Immune diseases Flashcards
What enzyme and what cells type is involved in X-linked agammaglobulinaemia (Bruton’s)?
B-cell tyrosine kinase abnormal due to mutation in it’s gene => affect B-cell maturation => Low numbers of B cells (= Low Ig levels)
Describe DiGeorge syndrome
hypoplasia (low cell no.) of thymus in infants => fail to form T-cells
What is SCID?
Severe combined immune deficiency
- fail to develop B & T cells
- Thymus & lymphoid tiss. reduced
- Adenosine deaminase deficiency => accumulation of toxic waste in lymphocytes
HIV destroys what cell type and what is the effect?
HIV destroys T helper cells (CD4) = immunosuppression bc Thelp cells can no longer help B cells & cytotooxic T cells
Describe what happens to CD4 T cells, antibody levels and virus levels in the course of AIDS.
4-8wks: Hi [virus], 0-low [Ab], some CD4 T cells affected
12 yrs: Lo [virus], Hi [Ab], some CD4 T cells recover
14-15 yrs: body unable to replace CD4 T cells lost = B cell stop making Ab = dec. [Ab] (no adaptive IR) = Inc. [virus]
List & describe the four types of hypersensitivity.
- Type I: excess IgE to allergens = immediate hypersensitivity = anaphylactic chock
- Type II: circulating IgG inappropriately binds to Ag on cell/tissue = complement activation = phagocytosis & NK cells = tissue destruction
- Type III: Soluble Ag w/ Ab = Ag-Ab complexes deposit in tiss. = complement activation = mast cell degranulation = attracting neutrophils
- Type IV: Delayed hypersensitivity
What antibody type and cells types are involved in an allergic reaction?
- TH2 cells, IgE, mast cells, neutrophils
- TH2 cells activated by allogen => make interleukin-4
- B cells => make IgE
- Mast cells release granules when it crosslinks w/ IgE => attracting eosinophils
List the 4 factors that may result in autoimmune disease.
- Sequestered Ag: Ag normally hidden but then exposed accidentally (e.g. cartilage)
- Cross reactivity w/ microbial Ag: molecular mimicry e.g. Ab that binds to strep. may bind to <3
- Polyclonal activation: microbial activatation of many clones of T or B cells w/ some being auto-reactive clones - may produce Ab to self Ag
- Non-infectious triggers: drugs, hormones, chemicals
Why do most people not make an immune response to self?
because of (self) tolerance: unresponsiveness to self Ag
- only lymphocytes have receptor for self Ag = so make sure not react w/ self Ag
- T & B cells reacting to self-Ag removed/down regulated
- B cells require help from CD4 cells to make Ab
Describe the mechanisms of self tolerance.
- Anergy: cells not respond to Ag
- Receptor editing: change the variable region on BCR & TCR (Ab)
- Clonal deletion: Auto reactive T & B cells eliminated by apoptosis (if their Ab binds to self Ag)
- Clonal ignorance: cells remain inactive bc low affinity for self Ag
- T cell suppressors: T reg cells regulate/suppress non-specifically
Describe the immunopathology of Myasthenia Gravis.
- Ab bind to acetylcholine receptor @ neuromuscular junction on muscle = block acetylcholine from receptor
=> weakness & fatigue of voluntary muscles bc muscle not stimulated to work
Why do some people produce anti-nuclear antibodies (ANA)?*
*women common & @ higher risk bc high estrogen lvls accelerate disease
& bc female ISys. is set higher bc have babies (lots of Ab for foetus)
Describe the immunopathologies of Systemic Lupus Erythematosus (SLE)
mediated by auto-Ab w/ Type I & type II hypersensitivity Ab that are anti: - dsDNA, ssDNA - nucleohistones - other extractable nuclear Ag (ENA)
Describe the immunopathologies of Rheumatoid arthritis (RA)
Inflammation of synovium maybe by:
- infection
- Auto reactive CD4 T lymphocytes activate macrophages
- Production of pro-inflammatory cytokines: IL-1, -6, -17, TNF-alpha
- cytokines surround fibroblast & induce production of metallopoteinases (MMP) [>destroy tissue] & RANK [> bone destruction via osteoclast]
What clinical findings are used to differentiate SLE and RA?
- SLE: woman <40yo,; facial rash; no joint erosion; venous thrombosis
- RA: >40 yo; joint erosion & deformity; Rheumatoid nodules of elbows & knees
