Autoimmunity and immunodeficiency Flashcards
what is autoimmunity
when the own body’s components are seen as a pathogen
what is immunodeficiency
a suppression of the immune system, such as medically induced.
there are situation when the immune system needs to be damped down e.g. when transplant patient is put on powerful immuno suppressants/drugs, or can be born with immunodeficiency or can acquire it
when can a person have immunodeficiency
when the immune system needs to be damped down e.g. when transplant patient is put on powerful immuno suppressants/drugs, or can be born with immunodeficiency or can acquire it e.g. via AIDS
what is the difference between the antigens in hypersensitivity and autoimmunity
- hypersensitivity - the antigens which the immune system respond to are extraneous, e.g. pollen grains causes a typical allergic fashion
- autoimmunity - its our own body’s components which are seen as foreign and antigenic, so the immune system is responding against itself
what does the bodies self tolerance mechanism distinguish and what for
between self and non-self, to avoid autoimmunity
what does the self tolerance mechanism by the body breakdown with
the production of autoantibodies and auto reactive T-cells
what do autoimmune mechanisms target
a variety or organs and tissues and underlie many diseases
what two types of autoimmune diseases are there
- organ specific
or - systemic (effects whole body)
where to T cells from the bone marrow go to
the thymus
what do T cells become in the thymus
matured into fully functional T cells and acquire their T cell receptor which is either a CD4 or CD8 receptor which determines whether they are T helper cells or T cytotoxic cells
how does the process in the thymus = self tolerance
the thymus shows the immature T cells e.g. MHC proteins in our body’s tissues to lymphocytes, & any lymphocyte that responds to them is immediately eradicated
what are many autoimmune diseases associated with
anterior & posterior uveitis
name some autoimmune diseases which are more prevalent in women
- Graves disease (hyperthyroid)
- Rheumatoid arthritis
- Hashimoto’s thyroiditis (hypothyroid)
which type of diabetes is an autoimmune disease
type 1
which type of thyroid is not an autoimmune disease
type 2
which types of hypersensitivity mechanisms are involved with autoimmune diseases
types, 2, 3 & 4
which types of hypersensitivity mechanisms are involved in organ-specific
types, 2 & 4
which type of hypersensitivity mechanism is involved in non organ-specific autoimmune disorders
SLE type 3 reactions (deposition in immune complex mediated) predominate
what are the three ways in which diseases cause tissue destruction
- complement activation by autoantibodies
- autoantibody recognition of self antigens
- auto reactive T cell recognition of self antigens
how does a disease cause tissue destruction via complement activation by autoantibodies
cells are targeted by autoantibodies
the antibody which is binding to some cell surface proteins & in doing so, activates the complement pathway which can cause cell lysis/breakdown
they are there to protect us as they breakdown bacterial cell walls, but can also damage tissues
the complement system attracts phagocytes to the inflammatory region
how does a disease cause tissue destruction via autoantibody recognition of self antigens
formation of immune complexes = cell antigen combining with the antibody & when present in excess, they deposit in cell tissues or blood vessel walls, lungs, kidneys etc
how does a disease cause tissue destruction via auto reactive T cell recognition of self antigens
cell mediated reactions
T cells are involved with surveillance e.g. looking for tumour cells & virally infected cells and are able to destroy these cells, but in the case of autoimmunity, they can damage our own cells
which factors play a role in the development of autoimmunity
genetic
autoimmune diseases tend to be associated with particular HLA specificies (i.e. inherit specific HLA/MHC proteins)
what is the major histocompatibility complex (MHC)
a gene locus that codes for histocompatibility antigens
present on every cell with a nucleus so not on red blood cells
what are histocompatibility antigens
cell surface glycoproteins that play important roles in interactions amongst immune cells
where are class 1 gene products found
on all nucleated cells
what do class 1 gene products participate in
antigen presentation to cytotoxic T cells (CD8+ve)
what are class 2 products found on
antigen presenting cells e.g. macrophages, have T 2 MHC proteins
what do class 2 products participate in
antigen presentation to T helper cells (CD4+ve)
what is the MHC locus designated in humans
in the human leukocyte antigen (HLA) locus
but is found on lots of cells, not just on leukocytes, its known as HLA as it first first studied on white blood cells
where is HLA locus found
on the short arm of chromosome 6
what does the class 1 region of HLA consist of
HLA A B and C loci/proteins with subdivisions within those
