Introduction to Autoimmunity Flashcards
(27 cards)
1
Q
What is an autoimmune disease?
A
- A disease caused by a harmful immune reaction to the body’s own proteins.
- Arises from a failure in self-tolerance.
- The immune system mistakenly targets self-antigens.
- First referred to as “Horror autotoxicus” by Paul Ehrlich in 1900.
2
Q
What is self-tolerance and why is it important?
A
- A function of the adaptive immune system.
- Prevents the body from attacking its own proteins.
- Its breakdown leads to autoimmune diseases.
3
Q
What is the immune response?
A
- A coordinated reaction of immune cells and molecules to a foreign substance.
4
Q
What are T-lymphocytes and what do they do?
A
- Mediate cell-mediated immunity.
- Mature in the thymus.
- Circulate in the blood and migrate to infection sites.
- Use a T-cell receptor to recognize antigens.
- Differentiate into effector or memory T-cells.
5
Q
What are B-lymphocytes and what do they do?
A
- Produce high-affinity antibodies.
- Responsible for humoral immunity.
- Originate and mature in the bone marrow.
6
Q
What are the phases of a T-cell response?
A
- Priming of naïve T-cells occurs within 3 to 4 days of infection.
- Clonal expansion into effector T-cells.
- Effector T-cells carry out immune functions.
- Most die via apoptosis, some form long-lived memory T-cells.
7
Q
How can a T-cell response cause autoimmune disease?
A
- If T-cells recognize self-proteins, they can become activated.
- Chronic presence of self-antigen leads to inflammation.
- The immune system attacks the tissue where the self-protein is expressed.
8
Q
What are CD4+ and CD8+ T-cells?
A
- CD4+ T-cells are helper T-cells that assist other immune cells.
- CD8+ T-cells are cytotoxic T-cells that kill infected or abnormal cells directly.
9
Q
What are the functions of Th1 and Th2 cells?
A
- Th1 cells secrete interferon-gamma and activate macrophages; involved in autoimmune diseases.
- Th2 cells secrete interleukins 4 and 5 and promote IgE production and mast cell activation.
10
Q
What is antigen processing?
A
- The breakdown of proteins into peptide fragments inside antigen-presenting cells.
- Peptides are loaded onto MHC molecules for presentation to T-cells.
11
Q
What is antigen presentation?
A
- The display of processed peptide antigens on the surface of antigen-presenting cells via MHC molecules.
- Necessary for T-cell recognition and activation.
12
Q
What are antigen-presenting cells?
A
- Cells that process and present antigens to T-cells using MHC molecules.
- Include dendritic cells, macrophages, and B-cells.
- Express MHC class I and class II depending on antigen source.
13
Q
How does exogenous antigen presentation via MHC class II work?
A
- Exogenous proteins are taken up by phagocytosis into endosomes.
- Proteins are degraded by proteases.
- MHC class II molecules are synthesised, transported to the endosome.
- Peptide fragments are loaded onto MHC II.
- The complex is presented to CD4+ T-cells.
14
Q
What types of cells express MHC class II?
A
- Professional antigen-presenting cells.
- Includes dendritic cells, macrophages, and B-lymphocytes.
15
Q
How does endogenous antigen presentation via MHC class I work?
A
- Intracellular proteins such as viral or defective proteins are degraded by the proteasome.
- Peptides are transported into the ER via TAP.
- They are loaded onto MHC I and presented to CD8+ T-cells.
16
Q
Which cells express MHC class I?
A
- All nucleated cells in the body express MHC class I.
17
Q
What is the structure of MHC molecules?
A
- Each MHC molecule has an antigen-binding groove.
- A co-receptor binding site for CD4 or CD8.
- A transmembrane region that anchors it to the cell membrane.
18
Q
How do peptides bind to MHC molecules?
A
- Peptides bind in a linear conformation.
- Anchor residues fit into pockets / clefts in the MHC groove.
- Other amino acid side chains bind to other locations through hydrophobic, hydrogen, and ionic interactions.
- The peptide-MHC complex must be stable for T-cell recognition.
19
Q
What does the T-cell receptor recognize?
A
- The TCR recognizes both the peptide and parts of the MHC molecule.
- Binding initiates T-cell signalling.
- CD4 or CD8 co-receptors stabilize the interaction.
20
Q
What are key features of T-cell antigen recognition?
A
- T-cells recognize short linear peptides that are cell-associated and presented on MHC molecules.
- CD4+ T-cells interact with MHC II.
- CD8+ T-cells interact with MHC I.
- TCR specificity may depend on just one or two amino acids.
21
Q
What is the two-signal model of T-cell activation?
A
- T-cell activation requires two signals.
- Signal one is cross linking MHC and TCR via TCR binding to peptide.
- Signal two is additional receptor-ligand interaction between antigen
presenting cells and T-cells. - Both signals are necessary to activate the T-cell.
22
Q
What are co-stimulatory receptors involved in T-cell activation?
A
- CD80 on APCs binds to CD28 on T-cells to activate them.
- CD86 on APCs binds to CTLA-4 on T-cells to inhibit activation.
- Without co-stimulation, T-cells will not react.
- For any given immune response, the binding of CD80 to CD28 will dominate, resulting in T-cell activation.
23
Q
What are chemokine receptors and what do they do?
A
- Surface proteins on immune cells that bind chemokines secreted by inflamed tissues.
- Guide directed movement of immune cells to sites of inflammation.
- 16 different chemokine receptors are known.
24
Q
How are chemokine receptors involved in autoimmune disease?
A
- They help immune cells migrate from the blood to inflamed tissues, by interacting with chemokines.
- Targeting them could limit immune infiltration and inflammation.
25
What are chemokines?
Small (8-10KDa), soluble proteins released from inflamed tissue that stimulate movement of immune cells from blood to tissues.
26
What are the specific functions of IL-2?
IL-2 promotes T cell proliferation differentiation and survival.
27
What are the roles of TNF-α?
TNF-α is a pro-inflammatory cytokine that increases vascular permeability recruits immune cells and induces fever.
