Immunology Flashcards
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors 3D folded structure.
Cells and antibodies can recognize
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
T cells only recognize this one when in certain length and presented by mhc.
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Polyclonal antiserum and B cells
Different epitome specificity.
B cells produce antibodies to different epitome but specific to 1 bacteria
Monoclonal antibodies and B cell
Important in pharmaceutical therapies
B. Cell and daughter cells produces antibodies that recognize same 1 epitome
Immunogens
Produce good immune response
Can bind AND induce an immune response.
Subsequent exposures result in increased responsiveness.
Proteins tend to be more immunogenicity than lipids carbohydrates and nucleic acids.
Why are proteins more immunogenicity
More specific to pathogen. Can tell difference.
Haptens
Don’t illicit immune response.
Need a carrier molecule
Small molecules that can bind to antibodies and receptors but cannot induce an immune response by themselves.
Can be immunogenicity when linked to carrier.
Tolerogens
Illicit little bit of immune response
Small but exposed over and over again for tolerance
Can bind and induce immune response.
Subsequent exposures or a different route of exposure results in decreased responsiveness
Explain how the new treatment for reversing a peanut allergy works, as well as drawbacks of this treatment
Using tolerogens.
Exposed to small doses of the peanut antigen over and over again can build a tolerance / decreased responsiveness.
Drawbacks are that if too much time elapses between doses or completely stop use can result in a worse reaction
Mitogens
Super immunogen
Strong nonspecific response.
T and B cell response
Polyclonal activators
Polyclonal activators
Mitogens
Induce nonspecific division and differentiation.
Response is not directed at specific antigen
T cell polyclonal activators
Produce nonspecific cytokines and nonspecific killing
B cell polyclonal activators
Nonspecific antibody production
Superantigens
Mitogens
Hold TCR:MHC together no matter what antigen is being presented and leads to unregulated cytokine production.
Cytokine storm
Produced by some pathogen.
Super activated >lots of clones > lots of cytokines> septic shock> immune cells to tissues> bp drops and edema
Adjuvants
Added to vaccines for boosted immune response
Patent protected so dont know exactly what it is
Factors that influence immunogenicity of proteins
Size Dose Route Composition Form Similarity to self protein Adjuvants Interaction with host MHC
Why does subcutaneous route increase immunogenicity. Why is intragastic the least?
Dendritic cells prevent it from gettin in. Dermatological response is the biggest part of the immune system
Gastric immune is the least amount. Don’t want to attack our healthy gut microbes, because inflammation is a huge problem there.
Why are large proteins more immunogenic
More surface area and epitopes
Why are less differences in similarity to self protein have decreased immunogenicity
Some bacteria make similar self antigens. The body’s respond to those antigens but then because they are so similar to self, they end up also attacking itself. >autoimmune
Antigen receptors adaptive and innate immune system
Innate immune system uses pattern recognition receptors (PRR)
B and T cells of the adaptive immune system have antigen specific receptors
Explain the pattern recognition receptors
Common component is recognized. Such as CPG repeats in pathogens since we do not have that.
Explain adaptive immune system antigen receptors
1 adaptive cell recognizes 1 epitope.
Innate antigen receptors
uses PRR to facilitate pathogen removal
Recognize PAMPs, pathogen associated molecular patterns
MAMPs microbe associated molecular patterns
DAMPs danger associated molecular patterns
PRR TLR
Toll like receptors
Membrane bound cell surface or in endosomes
Found predominantly on cells of immune system.
Have bunch of different ones specific to something/ component of pathogen
Flagella, parasite etc
Antigen receptors of adaptive immunity B cell receptors
B cell receptors recognize unprocessed antigen.
Recognize conformational and/or linear epitopes.
Can just bump into pathogen
Antigen receptors adaptive immunity T cell receptors
Recognize processed peptides presented by MHC molecules.
Peptides have to be linear and of a certain short length.
It is held for quite some time to recognize and then create antibodies for response. > why takes 8-10 days to have adaptive response and symptoms statutory to subside
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
Primary (central) lymphoid organs
Site of lymphocyte production and maturation
Bone marrow, thymus, fetal liver
Secondary / peripheral lymphoid organs
Site of lymphocyte activation
Lymph nodes, spleen, mucosal associated lymphoid tissues (MALT)
Bone marrow
Responsible for formation of all postnatal blood cells.
