Rheumatology Pathophysiology

rapid, specific, memory, effector

Natural/Innate Immunity

• ______/Non-inducible (mins)

• Not antigen _________

• No __________

• Uses pre-formed __________ cells

• Phagocytes, NK, complement

slow, specific, memory, B, T

Specific/Adaptive/Acquired Immunity

• ____, inducible (days)

• Antigen _________

• __________

• Limited

• _ and _ cells

first, inherited, microorganisms, birth, hours, broad, memory, exposure, adaptive, inflammation, homeostasis

Immunology Review

• Innate Immunity

  • _______ line of defense

    • __________, germ-line defense mechanisms that are directed against molecular components found only in ______________

  • Functional at _______

  • Pre-formed and available within ______ of infection/inflammation

  • ______ specificity through pattern recognition receptors

  • No _________, not enhanced by prior __________

  • Evolutionalry memory

  • In addition to providing a 1st line of defense against microbes, the innate immune system:

    • Activated and instructs ___________ immune responses

    • Regulates ___________

    • Mediated immune _____________

macrophages, epithelial cells, mast cells, innate lymphoid cells

Which types of cells do the activation of the innate immune system that begins with resident cells in the tissues at the site of the insult?

neutrophils, NK cells, dendritic cells, monocytes, platelets

Which types of cells get recruited if the threat of infection accelerates?

T, B, hosts, autoreactive, bone marrow, thymus, central, circulation

Overview of Tolerance

• Adaptive Immunity

  • Central/Peripheral Tolerance

    • _ and _ cells

  • Goal

    • Prevent detrimental immune response against _______ own cells/tissue

• Central Tolerance

  • Minimizes self reactive (__________) lymphocytes

  • Occurs in ____ _________ and __________

• Peripheral Tolerance

  • Eliminates self reactive (autoreactive) lymphocytes that have escaped ________ mechanisms

  • Occurs in ___________ or lymph nodes

thymus, negative, apoptosis, autoreactive, tolerance

Central Tolerance (T cells)

• Acquired in the _______

• ___________ selection

  • If developing T cell binds too strongly with a self antigen it will undergo ___________

  • Prevents development of ____________ T cells

  • Ensures self __________

naive, partially, foreign, co-stimulatory, naive, complete, specific

Peripheral Tolerance (T cell)

• Normal Response

  • Antigen presenting cell (ex: dendritic cell) picks up antigens → presents to ______ T cell → ____________ activates T cell

  • If antigen is __________ → induces __-______________ proteins on the antigen presenting cell → this protein binds to a receptor on _________ T cell → causes ___________ activation of T cell → T cell differentiates into ___________ types (ex → effector or memory T cells)

co-stimulation, incompletely, self, nonresponsive, proteins, apoptosis

Peripheral Tolerance (T Cell)

• T Regulatory Cells

  • Natural vs Acquired

  • Limit ability of antigen presenting cells to provide __-______________ to naive T cells → leaves T cell _____________ activated

• Anergy

  • ____ reactive T cells with no co-stimulation become ____________

• Deletion

  • When T cells repeatedly recognize self antigens and lack co-stimulation → produce less __________ required for survival → leads to ____________

bone marrow, apoptosis, anergic, receptor editing, self

B Cell Central Tolerance

• Happens in the ____ _______

• Negative Selection

  • If B cells binds too strongly with a self antigen it will undergo ___________ or be rendered ___________

    • Clones can escape apoptosis/anergy through __________ _________ (unique to B cells) → no longer binds to ____ antigens

MHC, multifactorial, HLA-B27

Genetic Factors

• ___ alleles give largest known contribution to autoimmune diseases

• However, autoimmune disease is ___________ and does not occur in all individuals with a particular allele

• Ankylosing spondylitis is associated with ___-___ MHC allele

hypersensitivity, source, mechanism, autoimmunity, autoimmune disease

Definitions

• ____________ → altered immune response to an antigen that results in disease or damage to the host

