3.3.13 Autoimmunity Flashcards
Immune Complex disease is type ___. What’s it initiated by & what type of response does it produce?
Type III
Initiated by antigen-antibody complexes that can induce an inflammatory response
Describe systemic reaction for type III reaction
AG-AB complexes circulate throughout blood stream & settle in certain target organs like kidney initiating an inflammatory response
Major organ in systemic reaction
Kidneys
___ can remove immune complexes
Neutrophils
Diseases associated w/ immune complex diseases
Infectious & postinfectious disease
Autoimmune disease
Drug reactions
Immune complexes that fix complement express ___ which attach to ___ on surface of RBC
C3b
CR1
Define kupffer cells
(hepatic macrophages) macrophage like cells in liver that remove AG-AB complex from RBC
Site, T cells involved, & time of reaction for cell-mediated delayed hypersensitivity (type IV reaction)
- Site: skin or mucosa
- T cells involved:
CD4+ TH1 that release cytokines - Time of reaction: 24-72 hours
Examples of type IV reaction
tuberculin reaction, contact dermatitis & contact stomatitis
___ is used interchangeably w/ cell mediated immunity
Delayed type hypersensitivity
Steps for delayed type hypersensitivity
- Tuberculin’s introduced subcutaneously (already have effector cells from previous rxn) → processed by APC
- TH1 effector cells recognize antigen & releases cytokines
- Recruitment of T cells, phagocytes, fluid, & protein to site of antigen injection causes visible lesion
Stimulated TH1 cell causes release of chemokines, cytokines, & cytotoxins. What do each of these result in?
- Chemokines –> macrophage recruitment
- IFN-gamma –> activates macrophages, increasing release of inflammatory response
- TNF-alpha & LT –> local tissue destruction, leads to inflammatory response
Contact hypersensitivity 2 phases & steps
Sensitization phase
1. Something comes in contact with skin (usually haptens)
2. Haptens are lipid soluble so go into epidermis & interact w/ proteins
3. Langerhans’ cells process the AG-AB complex & take it to lymph node
4. DC interacts w/ naive CD4+ T cell → effector T cell
Elicitation phase
Activation of keratinocytes
What’s significant about haptens?
They don’t produce immune response unless they interact w/ protein
Langerhan’s cells vs. DC
Langerhan’s process & don’t present
DC present, but DON’T process
Describe patch test
- For contact dermatitis
- Consists of gauze & gel w/ antigen of interest
- Held on skin for 24-72 hours
___ causes poison ivy reaction. What happens?
Pentadecacatechol
- It penetrates the cell membrane & modified intracellular proteins
- Modified proteins are broken down & become incorporated into MHC I & are recognized by CD8+
Delayed hypersensitivity reaction types & reaction times
Contact → 24-72 hours
Tuberculin → 24-72 hours
Granuloma → 21-28 days
Granuloma reaction steps
- IL-12 presented by DC to stimulate naive TH1 cell
- Effector CD4+ TH1 produced → releases IFN-gamma & TNF-alpha
- Activation of immature macrophage
- Macrophage changes in morphology & looks like an epithelial cell
- Fusion of epithelioid cells in the presence of tumor necrosis factor (TNF)
- Multinucleated giant cell
Structure of granuloma
Center of it contains multinucleated giant cells & epithelioid cells that are derived from macrophages, which is then surrounded by T cells
Define autoimmunity
response to self antigens due to lack of tolerance or was never there
- Response may not be harmful
Define autoimmune disease
loss of tolerance to self antigen that results in immune response that produces a clinical disease
- Produces harmful response
What are the 6 mechanisms of self tolerance?
- Negative selection of B cells in BM
- Expression of tissue-specific proteins in the thymus so that they participate in negative selection of T cells
- Negative selection of T cells in the thymus
- Exclusion of lymphocytes from certain peripheral tissues: brain, eye, testis (examples of sequestered antigens)
- Induction of anergy in autoreactive B & T cells that reach the peripheral circulation
- Suppression of autoimmune responses by regulatory T cells
Example of sequestered antigens?
sympathetic ophthalmia
Define sequestered antigens
antigens that aren’t exposed during development of immune system
Treg cell have __ expressed on the surface & ___ transcription factor
CD25+
FoxP3
Describe central tolerance when autoreactive B cell encounters autoantigen after it leaves BM
Autoreactive B cell gets into FDC & sees antigen → no T cell help → B cell destroyed by apoptosis
Co-stimulatory signal & specific signal results in
Active T cell
Specific signal alone (no co-stimulatory signal - missing B7) results in
T cell becomes anergic
Co-stimulatory signal alone (missing MHC & TCR) results in
No effect on T cell
5 possible causes of autoimmune diseases
- Cross-reacting antigens (molecular mimicry)
- Breakdown in lymphocyte regulation
- microbes
- environmental
- genetic
Describe cross-reacting antigens
- Antigens shared between humans & microbes
- Both express same epitope
- If you make antibody against microorganism, there’s a chance the antibody can react w/ antigens we normally express
Example of cross-reacting antigens. What are the steps to develop rheumatic fever?
Rheumatic heart disease
Caused by streptococcus (strep throat) → immune response is antibody formation → elimination of streptococcus OR reaction w/ myocardial antigen (can develop rheumatic fever if not treated)
Loss of ___ cells can contribute to autoimmune disease
Treg
Ankylosing spondylitis is associated w/ expression of ___. ___% of patients express it. What’s the relative risk?
B27
95%
> 150