B and NK cells continue to develop in bone marrow.
Red marrow
Highly vascularized spongy reticular framework filled with hematopoietic tissues
All lymphocytes begin development here
Thymus
Blooped gland above the heart
Encapsulated organ - 2 lobules cortex and medulla
Site of T cell maturation
Thymocytes
Progenitor T cells that enter thymus via small blood vessels
Embed in mesh work of stromatolites cells
Thymus cortex
Darker staining
More T cells
Thymus medulla
Lighter staining. Fewer T cells Dendritic cells Epithelial cells Macrophages Hassan’s corpuscles (but dont know what they do yet)
Thymus involution
Volume of active tissue decreases over time
Does not completely lose function
Lymph nodes
“Grand central station” of immune responses
Cells bring pathogens here to activate immune system
Antigens diffuse in via afferent lymphatic vessels
Dc migrate via afferent lymphatic vessels
Follow chemokine signals
What do lymph nodes swell
Commonly due to viral or bacterial infections
Can swell several times their normal size
May feel firm and look misshapen
Surrounding skin may be warm
Return to normal with resolution of infection
Spleen
Blood filtration system
Red pulp spleen
Phagocytosis of old or damaged RBC and antigens/microbes from blood
White pulp
Areas of lymphocytes around arterioles
Some separation of b and T cell areas
What happens if you don’t have a spleen
Life long risk of serious infection.
Most instances of serious infection are due to infections with encapsulated bacteria (just slip away)
Vaccination to minimize/prevent
Daily therapy commonly includes low doses of prophylactic antibiotics.
Mucosal immune system
Secondary lymphoid organ/tissue Encounters antigen/pathogens in great number and frequency compared to systemic GI tract Respiratory Urogenital Salivary
Peyer’s patches
Almost like lymph nodes without encapsulation
Mucosal layer of the gut
Lymphatic vessels system
Not closed loop - meets circulatory system
Where are lymphatic vessels found?
Everywhere except: Cartilage CNS Cornea Epidermis
Lymphatic vessels
Network of capillaries that transport cells and anything foreign from tissues to lymph nodes
How does lymph move
Result of muscle contraction and one way valves
Extravasation
Cell migration
Movement of blood cells through an unruptured vessel wall into surrounding tissue
Mediated by two groups of cell adhesion molecules (CAM)
Selectins and integrins.
Selectins
Rolling / weak adhesion. Post it note
Cell migration
Integrins
Tight adhesions - superglue
Cell migration
Chemotaxis
Receptor mediated movement of cells through tissues. Elicited by chemokines
Neutrophil migration to infection site
T/b cell migration to areas within secondary lymphoid tissues
Extravasation general process
Rolling adhesion,
Stable / tight adhesion
Rolling adhesion
A weak interaction between WBC and endothelial cell via selectins binding to ligand
Expression is constitutive, allowing all wbc to slow down in capillaries
Stable / tight adhesions
Strong interaction between wbc and endothelial cell via integrins binding to ligands
Expression is unregulated by inflammatory mediators, allowing wbc to adhere tightly and extravasated
Leukocyte adhesion deficiency
Genetic disorder characterized by deficiency of integrins
Marked by recurrent bacterial infections and severe neutrophilia (can get out of blood)
Lack of pus at infection sites.
Can’t exit vasculature to get to tissues
Chemokine directed migration
Cells follow concentration gradient of chemokine
Cellular movement depends on the chemokine and chemokine receptor
Homing of lymphocytes to specific areas of lymphoid tissue is mediated by chemokines.
Lymphocyte recirculating
Naive lymphocytes recirculate between blood and lymph until antigen encounter or death.
If antigen is encountered then activation, proliferation and differentiation
If antigen is not encountered then re enter blood/lymph after 1 day.
Enter lymph nodes via high endothelial venules, re enter blood via lymphatics and thoracic duct.
Enter and exit spleen through blood vessels
Functions of immune response
Recognition
Removal/restraint
Regulation
Memory
Antigens
Any molecule that can bind specifically to an antibody or antigen receptors on cells of immune system.
Epitomes
Smallest unit of an antigen that are recognized by antibodies and antigen receptors.
Can have 1 or more epitopes.
