Immunity to infectious micro organisms
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Immunity to Infectious Micro-Organisms. Anti-viral Immune Responses and Viral Evasion of Host Responses . ********** Immunity to Bacterial Diseases and Bacterial Evasion of Host Responses. ********** Emerging Infectious Diseases, Pandemic Disease, and Bioterrorism **********

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Immunity to Infectious Micro-Organisms

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Immunity to infectious micro organisms

Immunity to Infectious Micro-Organisms

Anti-viral Immune Responses and Viral Evasion of Host Responses.

**********

Immunity to Bacterial Diseases and Bacterial Evasion of Host Responses.

**********

Emerging Infectious Diseases, Pandemic Disease, and Bioterrorism

**********

Immunity to Protozoa, Multicellular Parasites, and Fungi

Folder Title: MicroInfect(NoTP)

Updated: November 20, 2013


Infectious agents pathogenic for humans and for veterinary and farm animals part 1

Infectious Agents Pathogenic for Humans and for Veterinary and Farm Animals (Part 1)

Viruses

  • Enveloped RNA Viruses (HIV, Influenza, Hepatitis C)

  • Naked RNA Viruses {Polio, Hepatitis A, Rhino-viruses (common cold)}

  • Enveloped DNA Viruses (Herpes Simplex, Epstein Barr – Mononucleosis, Variola major - Smallpox, Vaccinia - cowpox, Hepatitis B)

  • Naked DNA Viruses (Adeno-viruses; SV40 Virus; Polyoma viruses)

    “Envelop” = lipid bilayer membrane, host-derived;Contains proteins and glycoproteins derived from pathogen or from the host.

    Bacteria

  • Gram Positive (No 2nd cell envelop) - Anthrax, Staphylococci, Streptococci

  • Gram Negative (2nd Cell envelop with membrane endotoxins) - E coli

  • Extra-cellular (i.e. pathogen is outside of host cells):Neisseria gonorrhoeae; Streptococcal pneumonia

  • Intracellular (i.e. pathogen gets inside of host cells): Listeria Monocytogenes; Tuberculosis; Typhus (rickettsia)

  • Exotoxin Producers: Diptheria, Anthrax, Botulism, Tetanus, Yersinia pestis


Infectious agents pathogenic for humans and for veterinary and farm animals part 2

Infectious Agents Pathogenic for Humans and for Veterinary and Farm Animals (Part 2)

Protozoans

  • Plasmodium falciparum - Malaria

  • Trypanosoma brucei - Sleeping Sickness

  • Trypanosoma cruzei - Chagas Disease

    Fungal (Yeast) Diseases

  • Ring-worm; Athletes feet

  • Candidiasis

  • Oral "Thrush"; Other opportunistic fungal pathogens

    Multi-Cellular Parasitic Diseases

  • Parasitic Worms - (Helminths)

  • Schistosomiasis (worm pathogen transmitted by snails


Pathogenicity of infectious diseases in humans

Pathogenicity of Infectious Diseases in Humans

1 Billion Infected World-Wide

15 Million Deaths per Year

Greatest Impact in Third-World Countries

  • No Economic Incentive to Develop Treatments

  • Potential Liabilities in Testing and from Failures

    Significance of the "Global Village”

  • Emergence of resistance to Tuberculosis

  • Emigration of cholera and leishmaniasis

  • Disease survival in susceptible patient pools – polio; measles

  • Pandemic Influenza


Infectious diseases in 1996

From Kuby

Immunology, 4th Ed.

p. 426

Infectious Diseases in 1996

Viral and Bacterial

Viral, Bacterial and Protozoan

Bacterial

Protozoan

Viral

Viral

Viral and Bacterial

Bacterial

Protozoan

Protozoan

Viral

Protozoan

Multi-cellular (Helminth)

Multi-cellular (Helminth)

Viral

Multi-cellular (Helminth)

Infect1996


Causes of death worldwide

Causes of Death - Worldwide

p. 448


Non immunological host barriers to infection

Non-Immunological Host Barriers to Infection

Epithelial Surfaces

  • Gastrointestinal, respiratory, genito-urinary linings

  • Ciliated epithelium and mucous secretions

  • Epidermal barriers

    Cellular Secretions

  • Biochemical barriers : Enzymes (can come from innate immune response system)

