Clinical features of autoimmune diseases Flashcards
What is an epitope?
1 - part of an antigen that does not bind with antibodies 2 - part of antigen that binds to antigen receptor 3 - part of antigen involved in type I hypersensitivity 4 - part of antigen involved in class switching
2 - part of antigen that binds to antigen receptor
What is molecular mimicry?
1 - pathogenic epitopes on antigen resemble self-antigens
2 - pathogenic epitopes on antigen do not resemble self-antigens
3 - pathogens use antigens on their surface to imitate self antigens
4 - pathogens that are not detected by innate immunity as no PAMPs
1 - pathogenic epitopes on antigen resemble self-antigens
- triggers activation of B and T cells and autoimmunity
Mycoplasma is a bacteria that can infect different parts of your body. The body part that will be affected is your lungs, skin, or urinary tract, depending on which type of mycloplasma bacteria is causing the infection. The antigen that is present on mycloplasma has a similar peptide to the I antigens present on RBCs. This means that the host immune system could become self reactive and attack the I antigens on healthy RBCs causing haemolysis (destruction of RBCs). What is this similarity between epitopes on the antigen called?
1 - pathogen association recognition receptor
2 - epitope similarity
3 - molecular mimicry
4 - genetic drift
3 - molecular mimicry
Rheumatic fever is an example of molecular mimicry. What bacteria is responsible for causing rheumatic fever?
1 - streptococcus
2 - e.coli
3 - faecalbacterium
4 - MRSA
1 - streptococcus
Rheumatic fever, caused by an infection with streptococcus is an example of molecular mimicry. What is it on streptococcus that can cause autoimmunity?
1 - M-protein antigen
2 - viral peptides
3 - S protein
4 - MHC-I molecule
1 - M-protein antigen
- M-protein antigen contains similar peptides to antigens on host tissue
- B cells secrete anti-streptococcus antibodies that target M-antigen on streptococcus but inadvertently target host tissue as well
- specifically present in the heart, skin, joints and brain
From the point of infection with streptococcus, how long is it generally before rheumatic fever or scarlet fever present?
1 - <12 hours
2 - <12 days
3 - 1-5 weeks
4 - 5-10 weeks
3 - 1-5 weeks
What is monogenic diabetes?
1 - repeated infections cause diabetes
2 - single infection causes diabetes
3 - single gene mutation causes diabetes
4 - multiple genes cause diabetes
3 - single gene mutation causes diabetes
- mono = one and genic = gene
- rare genetic form of diabetes causes low insulin
85% of patients with type 1 diabetes contain what in their circulation?
1 - non-islet cell antibodies
2 - high insulin
3 - islet cell antigens
4 - islet cell antibodies
4 - islet cell antibodies
- means antibodies will attack islet cells, this is what has caused their type I diabetes
How can a viral infection cause type I diabetes?
1 - epitope on virus have similar structure to self antigens
2 - virus can infect B cells making them secrete self reactive antibodies
3 - virus causes B cells to go into overdrive and self-reactive antibodies are produced
1 - epitope on virus have similar structure to self antigens
- in diabetes the viral epitope is similar to that present on islet cells
- ant-viral antibodies then attack islet cells, called molecular mimicry
What is the most common antibody directed against that has been linked with type I diabetes?
1 - CRP
2 - glutamic acid decarboxylase
3 - RAG1 and Rag2
4 - MHC-I on islet cells
2 - glutamic acid decarboxylase
- important enzyme responsible for insulin production
In a pancreatic biopsy, prior to the diagnosis of type I diabetes, what immune cells are we likely to see present?
1 - neutrophils
2 - CD4 and 8 cells
3 - natural killer cells
4 - macrophages
2 - CD4 and 8 cells
- CD4 T cells activate B cells and CD8 T cells will induce apoptosis
HLA class 2 alleles (MHC-II) molecules are the major determining genetic risk factor for developing type I diabetes. Specifically, which forms of the MHC-II molecules are most commonly linked with type 1 diabetes?
1 - HLA-DR1 and HLA-DR2
2 - HLA-DR3 and HLA-DR4
3 - HLA-DR2 and HLA-DR3
4 - HLA-DR5 and HLA-DR6
2 - DR3 or DR4 alone = relative risk of 6
2 - DR3 and DR4 alone = relative risk of 15
New developments have shown that coxsackie virus can initiate a strong immune response and lead to diabetes. What is present on the virus that can cause antibodies to target the virus and islets cells for destruction?