Conformational epitope
Found in native structure Type of epitope recognized by Antibodies B cell receptors Innate receptors
Linear (continuous) epitope
Found in denatured structure
Only type of epitope presented by MHC and recognized by T cell receptors
Can also be recognized by antibodies / B cell receptors/ innate receptors
4 types of antigens
Immunogens
Haptens
Tolerogens
Mitogens
antibodies/ immunoglobulins
proteins used by mmune system to neutralize pathogens
secreted by b cell receptor
what are the two major functions of antibodies
specifically bind to a pathogen or its proguces
recruit cells/ molecules to destroy or get rid of pathogen
serology
identification of antibodies against a specific antigen in serum
what can serology tell you
if vaccinated
distinguish between 2 closely related pathogens
id specific pathogen
id noninfectious diseases
fators affecting strength of ab response
t cell help
locations
protein or nonprotein
how do cells have ab dversity
combinatorial diversity via rag
junctional diversity
combinatorial diversity
vdj segments can comvine in different ways mediated by rag - recombinant activatiing gene
junctional diversity
additions and deletions of nucleotides at juncions beteen segments during recombination
valence
number of binding sites
affinity
strength of binding at single site
avidity
total strength when all binding sites are included
omenn syndrome
defect in rag
partial enzyme activaty
have b cells but can’t make diverse ab
lack / have few b and t cells
SCID
no rag activity
fatal
total lack of b and t cells
no adaptive immune system
variable region
vinds noncovalently to conformatonal epitopes
what do mature naiive b cells express
igm and igd
memory b cells can express
any 1 isotype as bcr
functions of bcr
recognize and bind antigen via variable region
after antigen is bound signal is transmitted - b cell activation
activation- ab production, clonal expansion
functons of secreted antibodies
function is dependent in isotype class neutralization complement ativation opsonization ab dependent cell mediated cytotoxicity mast cell degranulation
neutralization
igg subtypes in blood / tissues
dimeric iga at mucosal surface
ab blocks penetration of microbe and infection of cells
ab blocks binding of toxin to cellular receptor
opsonization
ab on pathogen surfaces are recognized by fc receptors on phagocytes - enhanced phagocytosis
igg
abs attach to pathogen coating it and making it look more attractive
adcc
ab dependent cell mediated cytotoxicity
virally infected cells often express viral proteins on their surface and can be recognized by other abs
infected cells coated with ab are recognized by binding fc receptor on nk cells
nk cell then kill infected
degranulation - eosinophile
ige opsonizes parasite
eosin binds to ige coated parasite using fc receptors, stimulating to degranulate
toxic effect of granule contents on parasite is to cause fragmentation then can phagocytose
degranulation - mast cells
allergies
ige can bind to fc on mast cell then is cross linked by ag leading to massive histamine release
what determine ab function
different heavy chain constant regions determne ab class which determines ab function
igm
secreted as pentamer and membrane bound as monomer
can activate complement through classical pathway
has variable regions with variable affinity but high avidit
can be transported across epithelum b/c j chain
igg
secreted as monomer
most abundant in serum
can pass through placenta
ige
secreted as monomer
<1% serum ab
role in allergies and important to parasites
iga
secreted monomer in blood dimer in secretions and mucus
predominant class in secretions / mucosal surfaces
binds to polymeric ig receptor for easy transport through epithelial cells
antibody tter
measure how much ab a person has to a specific antigen
characteristic infections associated with ab deficiencies
recurrent pyogenic nfections with extracellular pathogens
encapusulated bacteria
recurrent respiratory infection
enteritis
how pathogens evade ab
antigenic variation - mutate surface antigens
encapsulation
cytokines
intercellular regulatory proteins produced in response to microbes and other antigens
communication between immunce cells
not stored as preformed molecules
types of cytokines
interferons chemokines interleukins tnf alpha growth factors
interferons
innate antiviral response
chemokines
chemotaxis
proinflammation
interleukins
leukocyte development
tnf alpha
acute phase response
coagulation
growth factors
growth differentiation
general properties of cytokines
function is to stimulate, regulate, inhibit and/or modfy innate and adaptive responses can regulate growth and diffrentiation of hemopoietic cells
cytokine mechanism of action
activation of JAK STAT pathway
cytokine signal to nucleus to turn on transcription binding of cytokine to receptor= JAKs activation function of activated JAKs phosphorylate receptor to provide binding sites for stat protein stat proteins dmerize, translocate into nucleus and activate/inhibit transcription of specific genes
pleiotropism
1 cytokine - different receptors
redundancy
many cytokines for same receptor
synergy
2 cytokines work together fo ran effect
antagonism
1 upregulates 1 downregulates
type 1 interferons
binding of viral components to certan TLRs also stimulates the release of IFN alpha and beta from macrophages and other virally infected cells
functons of type 1 interferons
activate antiviral mechanisms n neighboring cells increase class 1 MHC expression to present antigens to CD8 t cells stimulate nk cell activity
antiviral state
type 1 interferons from neighboring cells land on surface receptors
signal activation of rnase
rnase chops up viral rna before can be translated
viral replication is halted b/c no viral proteins willbe translated
most important cytokines that induce inflammation
il1
il6
tnf alpha
acute phase response
inflammation
subset of innate immune response
results in dramatic hcanges n metabolism, vasculature and plasm protein composition
interferon gamma
not type 1 ifn
naturally ireleased by t cells and nk cells to stimulate activity of many cells
increases microbicidal activity of macrophage
increases cytotoxic activity of nk cells
stimulates b cells to produce ab
Inflammation
Localized, protective response elicited by injury, infection, toxin, allergy or autoimmune disease.
