c39 lec 11 Flashcards
genes in the body that play an important role in recognition of self vs non self
HLA genes- part of MHC
certain _____ genes predispose individuals to developing autoimmune disorders
HLA
why? Some HLA variants are strongly associated with specific autoimmune diseases, because they are more likely to present self-antigens in a way that triggers an immune attack.
what is the first step in developing an autoimmune disorder?
loss of T cell tolerance
majority of autoimmune diseases are more common in
women (14 out of 19)
why are autoimmune disorders more prevalent in women
due to estrogen, estrogen promotes pro-inflammatory responses and promotes a stronger immune system (more estrogen in women)
stronger immune system but also predisposes women to autoimmune disorders
autoimmune disorders can be (2 things)
- organ specific
- systemic
autoimmune disorder whose target antigen is unique to an organ
organ specific
autoimmune disorder whose target antigen is more widespread
systemic
progressive involvement of more epitopes (and more auto-reactive immune cells) that can cause disease
epitope spreading
describes two individuals with the same or near-identical HLA types and so will not mount strong immune rejection reactions against each other’s tissues.
histocompatible
hyperactive thyroid gland due to agonist auto-antibodies
Grave’s disease
- type II autoimmune disease
AGONIST auto antibodies
what are the three types of autoimmune diseases
type 2: cell bound molecules (antibody mediated)
type 3: immune complexes (antibody mediated)
type 4: T cell mediated
pregnant mothers can pass on autoantibodies to fetus
transient autoimmune disorders
antibodies produced by your immune system that mistakenly target and react with your own body’s cells, tissues, or proteins
autoantibodies
removal and replacement of blood plasma
plasmapheresis
example of an antagonist autoantibody
myasthenia gravis
- they create autoantibodies that block the acetylcholine receptors
- impaired muscle contraction
antagonistic antibodies make muscle less sensitive to neuronal stimulation
can severely affect breathing
any antigens, peptides, carbohydrates, DNA that are bound to antibodies and then can get accumulated in our tissues
immune complexes
SLE is a type ____ autoimmune disorder
SLE
antibodies recognizing DNA in _____ results in the deposition of immune complexes
SLE (systemic lupus erythematosus)
what type of autoimmune disease category does rheumatic diseases fall under
type III
Rheumatic diseases:
- immune complex deposition happens mostly in the joins (inflammation of synovium)
- chronic and episodic inflammation of joints
- association with autoreactive T cells
inflammation in heart, joints, and kidney after infection leads to transient autoimmunity due to viral molecular mimicry
rheumatic fever
rheumatoid arthritis is what type of autoimmune disorder?
rheumatoid arthritis
can be initiated by conversion of arginine to citralline = less stable protein
Rheumatoid arthritis
initiated by just one change!
multiple sclerosis (MS) is a type what autoimmune disorder
type IV (4)
targets the central nervous system (CNS) leading to severe neurological symptoms
multiple sclerosis (MS)
type I diabetes is what type of autoimmune disorder
Type IV
when CD8 T cells kill our insulin producing cells (B cells), then we cannot make insulin
Type I diabetes, type IV autoimmune disorder
10% of transplants are from
transplant tourism
its when people looking for a match for organ donation go to other countries in search for it
deprivation of blood to organs and tissue damage due to inflammation
ischemia
why does the transplant of cornea have one of the highest success rate
because eyes are immunologically privileged sites = no HLA matching required because there is no rejection response generated
refers to certain areas of the body where immune responses are limited or actively suppressed. This means the immune system doesn’t react as strongly—or sometimes at all—in these areas, even if there’s a foreign substance or potential threat.
immunological privileged sites
how do improve transplant outcomes
match as many MHC/HLA proteins between organ recipient vs organ donor
what is the most commonly transplanted thing
blood!
Blood transfusions
blood can be donated regularly with no health effects
- simple and inexpensive
- only required temporarily
- no HLA molecules(proteins) that cause incompatibility but do have HLA antigens (also called ABO antigens)
carbohydrates on red blood cells (erythrocytes)
HLA or ABO antigens
HLA antigens on red blood cells act as
alloantigens
antigens that differ between unrelated members of a species
alloantigens
antibodies against alloantigens
alloantibodies
universal blood donors
type O negative donors (don’t have type A and type B antigens nor Rhesus D antigens)
ABO incompatibility mirrors what
type II hypersensitivity allergy responses
donor and recipient have similar tissue types
histocompatibility
who are the universal recipients who can receive blood from any individual but only donate to individuals with their blood type?
AB+
type of transplant where you transfer tissue from one sit to another in the same individual
autograft
type of transplant that is between genetically identical individuals (very rare)
syngenic or isogenic transplant
type of transplant between two genetically different individuals
allogenic transplant or allograft
types of transplant between two different species
xenograft
what is the type II hypersensitivity reaction of transplantation
hyperacute rejection
what is the type III hypersensitivity reaction of transplantation
chronic rejection
what is the type IV hypersensitivity reaction of transplantation
acute rejection
what is an example of a type II hyperacute rejection of tranplantation
rejection of a blood transfusion: immediately reacting to AB and Rhesus D antigens
hyperacute rejection happens
almost instantaneous (REALLY FAST)
assessment of patient serum for antibodies towards donor blood
cross-match test
for solid organ transplant we need to check for only what
if recipient antigens will attack donor antigens
for bone marrow transplant we need to check for what
if BOTH recipient antigens and donor antigens will attack each other
type of reaction that usually occurs a couple weeks after the transplant
type IV transplantation reaction, acute rejection
- transplantation causes inflammatory environment that leads to immune cell activation and infiltration
- typically prevented with immunosuppressive drugs (have to be on it for entire life)
donor DCs interact with recipient T cells leads to killing of donor DCs
direct pathway of allorecogntion
apoptosis of donor DCs leads to recipient DCs presenting alloantigens
indirect pathway of allorecognition
refers to immune system changes that occur after someone receives a blood transfusion
transfusion effect
type of transfusion rejection: rejection caused by immune complexes
type III reaction
- causes failure of more than half of transplants within a 10 year period
- caused by B cells making alloantibodies, alloantibodies deposit onto actual transplant
treatment: get rid of B cells in the body
Rituximab: anti-B cell antibodies
