Module 6 Flashcards
Autoimmunity
Some mechanisms that contribute to immunological self-tolerance
negative selection of B cells and T cells, exclusion of lymphocytes form some peripheral tissues (brain, eyes, testes), anergy in autoreactive cells that make it to the periphery, suppression of autoimmune responses by regulatory T cells
hypersensitivity reaction developed against self-antigens
autoimmunity
3 factors that can contribute to autoimmunity
infections (esp viral), molecular mimicry from pathogens, and tissue damage/injury releasing self-antigens
when some pathogens that express antigens that resemble self-antigens
molecular mimicry
disease caused by Strep pyogenes that creates autoantibodies that cause myocarditis, nephritis, and arthritis
Rheumatic fever
Some non-infectious triggers of autoimmunity
toxins, drugs, hormones, loss of regulatory cells
these places are separate from circulation and have mechanisms to inhibit self-antigenic response either through regulatory or anatomical barriers
immunologically privileged sites
Examples of immune privileged sites
brain, eyes, testes, and uterus
damage to the eye that initiates autoimmunity and destroys vision
sympathetic opthalmia
Examples of type II autoimmune reactions
hemolytic anemia, myasthenia gravis, graves disease
Example of cytotoxic/cytolytic reaction
autoimmune hemolytic anemia
What antibodies are generated against RBC antigens in hemolytic anemia?
IgG and IgM
Non-cytotoxic/cytolytic reactions
Myasthenia gravis and Grave’s disease
Does inflammation occur in non-cytotoxic reactions?
no
Disease where antibodies are generated against the Ach receptor and inhibit binding of Ach to AchR
myasthenia gravis
Most common cause of hyperthyroidism
Grave’s disease
Disease where antibodies are generated against the TSH receptor and leads to hyperthyroidism, goiter, exophthalmos, tremors, tachycardia, diaphoresis
Grave’s disease
Examples of Type III autoimmune reactions
SLE and rheumatoid arthritis
immune complex diseases are also what type of autoimmune reaction?
Type III
What reaction occurs when immune complexes get trapped in the basement membrane of small blood vessels, cause complement activation and degranulation?
Type III/immune complex diseases
Where do immune complexes accumulate in SLE?
kidneys, joints, and blood vessels (esp in the cheeks to give butterfly rash)
self-antigens often found in SLE
nuclear antigens
Rheumatoid factors are usually which antibodies?
IgM that reacts with the Fc of IgG usually and creats an IgM-IgG immune complex
Which disorder can be a type III or type IV reaction?
Rheumatoid arthritis
What does IgM and/or IgG form against in RA?
synovial joint antigens
How can RA lead to a type IV reaction?
by fixing complement
Examples of Type IV autoimmune reactions
RA, insulin dependent DM, MS
What’s the difference between a type III and type IV RA reaction?
type III: immune complexes deposit in the joints. Type IV: autoreactive CD4 T cells activate macrophages which release cytokines and can cause systemic inflammation
Cytokine involved in RA
TNF-alpha
What type of DM is insulin-dependent DM?
Type 1
insulin producing cells in pancreas
beta islet cells
What type of T cells attack the beta islet cells in T1DM?
CD8 T cells
Disease characterized by an autoimmune t cell response against myelin
MS
What type of T cells activate macrophages to release proteases and cytokines in MS?
CD4 T cells
genetic immune deficiencies are msot often caused by what kind of gene defects and on what chromosome?
recessive and on X chromosome
When are most primary immune deficiencies diagnosed?
after 6 months of age after maternal/placental IgG has waned
What defects can cause inherited primary immune deficiencies?
defects in phagocytes, antibody production or isotype switching, B cells, T cells, complement factors, cytokine production or receptors, or MHC II or II deficiency
How do secondary immunodeficiencies develop?
they are acquired
recurrent bacterial and fungal infections often signal what?
phagocyte deficiencies
Examples of phagocyte deficiency disorders
chronic granulomatous disease and myeloperoxidase deficiency
disease where neutrophils cannot produce superoxide radicals and bactericidal activity is reduced
Chronic granulomatous disease
NADPH oxidase defect is associated with what disease?
chronic granulomatous disease
Disease where myeloperoxidase affects the ability to convert hydrogen peroxide to hypochlorite
Myeloperoxidase deficiency
A deficiency in this system leads to impaired humoral immune function and persistence of immune complexes
complement deficiency
Mutations in which complement pathway make a patient more susceptible to extracellular pathogens due to accumulation of opsonized bacteria?
classical pathway
Improper formation of what leads to impaired defense against Neisseria?
membrane attack complex
What are some examples of antibody deficiency disorders?
Bruton X-linked agammaglobulinemia (XLA), X linked hyper-IgM syndrome, Selective IgA deficiency
Disorder resulting from a loss of Btk and causes a loss of B cells
Bruton’s X-linked agammaglobulinemia (XLA) (think BBB: bruton, Btk, B cell)
Protein kinase involved with XLA
Bruton’s tyrosine kinase (btk)
Which stage of B cell maturation is affected by XLA?
pre-B cell stage
CD40L is altered in what disorder?
X linked hyper-IgM syndrome
What disorder occurs when T cells cannot activate B cells via CD40/CD40L?
X linked hyper-IgM syndrome
Most common immune deficiency
selective IgA deficiency
What are some examples of lymphocyte deficiencies?
Severe combined immune disease (SCID), Bare lymphocyte syndrome Iand II (BLS I and II), DiGeorge syndrome
What disorder is characterized by complete deficiency in T and B cells, often caused by a mutation of RAG-1/2?
Severe combined immune disease
What disorder is classified by a deficiency of MHC class I and CD8+ T cell?
Bare lymphocyte syndrome I (BLS I)
What disorder is classified by a deficiency of MHC class II and CD4+ cells?
Bare lymphocyte syndrome II (BLS II)
What disorder is characterized by abnormal thymic epithelium and a failure of T cell development?
DiGeorge syndrome (22q11.2 deletion syndrome)
What is the usual treatment for immunodeficiencies?
IVIG
