset of the disease