Serve to destroy, dilute, or wall off both the injurious agent and injured tissue.
Acute inflammation
Rapid and short lived
Release of vascular components into extra vasculature
5 cardinal signs; influx of neutrophils (PMNs)
Chronic inflammation
Longer duration, slow progression
Influx of macrophages and lymphocytes
Can result in granuloma formation
5 cardinal signs of acute inflammation
Fever Erythema Edema Pain Loss of function
Erythema
Result of increased blood flow and permeability
Edema
Result of increased vascular permeability, allowing serum components and cells into tissue spaces
Hallmark of acute inflammation
Influx of PMNs (1st leukocyte on scene) into tissues
Activation of innate immune mechanisms in acute inflammation result in
Vasodilation
Increased expression of cell adhesion molecules
Influx of PMNs
Most important cytokines that induce inflammation
IL1
IL6
TNF alpha
Acute phase response
Results in dramatic changes in metabolism, vasculature and plasma protein composition.
Serve as red flag to rest of body
Effects occur within hours and assist in protecting before and during adaptive process
Acute phase is prolonged
Adverse effects may arise
Haptoglobin
Binds hemoglobin and protects the iron from being used by iron utilizing bacti
Increase in acute phase proteins
Causes RBCs to sediment faster than usual
ESR
Simple measure of inflammation
Complement proteins
Anaphylatoxins
Opsonins
Chemotaxins
Anaphylatoxins
C5a, c3a
Complement products that mediate mast cell degranulation
Opsonins
C3b
Assist in phagocytosis
Chemotaxins
Attract WBC and macrophages to sites of injury
C Reactive Protein CRP
Most sensitive of acute phase proteins.
Rise 1000x.
CRP as useful marker
Assesses and monitors presence, severity and course of inflammation response.
Plasma derived inflammatory mediators
Kinins/ bradykinin
Coagulation factors
Acute phase proteins
Ferritin
Kinins/ bradykinin
Group of plasma proteins that form potent vasodilator
Contribute to pain associated with inflammation
Ferritin
Reduces amount of iron present in locale, inhibits select microbial growth
Inflammatory mediators
Cell derived
Histamine and serotonin
Nitric oxide/ RNS
Arachidonic acid metabolites
Inflammatory cytokines
Histamine and serotonin
Released from mast cells
Vasodilator
Nitric oxide/ reactive nitrogen species
Produced by endothelial cells and macrophages
Vasodilator
Arachidonic acid metaobolites
Prostaglandin Leukotrienes Thromboxane Produced mainly by WBC and injured cells Vasodilators that funciton in fever and pain Can act as chemotactic agents
Inflammatory cytokines
IL1 IL6 Tnf alpha Il12 Il18 Gm csf
Inflammasome
Multiprotein complex that functions in regulation of cytokine release following infections
Promotes the maturation of inflammatory cytokines IL1 and IL18
Novel target for anti inflammatory therapy
Vasodilation goals
Increase permeability of endothelium to allow proteins and cells to move from blood into tissue spaces to fight infection
As vessels increase in diameter, intercellular spaces increase in vessel walls to allow movement of cells out of vessel
Extravasation
Mediated by cell adhesion molecules CAMs
WBC adhere to endothelium and squeeze through pores between endothelial cells
Rolling adhesion
Weak interaction
Selectins
Stable/tight adhesion
Strong interaction
Integrins
Expression of selectins
Constitutive
Slow down