  • Classified by:

    • _______ of antigen (environmental, self, another’s)

    • ____________ (Type I-IV reactions)

• _____________ → disturbance in immune tolerance of self antigens

• _____________ ____________ → pathologic state when immune system reacts against self antigens to a degree the person’s own tissues are damaged

genetic, tolerance, environmental, tissue, APCs, autoreactive, disease

Mechanism of Autoimmunity

• ____________ susceptibility → Failure of self ___________ → self reactive lymphocytes → ______________ stimuli → _____________ injury and/or inflammation → activation of tissue ____ → activation of ___________ lymphocytes → tissue injury and autoimmune ___________

mimics, stimulus, bacteria, viruses, drugs, immunogenic, lupus, sequestered, circulation, virus, T

Mechanism of Autoimmunity

• Molecular Mimicry

  • Environmental trigger ________ a component of the body → immune attack directed against _________ and body (often _______ or _________)

• Alteration of Normal Proteins

  • ______ bind to normal proteins → proteins become ___________

    • Ex: drug induced _______

• Release of sequestered antigens

  • ___________ antigens housed in tissue → tissue is damaged → antigens released into ______________ → immune response

• Epitope Spreading

  • New exposure of sequestered autoantigens d/t tissue damage by _______

• Failure of Regulatory T Cells

  • Can’t suppress inflammatory effects of other _ cells

B, IgM, IgG, complexes, complement, inflammatory, drug, anemia, Goodpasture

Antibody Mediated Type II Reaction

• Cytotoxic

  • Self reactive _ cells become activated → produce ___ or ___ antibodies that attach to antigens on host cells → form antigen-antibody __________ on host tissue → ___________ system activated → recruitment of _____________ cells → host tissue attacked

    • Ex: Some ____ reactions, autoimmune hemolytic ________, _____________ syndrome (affects kidney and lung)

dysfunction, Ach, muscle, weakens, thyroid, over

Antibody Mediated Type II Reaction

• Non-cytotoxic

  • Antibody causes ____________

  • Examples

    • Myasthenia Gravis → Antibody blocks ___ receptors at neuromuscular junction → _______ doesn’t get stimulated → progressively _________

    • Graves Disease → antibody activates _________ receptors → _____ production of thyroid hormone

complexes, vessel, complement, inflammatory, damage

Antigen-Antibody Complex Mediated - Type III

• Antigen-antibody __________ deposit in blood ________ walls → ____________ system activated → recruitment of _____________ cells → tissue ___________

Type III

What type of hypersensitivity reactions are these diseases associated with

• Systemic lupus erythematosus

• Polyarteritis nodosa

• Post-streptococcal glomerulonephritis

• Serum sickness

• Arthus reaction

RA

What is the main disease we have talked about that is associated with a type IV hypersensitivity reaction?

joints, ligaments, connective, pain

Definition of Rheumatic Disease

• Autoimmune and inflammatory disease where your immune system attacks the _______, muscles, bones, __________, and ___________ tissues

• Causes inflammation, swelling, and ____ in those structures

Monoarticular, oligoarticular, polyarticular

Number and Pattern of Joint Involvement

• Number

  • _____________ → single joint

  • _______________ → 2-3 joints

  • ____________ → >4 joints

• Pattern

  • Specific joint(s) involved

  • Asymmetric vs symmetric

  • Migratory vs non-migratory

  • Axial vs appendicular

  • Acute vs chronic

broad, gout, RA, SLE, vasculitis, osteoarthritis

Rheumatic Disease

• Covers ______ spectrum of diseases

• Inflammatory

  • ____

  • Rheumatoid arthritis (__)

  • Systemic lupus erythematosus (___)

  • Some __________

• Non-inflammatory

  • _______________

  • fibromyalgia

gout, complex, SLE, RA

Rheumatic Disease

• Inflammatory

  • Acute

    • _____

    • Immune _________ vasculitis

  • Chronic

    • ___

    • __