Yet Again another Pandemic threat

http://www.who.int/csr/disease/avian_influenza/phase/en/index.html

• An influenza pandemic occurs when a new influenza virus appears against which the human population has no immunity, resulting in epidemics worldwide with enormous numbers of deaths and illness.

• Outbreaks of influenza in animals, especially when happening simultaneously with annual outbreaks of seasonal influenza in humans, increase the chances of a pandemic, through the merging of animal and human influenza viruses.

• During the last few years, the world has faced several threats with pandemic potential, making the occurrence of the next pandemic a matter of time.

Some Links

• Timeline for vaccine• A fact sheet on swine flue• who Now list this a N1H1 post pandemic p

eriod, N1H1 becomes pare of our seasional flue

Some Numbers

• Many Millions get flue• Each year 200,000 hospitalized• 35,000 die

• Mortality rate 0.1%• SARS 10%• Bird flue up to 90%• Swine flue? Is it really 10%?

Nonspecific Immunity

Resistance don’t get itSusceptibility get it

• Nonspecific immunity (innate immunity) are the defenses that protect the body against any pathogen.– Are not normally set up against any particular

pathogen.• Adaptive immunity: Immunity, resistance

to a specific pathogen

An Overview of the Body’s Defenses

Figure 16.1

ANIMATION Host Defenses: The Big Picture

The Concept of Immunity

• Host Toll-like receptors (TLRs) attach to Pathogen-associated molecular patterns (PAMPs)

• TLRs induce cytokines that regulate the intensity and duration of immune responses

The skin• Mechanical

– Skin Structure– Saliva washes– Mucus traps and ciliary escalator– Urine, vaginal flows out

• Chemical– Sebum w/ unsaturated fatty acids– Perspiration– Lysozyme– Acid conditions stomak(1.2-3pH) skin (3-5pH)– Normal microbiota– Transferrins, and NO

Physical Factors

• Skin• Epidermis

consists of tightly packed cells with– Keratin, a

protective protein

Figure 16.2

Ciliary Escalator

Figure 24.7

Ciliary Escalator

Figure 16.4

Phagocytosis

• Define.• What does this look like?• What does this do?

Chemical Factors

• Fungistatic fatty acid in sebum• Low pH (3–5) of skin• Lysozyme in perspiration, tears, saliva, and

urine• Low pH (1.2–3.0) of gastric juice• Low pH (3–5) of vaginal secretions

Normal Microbiota and Innate Immunity

• Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens or alter the environment

• Commensal microbiota: One organism (microbe) benefits and the other (host) is unharmed– May be opportunistic pathogens

Red Blood Cells Transport O2 and CO2

White Blood Cells:Neutrophils Phagocytosis

Basophiles Histamine

Eosinophils Kill parasites

Formed Elements in Blood

Formed Elements in Blood

Monocytes Phagocytosis

Dendritic cells Phagocytosis

Natural killer cells Destroy target cells

Formed Elements in Blood

T cells Cell-mediated immunity

B cells Produce antibodies

Platelets Blood clotting

• 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%

Differential White Cell Count

• Neutrophils: Phagocytic• Basophils: Produce histamine• Eosinophils: Toxic to parasites, some

phagocytosis• Monocytes: Phagocytic as mature

macrophages• Fixed macrophages in lungs, liver, bronchi• Wandering macrophages roam tissues• Lymphocytes: Involved in specific immunity

White Blood Cells

Components of Lymphatic System

Figure 16.5a

The Lymphatic System

Figure 16.5b–c

ANIMATION Host Defenses: Overview

Phagocytosis

• Phago: From Greek, meaning eat

• Cyte: From Greek, meaning cell

• Ingestion of microbes or particles by a cell, performed by phagocytes

Figure 16.6

Figure 16.7

Phagocytosis

Phagocytosis

ANIMATION Phagocytosis: Mechanism

ANIMATION Phagocytosis: Overview

Inhibit adherence: M protein, capsules

Streptococcus pyogenes, S. pneumoniae

Kill phagocytes: Leukocidins

Staphylococcus aureus

Lyse phagocytes: Membrane attack complex

Listeria monocytogenes

Escape phagosome Shigella, Rickettsia

Prevent phagosome-lysosome fusion

HIV, Mycobacterium tuberculosis

Survive in phagolysosome

Coxiella burnettii

Microbial Evasion of Phagocytosis

Actions of phagocytic cells

• Neutrophils (granulocyte) phagocyte• Increase in number during infection

(leukocytosis)• Neutrophils are most important• Can act as antigen presenting cells (APC)

– Important in specific resistance

Mechanism of phagocytosis

• Chemotaxis to pathogen• Adherence• Engulfment• Killing

• Resistance of microbes can be seen in some ability to live even after phagocytosis.

• Redness• Pain• Heat• Swelling (edema)• Acute-phase proteins activated (complement,

cytokine, kinins)• Vasodilation (histamine, kinins,

prostaglandins, leukotrienes)• Margination and emigration of WBCs• Tissue repair

Inflammation

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

Fever

• Body temp is controlled by the brain• High temp in response to IL-1• Caused by

– Bacterial endotoxins– Interleukin-1– Chills indicate rising body temp (crisis)

Fever

• Advantages– Increases

transferrins– Increases IL–1

activity– Produces Interferon

• Disadvantages– Tachycardia– Acidosis– Dehydration– 44–46°C fatal

Antimicrobial substances

• IFN- and IFN-: Cause cells to produce antiviral proteins that inhibit viral replication

• Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

• Lysozyme• Acids on skin• Complement

Antiviral Actions of Interferons (IFNs)

Figure 16.15

Innate Immunity

• Transferrins– Bind serum iron • Antimicrobial

peptides– Lyse bacterial cells

• Deficiencies in complement can result in an increased susceptibility to disease

The Complement System

• Serum proteins activated in a cascade• Activated by

– Antigen-antibody reaction– Proteins C3, B, D, P and a pathogen

ANIMATION Complement System: Activation

ANIMATION Complement System: Overview

The Complement System

• C3b causes opsonization• C3a + C5a cause inflammation• C5b + C6 + C7 + C8 + C9 cause cell lysis

ANIMATION Complement System: Results

The Complement System

Figure 16.9

Effects of Complement Activation• Opsonization or immune adherence:

Enhanced phagocytosis• Membrane attack complex: Cytolysis• Attract phagocytes

Figure 16.10

Inflammation Stimulated by Complement

Figure 16.11

Classical Pathway of Complement Activation

Figure 16.12

Alternative Pathway of Complement Activation

Figure 16.13

Lectin Pathway of Complement Activation

Figure 16.14

Some Bacteria Evade Complement

• Capsules prevent C activation• Surface lipid-carbohydrates prevent

membrane attack complex (MAC) formation• Enzymatic digestion of C5a