Download IMMUNITY MEDIATED BY B LYMPHOCYTES AND ANTIBODIES

HUMAN DEFENSE
MECHANISMS
Categories of Defense Mechanisms
• Physical barriers
> Skin and mucous membranes
– Chemical factors
– Mechanical factors
– Microbiological factors
• Innate immunity
• Adaptive immunity
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
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
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
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
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
PROBIOTICS
• 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
• 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 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)
Figure 8-15
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
Figure 8-25
Natural 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
Natural 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
Adaptive 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
Primary 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
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
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
Secondary 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
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)
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
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
Summary of the
Immune Response
• Ubiquitous response of innate immunity
• Induced response of innate immunity
• Adaptive response
• Protective immunity
• Immunological memory