human defense mechanisms. categories of defense mechanisms physical barriers > skin and mucous...
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HUMAN DEFENSE MECHANISMS
HUMAN DEFENSE MECHANISMS
Categories of Defense MechanismsCategories of Defense Mechanisms
• Physical barriers> Skin and mucous membranes
– Chemical factors– Mechanical factors– Microbiological factors
• Innate immunity
• Adaptive immunity
• Physical barriers> Skin and mucous membranes
– Chemical factors– Mechanical factors– Microbiological factors
• Innate immunity
• Adaptive immunity
Physical Barriers of Defense - Skin Physical Barriers of Defense - Skin
• Stratified squamous epithelium
• Chemical factors> Sebum (fatty secretion from sebaceous glands)> Lysozymes (perspiration produced by sweat glands)
• Mechanical factors> Desquamation> Perspiration
• Microbiological factors> Normal flora
• Stratified squamous epithelium
• Chemical factors> Sebum (fatty secretion from sebaceous glands)> Lysozymes (perspiration produced by sweat glands)
• Mechanical factors> Desquamation> Perspiration
• Microbiological factors> Normal flora
Physical Barriers of Defense – Mucous Membranes
Physical Barriers of Defense – Mucous Membranes
• Columnar to squamous epithelium
• Chemical factors> Lysozyme in tears, saliva and nasal secretions> Enzymes and HCl in stomach secretions> Defensins in small intestine
• Mechanical factors> Lacrimal apparatus> Mucociliary clearance mechanism
• Microbiological factors> Normal flora
• Columnar to squamous epithelium
• Chemical factors> Lysozyme in tears, saliva and nasal secretions> Enzymes and HCl in stomach secretions> Defensins in small intestine
• Mechanical factors> Lacrimal apparatus> Mucociliary clearance mechanism
• Microbiological factors> Normal flora
Normal Flora of Skin and Mucous Membranes
Normal Flora of Skin and Mucous Membranes
• Population of microorganisms that may at any time be found residing on skin and mucous membranes of human host in the absence of disease
• Skin> Staphylococcus epidermidis
> Propionibacterium acnes
> Corynebacterium species
• Population of microorganisms that may at any time be found residing on skin and mucous membranes of human host in the absence of disease
• Skin> Staphylococcus epidermidis
> Propionibacterium acnes
> Corynebacterium species
Normal Flora of Mucous Membranes
Normal Flora of Mucous Membranes
• Nasal mucosa> Staphylococcus aureus
– Methicillin-susceptible (MSSA)– Methicillin-resistant (MRSA)
• Nasopharyngeal mucosa> Streptococcus pneumoniae, Haemophilus influenzae, Moraxella
catarrhalis
• Buccal mucosa> Viridans streptococci, Neisseria species, Haemophilus species,
Lactobacillus species, Prevotella species, Porphyromonas species, Fusobacterium species, Peptostreptococcus species
• Nasal mucosa> Staphylococcus aureus
– Methicillin-susceptible (MSSA)– Methicillin-resistant (MRSA)
• Nasopharyngeal mucosa> Streptococcus pneumoniae, Haemophilus influenzae, Moraxella
catarrhalis
• Buccal mucosa> Viridans streptococci, Neisseria species, Haemophilus species,
Lactobacillus species, Prevotella species, Porphyromonas species, Fusobacterium species, Peptostreptococcus species
Normal Flora of Mucous Membranes
Normal Flora of Mucous Membranes
• Colon mucosa> Bacteroides fragilis group, Clostridium species,
Escherichia coli and other Enterobacteriaceae, Enterococccus species, Lactobacillus species, Candida albicans
• Vaginal mucosa> Lactobacillus species, Gardnerella vaginalis,
Mobiluncus species, Prevotella species, Porphyromonas species
• Colon mucosa> Bacteroides fragilis group, Clostridium species,
Escherichia coli and other Enterobacteriaceae, Enterococccus species, Lactobacillus species, Candida albicans
• Vaginal mucosa> Lactobacillus species, Gardnerella vaginalis,
Mobiluncus species, Prevotella species, Porphyromonas species
PROBIOTICSPROBIOTICS
• Definition > Food and Agriculture Organization of UN (FAO) and
WHO> ‘live microorganisms which when administered in adequate
amounts confer a health benefit on the host’
• Microorganisms> Bifidobacterium species> Lactobacillus bulgaricus> Lactobacillus casei> Streptococcus thermophilus
• Definition > Food and Agriculture Organization of UN (FAO) and
WHO> ‘live microorganisms which when administered in adequate
amounts confer a health benefit on the host’
• Microorganisms> Bifidobacterium species> Lactobacillus bulgaricus> Lactobacillus casei> Streptococcus thermophilus
The Innate Response to Bacterial Pathogens
The Innate Response to Bacterial Pathogens
• Complement activation via alternative pathway
• Phagocytosis of pathogens by > Macrophages