what does the class 2 region of HLA consist of
divided into HLA-DP
DQ
and DR sub regions
they are particular types of protein and very variable, e.g. they must match HLA proteins with a donor & a host for e.g. an organ transplant)
what type of structure is HLA antigens
highly polymorphic with multiple allelic forms which differ from one person to another
eg HLA DR2, HLA DR4, HLA B27
what are HLA antigens important for
the ability of the T cells to differentiate between self and non-self (HLA antigens not possessed by an individual are seen as foreign)
what do class 1 proteins interact with and which in particular
interact with T cell receptors, particularly cytotoxic T helper cell receptors as they are proteins which show antigens to the immune system
what does the pocket of a class 1 protein hold
the antigen & shows it to the immune system i.e. immune surveillance
what do class 2 protein pockets hold on to
only to APC receptors
what usually produces a single antigen receptor out of billions possible
each lymphocyte
what are eliminated in the thymus
for developing T cells, the majority of self-reactive cells
in the thymus, what are self peptides and MHC molecules displayed on
the surface of cortical thymic epithelial cells, and TCRs that bind to these ligands are eliminated
what still occurs despite the fact that TCRs which bind to the ligands of the surface of cortical thymus epithelial cells are eliminated
a significant fraction of the receptors of mature T cells and B cells bind to one or more self components in the body
in autoimmunity, what do T cells recognise their own cells as foreign through
MHC proteins
what are the specificity on the T cells used to determine
if the cell is foreign or whether it belongs to our cells
name and describe the three strategies used to deal with self reactive lymphocytes (when the process in the thymus is not perfect and allows some reactive T cells to go through)
- a cell displaying a self-reactive receptor can be triggered to die by apoptosis
- a self reactive receptor can be edited to display a different receptor that is not self reactive (i.e. can remodel T cell receptors & no longer reactive against self antigen)
- intrinsic or extrinsic regulation can reduce the ability of the cell being activated by self reactive receptors (suppress themselves so they’re less likely to become activated)
name 3 examples of autoimmune diseases (breakdown of self tolerance)
- graves disease
- rheumatoid arthritis
- SLE - systemic lupus arithmetosis
what does the development of lesions in rheumatoid arthritis involve
both cell mediated and antibody responses
what are present in the synovium of patients diagnosed with rheumatoid arthritis
CD4+ve T cells
activated B lymphocytes
plasma cells
what leads to inflamed synovium and formation of pannus (inflammatory granulation tissue) in rheumatoid arthritis
cytokine secretion by activated T cells
what is the problem with in rheumatoid arthritis
the joint capsule where a normal joint has cartilage and one with rheumatoid arthritis has not
&
inflammation within the sinovium = deformation of granulous tissue
what is graves disease a common cause of
hyperthyroidism (over production of thread hormone)
what is graves disease associated with
- enlargement of thyroid (goitre)
- exophthalmos (ocular manifestation)
- heat intolerance (cannot regulate body temp)
- anxiety
what are the hyperthyroidism and goitre of graves disease caused by
stimulation of the thyroid by thyroid stimulating hormone (TSH) receptor antibodies
where does production of thyroid stimulating hormone receptor TSH antibodies occur in graves disease
within the thyroid gland itself
in graves disease, which receptors do the TSH bind to
receptors of the follicular cells on the thyroid
in graves disease, what do the TSH which bind to receptors of the follicular cells on the thyroid stimulate
thyroid cells to produce two types of thyroid hormone
T3 & T4
in graves disease, what binds to TSH receptors and produces excess T3 & T4 thyroid hormone
autoantibodies
in graves disease, what is the proposed hypothesis for the pathogenesis of ophthalmopathy
that an immune response to a TSH receptor - like protein in orbital connective tissue
what happens to the extra ocular muscles in graves disease and what does it result in
they become enlarged and theres an increase in orbital fat
all this takes up space as bone is on either side it has to expand forward
eye don’t close which causes dry eye
what does the forward expansion of the EOM’s in graves disease cause to the ONH
the forward expansion pulls on the slack of the optic nerve and the ONH gets stretched and loses vision
what does autoimmunity and the eye tend to be associated with
particular HLA antigens/organ specific e.g. HLA B27
what can ocular autoimmunity occur with the presence or absence of
systemic autoimmune disease
what are the ocular autoimmune diseases in the absence of systemic involvement include
- moorens ulcer
- sympathetic ophthalmia
both only exclusive to the eye
what is moorens ulcer