Expression of integrins
Unregulated by inflammatory mediators
Adhere tight and exit
Leukocyte Adhesion Deficiency
Genetic disorder
Deficiency of integrins CD18 deficiency
Marked by recurrent bacterial infections and severe neutrophilia
Resolution of inflammation
Stimulus removed/eradicated
Often occurs with no tissue injury
Rate of arrival of new cells decreases rapidly
Leukocytes present at site undergo apoptosis and are removed by macrophages
Fibroblasts repair CT
Epithelium heals
Acute inflammation link to adaptive immune system
Enhances Ag presentation
APC at site take up antigen and become activated and migrate to regional lymph nodes
Resolution of inflammation
Removal of microbes, dead cells and debris
Restoration of vascular integrity and perfusion
Regeneration of tissue
Remission of fever
Relief of pain
Resolution of inflammation
Monocytes steps
Phagocytosis of leftovers
Release collagenases and elastase to soften tissue matrix
Release cytokines to stimulate fibroblasts to produce collagen and repair damaged tissue
Produce angiogenic factors to promote new cap growth
Chronic inflammation
Prolonged duration
Associated with impaired function
Chronic inflammation can be due to
Persistence of antigen
Autoimmune disease
Cancer
Chronic inflammation hallmark
Infiltration of tissue with monocytes/macrophages and lymphocytes (t and B cells)
Granulomatous inflammation
Specific type of chronic inflammation that is associated with macrophage activation driven by IFN gamma producing T cells
Granulomatous inflammation characterized by
Macrophages that have been transformed into epithelioid cells
Granulomatous inflammation surrounded by
Lymphocytes fibroblasts and local parenchymal cells
Granuloma
Lesion that develops as result of prolonged chemotactic stimulation
Can become necrotic in center
Granuloma consists of
Epithelioid cells and/or multinucleated giant cells surrounded by fribroblasts and T cells
Epithelioid cells
Enlarged macrophages
Multinucleated giant cells
2+ macrophages that have fused together
Function of granuloma
Wall off the offending pathogen or injury if it cannot be eliminated.
Chronic granulomatous disease
Phagocytes lack ROI and have defect in killing intracellular microbes.
Immune system responds by granuloma.
Granuloma replaces healthy tissue to point of organ dysfunction.
Patients present with recurrent infection and multiple granuloma.
Chronic granulomatous disease treated with IFN-g
IFN g further activates macrophages
Ulceration
Another manifestation of chronic inflammation
Local defect/excavation in surface of tissue/organ which is produced by shedding of inflammatory necrotic tissue.
Anti-inflammatory agents
Corticosteroids
Prednisone, prednisolone
Inhibit phospholipase A - decreases production of arachidonic acid metabolites
Inhibits T cell activation and cytokine production (IL2)
Decreases phagocytic and killing ability of macrophages nad PMNs
Decreases chemotaxis.
Decreases IL1 secretion by macrophages
Anti inflammatory Agents
NSAIDS
Aspirin, naproxen, ibuprofen
Inhibit cyclooxygenase pathway
Decrease production of prostaglandin
Help limit increase in vascular permeability and neutrophil chemotaxis.
Alternative targets for treatment of inflammation
TNF neutralizing agents
Monoclonal antibodies
Block action of proinflammatory cytokines like TNF-alpha
Decreases WBC inflammation.