  • Chemical barriers: pH, oxidants (can come from innate immune responses)

    Physical Barriers

    Elevated Temperature (Fever)

    Cellular Competition: Gut flora


Innate natural immune responses to infectious agents

Innate Natural Immune Responses to Infectious Agents

Gram-positive Bacteria - Peptidoglycan (exposed)

  • Activates alternative complement pathway - C3b

  • Opsonizes Bacteria for Enhanced Host Phagocytosis

    Gram-negative Bacteria - 2nd Envelope over Peptidoglycan

  • Bacterial Endotoxins - e.g. Lipopolysaccharide

  • Stimulates Cytokines (TNF, IL-1, IL-6)

  • From Macrophages and endothelial cells

  • Activates Macrophages

    Interferon Stimulation by Viral Infectious Agents

  • Can Directly inhibit viral production

  • Can activate and stimulate NK Cells to attack virally infected cells

  • Possibly by viral effect on MHC Class I Protein Synthesis


Innate natural immunity and anti viral responses

Innate Natural Immunity and Anti-Viral Responses

Type I Interferons (IFN and IFN)

  • Produced by Virally-infected Cells

  • Also from Monocytes, Macrophages, and Fibroblasts

    Mechanims of Action of IFN and IFN

  • Infected cell produces membrane receptors for IFN and 

  • Activates an RNAase that cleaves viral RNA

  • Inactivates viral protein synthesis by effects on dsRNA-dependent protein kinase

  • Induces Anti-viral response and resistance to intra-cellular viral replication

    NK Cells

  • Activated by IFN and IFN; become cytotoxic for virally-infected cells

  • Also activated by IL-12 - produced in response to viral infection


Humoral immunity anti viral responses

Humoral Immunity & Anti-Viral Responses

Antibody-mediated Anti-viral Responses

  • Prevent initial infection or reinfection

  • Less effective against intracellular viral infections

  • Less effective against viral DNA incorporated into host genome

    Secretory IgA - Blocks viral binding to target cells

    General Immunoglobulin Isotypes

  • Block Fusion Between Virus Envelop and Host Cell Membrane

  • Enhance phagocytosis by opsonization of viral particles

    IgM - Agglutinates viral particles

    IgM and IgG - Activates Complement

  • Opsonization by Complement Fragment C3b for phagocytosis

  • Lysis of virus envelop by membrane attack complex


Cell mediated immunity anti viral responses

Cell-Mediated Immunity & Anti-Viral Responses

Interferon 

  • From TH1 Helper T-Cells or Tc

  • Direct Anti-viral Action

    Cytoxic T-Cells (CTLs)

  • Kill virus-infected cells; Eliminates source of additional virus

  • Presentation of Viral Peptides by MHC-Class I Proteins

  • Virus-specific T-cell Clones; Can confer specific immunity by passive (adoptive) transfer to unifective recipient

    NK Cells and Macrophages

  • Antibody recognition of virus antigens on cell surface

  • Kill by ADCC (Antibody-dependent Cell-mediated Cytotoxicity)

    Activated TH1 Cells

  • IFN, IL-2, TNF attack virus directly or indirectly

  • IFN has direct anti-viral effects

  • IL-2 Recruits Tc to become Effector CTL


Mechanisms of anti viral immunity

Mechanisms of Anti-viral Immunity

p. 449


Immunity to infectious micro organisms

Interferon Inhibition

Of Viral Replication

In Virally-infected

Cells

Shuts down protein synthesis needed for viral replication

Degrades RNA needed for viral replication


Viral evasion of host responses effects on infected cells

Viral Evasion of Host Responses:Effects on Infected Cells

Block Intra-cellular Effects of IFN and IFN

  • Blocks intra-cellular effects on PKR - RNA-dependent protein kinase

  • By hepatitis C virus

    Inhibition of Antigen-Presentation in Virally-infected Cells

  • By Herpes Simplex 1 and 2 (HSV1 and HSV2) Early Proteins

  • Inhibits TAP (Transporter Associated with Antigenic Protein)

