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Immunology . Quiz!. Covering of the body (skin, mucous membrane) Innate Adaptive (acquired) . What are the three lines of host defenses ?. Skin and mucous membranes . Physical barrier Epidermis, cilia movement, low of air/fluid Chemical pH, enzymes, other antibacterial peptides
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Quiz! • Covering of the body (skin, mucous membrane) • Innate • Adaptive (acquired) What are the three lines of host defenses?
Skin and mucous membranes • Physical barrier • Epidermis, cilia movement, low of air/fluid • Chemical • pH, enzymes, other antibacterial peptides • Microbiological: • Normal flora
Quiz! • Primary • bone marrow • thymus gland • fetal liver and yolk sac • Secondary • lymph nodes • Spleen • mucosa-associated lymphoid tissue What are the organs of the immune system?
Innate • NO MEMORY • Cellular • Phagocytic cells • Cells with inflammatory mediators • Humoral • Acute phase reactant • Cytokinins
Order of recruitment • Macrophage • Innate immune system • Found in all organs/tissues • Especially where epithelia are in contact with exterior • Pseudopods attracted to bacteria • Derived from monocytes • Major function: engulf particles • Send signals for neutrophil via cytokines (Interferon alpha)
Order of recruitment • Neutrophils • Innate • Polymorphonuclear cell family PMNs (with basophils and eosinophils) • Found in blood stream • Come in massive number • Eats the bacteria • Then dies
Order of recruitment After macrophage does its job, it returns to regional lymph nodes and calls for • Dendritic cells • Borderline between innate and adaptive • Eats virtually everything • Takes in bacteria, carries pieces of it on its surface • Gets back to lymph node
How does phagocytic cells recognizes bacteria from self? • Toll-like receptors • PRR – pattern recognition receptors • Recognized PAMP – pathogen-associated molecular patterns • Type I trans-membrane receptor • N-terminal: outside the cell, recognize ligands • C-terminal: inside the cell • Activate inflammation and kick starts immunity
Quiz • They are PAMP • Gram-negative bacteria • Peptidoglycan (PGN) are Gram-positive bacteria What are Lipopolysacchides (LPS)?
Adaptive • Antigen (and epitope) specific • Antigen presenting cells (APC) – (MHC+peptide) • Interdigitatingdendritic cell • Macrophage • B lymphocyte (B cell)
Adaptive I. Humoral Immunity RESPOND TO • Extracellular pathogens (e.g., bacteria) • Antigen presenting cells (APC) MHC II+peptide PARTICIPANTS • TH2 (CD4+)-helper lymphocyte • B lymphocyte • T cell-B cell interaction (cooperation) • Immunoglobulin antibody production
Adaptive II. Cell-mediated Immunity • Antigen presenting cells (APC) MHC+peptide RESPOND TO • Intracellular pathogens (e.g., viruses) PARTICIPANTS • TH1(CD4+)-helper lymphocyte • Tc (CD8+)-cytotoxic lymphocyte • T cell-Tcell interaction (cooperation) • Effector cell is the CD8+ cytotoxic lymphocyte
Quiz Side-chain theory cell under threat grew additional side-chains to bind the toxin, and that these additional side chains broke off to become the antibodies that are circulated through the body Who is Paul Ehrlich and what was his theory?
Major Histocompatibility Complex • Two molecular system • MHC I • present in almost all nucleated cell • MHC II • Present in APC (macrophage, dendritic, B-cell) In each class, molecules have two chains - alpha and beta
Quiz How many alpha chain does MHC I has?
Lymphocytes • All starts in the bone marrow – stem lymphocytes • Some will go to Thymus • T-cells • Specialized in that microenvironment • Becomes either CD4 or CD8 • Some will remain in the Bone marrow • B-cells • Migration to lymph nodes
Maturation • TCR (T-cell surface receptors) and slg (B-cells – Specific Ig) are formed randomly • Early T-cells are double positive (both CD4 and CD8) • CD4 – TH1, and TH2, recognizes MHC II • CD8 – Cytotoxic T-cells, recognizes MHC I • 95% of all T-cells are deleted in the thymus • If they don’t recognize MHC or recognize it too well
QUIZ False, it is a life long phenomenon (T/F) Deletion of T-cells (selection for reactivity to MHC-peptide tolerance) stops at the age of 6 month
Quizzzzz Cytotoxic T-cell CD 4 becomes helper T-cell: target for HIV CD 8 becomes what cell?
