Two Clicker questions at the start of class

• T-helper cells play several very important “central” roles in the immune system. This importance becomes clear when which one of the following pathogens attaches to CD4 molecules on the surfaces of the T-helper cells, infects those cells and eventually destroys them. As the number of T-helper cells diminishes, a rather dramatic decline in the effectiveness of the entire immune system also occurs.

• In which one of the following instances has the body’s own immune system lost the ability to discriminate between “self” and non-self”, with the result being an attack by that “misdirected” immune system on tissues and organs in the same body in which it (that immune system) resides?

T-helper cells play several very important “central” roles in the immune system. This importance becomes clear when which one of the following pathogens attaches to CD4 molecules on the surfaces of the T-helper cells, infects those cells and eventually destroys them. As the number of T-helper cells diminishes, a rather dramatic decline in the effectiveness of the entire immune system also occurs.

• A. H1N1 “swine flu” virus

• B. the smallpox virus (this is why smallpox is still considered a serious public health threat)

• C. the HIV virus (the word “virus” is redundant)

• D. Pneumocystis carinii

In which one of the following instances has the body’s own immune system lost the ability to discriminate between “self” and non-self”, with the result being an attack by that “misdirected” immune system on tissues and organs in the same body in which it (that immune system) resides?

• A. miscarriage of a fetus during the first trimester

• B. diseases such as lupus, multiple sclerosis and type 1 diabetes

• C. destruction of a tumor cell that arose from a change in a normal body cell

• D. SSPE (sub-acute sclerosing panencephalitis), a complication of a measles infection

Elements of the Immune System• Protective barriers

– Skin – tough layer of keratinized cells– Mucous membranes – much more fragile

• Designed to allow movement across membrane epithelia

Elements of the Immune System

• Protective barriersSkin – tough layer of keratinized cells

Mucous membranes – much more fragile

Designed to allow movement across membrane epithelia

• Mechanical, chemical and microbial components

The Innate Immune System

• Genetically determined at birth• Always ready to respond

Pathogen

Pathogen

Pathogens

Pathogen

The Innate Immune System

• Genetically determined at birth• Always ready to respond

• Provides protection from almost all potential pathogens• Mostly associated with the barriers (skin, membranes)

The Innate Immune System

• Cellular and molecular components• Effector cells

– Phagocytes• Macrophages• Neutrophils

• Carry out Phagocytosis (destroys pathogens)

Phagocytosis

• Toll-like receptors (TLR) on phagocyte surface “recognize” PAMPS (pathogen-associated molecular patterns) on surface of pathogen

The Innate Immune System

• Phagocytes also send out chemical signals (inflammatory cytokines)

• Cytokines have several affects– Make blood vessels “leaky” – vasodilation

– Attract other phagocytes into the site of infection from blood vessel

– Vasodilation also allows molecules to enter into infected area

– Result is called an inflammatory reaction (inflammation)

• Neutrophils (the “other” phagocytes) are attracted into the infected area– Bacterial cells are all phagocytized

– Macrophages also remove dead body cells and dead neutrophils

– Injured tissue is repaired

• Complement is an important molecular component of innate system

– Is always present (in body fluids) in an inactive state until needed– Activated by the presence of most bacterial pathogens– Activated complement attracts phagocytes and provides an additional

attachment mechanism for those phagocytes• Activated complement attaches to bacterial surface• Phagocyte has a complement receptor that attaches to activated complement• Attachment initiates phagocytosis

Natural Killer (NK) cells

• Another cellular member of the innate immune system– NOT a phagocytic cell

• Phagocytosis and complement not very effective against many viruses

NK cells kill virus-infected cells (and many tumor cells)

Innate Immune Response not always successful

• Phagocytosis may not occur– No attachment to bacterial surface

• Bacteria may not display any PAMPs• Bacteria may have a capsule which masks PAMPS (e.g., pneumonia)• http://student.ccbcmd.edu/courses/bio141/lecguide/unit1/prostruct/phag_pampcap.html

– Engulfed bacteria may be able to resist degradation (e.g., tuberculosis)– Many viruses can not be phagocytized (no PAMPs)

• Many virus-infected cells do not stimulate destruction by Natural Killer cells

• Complement may not be activated

• Pathogens may simply multiply faster than they can be degraded

• Bacterial exotoxins can not be phagocytized, do not activate complement

• Many tumor cells are not destroyed by innate immune response

Two clicker questions at the start of class

• Many bacteria have an extracellular “covering” that can prevent attachment of toll-like receptors (TLRs) on the surface of phagocytic cells with certain molecules (called PAMPs) on the underlying cell-wall surface of the bacterial cell, thus preventing the initiation of phagocytosis. This bacterial component is which one of the following?

• Which one of the following does NOT describe innate immunity?

Many bacteria have an extracellular “covering” that can prevent attachment of toll-like receptors (TLRs) on the surface of phagocytic cells with certain molecules (called PAMPs) on the underlying cell-wall surface of the bacterial cell, thus preventing the initiation of phagocytosis. This bacterial component is which one of the following?

• A. a cytokine

• B. a vasodilator

• C. a capsule

• D. a complement

BONUS Clicker question

Which one of the following DOES describe innate immunity?

