Host Defense MechanismsHost Defense Mechanisms

Sofronio Agustin

Professor

Sofronio Agustin

Professor

LECTURES IN MICROBIOLOGYLECTURES IN

MICROBIOLOGY

LESSON 12LESSON 12

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TopicsTopics

Nonspecific Resistance:

(1) Intact skin, mucous membranes, normal microbiota.

(2) Phagocytic leukocytes, inflammation, fever

Specific Resistance:

(1) Antibodies

(2) Specialized T- and B-cells

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TermsTerms

Susceptibility vulnerability of the host to disease

Resistance ability of the host to ward off disease

Nonspecific resistance host defenses against any pathogen

Specific resistance host defenses against a specific pathogen

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Mechanical FactorsMechanical Factors

Skin

Epidermis consists of tightly packed cells with protective layer of keratin

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Mechanical FactorsMechanical Factors

Mucous membranes

Ciliary escalator – transport microbes trapped in mucus away from the lungs

Lacrimal apparatus – washes eye

Saliva – washes microbes off

Urine – flows out

Vaginal Secretions – flows out

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Mechanical FactorsMechanical Factors

Ciliary escalatorLacrimal glands

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Chemical FactorsChemical Factors

Fungistatic fatty acids in sebum

Low pH (3-5) of skin

Low pH (1.2-3.0) of gastric juice

Lysozyme in sweat, tears, saliva and tissue fluids

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Normal MicrobiotaNormal Microbiota

Microbial antagonism – normal microbiota

compete with pathogens for food and

space.

Also known as Competitive exclusion

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Formed Elements in BloodFormed Elements in Blood

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LeukocytesLeukocytes

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LeukocytesLeukocytes

Neutrophils Phagocytic

Basophils Produce histamine

Eosinophils Toxic to parasites

Monocytes Phagocytic as mature macrophages

Lymphocytes Involved in specific immunity

Mast cells Wandering macrophages that roam tissues

Fixed macrophages in lungs, liver, bronchi

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MacrophageMacrophage

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PhagocytosisPhagocytosis

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InflammationInflammation

RednessPainHeatSwelling (edema)

Acute-phase proteins activated - complement, cytokine, kininsVasodilation - histamine, kinins, prostaglandins,

leukotrienesMargination and emigration of WBCsTissue repair

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InflammationInflammation

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InflammationInflammation

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FeverFever

•Hypothalamus normally set at 37°C•Gram-negative endotoxin cause phagocytes to release interleukin 1•Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature•Body increases rate of metabolism and shivering to raise temperature•When IL-1 is eliminated, body temperature falls. (Crisis)

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The Complement SystemThe Complement System

Serum proteins are activated in a cascading fashion

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Effects of Complement ActivationEffects of Complement Activation

Opsonization or immune adherence: enhanced phagocytosis

Membrane attack complex: cytolysis

Attract phagocytes

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InterferonsInterferons

Alpha IFN & Beta IFN - cause cells to produce antiviral proteins that inhibit viral replication

Gamma IFN - causes neutrophils and macrophages to phagocytize bacteria

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InterferonsInterferons

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The Immune ResponseThe Immune Response

Immunity ability of the host to counteract effects of invading microbes and other foreign substances.

Innate immunity genetically predetermined resistance of the host to certain diseases.

Acquired immunity specific resistance to diseases developed after birth or during the life of the individual.

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Acquired ImmunityAcquired Immunity

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AntigenAntigen

Antigen (Ag) a substance that causes the body to produce antibodies and sensitized T cells.

“Foreign” substance with molecular weight > 10,000.

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HaptenHapten

Hapten - low molecular weight substance that reacts with antibody but cannot stimulate antibody formation without a carrier molecule.

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EpitopesEpitopes

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Humoral ImmunityHumoral Immunity

Antibody (Ab) a protein, specifically an immunoglobulin (Ig) produced in response to antigenic stimulation

Humoral response involves antibodies produced by B cells

Sensitized T Cells specialized lymphocytes that interact with and respond to cellular and intracellular antigens.

