Autoimmune Diseases

Question 1

Autoimmune response

Answer 1

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

Question 2

Autoimmune diseases

Answer 2

Focus on particular organ or cell type, others are systemic

- females more commonly affected

Question 3

Autoimmune disease components

Answer 3

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

Question 4

Damaging responses are due to ____

Answer 4

Immune effector mechanisms

Question 5

Mechanisms that contribute to immunological self tolerance

Answer 5

• 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)

Question 6

Types of autoimmunity

Answer 6

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

Question 7

Autoimmune hemolytic anemia

Answer 7

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

Question 8

Graves’ disease

Answer 8

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

Question 9

Myasthenia gravis

Answer 9

• type 2
• autoantigen: acetylcholine receptor
• consequences: progressive weakness

Question 10

Type 2 diabetes (insulin resistant)

Answer 10

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

Question 11

Systemic lupus erythematosus

Answer 11

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

Question 12

Type 1 diabetes (insulin dependent)

Answer 12

• type 4
• autoantigen: pancreatic beta cell antigen
• consequence: beta cell destruction

Question 13

Rheumatoid arthritis

Answer 13

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

Question 14

Multiple sclerosis

Answer 14

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

Question 15

3 mechanisms that destroy RBCs in autoimmune hemolytic anemia

Answer 15

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

Question 16

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

Answer 16

stimulate (agonist); inhibit (antagonist)

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

Question 17

Myasthenia gravis mechanism

Answer 17

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

Question 18

Systemic lupus erythematosus

Answer 18

• 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)

Question 19

How does lupus involve all aspects of the immune response?

Answer 19

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

Question 20

SLE mechanism of autoantigen accumulation

Answer 20

Possible defects in the clearance of apoptotic cells

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

Question 21

Type 1 diabetes mechanism

Answer 21

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

Question 22

What causes rheumatoid arthritis?

Answer 22

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

Question 23

Therapy of rheumatoid arthritis

Answer 23

Anti-TNF alpha

Question 24

Breaking T cell tolerance is a feature of all autoimmune diseases

Answer 24

• 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

Question 25

____ is the dominant genetic factor affecting susceptibility to autoimmune disease

Answer 25

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

Question 26

Autoimmunity is initiated by

Answer 26

``` 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 ```

Question 27

Autoimmune response is started by _______

Answer 27

Autoreactive T cells being stimulated by specific self peptide MHC

Question 28

Autoimmunity is _____ and tolerance is the ______

Answer 28

Exception; rule! | - when tolerance is broken it involves just one autoreactive T cell clones that initiate autoimmunity

Question 29

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

Answer 29

Transfer disease

Question 30

Infections as environmental factors that can trigger autoimmune disease

Answer 30

- streptococcal cell wall stimulates antibody response | - some antibodies cross-react with heart tissue, causing rheumatic fever

Question 31

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

Answer 31

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

Question 32

______ of the T cell population can contribute to autoimmunity

Answer 32

Senescence

Question 33

Genetic factors that predispose to autoimmune disease

Answer 33

``` 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 ```

Question 34

Environmental factors that predispose to autoimmune disease

Answer 34

- damage integrity of tissues and stimulate adaptive immunity - trauma, chemical, irradiation, certain food

Question 35

Difficulties in identification of the infectious triggers of autoimmune diseases

Answer 35

- infections are successfully resolved and rarely recorded | - symptoms of autoimmune disease usually begin long after the event that triggered the response