Chapter 18: Autoimmune Disorders Flashcards
How do autoimmune disorders occur?
Can happen when out T and B cells that targeted our own cells failed to delete during development stayed
Molecular mimicry with Strep Pyogenes
Mimics the proteins on our heart and our antibodies formed against strep pyogenes can end up targeting our heart
Which cell turns off immune response when no longer needed?
T Regulatory cells
What can cause an autoimmune disease as you grow older?
You can acquire a change in your cell makeup, possibly in A.A and your immune system picks up the mutation change as foreign and has an immune response
What is an autoimmune response?
Mounting an immune response to your own tissue
Treatment of autoimmune diseases
No treatment to cure but you can take immune suppressor drugs
Autoantibodies
Antibodies against ones own tissue (a) can be T cell mediated as well (b) cell destruction in various hypersensitive reactions
Auto-immunization
(1) The process by which hypersensitivity to “self” develops (2) Response usually sustained and long-lasting and can cause long-term tissue damage
Mechanism of autoimmunity: Genetic factors
these factors may predispose a person toward autoimmune disorders likely to develop autoantibodies to the same or to a different single organ
Mechanisms of autoimmunity: Antigenic or molecular mimicry
(1) Th cells might attack tissue antigens that are similar to antigens of some pathogens (2) Rheumatic fever can lead to rheumatic heart disease later in life because heart valve tissue is seen similar to certain streptococcal antigens
Mechanisms of autoimmunity: Thymus and development of Th cells
TH cells instead of just recognizing foreign antigens recognize self-antigens (happens if the clonal deletion doesn’t take out the self-reactive TH cells)
Mechanisms of autoimmunity: Mutations
Might give rise to aberrant proteins to which B cells react, producing plasma cells that make autoantibodies
Mechanisms of autoimmunity: Viral components
(1) Inserted into host cell membrane (2) might act as antigens or virus antibody complexes (3) Might be deposited into tissue
Mechanisms of autoimmunity: Sympathetic nervous system and parasympathetic system
When NS is damaged, the number of regulatory T cells decreases
Autoimmune disease: Myasthenia Gravis
(1) Affects women early on, men later on (2) Affects skeletal muscles of the limbs and those involved in eye movements, speech and swallowing (affects single organs) (3) Progressive weakness of muscle fatigue (4) Eyelid drooping (5) Muscle contraction is prevented by IgG which block Acetylcholine receptors or cause reduction in number of receptors (6) People tend to have tumors of the thymus as a result
Autoimmune disease: Rheumatoid Arthritis
(1) Affects mainly the joints of the hands and feet (2) Initially a T cell problem (3) Joints are affected in pairs, meaning on both sides of the body (4) Inflammation and destruction of the cartilage in joints
Rheumatoid Arthritis: cell action
(1) People with RA have a Th2 cell dependent B cell response to the Fc portion of IgG (2) IgG complex leads to RA
Rheumatoid factors
Autoantibodies used in diagnostic test of RA
Hydrocortisone and Aspirin
Can be used to ease pain and inflammation
Systemic Lupus Erythematosus
(1) SLE is a systemic autoimmune disease derived from reddened skin rash (erythematose) that resembles a wolfs mask (lupus) (2) Autoantibodies IgA, IgM, IgG are made against components of DNA and blood cells, neurons and other tissue (3) Immune complexes deposited between dermis and epidermis, joints, blood vessels leads to inflammation (4) Butterfly shape rash (5) No cure (Rash precipitated through exposure to sunlight
Transplantation
Transfer of tissue called “graft tissue” from one site to another
Autograph
Involves graphing of tissue from one part of your body to another
Isograft
Skin graft between genetically identical individuals
Allograft
Graft between 2 people who are NOT genetically identical
Xenograft
A transplant between individuals of different animal species
Transplant rejection
Rejection of skin tissue due to destruction of the grafter tissue by the recipients immune system (Depends on T cells)
Graft Versus Host Disease (GVS)
Less common, transplanted tissue contains immunocompetent T cells that launch a cell mediated response against the recipients tissue (commonly in immunodeficient individuals receiving bone marrow transplant and cannot reject the graft tissue
Histocompatibility antigens
All human cells and those of other vertebrate that have a set of self-antigens
MHC
Genes that produce histocompatibility antigens
Who can have identical MHC molecules
Twins
Importance of matching Histocompatibility complex
Histocompatibility antigens need to be the same in order for tissue to be accepted, because if not, T cells destroy donor tissue
HLAs (Human Leukocyte antigen)
determined by a set of genes located on chromosome 6
HLA- B
Highly variable
HLA-DR
antigens are known to generate the strongest rejection reactions
Presence of HLA antigen is associated with higher than normal risk for developing what?
Specific diseases
Transplant rejection
Displays specificity and memory and is associated with mismatched HLA-DR antigens (found on T cells and macrophages responsible for rejection)
Which T cells are the ones most likely to reject tissue?
TH2 cells (they also stimulate cytotoxic T cells which reject the transplant through cell mediated cytotoxicity
TH2 cells also activate B cells to produce what during transplant rejection?
Produce plasma cells and antibodies that cause rejection through lytic damage
Macrophages that are activated by TH1 cells do what during transplant rejection?
