Introductory Microbiology BIOL 228 Lecture 14 Immunology PDF

Introductory Microbiology BIOL 228 Nusrat J. Urmi Biology Dept. , OC © 2016 Pearson Education, Inc.  Lecture 14 Immunology...

Introductory Microbiology BIOL 228 Nusrat J. Urmi Biology Dept. , OC © 2016 Pearson Education, Inc.  Lecture 14 Immunology Nusrat J. Urmi Biology Dept. , OC © 2016 Pearson Education, Inc. Key Concept 1: Basic Properties of the Immune System Basic Properties of the Immune System Immunity is the ability of an organism to resist infection Innate immunity (nonspecific immunity) – built-in capacity of the immune system of multicellular organisms to target pathogens that are seeking to colonize the host – does not require previous exposure to a pathogen or its products Adaptive immunity – the acquired ability to recognize and destroy a particular pathogen or its products – dependent on previous exposure to the pathogen or its products (specificity) – directed toward an individual molecular component of the pathogen (antigen) Basic Properties of the Immune System Figure 26.1 Overview of the Two-Pronged Immune Response Barriers to Pathogen Invasion Natural Host Resistance – Normal microbiota helps host resist pathogens, particularly on the skin and in the gut via competitive exclusion – Pathogens do not easily infect tissues because the harmless microbes limit available nutrients and sites for infection Infection site and tissue specificity – Different pathogens invade different tissues – Even if pathogens adhere to an exposure site, the organisms cannot colonize the host if the site is not compatible with the pathogen’s nutritional and metabolic needs Routes of infection are crucial (e.g., tetanus is in wounds, while Salmonella is ingested, not vice versa) (Table 26.1) Table 26.1 Tissue Specificity in Infectious Disease Disease Tissue or cell type infected Pathogen Acquired Immunodeficiency Human Immunodeficiency virus T-helper lymphocytes syndrome (AIDS) (HIV) Botulism Motor end plate Clostridium botulinum Cholera Small intestine epithelium Vibrio cholerae Streptococcus mutans, S. Dental caries Oral epithelium sobrinus, S. mitis Diphtheria Throat epithelium Corynebacterium diphtheriae Gonorrhea Mucosal epithelium Neisseria gonorrhoeae Influenza A and influenza B Influenza Respiratory epithelium viruses Malaria Blood (erythrocytes) Plasmodium spp. Pyelonephritis Kidney medulla Proteus spp. Spontaneous abortion (cattle) Placenta Brucella abortus Tetanus Inhibitory interneuron Clostridium tetani Barriers to Pathogen Invasion Physical and chemical barriers to infection – The tight junctions between epithelial cells that line body tissues inhibit invasion and infection – Mucosal membranes are coated with a thick layer of mucus – Stomach acid inhibits bacterial growth – Skin is salty and acidic, limiting bacterial growth Figure 26.2 Barriers to Infection in the Human Body Key Concept 2: Cells and Organs of the Immune System The Blood and Lymphatic Systems The lymphatic system is a separate circulatory system that drains lymph fluid from extravascular tissues Blood is pumped through arteries and capillaries and returns from the body through veins In capillary beds, leukocytes and solutes pass from blood into the lymphatic system Lymph nodes contain high concentrations of immune system cells Figure 26.4 The Blood and Lymphatic Systems The Blood and Lymphatic Systems About 0.1 percent of the cells in blood are white blood cells, also called leukocytes – Include lymphocytes, granulocytes, and monocytes Whole blood is composed of plasma and cells – Plasma contains proteins and other solutes Serum is the portion of blood that is not cells or clotting proteins Leukocytes are nucleated white blood cells – Lymphocytes are specialized leukocytes involved exclusively in adaptive immune response two types of lymphocytes – B cells: originate and mature in bone marrow – T cells: originate in bone marrow, but mature in thymus Bone marrow and thymus are primary lymphoid organs Figure 26.5 Lineage and Diversity of Immune Response Cells Key Concept 3: Phagocyte Response Mechanisms Pathogen Challenge and Phagocyte Recruitment Microbial invasion is the ability of a pathogen to enter host cells or tissues, multiply, spread, and cause disease. Tissue damage triggers the recruitment of a large number of phagocytes. Microbial invasion and the innate immune response: (a) Tissue damage, such as that caused by a tack puncturing the skin, can lead to invasion by microorganisms and the release of cytokines and chemokines from damaged host cells. (b) Phagocytes, especially neutrophils, are recruited to the site of infection by the cytokine–chemokine gradient, squeezing out of dilated capillaries via diapedesis. (c) Invading microorganisms are cleared by phagocytosis, and the tissue is restored to health. Pathogen Recognition Pathogen-associated molecular patterns (PAMP) – Pathogens have structures and molecules not found in or on host cells (e.g., peptiglycan, flagellin, dsRNA) – A common PAMP: lipopolysaccharide (LPS) common to all gram-negative bacterial outer membranes Pattern recognition receptors (PRR) – Leukocytes have membrane bound or soluble proteins (PRR) that Figure 26.7 Pathogen recognize PAMPs Recognition by Phagocytes Phagocyte Signal Transduction Signal