BIOLOGY 1A Lecture Notes - Lecture 35: Natural Killer Cell, Innate Immune System, Adaptive Immune System
THE IMMUNE SYSTEM
Infectious diseases are a leading cause of death worldwide- 15 million deaths
Origination from pathogens that invade your body
○
•
Pathogens= bacteria, viruses, parasites or fungi that cause disease in otherwise
healthy people
•
Immune system= recognizes pathogens and responds with immune cells and
proteins
Innate immune system
Adaptive immune system
Early response
Late response
Responds to pathogens in a GENERIC
way
Responds to PARTICULAR
features of pathogen
NO memory
IMMUNOLOGICAL MEMORY
Dominant system in animals and
plants
Only in vertebrates
Basis of vaccines
○
•
INNATE IMMUNITY (all animals)
Recognition of traits shared by broad ranges of pathogens, using a small
set of receptors
○
Rapid response
○
Barrier defenses: 1st line= physical barriers
Skin
§
Mucous membranes
§
Secretions
§
Intestinal system is not friendly for bacteria- low pH
§
○
Internal defenses: 2nd line of response
Phagocytic cells
§
Natural killer cells
§
Antimicrobial proteins
§
Inflammatory response
§
○
Cellular component of innate defense:
White blood cells (leukocytes) engulf pathogens by phagocytosis:
internalization of pathogens
§
1.
Neutrophils: most common white blood cells
Fastest to site of infection
§
Form pus
§
○
Macrophages and dendritic cells:
Found in all tissues of the body
§
Important for activating the acquired immune system by "antigen
presentation"
§
○
Second line of defense for innate immune response: the inflammatory
response
The inflammatory response: physiological response to harmful
stimuli (such as pathogens) positive feedback
§
Mast cell releases signaling molecules that are sensed by
epithelial cells and become leak-y. the neutrophils and
immune cells leak out to find the bacteria. Macrophage sends
out signaling molecule to tell neutrophil where to go.
□
Histamines are released from Mast cell which activate
inflammatory response. Cytokines released from macrophage.
□
Sense of pathogen which leads to signaling and phagocytosis□
The more signaling the more immune cells- positive feedback□
§
2.
I.
PHAGOCYTOSIS
Killing microbes by phagocytosis:
Pseudopodia are formed and surround pathogens1.
Pathogens engulfed by endocytosis2.
Vacuole forms3.
Vacuole and lysosome fuse4.
Pathogens destroyed by the hydrolytic enzymes in lysosomes5.
Debri gets released6.
7.
○
Neutrophil recognizes bacterium peptides
○
How to recognize Pathogens: Phagocytes have Toll-like receptors (TLRs)
that stimulate immune response
TLRs recognize PAMPs (pathogen-associated molecular patterns)=
molecules specific to broad range of pathogens
Ex. components of cell membrane, flagella, double stranded
RNA
□
§
Some TLRs have their binding sites face the extracellular fluid and
some face into vacuoles/vesicles
§
§
○
II.
ADAPTED IMMUNITY (vertebrates only): 3rd line of defense
Recognition of traits specific to particular pathogens, using a vast array of
receptors
○
Slower response
○
Humoral response: antibodies defend against infection in body fluids
Noncellular response
§
Proteins circulating in system interact w pathogen and neutralize it
§
○
Cell-mediated response: Cytotoxic cells defend against infection in body
cells
○
Adaptive immunity is mediated by B and T cells
Antigen= molecule on pathogen that elicits T or B cell response
§
Antigen receptors and antibodies= proteins that bind antigens
On B cells and T cells□
§
Epitope= portion of antigen recognized by antigen receptor
§
Only 1 type of receptor on each B and T cell- high specificity
§
○
Antigen recognition by B cell receptors and generation of antibodies
Humoral response:
Antigen receptor on an immature B-cell binds to a part of a
bacteria (epitope)
1)
B-cells is activated and begins to secrete antibodies (receptors
that are proteins that can circulate and can bind to
pathogens)
2)
Antibodies bind to pathogens and send signaling to
phagocytes to engulf. They can also neutralize the pathogen.