• A. the innate immune system can provide protection from some viruses

• B. even if a very dangerous pathogen has just entered into the body (already passed through a membrane), the response of the innate immune system is still very delayed, often taking 10-14 days to provide any type of rotection from that pathogen

• C. phagocytosis and complement activation contribute little, if any, protection from even the most benign of bacterial infections

• D. each innate immune response is specific for only one unique genus and species of pathogen

Innate Immune Response not always successful

• Phagocytosis may not occur– No attachment to bacterial surface

• Bacteria may not display any PAMPs• Bacteria may have a capsule which masks PAMPS (e.g., pneumonia)• http://student.ccbcmd.edu/courses/bio141/lecguide/unit1/prostruct/phag_pampcap.html

– Engulfed bacteria may be able to resist degradation (e.g., tuberculosis)– Many viruses can not be phagocytized (no PAMPs)

• Many virus-infected cells do not stimulate destruction by Natural Killer cells

• Complement may not be activated

• Pathogens may simply multiply faster than they can be degraded

• Bacterial exotoxins can not be phagocytized, do not activate complement

• Many tumor cells are not destroyed by innate immune response

Adaptive Immune System

• Phagocytosis may not occur• Can assist phagocytes to attach to bacteria AND viruses• Many virus-infected cells do not stimulate destruction by Natural Killer cells• Can assist Natural Killer cells to “recognize” virus-infected cells• Can prevent viruses from infecting body cells• Can directly destroy virus-infected cells• Complement may not be activated• Can activate complement• Pathogens may simply multiply faster than they can be degraded• Can dramatically increase speed of response• Bacterial exotoxins can not be phagocytized, do not activate complement• Can “neutralize” exotoxins• Tumor cells are rarely destroyed by innate immune response• Can destroy many tumor cells

Pathogen

Pathogen

Pathogens

Pathogen

Adaptive Immune System

• Cellular components• Lymphocytes

– B-lymphocytes• Produce antibodies

– T-lymphocytes (3 functional groups)• T-helper lymphocytes (that “central” cell)

– Assist B-lymphocytes and other T-lymphocytes

– Enhance phagocyte degradation of ingested bacterial cells

• T-cytotoxic lymphocytes– Destroy virus-infected cells

• T-regulatory cells– Control certain functions of the adaptive immune response

Adaptive Immune System

• Cellular components• Molecular components

– Antibodies (secreted by B-lymphocytes)

– Assist phagocytes to attach to bacteria• Capsules – antibodies attach to capsules• No PAMPs – antibodies attach to other surface molecule• Phagocytes have receptors for antibody molecules

Adaptive Immune System

• Antibodies (secreted by B-lymphocytes)– Assist phagocytes to attach to bacteria

– Assist phagocytes to attach to viruses -> phagocytosis of viruses

– Assist phagocytes to attach to exotoxins -> phagocytosis of exotoxins

– Can activate complement

– Can directly “neutralize” exotoxin

– Can prevent viruses from attaching to body cells

– Can assist Natural Killer cells to “recognize” virus-infected cells

TWO Clicker questions at the start of class

• Which one of the following cell types is considered responsible for direct destruction of most virus-infected cells?

• Which one of the following letters BEST describes the properties of the Adaptive immune system?

Which one of the following cell types is considered responsible for direct destruction of most virus-infected cells?

A. B-lymphocytes

• B. CD4+ lymphocytes (especially good at destroying cells infected with HIV)

• C. encapsulated bacterial cells (especially good at assisting phagocytes to attach to virus-infected cells using TLRs)

• D. T-cytotoxic lymphocytes

Which one of the following letters BEST describes the properties of the Adaptive immune system?

• A. Can assist phagocytes to attach to bacteria AND viruses

• B. Can assist Natural Killer cells to “recognize” virus-infected cells

• C. Can activate complement

• D. Can “neutralize” exotoxins

• E. Capable of ALL of the above

BONUS Clicker question

Which one of the following DOES describe innate immunity?

• A. the innate immune system can provide protection from some viruses

• B. even if a very dangerous pathogen has just entered into the body (already passed through a membrane), the response of the innate immune system is still very delayed, often taking 10-14 days to provide any type of protection from that pathogen

• C. phagocytosis and complement activation contribute little, if any, protection from even the most benign of bacterial infections

• D. each cell participating in an innate immune response is specific for only one unique genus and species of pathogen

Specificity of Lymphocytes

• Each lymphocyte has replicate receptors that will bind to only ONE molecule

• Different from the phagocytic cells

Phagocytosis

• Several different Toll-like receptors (TLR) on one phagocyte surface “recognize” a wide variety of PAMPS (pathogen-associated molecular patterns) on surface of a wide range of pathogens

Specificity of Lymphocytes

• Each lymphocyte has replicate receptors that will bind to only ONE molecule– Different lymphocytes have different specificities

– One specificity/lymphocyte

• B-lymphocyte receptor– Immunoglobulin

– Looks like an antibody attached to the B-cell surface

• T-lymphocyte receptor

“Clonal selection” from pool of lymphocytes

• Literally trillions of individually specific lymphocytes are in the body

“Clonal selection” from pool of lymphocytes• Literally trillions of individually specific lymphocytes are in the body

• Lymphocyte interacts with pathogen for which it is specific

• That responding lymphocyte replicates -> expanded population results

• The expanded population of cells are also now prepared to participate in eliminating the pathogen more rapidly than during the initial encounter

• Immune system has “adapted” to presence of pathogen

HiClicker response is worth 5 points

• A. Hi, I’m here in class

• B. I’m not in class

Adaptive System Tissues and Organs

• Primary Lymphoid Organs– Where lymphocytes develop and acquire characteristics

– Bone marrow – B-lymphocyte development

– Thymus – T-lymphocyte development

Adaptive System Tissues and Organs

• Secondary lymphoid tissues/organs– Where lymphocytes usually function

– Lymph nodes

– Spleen

– Peyer’s patches (GALT)

Secondary organs well-designed to optimize adaptive immune responses

Connection between Innate and Adaptive Immune responses

Lymphocytes circulate constantly