Chapter 6 Flashcards
How is complement activated in innate immunity?
-by microbes using the alternative or lectin pathways
Follicular dendritic cells
- present in germinal centres
- have Fc receptors for IgG and receptors for C3b so can trap antigen bound to antibody of complement
- involved in antigen presentation to B cells in humoral immunity
Roles of macrophages in immunity
- antigen presenting cells to T cells (activate T cells)
- activated by T cells to kill ingested microbes
- phagocytosis and destruction of microbes that are opsonized by IgG and C3b
Class I MHC molecules
- expressed on all nucleated cells and platelets
- encoded by HLA-A, B and C
- display peptides derived from cytoplasmic proteins (e.g. viral antigens, tumor antigens) and present them to CD8 T cells
- the TCR recognizes the MHC-peptide complex and the CD8 molecule is a coreceptor that binds the Class I heavy chain
- CD8 cells are class I - MHC restricted
Other genes encoding by the MHC locus
-complement components, TNF, lymphotoxin
Role of cytokines in immune system
- messengers that mediate interactions and effector functions of leukocytes (i.e. interleukins)
- some cytokines (colony stimulating factors) stimulate hematopoiesis to increase leukocyte responses during inflammation and to replace leukocytes killed during immune responses
Cytokines of innate immunity
- produced by macrophages, dendritic cells and NK cells
- produced rapidly and mediate inflammation and viral defense
- TNF, IL-1, IL-12, IFN-gamma
Cytokines of adaptive immunity
- made by CD4 T cells
- promote lymphocyte proliferation and differentiation
- IL-2, IFN-gamma, other interleukins
What is the clonal selection hypothesis?
-that lymphocytes specific for a large number of antigens exist before exposure to the antigen, and these get activated when antigen arrives
What is affinity maturation?
- process of producing antibodies with high affinity for the target antigen
- isotype switching is induced by cytokines such as IFN-gamma and IL-4, and helper T cells also stimulate production of specific antibodies
What is a hypersensitivity reaction?
-a pathologic reaction to an antigen that was previously encountered
Features of hypersensitivity reactions
- can be against exogenous or endogenous (autoimmune) antigens
- development of these diseases is often associated with specific HLA types
- reflects an imbalance between the effector and control mechanisms of immune responses
Features of type III (immune complex mediated) hypersensitivity
- antigen-antibody complexes are formed in the circulation and deposit in tissues (often kidney, joints), where they result in inflammation and tissue damage, often manifest as vasculitis/fibrinoid necrosis
- complement fixing antibodies (IgM and IgG) induce the pathologic lesions; complement is consumed in these reactions so the patient has hypocomplementemia
- examples: serum sickness, SLE, poststrep GN, polyarteritis nodosa
Features of type IV (delayed type/cell mediated) hypersensitivity reactions
- initiated by antigen-sensitized T cells, usually CD4 but also CD8
- upon repeat exposure to antigen, previously sensitized Th1 cells respond and secrete IFN-gamma and other cytokines that actiate macrophages that phagocytize and kill organisms
- the activated macrophages express more MHC class II on their surface, promoting further antigen presentation, secrete cytokines that produce inflammation, and produce IL-12 which amplifies the Th1 response
- Th17 cells secrete cytokines that recruit neutrophils and monocytes
- morphologically characterized by CD4 cells and macrophages that cuff around vascular structures
- with pesistent antigens, over 2-3 weeks macrophages dominate and form granulomas
- examples: DM1 (probably via CD8 mechanisms), MS, RA, Crohn’s disease, contact dermatitis
Define central tolerance
- immature self-reactive T and B cells are killed or inactivated during maturation
- immature lymphocytes that encounter the antigens for their TCR in the thymus die by apoptosis (negative selection)
- AIRE (autoimmune regulator) stimulates expression of “peripheral restricted” self antigens in the thymus and is required for deletion of self-reactive T cells
- developing B cells in the bone marrow that recognize self antigens undergo antigen receptor gene rearrangement so they no longer recognize self (receptor editing)
Define peripheral tolerance
- anergy: prolonged/irreversible functional inactivation of lymphocytes induced by encountering antigens under certain conditions, such as when antigen is presented by cells that lack costimulators
- suppression by regulatory T cells (cells produced in the thymus that express CD25 and Foxp3
- deletion by activation-induced cell death: CD4 cells recognizing self-antigens may express a pro-apoptotic member of the Bcl family and die by apoptosis