Disease control
Disease currently present
Reduce frequency of infection
Reduce effects of the disease
Disease prevention
Disease not yet present
Prevent disease intro to area/pop
Prevent infection of uninflected ind
Prevent disease development
Disease elimination
Zero incidence in defined geographic location w/ continued intervention required
Disease eradication
Zero incidence globally
No continued intervention required
Disease extinction
Not present in nature or lab
Threshold susceptible size
Related to basic reproduction number of pathogen
Susceptible population reduced below threshold size
Pathogen cannot continue to be transmitted
But can be reintroduced
R0=1
Each case generates a replacement> disease stable in population
R0> 1
Each case generates >1 new case
Disease increases in population
R0<1
Each case generates new case
Disease decreases in population
R0
Average number of secondary cases produced by one primary case in a completely susceptible population
Threshold
Percentage of population that needs to be immune for strong herd immunity
1-1/R0
As R0 increases what does threshold have to do
Increase as well
Cancer preventation vaccines
Prevents infection associated with cancer
Approved cancer preventative vaccines
HPV vaccine - genitourinary cancer
Hep B- liver cancer
Passive immunity pro
Immediate protection
Passive immunity cons
Short lived protection
No immunological memory
Passive immunity conferred by
Preformed antibodies
Passive immunity
Clinical examples
Tetanus Botulinum Rabies HPV Varicella Diphtheria Post venomous bites
Active immunity
Long lasting protection with development of immunological memory.
Adaptive immune response
Immunological memory
Bcell activated - starts proliferating and secreting specific ab. Some differentiate into B memory cells
B memory cells - long lived and carry same specificity as parent. Come into contact with same pathogen, respond more rapidly and robustly
Same applies to T cells
Vaccine modes of delivery
I trader all SubQ Intramuscular Oral Aerosol Ocular Transdermal In ovo
Non infectious vaccines
Low risk
Most need boosters
Cannot replicate in host
Infectious vaccines
Can replicate in host Have ability to actively infect the host without causing the disease or harsh symptoms Most effective vaccine type Higher risk Most single dose
Infectious types of vaccines
Live attenuated
Viral vectors
Noninfectious types of vaccines
I activated Recombinant DNA Ab fusions Toxoids Polysaccharides Purified protein Synthetic Virus like particles
Live attenuated vaccines critical component
Loss of virulence
Virulence
Capacity of a pathogen to cause disease
Live attenuated vaccines
Risks
Reversion to virulent - rare Recombination to virulent - rare Disease in immunocopromised pt’s Temperature sensitivity Contaminating viruses - rare Abortigenic / teratogenic
Live attenuated vaccines
Pros
Elicit some of the strongest immunity of all vaccination types
Protection can last lifetime/ decades
Examples of live attenuated vaccines
MMR Influenza Varicella Rotavirus Yellow fever Smallpox
Viral vectors
Can replicate in the host Infectious Vector virus is nonpathogenic Carries in genes from other pathogen Immune response to pathogenic proteins One and done though
Inactivated/ killed vaccines
Critical component
Loss of infectivity/ unable to replicate
How inactivate vaccine
Chemical
Temperature
Irradiation
Inactivated vaccines cons
Not as effected as live vaccines
DIVA problem
Incomplete inactivation - rare
Contamination - rare
DIVA
Distinguishing infected from vaccinated
Inactivated vaccines
Pros
Typically much safer than live vaccinated
Toxoids
Inactivated pathogenic toxins that retain their ability to induce host antitoxins
Genetically engineered vaccines
Recombinant DNA
Genetically modified DNA 2 or more species DNA stuck together Gene segments/fragments Plasmids Naked DNA
Virus like particles
Used in HPV vaccine
Virus like particles
Pros
Safety
Looks like the pathogen but is empty inside
Virus like particles
Cons
High production costs Lower immunogenicity Low yields Stability DIVA
Polysaccharides
Haptens
Need protein carrier to induce immune response
Adjuvants
Enhance host immune response to antigen
Enhance Ag presentation, improve ag stability or immunomodulation
Problem with adjuvants
Safety is inversely proportional to efficacy
Adjuvants
Alum
Promotes aggregates for phagocytosis Targets inflammasome activity Th2 skew Holds it in place so Ag can’t diffuse through body. Why arm aches. Allergies and granulomas possible
Adjuvants
Other emulsions
Squalene based
MF 59 and AddaVax
Approved in Europe, but not US yet.
Vaccine responsiveness
Genetic predisposition
Hypersensitivities to adjuvants or other vaccine components
MHC alleles
Size of person and vaccine doses
Average same number of immune response cells
Adverse events
Hypersensitivities
Injection site problems/scarring
Inadequate inactivation, recombination, disease in immunocompromised pt’s, loss of effectiveness due to temp variations in transport or storage.
Dengvaxia
Early 2016 promising dengue vaccine.
Live recombinant tetravalent vaccine
Up to 80% effective
Exposed after vaccination got horrific disease
Vaccination after infection eliminated response
