ICL 6.1: Autoimmunity Flashcards
what is the significance of immunological tolerance?
all individuals are tolerant of their own antigens (self-tolerance); breakdown of self-tolerance results in autoimmunity
therapeutic potential: inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases, and prevent immune responses in gene therapy
what is the pathology behind autoimmunity?
- susceptibility genes –> failure of self-tolerance –> persistence of functional self-reactive lymphocytes –> activation of self-reactive lymphocytes –> immune responses against self tissues
- environmental triggers like infections or tissue injury –> activation of self-reactive lymphocytes –> immune responses against self tissues
what environmental factors can induce autoimmune diseases?
- virus clustering (RA, Sjögren’s s., SLE, MS)
- infectious microorganisms (molecular mimicry)
- sun exposure (SLE)
- exogenous estrogens, sex hormones in general
- obesity
which gender is more prone to autoimmune diseases?
women are WAY more prone to like every single autoimmune disease
however, this doesn’t eliminate the possibility that a male will have an autoimmune disease!
what are the characteristics of autoimmunity?
- existence of self antibodies
- it is potentially reversible!!
- higher incidence in older people
why is autoimmunity higher in older populations?
when a cell dies, it releases the contents of the nucleus which can stimulate the immune system to produce antibodies
so everybody has a small amount of auto-antibodies in their body
as you get older, more neutrophils and cells die and you generate more auto-antibodies
autoimmunity is not a problem, it’s a normal process!
what are the characteristics of autoimmune disease?
there is severe 1. tissue damage!***
- there are clinical symptoms associated with the tissue damage
- protracted course but usually fatal
- familial clustering
what are the two categories of autoimmune diseases?
- organ specific
2. non-organ specific
what are the characteristics of organ-specific autoimmune diseases?
- autoimmune attack vs. self-antigens of given organ
- it results in a damage of organ structure and function
- treatment is focused on the replacement of organ function
what are the characteristics of non organ-specific autoimmune diseases?
- widespread self-antigens are targets for autoimmune attack
- damage affects such structures as blood vessels, cell nuclei etc.
- treatment is aimed to inhibit activation of the immune system
which diseases are examples of organ-specific autoimmune disease?
- type I diabetes
- goodpasture’s syndrome
- multiple sclerosis
- grave’s disease
- Hashimoto’s thyroiditis
what are examples of non organ-specific disease?
- rheumatoid arthritis
- scleroderma
- SLE
- primary Sjogren syndrome
what kind of autoimmune disease is SLE?
non organ specific
it effects your skin, heart, kidney, joints; it’s systemic!
what mediates autoimmune diseases?
autoimmune diseases caused by IgG mediated mechanisms require T cell help in order to produce antibodies
since IgG is involved, hypersensitivity reactions II, III and IV are involved
transfer of T cells from an animal with autoimmune disease to a healthy animal can transfer disease!!
autoimmune diseases are often linked to what?
specific MHC genes
MHC genes regulate T cells!
when do autoimmune diseases happen?
when auto-reactive T cells or auto-antibodies cause tissue damage through hypersensitivity reaction types II, III and IV
what is a type II hypersensitivity reaction?
IgG and IgM antibodies bind to antigens on human cells/tissue
this leads to lysis by complement or phagocytosis
which autoimmune diseases are type II hypersensitivity reactions?
- autoimmune hemolytic anemia
- autoimmune thrombocytopenia purpura
- goodpasture’s syndrome
- pemphigus vulgaris
- acute rheumatic fever
- grave’s disease
- myasthenia gravis
- insulin-resistant diabetes
- hypoglycemia
how are type II hypersensitivity reactions related to autoimmune disease?
antibodies that cause disease are most often autoantibodies against self antigen of human cells or tissues
Ab may modify the function of cells by binding onto receptors that cause disease by stimulating or blocking receptor function
human cells = autoimmune hemolytic anemia
tissues = good pasture’s syndrome, acute rheumatic fever
what can cause autoimmune hemolytic anemia?
after administration of certain drugs (like penicillin)
drug molecules bind to surface components of human cells and create new epitopes to which the immune system is not tolerant
these epitopes stimulate the formation of IgM and IgG antibodies that are specific for the conjugate of drug and cell surface component
what is type III hypersensitivity reaction?
antibodies may cause tissue injury and disease by forming
immune complexes that deposit in blood vessels or tissues
smaller immune complexes are less efficient at fixing complement, they tend to circulate in the blood and become deposited in blood vessel walls
when these complexes accumulate at such sites, they become capable of fixing complement and initiating tissue-damaging inflammatory reactions
Ag-Ab complexes activate complement
what type of hypersensitivity reaction is SLE?
type III
SLE is mediated by antibodies against DNA and other nuclear components
what lab results would be diagnostic of SLE?
immunoflurescence shows her blood contains an anti-nuclear antibody
skin biopsy shows to contain IgG and complement deposits
which parts of the body are commonly effected in immune complex disease?
joint, skin and kidney involvement are very typical of immune complex disease
