Immune System

Immune System : Immune System

What Does the Enemy Look Like? : What Does the Enemy Look Like? A wide range of organisms try to exploit our bodies:

How would you approach this problem? : How would you approach this problem? First line of defense: Secure the Borders Prevent a problem from occurring in the first place Skin and mucosa prevent entry of microorganisms Second line of defense: Mobilize Quickly to Block a Breach Antimicrobial proteins, phagocytes, and other cells localize the invasion Inflammation is the hallmark and most important mechanism Repair of the border is the ultimate solution Third line of defense: Hunt Down Successful Invaders Profile the enemy (this takes time) Catch, immobilize, & destroy invaders in the body fluids Identify, destroy, & remove body cells already infected

Nonspecific (innate immunity) and 3 lines of defense : Nonspecific (innate immunity) and 3 lines of defense

Barriers at Body Surfaces (First line) : Barriers at Body Surfaces (First line) Microbes on surfaces don’t cause disease unless they penetrate inner tissues Physical barriers: Skin and linings of the body’s tubes and cavities Mechanical barriers: Sticky mucus, ciliated cells, flushing action of urination and diarrhea Chemical barriers: Secretions of established populations of resident microbes

1st Line of Defense: Secure the Borders : 1st Line of Defense: Secure the Borders Skin, mucous membranes, and their secretions create a barrier Skin: Presents a physical barrier to most microorganisms Mucosa provide similar mechanical barriers Mucus-coated hairs in the nose trap inhaled particles Mucosa of the upper respiratory tract is ciliated Cilia sweep dust- and bacteria-laden mucus away from lower respiratory passages Epithelial membranes produce protective chemicals that destroy microorganisms Skin acidity (pH of 3 to 5) inhibits bacterial growth Ear wax contains chemicals toxic to bacteria Stomach mucosa secrete concentrated HCl and protein-digesting enzymes Saliva contain enzymes Mucus traps microorganisms that enter the digestive and respiratory systems

2nd Line of Defense: Mobilize Quickly : 2nd Line of Defense: Mobilize Quickly The second line of defense is still NOT for a specific invader The body uses nonspecific cellular and chemical devices to protect itself Phagocytes and natural killer (NK) cells Antimicrobial proteins in blood and tissue fluid Inflammatory response enlists macrophages, WBCs, and chemicals Harmful substances are identified by surface markers unique to infectious organisms

Phagocytes: Police the Fluid Areas : Phagocytes: Police the Fluid Areas 2nd Line of defense Macrophages are the chief phagocytic cells Free macrophages wander throughout a region in search of cellular debris Neutrophils become phagocytic when encountering infectious material Eosinophils are weakly phagocytic against parasitic worms

Natural Killer (NK) Cells: Look for Infected Cells : Natural Killer (NK) Cells: Look for Infected Cells 2nd line of defense NK cells can destroy cancer cells and virus-infected cells Natural killer cells: React nonspecifically and eliminate cancerous and virus-infected cells Kill their target cells by releasing chemicals Secrete strong chemicals that enhance the inflammatory response

Proteins Used To Kill Invading Microbes: Complement (2nd line) : Complement system ~ 20 different proteins that separately are inactive Kills invading microbes by forming holes in the cell membrane Increases all aspects of the inflammatory response Our cells are immune to complement Proteins Used To Kill Invading Microbes: Complement (2nd line) Is a major mechanism for destroying foreign substances in the body

The Inflammatory Response (Click for movie) : The Inflammatory Response (Click for movie) The inflammatory response is triggered whenever body tissues are injured Prevents the spread of damaging agents to nearby tissues Disposes of cell debris and pathogens Sets the stage for repair processes The four cardinal signs of acute inflammation are: Redness Heat Swelling Pain

Fever : Abnormally high body temperature in response to invading microorganisms The body’s thermostat is reset upwards High fevers are dangerous as they can denature our own enzymes Fevers are not used to directly kill invaders Fevers greater than 40.6oC (105oF) are often fatal Fever Moderate fever can be beneficial: The primary benefit is an increase in the metabolic rate, which speeds up tissue repair (1o in temperature = 10 X metabolic increase)

Innate (inborn) immunity and Adaptive Immunity3rd line of defense : Innate (inborn) immunity and Adaptive Immunity3rd line of defense

3rd Line of Defense: Attack Invaders : 3rd Line of Defense: Attack Invaders Acquired (or adaptive) immunity is a functional system that: Recognizes specific foreign substances Acts to immobilize, neutralize, or destroy them Amplifies inflammatory response and activates complement The adaptive immune system: Is antigen-specific An antigen is a molecule that provokes a specific immune response Is systemic It is not restricted to any region of the body Has memory Some “educated” cells remain after the invader is gone It has two separate but overlapping arms B cells: humoral immunity (body fluid) T cells: cellular immunity It is the most complex and slowest to respond It has to activate cells for each new invader (antigen) On first exposure it takes ~ 10 days to reach peak levels

T cells: Destroying Infected Cells : T cells: Destroying Infected Cells Originate in bone marrow and mature in the Thymus Develop ability to identify foreign agents by antigens present on cell surfaces Four main types of T cells Helper (TH) – Initiate the immune response (authorize the attack) Cytotoxic (TC) – Destroy virus-infected cells (licensed to kill) Memory (TM) – Provide a quick response on re-exposure (keep watch) Suppressor (TS) – Terminate the immune response (declare victory)

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Slide 17 : variable region of heavy chain antigen-binding site antigen-binding site hinge region (flexible) variable region of light chain constant region of light chain constant region of heavy chain antigen on surface of bacterial cell binding site on one kind of antibody molecule for this specific antigen antigen on surface of a virus particle binding site on a different antibody molecule for this specific antigen Fig. 35.13, p. 586

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Antigens : Antigens Substances that can Mobilize the immune system Provoke an immune response Targets of all immune responses are mostly Large, complex molecules Not normally found in the body

Molecule structure (Antibody) : Molecule structure (Antibody)

Agglutination (virus demo) : Agglutination (virus demo)

B cells: Catching Invaders in the Body Fluids : B cells: Catching Invaders in the Body Fluids Originate and mature in the bone marrow To help you remember the name, you can think of the “B” as standing for where they mature in humans: Bone marrow Circulate in blood and lymph Proliferate upon antigen exposure into: Plasma cells That produce antibodies Memory cells That provide a quick response on re-exposure

B Cell Activation : B Cell Activation

Great picture overview of immune system : Great picture overview of immune system

Primary & Secondary Immune Responses : Primary & Secondary Immune Responses

AIDS : AIDS

Slide 27 : Fig. 35.19, p.594 Some transcripts become new viral RNA; others are translated into proteins. Together, they self-assemble into new virus particles. Virus particles that bud from an infected cell may attack another cell. Viral DNA forms by reverse transcription of viral RNA. Viral RNA enters a T cell. The viral DNA becomes integrated into host cell’s DNA. DNA, including the viral genes, is transcribed. lipid envelope with proteins viral RNA viral enzyme (reverse transcriptase) viral coat proteins 25–30 µm nucleus viral DNA viral RNA viral proteins a b c d e f

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