3.3 Autoimmunity Flashcards
Type __ hypersensitivity reactions are initiated by Ag-Ab complexes which can induce an inflammatory response/complement system
III
what type of reaction is Arthus reaction an example of?
Type III, local
what is a systemic type III reaction?
Ag-Ab complexes circulate in bloodstream and settle in target organs and initiate an inflammatory response
Continuous buildup of Ag/Ab complexes can lead to ______
autoimmune disease
what are the 3 categories of immune complex lesion diseases?
- infectious/post-infectious disease
- auto-immune disease
- drug reactions
Renal disease, Streptococcal infections, Syphilis, and Hepatitis B are all examples of what kind of immune complex lesion diseases?
Infectious and post-infectious disease
Lupus and rheumatoid arthritis are all examples of what kind of immune complex lesion diseases?
autoimmune diseases
how do RBCs play a role in removal of immune complexes?
- IgG in fixed complement can attach to CRI receptor on RBC
- it can interact with C3b
- will circulate and come in contact with kupffer cell
- it will then be destroyed
the sites of type ___ hypersensitivity reactions are the skin or mucosa
IV
what kind of cells are involved in Type IV reactions?
CD4+TH1, cytokines, CD8+ cytotoxic T cells
what is the time frame for type IV rxns?
24-72hrs
Tuberculin, contact dermatitis, contact stomatitis, are all examples of type ___ reactions
IV
what are the steps of a tuberculin reaction?
- Antigen introduced into subcutaneous tissue → processed by APCs
- TH1 recognizes antigen and releases cytokines →
- recruitment of phagocytes, fluid, etc to site of antigen
what do these cytokines do in a tuberculosis reaction?
1. Chemokines
2. IFN-gamma
3. TFN-alpha & LT
- recruit macrophages
- activate macrophages
- tissue destruction
what are the steps of contact hypersensitivity?
- something comes in contact with skin (hapten)
- haptens go into epidermis where they interact with langerhan cells
- processed and go to lymph node
- will become dendritic cell and present antigen to CD4+ T cell → effector cell
- effector cell will interact with the macrophage and releases cytokines
- keratinocytes activated
what are the reaction times for these?
1. contact hypersensitivity
2. tuberculin
3. granuloma
4. IgE
5. Arthur
- 24-72h
- 24-72h
- 21-28 days
- <30min
- 5-6hr
what are some examples of contact hypersensitivity?
nickel, poison ivy
what happens in a poison ivy reaction?
- Pentadecatechol penetrates cell membrane and modifies intracellular proteins
- proteins broken down and become incorporated into MHC1
- MHC1 recognized by CD8+ cells
- this causes overall reaction
what type of MHC do we see in a poison ivy reaction?
MHC1
what type of T cells are seen in a granuloma reaction?
CD4 TH1
Granuloma is a multinucleated giant cells with _____ cells in center, surrounded by T-cells
epitheliod
what are the steps of a granuloma forming?
- APC + Naive T cell = IL-12 produced to stimulate T cell
- T cell proliferation, CD4 TH1+
- Activation of immature macrophages
- Macrophage changes in morphology to look like epithelial cells
- Epithelioid cells fuse and form multinucleated giant cell
- These form granuloma
in a granuloma reaction ______ changes in morphology to resemble a _____ cell
macrophage, epithelial
______ is a response to self antigens due to lack of tolerance, response MAY NOT be harmful
Autoimmunity
____________ is a loss of tolerance to a self antigen that results in an immune response that WILL produce a clinical disease
Autoimmune disease
what are the mechanisms of self tolerance?
- Negative selection of B cells
- Negative selection of T cells in thymus
- Sequestered antigens
- suppression of autoimmune response by Treg
- central tolerance
RBC removal of immune complexes is efficent for ___ but not ____ immune complexes
IgG, IgA
how can Treg get rid of self-reactive cells?
Treg has to attach to same APC as CD4 cell→ it will interact with TCR and MHC → then it will release cytokines that kills self-reactive CD4 cell
- Cd28/B7 + specific signal =
- Only specific signal =
- Only Cd28/B7 =
1.activated T cell
2. anergic T cell
3. no effect on T cell
- Cd28/B7 + specific signal =
- Only specific signal =
- Only Cd28/B7 =
1.activated T cell
2. anergic T cell
3. no effect on T cell
Autoimmune diseases are more prevalent in females than males, except for which disease?
ankylosing spondylitis
what are some possible causes of autoimmune diseases? (6)
- Cross reacting antigens
- Breakdown in lymphocyte regulation
- Microbes
- Sequestered antigens
- Environmental
- Genetic
what is an example of a cross-reacting antigen that can cause an AID? what can it cause?
streptococcus antigen, rheumatic fever
Strep uses _______ to cause loss of self-tolerance, interactions with myocardial tissue, and rheumatic fever
molecular mimicry
a breakdown in lymphocyte regulation causes loss of ___ cells
Treg
have we been able to ID microbes that are associated with human models for human AIDs?
NO, just animals
________ are antigens not exposed to IS during immunological development
Sequestered antigens
what are 2 examples of sequestered antigens?
- selective IgA deficiency
- trauma to eye releases sequestered antigen → carried to lymph and activate T cell → effector T cells return and attack BOTH eyes