transduction in phagocytes – Upon encountering a pathogen-associated molecular pattern, Toll-like receptors (TLR) present in the phagocyte cytoplasmic membrane will send a signal to the nucleus (Figure 26.8) Each TLR on a human phagocyte recognizes and interacts with a specific PAMP At least nine TLRs in humans interact with cell surface and soluble PAMPs from viruses, bacteria, and fungi Upon activation of TLRs, a leukocyte will start a phosphorylation cascade to transmit the activation signal to the nucleus, activating transcription factors in the nucleus. The result is transcription of genes encoding proteins that induce inflammation and other phagocyte activities. Phagocyte Signal Transduction Figure 26.8 A Toll-Like Receptor Phagocytosis and Phagocyte Inhibition Phagocytosis and the phagolysosome – Phagocytes will engulf pathogens upon recognition of PAMPs by their TLRs – When engulfed, the bacteria will be held in a membrane-bound vesicle called the phagosome – The phagocytic host cell will fuse lysosomes, making a phagolysosome – Phagocytes also produce toxic reactive oxygen intermediates to kill the bacteria within a phagolysosome Phagocytosis and Phagocyte Inhibition Phagocytosis: Overview Phagocytosis and Phagocyte Inhibition Inhibiting phagocytes Some pathogens can survive the phagolysosome – Mycobacteria tuberculosis produces carotenoids to neutralize singlet oxygen and has a waxy cell wall that absorbs free radicals. This pathogen lives and divides within phagocytes. – Some pathogens, such as Streptococcus pyogenes produce leukocidins, which kill white blood cells. Dead white blood cells are found in pus. Lastly, some pathogens contain a capsule, which makes it difficult for the phagocyte to engulf them. Host antibodies can counteract this, which is why pneumococcal vaccines are effective in preventing pneumonias caused by Streptococcus pneumoniae. Key Concept 4: Other Innate Host Defenses Inflammation and Fever Inflammation is a nonspecific reaction to noxious stimuli (such as physical injury, toxins, and pathogens) – Redness, swelling, pain, and heat localized at site of infection – Proteins called cytokines and chemokines draw white blood cells to a site of inflammation – Effective inflammatory response isolates and limits tissue damage, destroying damaged cells and pathogens Inflammation and Fever Fever – Certain cytokines, particularly IL-1, will cause the host’s body temperature to rise, causing a fever – A fever is beneficial because it increases circulation rate, which allows leukocytes to get to the site of infection – It is also beneficial because some pathogens cannot tolerate the increased temperature – Lastly, fever is associated with an increase in transferrins, which sequester iron, keeping it away from pathogens and limiting their growth Inflammation and Fever Systemic inflammation and septic shock – Widespread (systemic) inflammation can lead to shock as the increased vascular permeability decreases a host’s blood pressure, which can cause damage to multiple organs at the same time – Gram-negative bacteria are particularly dangerous because they contain LPS, which triggers a proinflammatory cytokine response from leukocytes as their Toll-like receptors are activated. This leads to a cytokine storm, which can be fatal. Examples: Salmonella species or Escherichia coli, which can be introduced into the peritoneal cavity or the bloodstream by a ruptured or leaking bowel Inflammation: Steps The Complement System The complement system (C’) is a set of circulating, inactive proteins that are sequentially activated in response to a pathogen Classical complement activation – The classical pathway of complement activation is initiated when complement binds to antibodies that are attached to a pathogen – The end result of complement activation is three-fold (Figure 26.15) direct attack via membrane attack complex (MAC). recruitment of phagocytes Opsonization The mannose-binding lectin (M B L) and alternative pathways rely on innate mechanisms rather than antibodies to activate the complement pathways While they start at a different place in pathway, all three complement systems end with opsonization, direct attack, and recruitment of phagocytes Some chemoattractants (C5a and C3a) are considered anaphylatoxins, because they can lead to immune over activation and potentially anaphylactic shock Innate Defenses Against Viruses Natural killer (NK) cells – NK cells are cytotoxic lymphocytes – NK cells recognize cells that do not display Major Histocompatibility Complex (MHCI) proteins, as all normal host cells should have MHCI – If a cell lacks MHCI and displays a stress protein, an NK cell will activate to destroy the target, which is likely a virally infected or cancerous host cell Granzyme: an enzyme that induces programmed cell death (apoptosis) Perforin: it pokes holes in (perforates) the target membrane Figure 26.16 Natural Killer Cells Innate Defenses Against Viruses Interferons are small cytokine proteins that are produced by virally infected cells Interferons serve as a warning system and prevent viral replication by stimulating the production of antiviral proteins in uninfected cells once they receive the interferon signal from infected cells Figure 26.17 Antiviral Activity of Interferons