Quizzz Then you have dendritic cells that moves in between B and T cells Interacts with both T cells are found in the superficial cortex of the lymph nodes
Continuing the sequence… 1st specific reaction Binding of MHCII (dendritic cell) to T-cell Genetically programmed to recognizes one epitope
Quiz • On dentritic cell: B7 • CD-80, CD-86 • On the T-cell: CD 28 • Confirms that it is not attacking self • Intracellular: costimulating factor giving the signal to attack What make sure that T-cell are not attacking “self”?
B-cell recruited: ligande CD40L (T-cell) with CD40 (B-cell) • B-cell receptor surface immunoglobuline recognizes the surface of the bacteria
Quiz!!! • What does IL 4, 5, 6 do? • Interleukins that causes the maturation and proliferation of B-cell • Produces more antibody
Quiz!! • False!!! • B-cells proliferate (under influence of interleukins) and makes antibody • When it becomes a plasma cell, it no longer makes antibody, only secrets it (T/F) B-cell becomes a plasma cell and start to make antibodies
Antibodies Humoral immunity Ig Structure 4 chains 2 identical light chains 2 identical heavy chains
Quiz (T/F) Both intra and inter chains are held together by disulfide bound
Five (5) Classes – determined by the Heavy (H) • Two (2) Types – determined by the Light (L) • κ kappa, λ lambda • Fab = antigen binding fragment • “hypervariable region” • Fc = crystalizable fragment • “Tail” • determines the biological actvity of the Ig Class
Classes of Ig • IgM – class mu • First activated • Recognizes A or B antigen on RBC • IgG – class gamma • Only one that can pass through placenta • Bacteria, virus, fungi, etc. • IgA – class alpha • Mucosal immunity • Found in saliva, tear, other secretion • IgE – class epsilon • Allergies
QUIZ Which Ig is monomeric?
After antibody binds… Antibody can’t do anything until it borrows complements from the innate system
What to remember? It’s a cascade, each amplifies the “waterfall” C3 and C5 calls for neutrophilphagocytosis Later molecules in the sequence – C9 – punches a hole in the bacterial membrane
In genome, 200 genes code for immunoglobulins • DNA from these genes cut, then rearranged and rejoined • Accounts for millions of possibilities • The last one C – determines the class (IgM, IgG, IgE, IgA)
Quiz True: Class switch can occur in the apical light zone IgM often switches class (T/F) B-cell can change the class of Ig it produces
Memory • After exposure, B cells differentiate into plasma cells that secrete antibodies • A small minority survives as memory cellsthat can recognize the same epitope • With each cycle, the number of surviving memory cells increases. Increase is accompanied by affinity maturation – survival of B cells that bind to the particular antigen with high affinity • secondary immune response
Quiz (T/F) B-cells need T-cell to activate and produce antigens. • False! • B-cell can produce and secrete antigen without T-cell • T-cell causes B-cell to proliferate and render them much more efficient
Major Divisions Afferent • Cranial Nerves • Spinal Nerves • Touch • Pain • Temperature • Visceral Efferent • Cranial Nerves • Spinal Nerves • Somatic (voluntary) • Involuntary • Enteric
Quiz! • What structure connects the two hemispheres? • Corpus Callosum
Quiz • T/F • The dorsal root carries motor neurons • False! • Ventral root carries motor neurons
Quiz • By which week of gestation do the neural plate start to form? • 3rd!
Neural tube • Ectoderm starts to fold and forms the neural groove • Neural groove eventually becomes neural tube (4 weeks) • Neural tube becomes CNS • Bits and pieces of ectoderm forms neural crest • Neural crest forms PNS
Cerebrospinal Fluid (CSF) • Produced by Choroid Plexus @ rate of 500 ml/day • Ventricle can only contain 150mL • Function is SNoW • Support and cushion the brain • NOurishment • Waste removal – arachnoidvilli