Innate Immunity Presentation PDF

INNATE IMMUNITY: NONSPECIFIC DEFENSES OF THE HOST BIOL 230 DR. JE NNIF ER LAING  IMMUNITY Immunity is the ability of the body to protect us from diseases caused by microorganisms and/or their products Immunity is also called resistance...

INNATE IMMUNITY: NONSPECIFIC DEFENSES OF THE HOST BIOL 230 DR. JE NNIF ER LAING  IMMUNITY Immunity is the ability of the body to protect us from diseases caused by microorganisms and/or their products Immunity is also called resistance Lack of immunity is called susceptibility There are two types of immunity: 1. Innate Immunity 2. Acquired or Adaptive Immunity  Innate Immunity Present at birth NOT microbe-specific There is no memory component Always present Acquired Immunity Must be acquired for each microbe Microbe specific- response to antigens Mediated by antibodies and T-cells Slower to respond, but has memory component  IMMUNOLOGY Immunology encompasses the study of the second and third lines of defenses The primary function of a healthy functioning immune system can be summarized as: Surveillance of the body Recognition of foreign material Attack and destruction of foreign material  BLOOD The blood contains both non-specific specific defenses Whole blood is liquid tissue that courses through the arteries, veins, and capillaries Whole blood is made of blood cells suspended in plasma Serum is like plasma except that is separated from clotted blood  BLOOD CELLS Wright’s Stain of human blood smear Leukocytes are cells of the immune systems that fight infection by phagocytizing microbes. Also kill infected cells, tumor cells, and recycle worn out RBCs and dead tissue Leukocytes include: Neutrophils- phagocytic and motile, active in initial stages of infection Basophiles- active in inflammation and allergic responses Eosinophils- destroy large eukaryotic pathogens such as helminths and fungi Monocytes- mature into macrophages which are Red blood cells (erythrocytes)- do not have phagocytic for microbes and dispose of worn out red nucleus and carry oxygen- most abundant cell blood cells in whole blood Lymphocytes- 2 types function in Adaptive Immunity Platelets- are not cells- required for blood T-cells function in cellular immunity clotting and function in inflammation B-cells function in humoral immunity (antibodies) Anatomical/physical Physiological/ Specific Response barriers chemical barriers FACTORS THAT AFFECT THE IMMUNE RESPONSE Invading microbes must overcome many defense mechanisms Direct factors influence the efficacy of the defense mechanisms Nutrition Physiology Age Genetics Indirect factors can also exert influence Personal hygiene Socioeconomic status Living conditions  PHYSICAL AND MECHANICAL DEFENSES Skin Waterproof keratin Acidic pH (sebum, sweat, organic acids from commensal S.a) Sheds microbiota Mucous membranes Mucus resists penetration Lysozymes (muramidase) Lactoferrin  PHYSICAL AND MECHANICAL DEFENSES Respiratory Tract >10um are trapped by cilia Mucus traps and expels Alveolar macrophages Gastrointestinal Tract Low pH Digestive enzymes microbiota  PHYSICAL AND MECHANICAL DEFENSES Genitourinary tract Kidneys, ureters and bladder are sterile Distal portion of urethra (and vagina) can be colonized Males have longer urethras and this helps exclude bacteria Females have shorter urethras and UTI are 14x more common  NORMAL FLORA FUNCTION IN INNATE IMMUNITY Normal flora prevent the overgrowth of pathogenic microorganisms Normal flora are antagonistic of pathogen growth through competition Bifidobacteria are Gram-positive, non-sporeforming, lactic acid bacteria. Bifidobacterium bifidum is the predominant bacterial species in the intestine of breast-fed infants, where it antagnozies growth and prevents colonization by potential pathogens. These bacteria are sometimes used in the manufacture of yogurts and are frequently incorporated into probiotics.  NORMAL FLORA(?) CAN CAUSE DISEASE Fusobacterium are anaerobic, non-spore forming, Gram negative bacteria Colonizes oropharynx (causes gingivitis), intestine and colon (causes IBD and Linked to colorectal ulcerative colitis) cancer Although it can be part Fusobacteria genomes of the normal flora its were found in 89% of presence is now the colon tumors considered pathogenic sampled CHEMICAL MEDIATORS OF IMMUNITY Chemical mediators are part of the second line of defense (still innate) Cationic peptides Human origin Cathelicidins, defensins and histatin Bacteriocins Produced by bacteria to kill other bacteria Colicins (plasmid origin) help E. coli lyse other strains of E. coli Complement Cytokines  COMPLEMENT Consists of 30 heat-labile blood proteins Complement proteins are activated by cleavage of a pro- protein Activation of the cascade by: Classical pathway- first discovered, but is slowest Alternative pathway- discovered second but is faster Lectin complement/Mannose-binding lectin pathway – discovered 3rd fast as an alternative pathway.  