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Immune System
Physiologic functions
prevent infection eradicate established infections
Impact of Vaccination
Innate Immunity
Mediates the initial protection against infection Natural or NATIVE always present, prepared to block entry of microbes and eliminate them and consists of
epithelium acting as a barrier specialized cells phagocytes, NK cells, complement system antibiotics present in the epithelium
Adaptive Immunity
Specific or acquired Stimulated by microbes invading the tissue, evading the innate system Develops more slowly and more effective defense against infection is mediated by the innate system and consists of
lymphocytes and their products, antibodies (Ab) recognize antigens (Ag) different substances produced by pathogenic and non-pathogenic organisms
Adaptive Immunity
There are 2 types of adaptive immunity
Humoral against extracellular microbes
recognizes proteins, carbohydrates and lipids Ab from the B-cell lymphocyte will prevent entry of the microbe and colonizing the host at mucosal surfaces and in the blood
Specificity
Diverse lymphocyte repertoire for Ag recognition Express clonally distributed receptors for Ag each receptor is unique for each clone Get a heightened response on exposure to that Ag on next contact but not to almost identical Ag
1 Ag = 1 cell that recognizes it
Each Ag elicits immune response by lymph activation after recognition Clonal expansion activated lymph undergoes proliferation and all progeny recognize same Ag
1 and 2 Response
Lymphocytes
Only cell that has specific Ag receptor as distinguished by surface proteins - CD (cluster of differentiation, also have number designation) Key mediators of adaptive immunity B-cell has membrane-bound receptors on the surface of the cell and/or secretes Ab
humoral immunity
T-cell Ag receptor will bind protein fragments on a major histocompatibility complex (MHC) molecule on the Ag-presenting cell (APC)
cell-mediated immunity
T-Cell Types
Helper T-cell CD4+ cells
help B-cells make Ab and phagocytes to destroy ingested microbes special subset that prevent or limit the immune response = regulatory T-cell
Origin of Lymphocytes
All come from stem cells in bone marrow and mature in the generative lymphoid organs
B-cells mature in BM T-cells mature in thymus
Maturation of Lymphocytes
Cells that also present the 2nd signal to activate the lymphocyte are professional APC
Nave Lymphocytes
Recognize microbial Ag and get additional signals to proliferate and differentiate into effector and memory cells Move thru peripheral lymphoid tissues for weeks to months, no Ag recognition then die by apoptosis and replace with new cells
Effector Cells
Lymphocytes and other leukocytes Effectors are in the innate and adaptive immune system
innate macrophages and some granulocytes directly recognize microbes and eliminate them adaptive B and T cells call in and activate other leukocytes to kill microbes
Most cells are eliminated when the infection is cleared but memory cells will live for very long periods of time
see antigen 2nd time - 2 immune response
Effector Cells
B-cells secrete Ab = plasma cell CD4+ T-cells secrete cytokines to activate B-cells and macrophages CD8+ T-cells kills infected cell Memory cells both B and T cells
long-lived but functionally inactive until sees Ag again
Peripheral 2 lymphoid organs where the adaptive immune response to microbes initiates
lymph nodes, spleen, mucosal and cutaneous immune system concentrate Ag so that APC and lymphocytes work in a way that optimize interaction among cells and development of adaptive immunity
Ag in
Lymph Nodes
Nodular aggregates along lymphatic channels fluid (lymph) moves thru nodes, APCs in nodes able to sample Ag that may enter through epithelial and tissues Concentrate Ag in draining lymph Must know parts of LN
Lymph out
Cells in
Spleen
Responds similarly to lymph nodes except filters blood thru sinusoids Dendritic cells and macrophages trap Ag and abundant phagocytes to kill extracellular microbes
Spleen
T cell are concentrated in periarteriolar lymphoid sheaths around small arterioles B cells in the follicles
Lymphocyte Distribution
Movement of Lymphocytes
Follicular dendritic cells (FDC) secrete chemokines chemoattractant cytokines that attracts B cells to follicle while T cells move to the edge of the follicle because contain CCR7 receptor that recognize chemokines B and T cells migrate to towards each other after activation by microbe antigens and function at edge of follicle
T cells help B cells make Ab
Activated B and T cells leave the lymph node by efferent lymphatic vessels or in spleen by veins
Recirculation
Refers to T cells in the LN Nave lymphocytes constantly recirculate between blood and lymph tissues where Ag are; activated lymph to sites of infection
have distinct life stages in different areas
Nave T cells enter lymph nodes through specialized post-capillary venules High Endothelial Venules (HEV) L-selectin on nave T cells bind carbohydrate ligands only on HEV cells loosely bound; chemokines cause tighter binding and T cell can move thru HEVs into the lymph node
Recirculation (continued)
Nave cells scan dendritic cells looking for Ag, binds and then activates which reduce the expression of adhesion molecules and chemokine receptors to keep lymphocytes in the LN
increase expression of receptor for phospholipid sphingosine-1-PO4 and draws activated lymphocytes out into circulation as effector T-cells (Chapter 6)
T cell can activate when encounter Ag specific for it but will usually will circulate through some lymph nodes once a day, can also have memory T cell
T-Cell Recirculation
Phagocytes ingest microbe, kill them and helper T cell will enhance microbiocidal ability of phagocyte Cytotoxic T cell destroy cells infected with microbes which are inaccessible to Ab
3. Elimination of Ag or effector phase effector cells and innate immune system remove microbe 4. Decline of lymph response apoptosis to remove cells activated by Ag cleared by phagocytes 5. Memory long-term response to Ag
Signal Types
1. Ag binding to Ag receptor on the lymphocyte 2. Signal from the microbe and the innate system Causes the cell to undergo clonal expansion through rapid cell division creates many effector lymphocytes become cells that produce substances to eliminate Ag