Innate Immunity PDF

The Concept of Immunity  Susceptibility: Lack of resistance to a disease  Immunity: Ability to ward off disease  Innate immunity: Defenses against any microbe  Adaptive immunity: Learned or acquired immunity--resistance to a specific antigen (microbe) Copyright © 201...

The Concept of Immunity  Susceptibility: Lack of resistance to a disease  Immunity: Ability to ward off disease  Innate immunity: Defenses against any microbe  Adaptive immunity: Learned or acquired immunity--resistance to a specific antigen (microbe) Copyright © 2010 Pearson Education, Inc.  An Overview of the Body’s Defenses ANIMATION Host Defenses: The Big Picture Figure 16.1 Copyright © 2010 Pearson Education, Inc. Physical Factors  Skin  Epidermis consists of tightly packed cells with  Keratin, a protective protein Copyright © 2010 Pearson Education, Inc. Figure 16.2 Ciliary Escalator and Mucus  Mucous membranes  Mucus: Traps microbes  Ciliary escalator: Microbes trapped in mucus are transported away from the lungs Copyright © 2010 Pearson Education, Inc. Figure 16.4 Physical Factors  Lacrimal apparatus: Washes eye  Saliva: Washes microbes off  Urine: Flows out  Vaginal secretions: Flow out Copyright © 2010 Pearson Education, Inc. Chemical Factors  Fungistatic fatty acid in sebum  Low pH (3–5) of skin  Low pH (1.2–3.0) of gastric juice  Low pH (3–5) of vaginal secretions  Lysozyme in perspiration, tears, saliva, and urine  Urea is a surfactant and a protein denaturant Copyright © 2010 Pearson Education, Inc. So urine is sterile?  Yes, urine is normally sterile in animals, but…  The urinary tract can become infected by enterics  E. coli  Pseudomonas aeruginosa  Staphylococcus saprophyticus (not an enteric but found in waste)  Cystitis (bladder inflammation, UTI) is 8 times more common in women than men due to short length of urethra as well as anal/urethra distance Copyright © 2010 Pearson Education, Inc. So urine is sterile?  Leptospiridosis (infection of the kidneys)  Caused by Leptospira interrogans, a spirochete  Shed in urine of domestic and wild animals  Humans infected by contact with contaminated urine  Fever, headaches, myalgia, potentially renal failure  Approximately 50 reported cases/year. Probably much higher…  There are a few rare viral infections of the kidney as well (polyomavirus) Copyright © 2010 Pearson Education, Inc. Normal Microbiota and Innate Immunity  Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens or alter the environment (commensal microbiota)  Normal microbiota protect the host by  Occupying niches that pathogens might occupy  Producing acids (waste products)  Producing bacteriocins (antimicrobial agents)  Consuming available resources (iron, for example)  Probiotics: Live microbes applied to or ingested into the body, intended to exert a beneficial effect Copyright © 2010 Pearson Education, Inc. Blood, Plasma, Serum, and Lymph  Blood = formed cellular elements suspended in a liquid matrix called plasma  Plasma = Electrolytes, solutes, proteins (including antibodies), clotting factors, etc  Serum = Plasma with no clotting factors  Lymph = Plasma, leukocytes (white blood cells), cellular waste products  Pus = lymph, increased leukocytes, bacteria and bacterial cell debris, host cell debris, etc Copyright © 2010 Pearson Education, Inc. Components of Lymphatic System Figure 16.5a Copyright © 2010 Pearson Education, Inc.  The Lymphatic System ANIMATION Host Defenses: Overview Figure 16.5b–c Copyright © 2010 Pearson Education, Inc. Formed Elements in Blood and Lymph Copyright © 2010 Pearson Education, Inc. Formed Elements in Blood and Lymph Red Blood Cells Transport O2 and CO2 White Blood Cells: Neutrophils Phagocytosis Granulocyte Basophiles and Mast Histamine Release cells Phagocytosis Granulocyte Eosinophils Kill parasites Granulocyte (helminths, protozoans) Copyright © 2010 Pearson Education, Inc. Formed Elements in Blood and Lymph Monocytes (macrophages) Phagocytosis Agranulocyte Antigen-presentation (not a granulocyte) Dendritic cells Non-circulating Antigen-presentation Agranulocyte Phagocytosis Natural killer cells Destroy target cells lymphocytes Copyright © 2010 Pearson Education, Inc. Formed Elements in Blood and Lymph T cells Cell-mediated lymphocytes immunity B cells Produce antibodies lymphocytes Antigen presentation Platelets Blood clotting Copyright © 2010 Pearson Education, Inc. Differential White Cell Count  Percentage of each type of white cell in a sample of 100 white blood cells Neutrophils 60–70% Basophils 0.5–1% Eosinophils 2–4% Monocytes 3–8% Lymphocytes 20–25% Some immune cells enriched in lymphatic tissues, mucus membranes, etc Copyright © 2010 Pearson Education, Inc. Phagocytosis  Ingestion of microbes or particles by a cell, performed by phagocytes  “Professional” phagocytes:  Neutrophils  Macrophages  Dendritic cells  Mast Cells ANIMATION Phagocytosis: Overview ANIMATION Phagocytosis: Mechanism Copyright © 2010 Pearson Education, Inc. Phagocytosis Phagocytes can also “present” antigens to other lymphocytes Figure 16.7 Copyright © 2010 Pearson Education, Inc.  