"FUNCTIONAL" IMMUNOLOGY HOST RESPONSES TO INFECTIOUS DISEASE PAUL A GULIG "FUNCTIONAL" IMMUNOLOGY HOST RESPONSES TO INFECTIOUS DISEASE PAUL A GULIG April 7, 2008 CONCEPTS 1 Immunity works! (usually) M[.]
"FUNCTIONAL" IMMUNOLOGY HOST RESPONSES TO INFECTIOUS DISEASE PAUL A GULIG April 7, 2008 CONCEPTS Immunity works! (usually) - Most infectious agents cannot evade innate immunity or early induced responses Hardly any can evade the adaptive response Levels of immunity/defenses a Innate defenses b Early induced response (cytokines, phagocytes, complement, inflammation) c Specific, adaptive immune response (Ig and CMI) The relevant adaptive immune response depends on the nature of the infectious organism, its anatomical site of infection, and intracellular/extracellular nature of infection Figure 2-1 INNATE DEFENSES OF SURFACES INNATE DEFENSES OF SURFACES A Physical: Epidermis - essentially impenetrable (except maybe some worms) Epithelial Surface - mucus and flow of luminal fluid (tears, urine, food, etc.) B Chemical: fatty acids of skin lysozyme in secretions digestion by enzymes of intestines acid - stomach antibacterial peptides in intestines C Microbial - normal flora of gut, lower genital tract, upper respiratory tract INNATE DEFENSES "INSIDE" THE BODY Humoral – complement Functions: Opsonization (C3b) Lysis of some organisms (C5-9 MAC) Chemotaxis and anaphylaxis (C5a Activation of Complement Alternative pathway - stabilizing C3b,Bb Classical pathway - IgM and IgG antibodies (not innate) Mannan-binding Lectin – microbial carbohydrates Cellular - phagocytes Polymorphonuclear leukocytes (PMNs) - short lived (T 1/2 - hours) - found in circulation and marginal zones of capillaries rapid recruitment - can be recruited as part of early induced response by chemotaxis – quickly - more oxidative than macrophages - granules with antimicrobial factors (defensins, proteases, lysozyme, bacterial permeability factor, etc.) Macrophages - long lived (T 1/2 - days) - produced from bone marrow precursors - slower - circulating monocytes, tissue macrophages in RES - can be activated by adaptive response and certain cytokines to kill intracellular pathogens - secrete cytokines to produce early induced response Dendritic Cells • Mainly antigen presentation • Not killing Receptors Toll-Like Receptors (TLRs) – 10 (at least): • • • • • TLR2 bacterial peptidoglycan, lipoproteins TLR3 viral dsRNA TLR4 bacterial LPS (with CD14) TLR5 bacterial flagella TLR9 bacterial CpG Nucleotide-binding oligomerization domain (Nod) proteins (Nod1 and Nod2) cytoplasmic – recognize peptidoglycan components Regulate cell activation and innate immune response