  • Blocks delivery of Antigenic Peptide to MHC-Class I Protein

  • No presentation to CD8+ CTL

    Down-regulation (Shutting Down) of Class I MHC Proteins

  • CMV (Cytomegalo Virus) and Adeno Viruses

    Block Class II MHC Protein

  • Blocks Antigen-specific Anti-viral Helper T-Cells

  • By CMV, Measles, HIV


Viral evasion direct viral effects

Viral Evasion: Direct Viral Effects

Inhibition of Complement Pathways

  • Vaccinia and HSV

    Antigenic Variation (Mutations in Virus Surface Proteins)

  • Rhino Viruses (Common Cold viruses)

  • Influenza

  • HIV

    Generalized Host Immuno-Suppression

  • Direct Effects on Macrophages and Lymphocytes

    Destruction of Immune Cells

    Alteration of Cell function

  • CMV, HIV, and EBV (Epstein-Barr Virus)

  • Paramyxo (Mumps) Virus; Measles Virus

    Cytokine-based Effects by Virus

  • Production of IL-10 Mimic by EBV

  • Suppresses TH1 Subset

  • Reduces Levels of TNF and IFN, and IL-2


Pathogenicity of influenza virus

Pathogenicity of Influenza Virus

Host Range:

  • Mammals, Birds

  • Can cross species barriers

    Duck influenza can infect pigs

    Pig influenza can infect humans

  • Can produce extensive antigenic reassortments - "antigenic shift"

  • Subject to Point Mutations in Hemagglutin (Binds to Host-Cell Sialic Acid) - "Antigenic Drift"

    Host resistance based on Ab to Hemagglutin is by-passed

    Influenza Pandemics

  • Killed 20 Million - Post World War I (1918 - 1919)

  • Largely Young Adults

    Lower prior exposure and cross-reactive immunity?

    More extensive exposure to infected persons? Over-aggressive inflammatory immune response?


Immunity to infectious micro organisms

Diagram of Influenza

Virus Structure

Figure 17-3

Kuby- Immunology

4th Edition

p. 429


Dimensions in cell biology microbiology

Dimensions in Cell Biology & Microbiology

100 um (100 microns)

  • 0.1 mm

  • Diameter of human hair

    10 um (10 microns)

  • Diameter of a red cell

  • 10 Red cell diameters = one human hair diameter

    1 um (1 micron)

  • One-tenth the diameter of a red cell

  • One-hundredth the diameter of a human hair

  • 1000 nm (1000 nano-meters)

    100 nm (0.1 um or 0.1 microns)

  • One-hundredth the diameter of a red cell

  • One-thousandth the diameter of a human hair

  • Size of an enveloped RNA or Enveloped DNA Virus


Structure of influenza virus

Structure of Influenza Virus

RNA Virus

  • RNA Genome in nucleocapsid of Matrix proteins

  • 8 Different Strand of Single-Stranded (ss) RNA

  • RNA associated with Viral nucleoproteins and RNA polymerase

  • Codes of 10 different viral proteins

    Enveloped RNA Virus

  • 100 nm Diameter (100 nano-meters - See "Dimensions" Graphic)

  • Host-derived plasma membrane (buds from infected host cell)

  • Contains Viral protein spikes

    Neuraminidase (for viral release from host membrane sialic acid

    groups)

    Hemagglutinin (for viral attachment to target cell)


Immunity to infectious micro organisms

Diagram of Influenza

Virus Structure

Figure 17-3

Kuby- Immunology

4th Edition

p. 429


Host response to influenza virus

Host Response to Influenza Virus

Humoral Immune Response to Influenza Virus

  • Antibody Strain-Specific for Virus Hemagglutinin in Virus Envelop

  • Prevents Virus Binding to Host Target Cell

  • Antibodies Block Binding Cleft in HA for Host Cell Membrane Sialic Acid

    Antibody titer peaks within a few days after infection

    Decreases for six months

    Plateaus and persists for several years

  • Antigenic Shift involving entire viral single-stranded RNA's incorporation and increase in infectivity of newly arising influenza strain.