3)
§
○
Vaccination promotes immune memory
§
Exposure to antigen A- produces antibodies; takes 2 weeks to get
maximum exposure
Antibodies will break down and secreted away in urine□
There are still B cells that remember they have been exposed
to the antigen
□
FASTER and GREATER response to antigen□
§
○
Antigen recognition by Helper-T cells
A macrophage will engulf a pathogen, will go through phagocytosis
and will take a piece of the fragment and it will bind to MHC and
present it out to the world for T cells to find.
§
Antigen presenting cell- some phagocytotic cells present a fragment
of a pathogen to extracellular space
MHC molecule□
§
T-cells bind to MHC/antigen combination. These are called Helper
T-cells
Helper T cells-are activated□
§
○
Helper T cells activate cytotoxic T cells
Activated Helper T cells have 2 effects
Promote antibody secretion by B cells 1)
Activate cytotoxic T-cells which will attack an infected cell
a)
2)
§
○
Cytotoxic T cells kill infected cells
§
Cytotoxic T cell recognizes antigen and bind and releases granzymes
(perforin) that poke holes in the infected cell and kill it
§
○
Immune checkpoints prevent T-cell response from getting out of control
Many of the symptoms associated with infections are responses of
our own body (fever, mucous generation, swelling, pain)
§
Important to prevent autoimmunity
§
Hijacked by cancer cells to hide from the immune system
§
○
III.
USING THE IMMUNE SYSTEM TO FIGHT CANCER
Immune checkpoints stop T cell killing of cancer cells and checkpoint
inhibitors activate killing by T cells
○
Cancer cell is foreing and presents antigen. T cell will come with
proteins (PD1) but a protein on the cancer cell activates PD1 and
tells it not to do anything
§
Put on a drug that blocks PD1 so that it cant get activated and Tcell
can kill cancer cell.
§
○
The idea of checkpoint blockade and the revitalization of immunotherapy
James Allison
§
○
IV.
Lecture 35-4/20
Saturday, April 21, 2018
1:12 PM
THE IMMUNE SYSTEM
Infectious diseases are a leading cause of death worldwide- 15 million deaths
Origination from pathogens that invade your body
○
•
Pathogens= bacteria, viruses, parasites or fungi that cause disease in otherwise
healthy people
•
Immune system= recognizes pathogens and responds with immune cells and
proteins
Innate immune system Adaptive immune system
Early response Late response
Responds to pathogens in a GENERIC
way
Responds to PARTICULAR
features of pathogen
NO memory IMMUNOLOGICAL MEMORY
Dominant system in animals and
plants
Only in vertebrates
Basis of vaccines
○
•
INNATE IMMUNITY (all animals)
Recognition of traits shared by broad ranges of pathogens, using a small
set of receptors
○
Rapid response
○
Barrier defenses: 1st line= physical barriers
Skin
§
Mucous membranes
§
Secretions
§
Intestinal system is not friendly for bacteria- low pH
§
○
Internal defenses: 2nd line of response
Phagocytic cells
§
Natural killer cells
§
Antimicrobial proteins
§
Inflammatory response
§
○
Cellular component of innate defense:
White blood cells (leukocytes) engulf pathogens by phagocytosis:
internalization of pathogens
§
1.
Neutrophils: most common white blood cells
Fastest to site of infection
§
Form pus
§
○
Macrophages and dendritic cells:
Found in all tissues of the body
§
Important for activating the acquired immune system by "antigen
presentation"
§
○
Second line of defense for innate immune response: the inflammatory
response
The inflammatory response: physiological response to harmful
stimuli (such as pathogens) positive feedback
§
Mast cell releases signaling molecules that are sensed by
epithelial cells and become leak-y. the neutrophils and
immune cells leak out to find the bacteria. Macrophage sends
out signaling molecule to tell neutrophil where to go.
□
Histamines are released from Mast cell which activate
inflammatory response. Cytokines released from macrophage.