– Long-lived cells
– Secrete cytokines in innate and adaptive immunity
– Function as professional APC’s
> Neutrophils– Historically called “microphages”
– Enter infected tissues in high numbers
– Short-lived cells
• Complement activation via alternative pathway
• Phagocytosis of pathogens by > Macrophages
– Long-lived cells
– Secrete cytokines in innate and adaptive immunity
– Function as professional APC’s
> Neutrophils– Historically called “microphages”
– Enter infected tissues in high numbers
– Short-lived cells
Activation of Tissue MacrophagesActivation of Tissue Macrophages
• Activated macrophages initiate inflammatory response by secreting > Cytokines> Inflammatory mediators
• Cytokines (chemoattractant cytokines / chemokines)> IL-1, IL-6, IL-8, IL-12 and TNF-alpha
• Inflammatory mediators> Prostaglandins, leukotrienes, plasminogen activator, platelet-activating
factor (PAF)
• Activated macrophages initiate inflammatory response by secreting > Cytokines> Inflammatory mediators
• Cytokines (chemoattractant cytokines / chemokines)> IL-1, IL-6, IL-8, IL-12 and TNF-alpha
• Inflammatory mediators> Prostaglandins, leukotrienes, plasminogen activator, platelet-activating
factor (PAF)
Figure 8-15Figure 8-15
The Innate Response to Viral Pathogens
The Innate Response to Viral Pathogens
• Virus infection of healthy cells results in production of> Interferon-alpha (IFN-alpha)
> Interferon-beta (IFN-beta)
• IFN-alpha and IFN-beta are type 1 interferons
• Type 1 interferons> Inhibit virus replication
> Activate natural killer (NK) cells
> Increases expression of MHC-1 molecules
• Virus infection of healthy cells results in production of> Interferon-alpha (IFN-alpha)
> Interferon-beta (IFN-beta)
• IFN-alpha and IFN-beta are type 1 interferons
• Type 1 interferons> Inhibit virus replication
> Activate natural killer (NK) cells
> Increases expression of MHC-1 molecules
Figure 8-25Figure 8-25
Natural Killer (NK) CellsNatural Killer (NK) Cells
• Large granular lymphocytes that circulate in blood
• Functions> Killing infected cells (cytotoxic)> Secretion of cytokines
• Activation by> Type 1 interferons
– Infected cells– Stimulates cytotoxic function
> IL-12 and TNF-alpha– Macrophages– Stimulates cytokine secretion
• Large granular lymphocytes that circulate in blood
• Functions> Killing infected cells (cytotoxic)> Secretion of cytokines
• Activation by> Type 1 interferons
– Infected cells– Stimulates cytotoxic function
> IL-12 and TNF-alpha– Macrophages– Stimulates cytokine secretion
Natural Killer CellsNatural Killer Cells
• Activated NK cells release IFN-gamma which activates> Macrophages
– Release IL-12
• Positive feedback system for NK and macrophages
• Differentiate infected from uninfected cells> NK cells express receptors for MHC class I molecules
> Binding of NK cells to MHC class I molecules turn off NK cells
• NK cells provide innate immunity to intracellular pathogens
• Activated NK cells release IFN-gamma which activates> Macrophages
– Release IL-12
• Positive feedback system for NK and macrophages
• Differentiate infected from uninfected cells> NK cells express receptors for MHC class I molecules
> Binding of NK cells to MHC class I molecules turn off NK cells
• NK cells provide innate immunity to intracellular pathogens
Adaptive Immune ResponseAdaptive Immune Response
• Environment for starting provided by innate immune response
• Consists of> Primary immune response
– Follows initial exposure to antigen– Naive B and T cells – Establishment of memory
> Secondary immune response– Follows second exposure to antigen– Memory B and T cells– Utilization of memory
• Environment for starting provided by innate immune response
• Consists of> Primary immune response
– Follows initial exposure to antigen– Naive B and T cells – Establishment of memory
> Secondary immune response– Follows second exposure to antigen– Memory B and T cells– Utilization of memory
Primary Immune ResponsePrimary Immune Response
• Begins with T cell activation and differentiation in secondary lymphoid tissue
> CD4 TH1, CD4 TH2 and CD8– Directed by cytokines
• IL-12 and IFN-gamma (TH1)• IL-4 and IL-6 (TH2)
• Continues with B cell activation in secondary lymphoid tissue
> Cognate interaction with CD4 TH2 specific for same Ag
• Begins with T cell activation and differentiation in secondary lymphoid tissue
> CD4 TH1, CD4 TH2 and CD8– Directed by cytokines
• IL-12 and IFN-gamma (TH1)• IL-4 and IL-6 (TH2)
• Continues with B cell activation in secondary lymphoid tissue
> Cognate interaction with CD4 TH2 specific for same Ag
Role of T Cells in Primary Immune Response
