Immunology (PREMATRIC)
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| Immune System Function | 1. Provide surveillance and defense against foreign substances.
2. Help maintain fluid balance.
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| Lymphatic System | a network of vessels and organs where the cells of the immune system reside.
-fluid balance
-immune cell development
-sites of interaction btw immune cells and foreign substances
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| Lymphatic vessels | collect fluid and lymphocytes from tissues and return them to the blood. (cells can enter directly thru afferent lymphatic vessels, or migrate thru cardiovascular system).
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| Immune tissues and organs | 1. Primary (development)
2. Secondary (trapping and activation)
-diffuse lymphatic tissue
-lymphatic nodules
-lymph nodes
-spleen
(T-cells: from Thymus; B-cells: from red Bone marrow)
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| 3 Step response to microbial encounter | 1. barriers: physical, chemical, biological
2. innate immunity (0-96 hours)
3. adaptive immunity ( >96 hours )
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| Innate Immunity | -phagocytosis
-complement (small proteins that help the ability of antibodies & phagocytic cells; can be recruited by adaptive immune system.)
-inflammation
-cytokine release
-NK (Natural killer cells) cell killing
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| Barriers to Infection | Protection at external and internal body surfaces
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| Respiratory Tract Barriers | -nose hairs
-mucous
-cilia
-microcidal molecules
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| Gastrointestinal Tract Barriers | -pH
-Mucus
-Microcidal molecules (antiseptic)
-commensal microbes (live on skin, protection from infection)
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| Skin Barriers | -RNases, DNases
-Microcidal molecules
-fatty acids
-commensal microbes (secrete antimicrobial agent)
(slightly acidic, cells slough off)
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| Urogenital Tract Barriers | -pH
-Mucous
-Microcidal molecules
-Fluid pressure
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| The Innate Immune System (4 main properties) | 1. immediate
2. non-specific
3. not enhanced upon repeat exposure
4. helps induce adaptive response
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| Innate Immunity - Phagocytosis | cellular process of engulfing solid particles by the cell membrane.
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| Innate immunity - Macrophage | fuctions:
1. phagocytosis
2. cytokine secretion (activate inflammatory system)
3. antigen presentation
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| Innate immunity - Neutrophil | 1. phagocytosis
2. granular release of antibacterial compounds
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| 4 hallmarks of Inflammation | 1. rubor (redness)
2. calor (heat)
3. dolor (pain)
4. tumor (swelling)
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| Inflammation | -increased blood flow: to dilate potentially toxic agents
-increased capillary permeability: to help transfer larger molecules across endothelium
-increased migration of cells into tissues: to destroy bacteria, remove debris, restore norm tissue structu
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| Purpose of inflammation | sequential recruitment of cells (bringing more immune cells and blood into the area of pathogen so they can eliminate the infection)
1. neutrophils - principle inflammatory cell
2. monocytes, macrophages
3. lymphocytes
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| 2 phases of inflammation | 1. acute (0-72 hours)
2. chronic (ex: autoimmune diseases, arthritis)
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| Adaptive (acquired) Immunity | -requires several days to develop
-response is SPECIFIC - recognizes features unique to each microbe
-carried out by B-lymphocytes (antibodies), T-lymphocytes (cytokines), and APC's (antigen presenting cells).
-provides long-lasting immunity
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| The Humoral Immune Response (HIR) | adaptive immunity - mediated by secreted antibodies produced in the cells of the B lymphocyte lineage (B cells)
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| Cell-mediated immunity | adaptive immune response that involves the activation of macrophages, natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. (T cells)
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| Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #1) | 1. each lymphocyte bears a single type of receptor with a unique specificity.
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| Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #2) | 2. interaction between a foreign molecule & lymphocyte receptor capable of binding that mol with high affinity leads to lymphocyte activation.
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| Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #3) | 3. the differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived (memory)
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| Clonal selection hyphothesis (4 tenants of adaptive immunity) (Tenant #4) | 4. lymphocytes bearing receptors specific for ubiquitious self molecules are deleted at an early stage in lymphoid cell development and are therefore absent from the repertoire of mature lymphocytes (recognizes self vs. non-self)
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| Cytotoxic T-cells (CD8+) | -Each T-cell is specific for a unique antigen fragment
-T-cells recognize antigen via their T-cell receptor (TCR)
-once activated, go out into body and find any other of the same cells that activated them, and destroys them.
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| CD8+ T-cell activation | CD8+ T-cells become activated when their TCR interacts w/ antigen/MHC I (major histocompatibility structures: secrete antigens)
-activated CD8+ T-cells directly kill target cells
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| T-cell receptors (TCR) | -has to recognize an antigen that is associated with MHCs (either I or II).
-they are specific receptors (because they are leukocytes).
-Structure is same for both CD8+ & CD4+ T-cells.
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| Rule of 8 | CD8+ --> MHC I (8*1=8)
CD4+ --> MHC II (4*2=8)
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| Helper T-cells (CD4+) | -become activated when their TCR interacts with antigen/MHC II
-MHC II is expressed on a subset of cells known as Antigen Presenting Cells (APC's)
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| CD4+ cell activation | activated CD4+ cells secrete cytokines
-help activate CD8+ cells
-help activate B-cells
-activate macrophages and NK cells
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| Antigen Presenting Cells (APC's) | is a cell that displays foreign antigen complexes with major histocompatibility complex (MHC) on their surfaces. T-cells may recognize these complexes using their T-cell receptors (TCRs). These cells process antigens and present them to T-cells.
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| Three types of APC's | 1. Macrophages
2. Dendritic cells
3. B-cells
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| T-cell receptor (TCR) structure | -monovalent
-interchain disulfide bonds
-intrachain disulfide bonds
-amino-terminal variable and c-terminal constant domains
-carbohydrate attachment
(alpha is light, beta is heavy)
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| TCR variable domains | - V-region (variable region)
- Hypervariable: site of contact (3 regions that contact the antigen; 3 from alpha, 3 from beta)
-CDR (complementary determining region): determines specificity
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| Antigen Binding site | is formed by the combination of CDRs from the alpha and beta chains
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| Complementary determining region(CDRs) | determine specificity for specific antigens. The CDRs are the most variable part of the molecule, and contribute to the diversity of these molecules, allowing the antibody and the T cell receptor to recognize a vast repertoire of antigens.
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| How does the TCR recognize an antigen? | -Helper T-cells (CD4): antigen binds with MHC II complex on APC.
-Cytotoxic T-cells (CD8): antigen binds with MHC I complex on target cell.
(TCR binding with antigen/MHC thru non-covalent interactions)
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| B-Cells | -recognize native antigen via their B-cell receptor --> antibody
(antibody can recognize free-floating, native antigen - doesn't need to be processed)
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| Antigen | a substance/molecule that, when introduced into the body, triggers the production of an antibody by the immune system, which will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader.
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| B-cell activation | activated when their antibody binds antigen AND they receive interactions/signals from CD4+ T-cells
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| Antibody | aka: immunoglobulin: large, Y-shaped protein used by immune system to identify and neutralize foreign objects (such as bacteria/viruses) by recognizing it's antigen. Antibodies are produced by plasma cells.
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| Antibody structure | -2 heavy chains (which are identical to each other)
-2 light chains (which are also identical to each other)
-hinge region
-domains
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| Antibody function | -bind foreign antigen
-initiate its destruction
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| Antibody Isotypes | -same structure (2 light/2heavy chains)
(GAMED)
1. IgM
2. IgD
3. IgG
4. IgA
5. IgE
(all have same capacity to bind the same antigen, but the heavy chain allows them to perform to specific functions)
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