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Immunology > Autoimmune Diseases > Flashcards

Autoimmune Diseases Flashcards

1
Q

Autoimmune response

A

Immune response that causes autoimmune disease and it produces state of autoimmunity
- mechanisms of antigen recognition and effector function in autoimmunity are the same as those used in responding to pathogens and environmental antigens

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2
Q

Autoimmune diseases

A

Focus on particular organ or cell type, others are systemic

- females more commonly affected

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3
Q

Autoimmune disease components

A

Presence of antibodies (autoantibodies) and T cells (autoimmune T cells) specific for antigens expressed by the targeted tissue (autoantigens)

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4
Q

Damaging responses are due to ____

A

Immune effector mechanisms

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5
Q

Mechanisms that contribute to immunological self tolerance

A
  • negative selection in bone marrow and thymus
  • expression of tissue-specific proteins in the thymus
  • no lymphocyte access to some tissues
  • suppression of autoimmune responses by Tregs
  • induction of anergy in autoreactive B and T cells (absence of costimulatory signal)
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6
Q

Types of autoimmunity

A

2: antibody against cell surface or matrix antigens
3: immune-complex disease
4: T cell mediated disease

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7
Q

Autoimmune hemolytic anemia

A
  • type 2
  • autoantigen: Rh blood group antigens, I antigen
  • consequence: destruction of RBC by complement and phagocytes, anemia
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8
Q

Graves’ disease

A
  • type 2
  • autoantigen: thyroid-stimulating hormone receptor
  • consequences: hyperthyroidism
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9
Q

Myasthenia gravis

A
  • type 2
  • autoantigen: acetylcholine receptor
  • consequences: progressive weakness
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10
Q

Type 2 diabetes (insulin resistant)

A
  • type 2
  • autoantigen: insulin receptor (antagonist)
  • consequences: hyperglycemia, ketoacidosis
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11
Q

Systemic lupus erythematosus

A
  • type 3
  • autoantigen: DNA, histones, ribosomes, snRNP, scRNP
  • consequence: glomerulonephritis, vasculitis, arthritis
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12
Q

Type 1 diabetes (insulin dependent)

A
  • type 4
  • autoantigen: pancreatic beta cell antigen
  • consequence: beta cell destruction
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13
Q

Rheumatoid arthritis

A
  • type 4
  • autoantigen: unknown synovial joint antigen
  • consequence: joint inflammation and destruction
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14
Q

Multiple sclerosis

A
  • type 4
  • autoantigen: myelin basic protein, proteolipid protein
  • consequence: brain degeneration, paralysis
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15
Q

3 mechanisms that destroy RBCs in autoimmune hemolytic anemia

A

Erythrocytes bind anti-erythrocyte autoantibodies

  • FcR+ cells in spleen = phagocytosis and RBC destruction
  • complement activation and CR1+ cells in spleen = phagocytosis and RBC destruction
  • complement activation and intravascular hemolysis = lysis and RBC destruction
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16
Q

Autoantibodies against cell-surface receptors can either ____ or ____ receptor’s function

A

stimulate (agonist); inhibit (antagonist)

Agonist: Graves’ disease and hypoglycemia
Antagonist: Myasthenia gravis and Insulin-resistant diabetes

17
Q

Myasthenia gravis mechanism

A

Signaling from nerve to muscle across the neruomuscular junction is impaired by autoantibodies

18
Q

Systemic lupus erythematosus

A
  • autoantigen: nucleosomes
  • pathogenic antibody: IgG
  • type 3 = large amount of immune complexes formed that deposit in capillaries of tissues (enter thru fenestrations and become trapped in basement membrane)
19
Q

How does lupus involve all aspects of the immune response?

A

T cells: pathogenic, help for antibody
B cells: present antigen to T cells
Antibody: pathogenic

20
Q

SLE mechanism of autoantigen accumulation

A

Possible defects in the clearance of apoptotic cells

- macrophages from SLE patients have a reduced capactiy to engulf apoptotic cells in vitro

21
Q

Type 1 diabetes mechanism

A

T cell responses and antibodies are made against insulin and other specialized proteins of pancreatic beta cell islets

22
Q

What causes rheumatoid arthritis?

A

Effector CD4 T cells and antibody

  • antibodies bind to all B cells in the body, Fc portion binds to NK cells = lysis of all B cells
  • ADCC: lysis of B cells by NK cells and therapeutic anti-CD20 antibody rituximab
23
Q

Therapy of rheumatoid arthritis

A

Anti-TNF alpha

24
Q

Breaking T cell tolerance is a feature of all autoimmune diseases

A
  • incomplete deletion of self-reactive T cells in the thymus, autoimmune polyendocirnopathy-candidiasis-ectodermal dystrophy
  • insufficient control of T cell co stimulation (CTLA-4 deficiency)
  • lack of Tregs, deficiency in foxP3 = immune dysregulation, polyendocrynopathy, enteropathy and X linked syndrome
25
Q

____ is the dominant genetic factor affecting susceptibility to autoimmune disease

A

HLA

- B27, A29, DQ6 found in >95% of patients and have a relative risk of >150

26
Q

Autoimmunity is initiated by

A 
Disease associated HLA allotypes presenting antigens to autoimmune T cells 
- greater number of HLA class 2 is expected because they present antigens to CD4 T cells
27
Q

Autoimmune response is started by _______

A

Autoreactive T cells being stimulated by specific self peptide MHC

28
Q

Autoimmunity is _____ and tolerance is the ______

A

Exception; rule!

- when tolerance is broken it involves just one autoreactive T cell clones that initiate autoimmunity

29
Q

Animal models of autoimmune disease demsonstrated that autoreactive T cell clones can _______

A

Transfer disease

30
Q

Infections as environmental factors that can trigger autoimmune disease

A
  • streptococcal cell wall stimulates antibody response

- some antibodies cross-react with heart tissue, causing rheumatic fever

31
Q

Autoimmune T cells can be activated in a pathogen-specific or non-specific manner by infection

A

Same MHC molecule presents both a pathogen peptide and a self peptide that mimics it –> naive T cell is activated by the pathogen peptide presented by particular MHC –> effector Th1 cell responds to self peptide mimic and activates the macrophage = inflammation

32
Q

______ of the T cell population can contribute to autoimmunity

A

Senescence

33
Q

Genetic factors that predispose to autoimmune disease

A 
Different MHC class 1 and 2 allotypes correlated with different disease suceptibilites and may present autoantigens to tolerance-breaking T cells
- HLA accounts for half of genetic predisposition, other factors include proteins in thymic selection and control of T cell activation
34
Q

Environmental factors that predispose to autoimmune disease

A
  • damage integrity of tissues and stimulate adaptive immunity
  • trauma, chemical, irradiation, certain food
35
Q

Difficulties in identification of the infectious triggers of autoimmune diseases

A
  • infections are successfully resolved and rarely recorded

- symptoms of autoimmune disease usually begin long after the event that triggered the response

Immunology (28 decks)

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