diseases Flashcards
autoimmune diseases
Immune responses of an organism against its own healthy cells
Results from recognition of self-antigens and inability to generate tolerance
Most common autoimmune diseases
- Rheumatoid arthritis*
- Hashimoto’s autoimmune thyroiditis
- Celiac disease
rheumatoid arthritis
Characterized by an inflammatory response of synovial membrane
Influx or local activation of T cells, B cells, plasma cells, dendritic cells, macrophages, mast cells, as well as by new vessel formation
Hallmark is bone destruction
- Joint spaces have narrowed or disappeared as a sign of cartilage degradation and destructions of the adjacent bone
Causes complex
- Auto Abs reacting with citrullinated self peptides (IgG) thought to be involved
- Include some of the ECM proteins that undergo PTM and conversion of normal arginine residues to citrullinated
- Causes T cell activation in the joints leading to inflammation, activated macrophages, osteoclast mediated cartilage degradation
multiple sclerosis
Damage to myelin sheath from inflammation and autoimmune CTL leading to disrupted BBB
Symptoms include weakness, paralysis, muscle atrophy and may last days to months then disappear and return again
APCs in the CNS present antigens from the myelin sheath
- Myelin fragments
Antigens are detected by T cells in the CNS, promoting destruction of the sheath
Blocking T cell entry to CNS reduces the harmful autoimmune response
Thought of being a T cell mediated autoimmune disease
- RA more related to antibodies
systemic lupus erythematosus
Chronic inflammatory disorder affecting skin, joints, kidneys, and other organs
High levels of antinuclear autoantibodies (ANAs) directed against dsDNA and nuclear proteins that lead to formation of immune complexes
Symptoms include fever, fatigue, weight loss, joint pain, arthritis, butterfly rash on face, nephritis
Lupus nephritis
- Secondary to SLE
- Causes inflammation in the kidneys
- Abnormal response to nuclear proteins, manifests in kidney, causing renal dysfunction
type 1 immune hypersensitivities
Immediate
Pathologic immune mech- Th2 cells, IgE, mast cells, eosinophils
Mech of tissue injury and disease- Mast cells, histamine, etc
- Mast cells release histamine
- Mast cells and cytokine mediated inflammation
Skin allergy test
type 2 immune hypersensitivities
Antibody mediated
Pathologic immune mech- IgM, IgG antibodies against cell surface or extracellular matrix antigens
Mech of tissue injury and disease-Complement and Fc receptor, cellular
- Complement and Fc receptor recruitment activate lymphocytes
- Opsonization and phagocytosis
- Abnormal cell function
More associated with autoimmune disease
Ex. Graves disease
type 3 immune hypersensitivities
Immune complex mediated
Pathologic immune mech- circulating antigens and IgM or IgG antibodies deposited in vascular basement membrane
Mech of tissue injury and disease-Complement and Fc receptor, vascular
- Activation of leukocytes
Pneumonitis, arthritis, dermatitis, vasculitis, glomerulonephritis
- Lupus, serum sickness
type 4 immune hypersensitivities
T cell mediated
Pathologic immune mech- CD4 and CD8 T cells for inflammation and cytolysis
Mech of tissue injury and disease-Causing sustained inflammation
- Macrophage activation and cytokine mediated inflammation (CD4)
- Direct target cell lysis (CD8)
MS, RA, T1 diabetes
TB test
poison ivy
Type 4 reaction
Chemicals on leaf initiate production of memory T cells
Not reaction the first time of exposure
Subsequent exposures lead to dermatitis
congenital immunodeficiencies
May be categorized based on which immune cell is impacted
Affecting either lymphocyte or innate immune cells
- B cell or T cell
B cell deficient- reduced antibody response
- Increased susceptibility to bacterial or viral infections
T cell deficient- decrease in T cell function, especially delayed reactions to common antigens or T cell proliferation responses
- Impacts infections, specifically intracellular infections and some cancers involving T cells
Innate immune deficiencies- highly variable
innate immune deficiencies
Leukocyte adhesion deficiency type 1
- Mutations in the gene that encodes for beta chain of beta 2 integrins
- Needed for cell adhesion
- Problems with adhesions
- Leukocytes and other immune cells can’t properly migrate
- Leads to delayed innate immune response to infections
Commonality- underlying mutations for genes needed for different immune cells
lymphocyte maturation deficiency
First category of lymphocyte issues
Reduce ability of lymphocytes to mature from naive to mature
Issues with genes involved in VDJ (RAG1 and 2) will prevent formation of pre-B and pre-T cells
- Or can happen later on in maturation chain
X-linked SCID
- Lack of IL-7 signaling
- Results in less T cells and normal or increased B cells, reduced serum Ig
lymphocyte activation
Affect mature lymphocytes in periphery
Mutations include
- Cell signaling/ transcription factors produced by activated T cells
- Cytokines or cytokine receptors
Selective Ig deficiency
- Results in decreased production of specific Igs, depending on gene affected
Any mutation affecting effector functions of lymphocytes
acquired immunodeficiencies
Most deficiencies are acquired
Some can be avoided, some can’t
Causes includes those in table, as well as *behavioral and environmental
- Stress
- Smoking
- Aging
- Malnutrition
- Lack of exercise
HIV
Affects 38 million people worldwide
- Most common
- 1 in 200 people
Infection difficult to clear from T cells, boosted by cytokine production
Develops into AIDS, complete loss of CD4 T cells
- Very immunodeficient
Mech of disease
- Goes through clinical progression
- Initial infection in blood, leading to establishment in lymphoid tissues and cells throughout body
- Immune response can produce anti-HIV antibodies and CTLs, but only causes partial control of viral replication
- Clinical latency- virus is present for a certain period with low level proliferation
- Ultimately, infected people will lose ability to control, leading to viral replication and destruction of lymphoid tissues including CD4 T cells
- AIDS
