autoimmune diseases Flashcards
Innate immunity
- Inflammation
- More WBC’s
- No memory
- Fast response short duration
Adaptive immunity
- T cells and B cells
- Highly specific receptors
- Strong memory
- Slow response long duration
What cells of the innate immune system are required in the adaptive system
- Dendritic cells (APC’S) present antigen to T cells
- T cell cytokines activate innate cells to cause inflammation
Phagocytic cells
Neutrophils - destroy pathogens
Macrophages - produce chemokines
Dendritic cells - present antigen to T cells
Histamine producing cells
Mast cells, basophils, eosinophils
- Produce histamine - vasodilation and attract other immune cells
Complement
Directly attacks pathogens via alternative and lectin pathways
- Activated by antibodies
Cytokines
Signal between different immune cells
Chemokines
Attract other immune cells to sites of inflammation
What is autoimmunity
The adaptive immune system recognizes and targets the body’s own cells
Main characteristics of autoimmunity
- T cells that recognise self antigens
- B cells and plasma cells that make autoantibodies
- Inflammation in target cells as secondary response
What is autoinflammation
- No component of immune system
- Dysregulation of innate system
Main characteristics of autoinflammation
- Spontaneous attacks of systemic inflammation
- No source of infection
- Absence of high-titre autoantibodies
Causes of autoimmune disease
Genes - lag in presentation
Immune regulation - checks to control the system
Environment - specific factors for diseases
Central tolerance in the thymus
- T cells in the thymus have to develop many receptors so they are auto-immune
- If receptors in the thymus match the body’s it is an auto-reactive T cell and it gets deleted
- If it doesn’t match self antigens, T cell released into circulation
How are T cells made
Develop in bone marrow from haematopoietic stem cells and mature in the thymus
What is +/- selection in the thymus
T cells with self antigens are deleted as negative selection. vice versa
What forms T regulatory cells
T cells with intermediate recognition with self-antigens - Regulate the suppression and expression of different T cells
Overcoming tolerance =
Autoimmune disease
What genes cause genetic susceptibility
genes in the MHC
- Major histocompatibility complex
MHC class 1
On all nucleated cells
- puts antigens inside cell on surface to be read
- Presents to CD8 cell - T killer
MHC class 2
Only in immune syst. (APC’s)
- cells find antigen in environment and presents to CD4 T helper cell
Mutation of FoxP3
Causes failure to develop regulatory T cells - severe autoimmunity from birth
Mutation of PTPN22`
Causes T cells to be activated more easily - stronger general immune response
Other causative autoimmunity associations
- Sex/hormonal influence
- Age
- Sequestered antigens
- Environmental triggers
What is molecular mimicry
Antigen on surface of pathogen is the same ass antigen in harmless body cell - antibodies will react against both
Molecular mimicry and Rheumatic fever
Antigen on streptococcus resembles antigen on heart valve - Antibodies attack both so people with Rheumatic fever can get heart disease as well
How do changes in nature of autoantigens cause autoimmunity
- Citrullination of proteins makes them more immunogenic
- Tissue transglutamase alters gluten
- Failure to clear apoptotic debris increases chances of sequestered antigens
Mechanism of inflammatiion
- TH1 cell stimulates macrophages to release cytokines
- TH2 cells help b cells differentiate into plasma cells and make autoantibodies
- T cells cause inflammation by inflammatory cytokines
How are Autoreactive B cells harmful
- Directly cytotoxic
- Activate complement which kill the cell
How are Autoreactive T cells harmful
- Directly cytotoxic
- Inflammatory cytokine production
Organ specific disease
- Affects a single organ
- Autoimmunity restricted to autoantigens of that organ
- Overlaps with diseases in other tissues
Systemic disease
- Affects several organs at the same time
- Autoimmunity associated with autoantigens found in most cells in body
2 Autoimmune thyroid diseases
Hashimoto’s thyroiditis
Graves’ disease
Hashimoto’s thyroiditis
- Destruction of thyroid follicles
- Autoantibodies of thyroglobulin
- Leads to HYPOthyroidism
Graves’ disease
- Inappropriate stimulation of thyroid gland by anti-TSH autoantibody
- Leads to HYPERthyroidism
Myasthenia gravis
- Autoantibodies block the ACh receptor
- ACh can’t bind so causes muscle weakness
- Particularly in the eyes
Pernicious anaemia
- Failure of vitamin B12 absorption
- B12 needs intrinsic factor in gut to be absorbed
- Autoantibody binds to intrinsic factor and blocks B12
SLE
- Apoptotic debris not cleared, immune system recognises nuclei of debris as foreign
- Antibodies against antigens in the nuclei form immune complexes
- Complexes circulate and deposit in any organ causing inflammation
Connective tissue diseases
(Systemic
- Systemic lupus
- Scleroderma
All have antibodies against nuclear antigens that cause inflammation and organ damage