Secrete inflammatory mediator and cause cytotoxic damage to transplant
NK cells actions during transplant rejection
Finds MHCII protein that are different than tissue of person and immediately start to take charge and release perforin
TH1 role in transplant rejection
Th1 cells activate macrophages which produce an inflammatory mediators
Th2 role in transplant rejection
Th2 cells trigger both Tc and B cell activation and B cells then give rise to plasma cells that synthesize antibodies (including HLA-DR) and with complement, rejects transplant. Tc cells just activate cell mediated toxicity and them reject transplant.
Ways to minimize rejection
Tissue typing and immune suppressant drugs
Hyper acute rejection
A cytotoxic hypersensitivity reaction occurs when the recipient is already sensitized at the time the graft is done leading to extensive damage right away
Accelerates rejection
Takes several days because it requires cells to reach the graft
Acute rejection
Occurs in days to weeks requiring T cell sensitization after transplantation
Chronic rejection
Begins months to years after transplantation, slow process typical of kidney and cardiac transplants
Reasons as to why mothers can tolerate fetus
(1) Considered “immunologically privileged site” (2) Cells on the surface and interior of the fetal portion of the placenta do not express MHC molecules (3) Certain HLA molecules prevent maternal NK cells from killing fetal cells
Alpha-fetoprotein
Protein produced by fetus has immunosuppressant properties
Women who have similar or different tissue types with their husbands suffer more miscarriages?
Similar
Foreignness of the sperm may trigger what?
Triggers maternal production of blocking antibodies that protect the fetus
Immunosuppression
(1) minimizing of immune reactions (2) Specifically leads to immune systems ability to tolerate only the antigen in [ex: transplants tissue] and allows the immune system to continue to respond to other infectious agents
Radiation or cytotoxic drugs
Impairs the immune response and minimizes rejection reactions (radiation destroys lymphocytes which inhibits the immune systems ability to recognize infectious microbes)
Cytotoxic drugs
Damage cells, Prevents B and T cell division
Drug reaction
Considered a hapten because it needs to bind to a protein in the body to be recognized
Drug molecules
Usually too small to act as allergen
Drug combined with proteins can induce what?
Hypersensitivity
Type 1 hypersensitivity
Can be caused by various drugs, mostly localized anaphylactic reactions, usually occurs with injection
Type 2 hypersensitivity
A drug may bind directly to the plasma membrane of a blood cell, when drug binds to drug plasma protein, complex binds to membrane of blood triggering autoantibody production through compliment
Type 3 Hypersensitivity
Appears as serum sickness and can be caused by any drug that participates in the formation of immune complexes, symptoms appear several days after
Type 4 hypersensitivity
Occurs as contact dermatitis after topical application of drugs
Immunodeficiency diseases are due to what?
Adsence or deficiency of active lymphocytes, NK cells or phagocytes
Primary immunodeficiency diseases
Caused by genetic defects in embryological development such as failure of the thymus gland or peyers patches to develop normally
Result of primary immunodeficiency
Lack of T cells or B cells or defective B and T
Agammaglobulinemia
B cell deficiency
DiGeorge syndrome
Results from a deficiency of T cells caused by an agent that interferes with embryological development of the thymus gland
SCID (Severe combined immunodeficiency)
Debilitating because both B and T cells are absent
Gene Therapy
Attempts to replace defective gene with a functional therapeutic copy of that gene
Serology
Antibodies in serum of blood, try to find titer of specific antibodies
Titer
Concentration of antibody in serum
Secondary Immunodeficiency diseases
Not genetic, can be impacted by physical condition and stress
3 things that can cause secondary immunodeficiency diseases
(1) Infectious agents: TB,AIDs, HIV, measles, leprosy (2) Malignancies: Hodgkins disease or multiple myeloma (3) Immunosuppressants: chemotherapeutic drugs, antibiotics, radiation
Precipitin Test
Done to see if someone has antibodies to a specific virus (done in liquid)
Zone of equivalence
Equal amount of antigens and antibodies present, Agglutination
Zone of excess antigen
You see a complex form , free antigens floating
Zone od excess antibody
Antibodies are more present than soluble antigen
What happens when IgG or IgM react with soluble antigens?
They form complexes
Immunodiffusion test
Done in agar, poke holes in agar and put antibody on the outside of each hole and then antigen goes inside the agar hole (if they recognize each other, there will be a line of spreading)
Blood Typing
RBCs and Anti Rh antibodies cannot be seen with naked eye when bound together, SO Rabbit anti-human immunoglobins are added for an agglutinated RBC that can be seen with the naked eye
Complement fixation assay: Negative
(1) Negative is person does not have antibodies to virus protein (2) Complement added and was not fixed/attached meaning no antibody-antigen complex (3) There was no antibody for antigen in humans serum (4) Loads of complement are free and lysing RBCs because aren’t bound to a complex
Complement fixation assay: Positive
(1) Positive test person has antibodies to virus (2) you start with a complex (3) Complement is added (4) Compliment binds with antibody-antigen complex (5) Add indicator RBCs to have better viewing (6) RBCs don’t lyse because complement is tied up with persons antibody-antigen complex
Immunofluorescence
Fluorescence dye put on part of the constant part of the antibody so that under UV microscope the dye on the antibodies fluoresce
ELISA
(1) Enzyme linked Immunosorbent Assay (2) done with radioactive molecules (3) uses enzyme linked dyes (4) Enzyme clips colorless substrate that is added, forming a red product due to complex formed (5) In hospitals for faster results, there is a red dye on the strip rather than it being enzyme linked