  • Antigenic Drift involves point mutations in Hemagglutinin or Neuraminidase allowing for viral escape from antibody inhibition.

    Host Protection from Influenza Infection

  • Antibody prevents reinfection by same strain of Influenza

  • Antigenic drift of viral HA requires re-vaccination for newly emergent or re-emerging strains

  • Serum antibody not required for recovery after infection

  • CTL's may play a role in responses after infection


Immunity to infectious micro organisms

p. 453


Immunity to infectious micro organisms

p. 453


Immunity to infectious micro organisms

p. 452


Immunity to infectious micro organisms

Sequence variations in 10 different proteins in three different strains of influenza type A viruses.

(HA = Hemagglutinin;

NA = Neuraminidase;

M = matrix protein;

N and P are nucleoproteins)

p. 453


Immunity to infectious micro organisms

The following slides are Turning Point Fill-in-the-Blank question. Please clear your desk and respond.

No talking or other kinds of consultation, please.


Bacterial infection and pathogenicity

Bacterial Infection and Pathogenicity

Bacterial Entry Points (Non-immunological Barriers)

  • Gastro-intestinal, Respiratory, Genito-urinary epithelial linings

  • Epidermal Barriers - Entry by Wounding or Animal and Plant Vectors

    Steps in Bacterial Infection

  • Attachment to Target Cells

    Surface Pili on Bacteria

    Adhesion Molecules

  • Proliferation

  • Invasion of Host Tissues

  • Toxin-induced Damage to Host Functions (Bacterial Exotoxins)

    Bacterial Pathogenicity

  • Bacterial Cell Wall Endotoxins

  • Bacterial Exotoxins

  • Pathological Host Responses

  • Bacterial Mimics of Host Antigens

  • Intra-cellular Bacterial Infections and Damaging Host Responses


Host response to extra cellular bacterial challenge infection

Host Response to Extra-cellular Bacterial Challenge & Infection

Blocking Bacterial Attachment to Target Cells

  • Secretory Antibody (IgA)

    Removal of Bacteria

  • Complement Pathways - Direct destruction of Bacterium, or Attracts PMN's for Anti-bacterial action, or Targets bacterium for Phagocytosis

    Antibody-dependent "Classical" Complement Response

    -Opsonization and phagocytosis

    - Inflammatory mediators (PMN Attraction and degranulation)

    - Bacterial Membrane lysis

    Antibody-independent "Alternative" Complement Pathway

    - Opsonization and phagocytosis;

    - Inflammatory mediators (PMN Attraction and degranulation)

  • Agglutination of bacteria by poly-valent antibody

  • Antibody-dependent phagocytosis of bacteria

    Neutralization of Bacterial Exotoxins

  • Antibodies to bacterial exotoxins


Immunity to infectious micro organisms

p. 456


Host response to intra cellular bacterial challenge infection

Host Response to Intra-cellular Bacterial Challenge & Infection

T-Cell Mediated DTH (Delayed-type Hypersensitivity)

  • Cytokines

  • Inflammatory mediators

  • PMN and Macrophage responses

    NK Cell Cytotoxicity of Bacterially-Infected Cell

    Pathogenicity due to host Responses

  • Granulomas in tuberculosis and leprosy


Granuloma tubercule in pulmonary tuberculosis kuby immunology figure 17 9 4th ed p 436

Granuloma(tubercule)in pulmonary tuberculosisKuby -ImmunologyFigure 17-94th Ed., p.436


Bacterial evasion of host responses

Bacterial Evasion of Host Responses

Host Responses Affecting Bacterial Attachment

  • Digestion of IgA

    - by Neisseria gonorrhoeae, and Neisseria meningitis

    -by hemophillus influenzae

  • Antigenic drift in bacterial attachment pili proteins

    Responses Affecting Bacterial Proliferation and Invasion

  • Inactivation of complement components

  • Induction of apoptosis in host response cells

  • Escape intra-cellular destruction in lysosomes

    Prevent lysomal membrane fusion with phagosome

    Block action of lysosomal oxidative components

    -Listeria moncytogenes

    -Mycobacterium avium


Immunity to infectious micro organisms

p. 457


Immunity to infectious micro organisms

p. 467


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