Toll-like Receptors  Host Toll-like receptors (TLRs) attach to Pathogen-associated molecular patterns (PAMPs)  Pathogen-associated molecular patterns (PAMPs) = peptidoglycan, LPS, flagellin, viral DNA and RNA, etc  TLRs induce adherence and recognition of phagocytes with foreign cell.  TLRs induce cytokines that regulate the intensity and duration of immune responses  Cytokines = small cell signaling molecules (proteins) that regulate immune response Copyright © 2010 Pearson Education, Inc.  Microbial Evasion of Phagocytosis Bacteria evade the innate immune response in a variety of ways…  Inhibit adherence  Kill (lyse) phagocytes  Escape phagosome  Prevent phagosome/lysosome fusion  Survive within phagolysosome Copyright © 2010 Pearson Education, Inc. Inflammation  Damage to host tissues and phagocytosis leads to production of inflammatory cytokines like TNF-α  Acute-phase proteins activated (complement, cytokines, and kinins)  Vasodilation induced (release of histamine, kinins, prostaglandins, and leukotrienes)  Redness  Swelling (edema)  Pain  Heat Copyright © 2010 Pearson Education, Inc. Chemicals Released by Damaged Cells Histamine Vasodilation, increased permeability of blood vessels Kinins Vasodilation, increased permeability of blood vessels Prostaglandins Intensity histamine and kinin effect Leukotrienes Increased permeability of blood vessels, phagocytic attachment Copyright © 2010 Pearson Education, Inc. The Process of Inflammation Figure 16.8a, b Copyright © 2010 Pearson Education, Inc. Phagocyte Migration and Phagocytosis [Insert Animation Inflammation: Overview, Steps.] ANIMATION Inflammation: Overview ANIMATION Inflammation: Steps Figure 16.8c Copyright © 2010 Pearson Education, Inc. Fever  Abnormally high body temperature  Hypothalamus normally set at 37°C  PAMP’s cause phagocytes to release interleukin–1 (IL–1)  Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature  Body increases rate of metabolism and shivering which raise temperature  Vasodilation and sweating: Body temperature falls (crisis) Copyright © 2010 Pearson Education, Inc. Fever  Advantages  Disadvantages  Increases transferrins  Tachycardia  Increases IL–1 activity  Acidosis  Produces Interferon  Dehydration  Increases WBC  44–46C = fatal production  May inhibit bacterial growth and replication Copyright © 2010 Pearson Education, Inc.  The Complement System  Serum proteins activated in a cascade  Acute phase response proteins (produced by liver)  Activated by the cleavage of C3 into C3a and C3b  C3b causes opsonization (phagocyte adherence)  C3b cleaves C5 into C5a and C5b  C3a + C5a induce inflammation  C5a = chemotactic response (attracts macrophages)  C5b + C6 + C7 + C8 + C9 cause cell lysis  The MAC attack complex Copyright © 2010 Pearson Education, Inc.  The Complement System Figure 16.9 Copyright © 2010 Pearson Education, Inc. Effects of Complement Activation  Opsonization or immune adherence: Enhanced phagocytosis  Attraction of phagocytes (chemotactic response)  Increased inflammation (histamine release)  Membrane attack complex: Cytolysis Figure 16.10 Copyright © 2010 Pearson Education, Inc. Classical Pathway of Complement Activation Antigen-antibody interaction Figure 16.12 Copyright © 2010 Pearson Education, Inc. Alternative Pathway of Complement Activation Acute phase response proteins and microbe interaction Figure 16.13 Copyright © 2010 Pearson Education, Inc.  Lectin Pathway of Complement Activation Carbohydrate- Lectin interaction Figure 16.14 Copyright © 2010 Pearson Education, Inc. Some Bacteria Evade Complement  Capsules prevent C activation  Surface lipid-carbohydrates prevent membrane attack complex (MAC) formation  Enzymatic digestion of C5a Copyright © 2010 Pearson Education, Inc. Interferons  “Interfere” with the replication of viruses.  Small protein cytokines.  3 types of interferon:  Type 1  Alpha and Beta, Produced by many cell types, is antiviral.  Type II  Gamma, Produced by T cells. Is an immunomodulator. Induces neutrophils and macrophages to kill bacteria by phagocytosis.  Type III  Lambda, antiviral and structurally different than type I. Newly identified, research ongoing. Copyright © 2010 Pearson Education, Inc. Interferons  IFNs are not virus specific. They will stop the replication of most viruses.  IFNs are species specific, i.e., animal IFNs cannot be used in humans.  IFNs are a major line of defense against viruses (although not exclusively). Copyright © 2010 Pearson Education, Inc.  Antiviral Actions of Interferons (IFNs) Figure 16.15 Copyright © 2010 Pearson Education, Inc.  Interferons  Recombinant interferons have been produced.  Used to treat Multiple Sclerosis, some types of cancer, HCV, etc.  Have side effects, they make a patient feel very ill. Improvements such as “PEGylating” have improved tolerance. Copyright © 2010 Pearson Education, Inc. Antimicrobial substances  Transferrins  Iron-binding proteins in blood, milk, saliva, and tears. Bind iron, reducing iron availability to pathogens.  Bacteria scavenge iron using siderophores  Antimicrobial peptides  Small, anti-microbial peptides (12 amino acids long)  Produced by mucous-membrane cells and phagocytes.  Bind to membranes of bacteria causing cell lysis*. *Additional mechanisms involved  Common in insects, plants, humans, etc. Copyright © 2010 Pearson Education, Inc.