a degenerative condition of the cornea
thinning of the cornea around the arc near the limbus
shows a deep ridge near the limbus and extremely thin cornea = sight threatening
what is moorens ulcer treated with
immunosuppression (damped down)
what is sympathetic ophthalmia
can occur following trauma to the eye weeks or months later can develop severe inflammation to the other eye which was not effected in the trauma and can lose sight
list the ocular autoimmune diseases with systemic involvement, i.e. which can cause anterior or posterior uveitis or both
- reiter’s disease
- ankylosing spondylitis
- rheumatoid arthritis
- behcet’s disease
- SLE
- sjogren’s syndrome
- sarcoidosis
- cicatricial pemphigoid
what 4 things can primary immunodeficiency effect and what can these lead to
- B cell deficiencies lead to recurrent bacterial infections
- T cell deficiencies lead to recurrent viral, fungal and protozoal infections
- phagocytic deficiency leads to recurrent bacterial infections
- complement deficiency leads to recurrent bacterial infections and defects in immune complex clearance
what was AIDS which was first described in the early 1980’s as a disease effecting
- homosexual men
& - iv drug users (injecting drugs into the vein)
what are previously healthy AIDS sufferers presented with
opportunistic infections such as:
- pneumocystis carinii pneumonia
&
- toxoplasmosis
what is pneumocystis carinii pneumonia caused by from AIDS sufferers
inhaling fungal spores
which virus is AIDS caused by
HIV-1 infection
what is HIV and what does it infect specifically
retrovirus
infects T-helper (CD4+ve) lymphocytes (by binding to receptor of T helper cell & depletes it) which causes profound immunodeficiency
what do T helper cells produce and what does it regulate
produce cytokines
regulates immune mechanisms
in HIV what is there initially a fall in and what does this cause
fall in T helper cells causes a primary infection, but soon recover
in the first few weeks of HIV/AIDS, whilst the T helper cells have fallen, what has risen and what does this cause
rise of HIV RNA, causes acute HIV syndrome wide dissemination of virus seeding of lymphoid organs, our immune system then kicks in following this
what happens during the clinical latency period of HIV/AIDS (weeks-years)
person doesn’t experience symptoms when the T helper cells are in excess over the virus/HIV RNA, many only experience flu like symptoms
what happens 8-9 years down the line during HIV/AIDS
T helper cells decline and opportunistic infections arise as the HIV RNA increases followed by death
list some infections/diseases caused by AIDS
- pneumonia - lungs congested
- sight threatening retinitis - virus from herpes
- skin cancer - kaposi’s sarcoma
- candita infection - thrush of oral mucosa
- raised lesions around the eye - molluscum loads (sign of an asymptomatic AIDS sufferer)
what type of tissue transplant is well tolerated
when tissue is transplanted from an individual to another location within the same individual - autografts
what type of tissue transplant has high success rates
organs transplanted between identical twins
when are grafts transplanted between genetically different individuals (allografts) tolerated
only when MHC antigens are matched
what type of testing attempts to match alleles between an donor and recipient during transplants
histocompatibility testing of class 1 and class 2 antigens
when can other cell surface markers still possibly induce rejection for transplants
even with a high degree or HLA similarity
what are transplant patients routinely prescribed
immunosuppressant drugs e.g. cyclotron, tacrolimus, corticosteroids
how can the blood system cause a mechanism of transplant rejection
blood system is essential to maintain host tissue but via the blood supply is where immune cells are bought into the vicinity so T cells which belong to the donor which are put into the body with the transplant (recipient) can attack the host tissue (called a graft vs host disease)
what type of transplant disease is more common and needs to be controlled, than the graft vs host disease
when the host immune system is attacking the donor tissue
what is the area where the blood is between the host and donor tissue called
interphase
when is a corneal transplantation required
in cases of corneal opacification
why do corneal transplants have high success rates
due to avascularity of cornea and lack of immune activation
when is the success rate reduced for a corneal transplant
in high risk patients e.g. neovascularisation
where immune system responds to attack foreign (donor) antigens, T cells and macrophages infiltrate the tissue and secrete a variety of cytokines and corneal graft rejection can occur
what two strategies are used in high risk corneal grafts
- HLA matching of donor and recipient
- immunosuppressive therapy
when can a corneal transplant cause astigmatism
when the suture is too tight, it can flatten the cornea in one meridian
what is used to control the immune system in high risk corneal grafts
steroid eyedrops