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Cell-mediated ImmunityCell-mediated Immunity

Sensitized T Cells specialized lymphocytes that interact with and respond to cellular and intracellular antigens

Cellular response involves activated specialized

T cells

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LymphocytesLymphocytes

Lymphocyte subsets involved in immune response

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AntibodiesAntibodies

Antibodies are serum proteins that migrate as gamma globulin in electrophoresis; hence, sometimes called immunoglobulins (Ig).

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Antibody StructureAntibody Structure

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Antibody StructureAntibody Structure

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Immunoglobulin ClassesImmunoglobulin Classes

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IgG AntibodiesIgG Antibodies

•Monomer•80% of serum antibodies•Fix complement•In blood, lymph, intestine•Cross placenta•Enhance phagocytosis•Neutralize toxins & viruses•Protects fetus & newborn•Half-life = 23 days

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IgM AntibodiesIgM Antibodies

•Pentamer•5-10% of serum antibodies•Fix complement•In blood, lymph, on B cells•First Ab produced in response to infection•Agglutinates microbes•Half-life = 5 days

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IgA AntibodiesIgA Antibodies

•Dimer•10-15% of serum antibodies•In secretions•Mucosal protection•Half-life = 6 days

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IgD AntibodiesIgD Antibodies

•Monomer•0.2% of serum antibodies•In blood, lymph, on B cells•On B cells, initiate immune response•Half-life = 3 days

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IgE AntibodiesIgE Antibodies

•Monomer•0.002% of serum antibodies•On mast cells and basophils•Allergic reactions•Lysis of parasitic worms•Half-life = 2 days

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Clonal SelectionClonal Selection

Bone marrow gives rise to B cells.Mature B cells migrate to lymphoid

organs.A mature B cells recognizes epitopes.

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Clonal SelectionClonal Selection

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Self-ToleranceSelf-Tolerance

•Self-tolerance - body does not make Ab against self

•Clonal deletion - the process of destroying B and T cells that react to self antigens

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Ag-Ab BindingAg-Ab Binding

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Antibody TiterAntibody Titer

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Cell-Mediated ImmunityCell-Mediated Immunity

•Specialized lymphocytes, mostly T cells that

respond to intracellular antigens.

•After differentiating in the thymus, T cells migrate

to lymphoid tissue.

•T cells differentiate into effector T cells when

stimulated by an antigen.

•Some effector T cells become memory cells.

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Antigen-Presenting CellsAntigen-Presenting Cells

•Pathogens entering the gastrointestinal and

respiratory tracts pass through:

•M (Microfold) cells in Peyer's patches which

contains Dendritic cells which are antigen-

presenting cells and T cells.

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Dendritic CellsDendritic Cells

An antigen-presenting cell

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Cell-Mediated ImmunityCell-Mediated Immunity

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T CellsT Cells

Helper T Cells (CD4, TH):•TH1 Activate cells related to cell-mediated immunity.•TH2 Activate B cells to produce eosinophils, IgM, and IgE

Cytotoxic T Cells (CD8, TC):•Destroy target cells with perforin

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T CellsT Cells

Delayed Hypersensitivity T Cells (TD):Associated with

allergic reaction, transplant rejection, and tuberculin skin test.

Suppressor T cells (TS):Turn off immune response when antigen isno longer present.

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Helper T CellsHelper T Cells

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Cell-Mediated CytotoxicityCell-Mediated Cytotoxicity

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Nonspecific CellsNonspecific Cells

Activated macrophages: Macrophages stimulated by ingesting antigen

or by cytokines

Natural killer cells: Lymphocytes that destroy virus-infected cells and tumor cells

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Antibody-Dependent Cell-Mediated CytotoxicityAntibody-Dependent Cell-Mediated Cytotoxicity

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Duality of the Immune SystemDuality of the Immune System