Inflammation and Tolerance Flashcards
inflammation
innate immune response that develops when our tissues are damaged
goals of inflammation
- recruit immune defenses to the injured tissue
- limit the spread of infectious agents
- deliver oxygen, nutrients, and chemical factors essential for tissue recovery
phases of inflammation
- vascular changes
- leukocyte recruitment
- resolution
vascular changes
- mast cells release vasoactive molecules from damaged tissue cells
- vasoactive molecules induce nearby vessels to dilate and become more permeable
- increased blood flow and vessel permeability promote swelling due to plasma seeping into tissues
leukocyte recruitment
- chemoattractants recruit leukocytes to the inflamed tissue
- neutrophils and monocytes are the first recruits
- leukocytes undergo margination and diapedesis to exit capillaries
- monocytes mature into macrophages as they migrate through the tissue
- as neutrophils and macrophages carry out phagocytosis they release cytokines to recruit other white blood cells
margination
- leukocytes slow as they roll along the vessel wall
- eventually leukocytes adhere to vessel wall
diapedesis
- leukocytes change shape
- leukocytes squeeze out of vessel
resolution
- begins as threat passes
- local capillaries return to normal while leukocytes and tissue cells in the area release chemical signals that reduce inflammation and promote healing
- stop secreting Th1 and start secreting Th2
- leukocytes undergo apoptosis (pus)
- swelling is reduced as exudate is collected by nearby lymphatic capillaries
chronic inflammation
- develops when an inflammatory response goes on too long
- exacerbates tissue injury
- promotes atherosclerosis, certain cancers, and progressive neurodegenerative disorders
tolerance
a state of indifference or non-reactivity towards a substance that would normally be expected to excite an immunological response
central tolerance
- in generative lymphoid organs
- lymphoid precursor cells become immature lymphocytes
- if they recognize self antigens they are triggered to: apoptosis, change receptors (B cells only), or develop regulatory T lymphocytes (CD4+ T cells only)
peripheral tolerance
- in peripheral tissues
- if mature lymphocytes recognize a self antigen they are triggered to: anergy, apoptosis, or can be suppressed by regulatory T cells
anergy
makes cell unresponsive and inactive to an immune response
T regulatory cells
- CD4 T cells that recognize self antigens may differentiate into regulatory cells in the thymus or peripheral tissues
- the regulatory cells have the transcription factor FOXP3
- regulatory cells inhibit the activation of naive T cells and their differentiation into effector T cells by contact dependent mechanisms or cytokines that inhibit T cell responses
Central T cell tolerance
recognition of self antigens by immature T cells in the thymus may lead to death of the cells (negative selection/deletion) or the development of T reg cells that enter peripheral tissues
peripheral T cell tolerance
- when a self antigen is recognized in the periphery 3 things can happen:
- anergy: functional unresponsive ness
- suppression via T reg cells to block activation
- deletion: induce apoptosis
central B cell tolerance
an immature B cell that recognizes self antigen in the bone marrow can:
- change its antigen receptor (VDJ)
- die by apoptosis (deletion)
- anergic: reduce antigen receptor expression and become functionally unresponsive
peripheral B cell tolerance
if a mature B cell recognizes a self antigen without T cell help it can:
- anergy: functionally inactivated
- die by apoptosis (deletion)
- have its activation suppressed by engagement of inhibitory receptors
stages of an infection
- establishment
- inductive phase
- effector phase
4.memory phase