1 - D protein
2 - M protein
3 - spike protein
4 - protein S2
4 - protein S2
- remember Sackie and S2
- called molecular mimicry where the epitope of the viral antigen is similar to the epitope on the MHC-1 molecule on islet cells
Systemic lupus erythematosus (SLE) is an autoimmune disease that can cause damage and inflammation to any tissue in the body, but generally connective tissue (blood vessels, cartilage, skin, heart, kidney, lungs). Which type of hypersensitivity is SLE?
1 - type I hypersensitivity
2 - type II hypersensitivity
3 - type III hypersensitivity
4 - type IV hypersensitivity
3 - type III hypersensitivity
- immune complexes build up here causing tissue damage and inflammation
- systemic in the name tells us its not tissue specific
- common visual sign is reddening of the skin looks like butterfly on the face
Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs. It has a common visual sign is reddening of the skin looks like butterfly on the face, but can also cause:
- serositis: Pleurisy (pleural effusion), Pericarditis
- renal
- nephritis
- pulmonary fibrosis
- joint pain
- autoimmune cytopenias
Is this more common in men or women?
- women of child bearing age
- most autoimmune diseases are more common in women
Some patients with systemic lupus erythematosus (SLE) also have deficiency of classical complement components. Which components of the complement system are generally affected?
1 - C1, C5, C6
2 - C1, C2, C4
3 - C1, C2, C3, C4
4 - C5b, C6, C7, C8
2 - C1, C2, C4
- means complement system will struggle to even get started if at all
Some patients with systemic lupus erythematosus (SLE) also have deficiency of classical complement components, specifically C1, C2, C4. Why is this important in in relation to immune complexes?
- C1 is need to start complement pathway and make a membrane attack complex
- C3 convertase (C4bC2a) cleaves C3
- C3a = chemotaxin
- C3b = opsonin, no opsonin means phagocytes cannot identify and clear immune complexes
What is direct immunofluorescence?
1 - antigen of interest added to well, human serum added, fluorescent marker is added
2 - host tissue added to well, detection antibody with fluorescent marker is added
3 - antigen of interest added to well, detection antibody with fluorescent marker is added
4 - host tissue added to well, human serum added, fluorescent marker is added
2 - host tissue added to well, detection antibody with fluorescent marker is added
- host tissue sample is added to slide
- detection antibodies are specific to auto-antibodies patient is suspected of having
- detection antibodies contain fluorescent marker that can be read on plate reader
What is indirect immunofluorescence?
1 - antigen of interest added to well, human serum added containing suspected auto-antibodies, detection antibody with fluorescent marker is added
2 - host tissue added to well, detection antibody with fluorescent marker is added
3 - antigen of interest added to well, detection antibody with fluorescent marker is added
4 - host tissue added to well, human serum added, fluorescent marker is added
1 - antigen of interest added to well, human serum added containing suspected auto-antibodies, detection antibody with fluorescent marker is added
- antigens of interest (generally animals) are added to the wells
- human serum is added and if patient has auto-antibodies they will bind to antigen in wells
- detection antibody is added to detect auto-antibodies and read on plate reader
What is the major difference between direct and indirect ELISAs?
- direct ELISA = requires only 1 antibody and less sensitive
- indirect ELISA = requires 2 antibodies and more sensitive
In a classic/indirect ELISA what do we coat the bottom of the wells with?
1 - antigen of interest
2 - auto-antibodies
3 - serum from patient
4 - fluorophore
1 - antigen of interest
- if looking at T1DM the antigen may be glutamic acid decarboxylase
- antigen sticks to the plate as its a protein and excess i washed away
In a classic/indirect ELISA, once we have coated the base of the wells with our antigen of interest and washed the plate. What is the next step?
1 - wash plate again
2 - add patients sample
3 - serum from lab
4 - fluorophore
2 - add patients sample
- if auto-antibodies (anti-glutamic acid decarboxylase (GAB)) are present they will bind with the glutamic acid decarboxylase antigen on bottom of the wells
- sample is incubated and then washed
In a classic/indirect ELISA, once we have coated the base of the wells with our antigen (glutamic acid decarboxylase (GAB)) and added the auto-antibodies (anti-glutamic acid decarboxylase (GAB)) and washed the plate, what is the next step?
1 - wash plate again
2 - read under microscope
3 - secondary antibody containing fluorophore is added
4 - fluorophore added alone
3 - secondary antibody containing fluorophore is added
- sedondary antibody binds with GAB auto-antibodies
- plates are then washed
B12 is released in the stomach following the digestion of foods containing B12 by pepsin. What do B12 cells then bind with in the stomach that is produced by parietal cells?
1 - intrinsic factor
2 - pepsinogen
3 - extrinsic factor
4 - amylase
1 - intrinsic factor
- forms the B12-intrinsic factor complex