CLASSICAL PATHWAY Opsonization Antibodies from the adaptive arm of the immune system Microorganisms are can bind to microbes coated by serum Binding reveals a set of amino acids on the antibody that components to prepare recruits and cleaves them for recognition and complement proteins destruction by immune cells Complement proteins can act as opsonins and connect the microorganism to the immune cell ALTERNATIVE AND LECTIN PATHWAY Molecules on the Mannose is a sugar that surface of the bacteria is found in many bind the complement bacteria cell walls proteins Mannose-binding Such as LPS and protein (from host) Staphylococcus protein A binds to mannose on bacteria MBP triggers complement  REGARDLESS OF ACTIVATION… All complement pathway end with the membrane attack complex (MAC) Activated complement proteins are inserted into the cell membrane Aids in lysis Which type of bacteria are more susceptible to complement?  CYTOKINES Cytokines are chemical mediators that provide a way for immune cells to communicate Soluble, low molecular weight protein or glycoprotein Chemokines- promote chemotaxis Interleukins (IL)- produced by leukocytes and act on other leukocytes Interferons (IFN)- produced in response to viral infections Colony-stimulating factors (CSF)- stimulate growth and differentiation of leukocytes Cytokine Target Function IL-1 Macrophages, T –cells, B- Upregulates inflammatory cells, NK cells response, fever, stimulates growth and differntiation of T cells, B-cells, NK cells IL-10 Macrophages and Down regulates inflammation neutrophils and cell response IL-17 CD-4 T cells, others? Upregulate inflammatory response, can cause autoimmune disease (RA, MS, JV diabetes) CSF-1 Monocytes/macrophages Upregulates their growth and development in bone marrow IFN-y T-cells, B-cells, macrophages Enhances immune response against viruses RANTES T-cells Chemotactic for T-cells, eosinophils and neutrophils TNF-a Monocytes/macrophages Upregulates inflammation, fever, represses tumor formation, mediates septic shock HOST CELLS THAT FUNCTION IN INNATE IMMUNITY  PHAGOCYTOSIS Phagocytic cells like neutrophils, monocytes/macrophages and dendritic cells are an important early defense against microbes Recognize foreign material Ingest it Kill it Opsonin-independent Opsonin-dependent  RECOGNITION Phagocytic cells recognize foreign cells using membrane bound pattern recognition receptors (PRR) The PRR on the phagocytic cells recognizes Pathogen-associated Molecular Patterns (PAMPs) PAMPs are molecules that are found on most microbes (like LPS, techoic acid, peptidoglycan etc)  TOLL LIKE RECEPTORS (TLR) Found on a wide range of cells (not just immune cells) TLRs are on the cell membrane and also in the cytoplasm Recognize PAMPs TLR4 detects LPS TLR2 detects techoic acid TLR9 and TLR3 are cytoplasmic and detect double stranded RNA (dsRNA) and CpG TLRs also recognize self-signals as well- damage-associated molecular patterns (DAMPS) come from cells being damaged and can trigger responses to tissue damage TRANSCRIPTION FACTOR ACTIVATION TLRs activate a signaling pathway called NF-κB pathway Regulates cytokine expression Activation of the NF-kB pathway links innate and adaptive immune response by production of inflammatory cytokines such as IL-1, IL-6, IL-8, TNF alpha, IL-12, chemokines  PHAGOCYTOSIS Upon recognition of a foreign microbe/material: Phagocytosis- engulfment of microbes by phagocytic cells Stages of Phagocytosis: 1. Chemotaxis- attraction to site of infection by chemical stimuli (endotoxins, microbial products, damaged tissue) 2. Adherence- phagocyte plasma membrane interacts with microbe. Microbial capsules interfere with adherence Opsonization (coating microorganism with antibodies) promotes adherence 3. Ingestion- Microorganism is brought into the phagocyte in a membrane bound vessicle called phagosome 4. Digestion- The phagosome fuses with a lysosome and the microbe is killed and digested  INFLAMMATORY RESPONSE Classic signs and symptoms characterized by: Redness (Rubor) – increased circulation and vasodilation in injured tissue in response to chemical mediators and cytokines Warmth – heat given off by the increased blood flow Swelling – increased fluid escaping into the tissue as blood vessels dilate-edema; WBC’s, microbes, debris and fluid collect to form pus; helping prevent spread of infection Pain – stimulation of nerve endings Steps in Localized Inflammation: 1. Vasodialation 2. Edema 3. Phagocyte Migration 4. Tissue Repair 1 1,2,3 Insert figure 14.13 Events in inflammation 2,3 3,4  INFLAMMATORY RESPONSE: FEVER Fever is a systemic inflammatory response Initiated by circulating pyrogens exogenous pyrogens – products of infectious agents (like LPS) Phagocytes recognize pyrogens and secrete chemicals called cytokines Cytokines effect the body’s internal thermostat located in the hypothalamus of the brain Benefits of fever: inhibits multiplication of temperature-sensitive microorganisms (higher than mesophillic range) impedes nutrition of bacteria by reducing the available iron increases metabolism and stimulates immune reactions and protective physiological processes