Role of T Cells in Primary Immune Response
• Effector TH1 cells> Leave 2nd lymphoid tissue for infected tissue> Activate destruction of extracellular pathogens by macrophages
• Effector CD8 cells> Leave 2nd lymphoid tissue for infected tissue> Kill infected cells
• Effector TH2 cells> Remain in 2nd lymphoid tissue> Stimulates B cell differentiation into plasma cells
• Effector TH1 cells> Leave 2nd lymphoid tissue for infected tissue> Activate destruction of extracellular pathogens by macrophages
• Effector CD8 cells> Leave 2nd lymphoid tissue for infected tissue> Kill infected cells
• Effector TH2 cells> Remain in 2nd lymphoid tissue> Stimulates B cell differentiation into plasma cells
Role of B Cells in Primary Immune Response
Role of B Cells in Primary Immune Response
• Differentiation into plasma cells and antibody production
• Locations for differentiation following CD4 TH2 cognate interaction> Medullary chords of lymph nodes
– First wave of antibody secretion
> Primary lymphoid follicles– Formation of germinal centers then migration to
• Medullary chords of lymph nodes
• Bone marrow
– Second wave of antibody secretion
• Differentiation into plasma cells and antibody production
• Locations for differentiation following CD4 TH2 cognate interaction> Medullary chords of lymph nodes
– First wave of antibody secretion
> Primary lymphoid follicles– Formation of germinal centers then migration to
• Medullary chords of lymph nodes
• Bone marrow
– Second wave of antibody secretion
Secondary Immune ResponseSecondary Immune Response
• Adaptive immune response following second antigen exposure
• Response is stronger and more rapid than primary• Classification
> Short term (False)– 4 months or less following primary infection– Antibodies and effector T cells from naive lymphocytes
> Long term (True)– 4 months or more following primary infection– Antibody and effector T cells from memory lymphocytes
• Adaptive immune response following second antigen exposure
• Response is stronger and more rapid than primary• Classification
> Short term (False)– 4 months or less following primary infection– Antibodies and effector T cells from naive lymphocytes
> Long term (True)– 4 months or more following primary infection– Antibody and effector T cells from memory lymphocytes
Secondary Immune Response Secondary Immune Response
• No activation of naive B and T lymphocytes with specificity for pathogen
• Mechanism for naive B cells> Suppression by
– Immune complex (IC) of pathogen and IgG
• IC’s bind to naive B cell> Receptor> Inhibitory Fc receptor (Fc-gammaRIIB1)
• No activation of naive B and T lymphocytes with specificity for pathogen
• Mechanism for naive B cells> Suppression by
– Immune complex (IC) of pathogen and IgG
• IC’s bind to naive B cell> Receptor> Inhibitory Fc receptor (Fc-gammaRIIB1)
Clinical Application of Memory B Cell Activation
Clinical Application of Memory B Cell Activation
• Prevention of> Hemolytic disease (anemia) of newborn
• Hemolytic disease of newborn > Rh- mother with Rh+ fetus> Fetal RBC enter maternal circulation> No intervention
– Maternal antibody against fetal RBC
> Intervention with Anti-Rh, IgG (Rhogam)– No maternal antibody against fetal RBC
• Prevention of> Hemolytic disease (anemia) of newborn
• Hemolytic disease of newborn > Rh- mother with Rh+ fetus> Fetal RBC enter maternal circulation> No intervention
– Maternal antibody against fetal RBC
> Intervention with Anti-Rh, IgG (Rhogam)– No maternal antibody against fetal RBC
Immunological Memory and a Variant Pathogen
Immunological Memory and a Variant Pathogen
• Infection with Influenza viruses> Influenza A and B viruses mutate surface antigens
– Antigenic drift (A and B)– Antigenic shift (A)
• Viral strategy> Erosion of protective immunity
• Strategy of immune system> Respond to strains with epitopes previously encountered> IM limited to epitopes shared by infecting and original strain
• Infection with Influenza viruses> Influenza A and B viruses mutate surface antigens
– Antigenic drift (A and B)– Antigenic shift (A)
• Viral strategy> Erosion of protective immunity
• Strategy of immune system> Respond to strains with epitopes previously encountered> IM limited to epitopes shared by infecting and original strain
Summary of the Immune ResponseSummary of the
Immune Response
• Ubiquitous response of innate immunity
• Induced response of innate immunity
• Adaptive response
• Protective immunity
• Immunological memory
• Ubiquitous response of innate immunity
• Induced response of innate immunity
• Adaptive response
• Protective immunity
• Immunological memory