Vaccination –weakened or attenuated diseases causing agents to provide protection

-Edward Jenner: cowpox

Robert Koch: what microorganisms causes particular disease?
-pathogens (disease-causing organism): viruses, bacteria, fungi and parasites
Louis Pasteur: chicken cholera, rabies, pass virus weakened pathogenicity
Antibodies: protein bind to toxin neutralized their activity
Innate Immune responses:
-immediately available, not specific, does not lead to memory immune response
Adaptive immune responses:
-specific, vaccinations induce memory information in lymphocytes
-antigens: any substance that induce adaptive immunity
-specific antigen activates T or B cells
-T cell receptor(TCR)< and B cell receptor(BCR) is a membrane around antibody
-antibody is a secreted form of the BCR, and TCR is never secreted
-for T cell to product antibody, the antigen must first be broken down into
fragments.
-T cell function by making contact with other cells and induce them to change
Cell of the immune system
-leukocyte: white blood cell (WBC)
-PMN or granulocytes (Multi-lobed nuclei)
-neutrophils (activate bactericidal mechanisms), eosinophils(kill antibody-
coated parasites), basophils(Promote anti-parasitic immunity)
-monocytes
-precursors of tissue macrophages
-Lymphocytes
-B bell (bone marrow), product antibodies
-T cell (thymus), CD4, CD8
Cytokines and Chemokines
-inflammation, signaling, recruit immune cells, increase flow of lymph
Lymphatic system
-lymph, interstitial space, interstitial fluid

Innate Immunity
-does not encoded in multiple gene segment, does not require gene rearrangement
-innate barrier to infections
-antimicrobial peptides is critical for innate immunity
-what if barrier failed?
-Pathogen associated molecular patterns (PAMPs)
-Pattern recognition receptors (PRR)
-four groups: free receptors in serum, membrane bound phagocytic
receptors, membrane bound signaling receptors, cytoplasmic signaling receptors
-found in macrophages, neutrophils, and dendritic cells
-recognize pathogen and engulfed it
-1. Membrane bound signaling receptors (Toll-like receptors (TLR))
 -extracellular viruses, distinct ligand, induce secretion of cytokines,
chemokines, and anti-microbial proteins and molecules
-2. Cytoplasmic receptors for PAMPs
-NOD-like receptors (NLR)
-recognize bacterial wall, induce secretion of inflammatory
cytokines, anti microbial products
-RIG-I-like helicases (RLH)
-recognize cytoplasmic viral RNA, intracellular, induce
inflammatory cytokines and interferons (cytokines with anti-viral activity)
-cyclic GMP AMP synthase
-recognize DNA that invades cytoplasmic, synthesizes cGAMP that
binds Sting and leads to antimicrobial responses
-NK cells (leukocytes), no antigen-specific receptor, cytotoxic (secret cytokines to kill other cells)
-after PAMPs
-cytokine secretion
-signaling
-autocrine: the cells that secretes cytokine
-paracrine: adjacent, different cell
-endocrine: exert effects on a cell that is far away
-IL, interleukins
-chemokine secretion
-chemotaxis
-CC and CXC
-attract more immune cells
-How do cells leave blood vessels and get into tissue?
-receptors on leukocyte interact with ligands or receptors on endothelial cells
-weak selectin-medicated adhesion allows the neutrophil to roll
-weak binding of leukocytes changes when other ligands are present on inflamed
endothelium
-enter through adhesion molecule interactions
-adhesion molecule deficiency
-LAD (leukocyte adhesion deficient, poor recruitment, can’t get to infection site)
-bone marrow transplant as therapy

Immunological Tools
-antiserum: serum that contained antibodies
-Sero-conversion: when have detectable Ab in blood to the immunogen
-adjuvants (enchanes the body’s immune response to an antigen)(to help)
-purified protein not highly immunogenic, helped by adjuvants
-convert protein, signal to antigen presenting cells
-Haptens ( to fast)
-small, do not induce Ab, linked to protein carrier, now Ab are generated
-making monoclonal antibodies
-plasma cells make and secrete Ab
 -fusion->hybridoma (myeloma cells with spleen cells)  monoclonal hybridomas
-Immunological Assays
-ELISA(enzyme-linked) detect presence of Ab or Ag

Immunohistochemistry and Immunofluorescence

-immunohistochemistry uses enzyme-linked Ab to detect antigens
-use of fluorescently labeled Ab to detect Ag
-antibodies can be conjugated to molecules which will fluoresce when stimulated
at particular wavelengths
-flow cytometry (used to look at several features of immune cells)
-fluorescence activated cell sorting (FACS)
-CD4 T cells. Use fluorescently labeled antibodies
-Magnetic activated cell sorting (MACS)
-Ab used to isolate specific population or deplete them
-detecting T cell-specific responses
-Evaluation of T cell killing of infected cells
-if healthy, the radioactivity stays within the cell, if note will leak into the
media
-individual antigen-specific T cells are detected by staining them with soluble
MHC complex (major histocompatibility complex)
-use tetramer as reagent study CD4 T cells
-Nucleic acid based
-RNAi/siRNA
-antiviral in plants and drosophila, to knock down mRNA
-CRISPR/Cas
-antiviral in bacteria, to edit genomes