□
Sense of pathogen which leads to signaling and phagocytosis
□
The more signaling the more immune cells- positive feedback
□
§
2.
I.
PHAGOCYTOSIS
Killing microbes by phagocytosis:
Pseudopodia are formed and surround pathogens
1.
Pathogens engulfed by endocytosis
2.
Vacuole forms
3.
Vacuole and lysosome fuse4.
Pathogens destroyed by the hydrolytic enzymes in lysosomes5.
Debri gets released6.
7.
○
Neutrophil recognizes bacterium peptides
○
How to recognize Pathogens: Phagocytes have Toll-like receptors (TLRs)
that stimulate immune response
TLRs recognize PAMPs (pathogen-associated molecular patterns)=
molecules specific to broad range of pathogens
Ex. components of cell membrane, flagella, double stranded
RNA
□
§
Some TLRs have their binding sites face the extracellular fluid and
some face into vacuoles/vesicles
§
§
○
II.
ADAPTED IMMUNITY (vertebrates only): 3rd line of defense
Recognition of traits specific to particular pathogens, using a vast array of
receptors
○
Slower response
○
Humoral response: antibodies defend against infection in body fluids
Noncellular response
§
Proteins circulating in system interact w pathogen and neutralize it
§
○
Cell-mediated response: Cytotoxic cells defend against infection in body
cells
○
Adaptive immunity is mediated by B and T cells
Antigen= molecule on pathogen that elicits T or B cell response
§
Antigen receptors and antibodies= proteins that bind antigens
On B cells and T cells□
§
Epitope= portion of antigen recognized by antigen receptor
§
Only 1 type of receptor on each B and T cell- high specificity
§
○
Antigen recognition by B cell receptors and generation of antibodies
Humoral response:
Antigen receptor on an immature B-cell binds to a part of a
bacteria (epitope)
1)
B-cells is activated and begins to secrete antibodies (receptors
that are proteins that can circulate and can bind to
pathogens)
2)
Antibodies bind to pathogens and send signaling to
phagocytes to engulf. They can also neutralize the pathogen.
3)
§
○
Vaccination promotes immune memory
§
Exposure to antigen A- produces antibodies; takes 2 weeks to get
maximum exposure
Antibodies will break down and secreted away in urine□
There are still B cells that remember they have been exposed
to the antigen
□
FASTER and GREATER response to antigen□
§
○
Antigen recognition by Helper-T cells
A macrophage will engulf a pathogen, will go through phagocytosis
and will take a piece of the fragment and it will bind to MHC and
present it out to the world for T cells to find.
§
Antigen presenting cell- some phagocytotic cells present a fragment
of a pathogen to extracellular space
MHC molecule□
§
T-cells bind to MHC/antigen combination. These are called Helper
T-cells
Helper T cells-are activated□
§
○
Helper T cells activate cytotoxic T cells
Activated Helper T cells have 2 effects
Promote antibody secretion by B cells 1)
Activate cytotoxic T-cells which will attack an infected cell
a)
2)
§
○
Cytotoxic T cells kill infected cells
§
Cytotoxic T cell recognizes antigen and bind and releases granzymes
(perforin) that poke holes in the infected cell and kill it
§
○
Immune checkpoints prevent T-cell response from getting out of control
Many of the symptoms associated with infections are responses of
our own body (fever, mucous generation, swelling, pain)
§
Important to prevent autoimmunity
§
Hijacked by cancer cells to hide from the immune system
§
○
III.
USING THE IMMUNE SYSTEM TO FIGHT CANCER
Immune checkpoints stop T cell killing of cancer cells and checkpoint
inhibitors activate killing by T cells
○
Cancer cell is foreing and presents antigen. T cell will come with
proteins (PD1) but a protein on the cancer cell activates PD1 and
tells it not to do anything
§
Put on a drug that blocks PD1 so that it cant get activated and Tcell
can kill cancer cell.
§
○
The idea of checkpoint blockade and the revitalization of immunotherapy
James Allison
§
○
IV.
Lecture 35-4/20
Saturday, April 21, 2018 1:12 PM
