ImmunologyImmunology

Immunity – First Line of Defense Immunity – First Line of Defense (Keeping pathogens from getting in)(Keeping pathogens from getting in)

• Skin and mucous membranesSkin and mucous membranes

– Epithelium traps pathogen – swallow or Epithelium traps pathogen – swallow or expel them from the bodyexpel them from the body

– Secrete oil and sweat – kills pathogens Secrete oil and sweat – kills pathogens with a pH of 3-5with a pH of 3-5

– Lysozyme is produced by eyes and Lysozyme is produced by eyes and upper respiratory tract – digests cell upper respiratory tract – digests cell walls so kills bacteriawalls so kills bacteria

Immunity – InternalWhite Blood Cells/Proteins

Non-SpecificNon-Specific• Cells (develop in bone Cells (develop in bone

marrow)marrow)– NeutrophilsNeutrophils– EosinophilsEosinophils– BasophilsBasophils– MoncytesMoncytes– Natural Killer CellsNatural Killer Cells

• Proteins Proteins

SpecificSpecific• B-cells B-cells

– originate from bone originate from bone marrowmarrow

– Make anti-bodies – destroy Make anti-bodies – destroy soluble pathogenssoluble pathogens

• T-cellsT-cells– Originate in bone marrow Originate in bone marrow

and then go to thymusand then go to thymus– T-killer – kill tumor cells T-killer – kill tumor cells

and infected cellsand infected cells– T-helper – activate T and B T-helper – activate T and B

cellscells

Non-Specific ImmunityNon-Specific Immunity

• Quick, short-lived, activated specific Quick, short-lived, activated specific immunityimmunity

• Activated by damaged cells releasing Activated by damaged cells releasing chemical attractants or break in skinchemical attractants or break in skin

• Limits the spread of pathogensLimits the spread of pathogens

Non-Specific Immune CellsNon-Specific Immune Cells• Neutrophils ( 60-70% of WBC’s) First

responders– Enter tissue, phagocytize invaders, die in the process

• Monocytes ( 5% of WBC’s)– Enter tissue, become macrophages (lg. phagocytes),

kills cells by NO, reactive oxygen, and digestive enyzmes in their lysosomes

– Releases cytokines to attract other immune cells– Later act as APC’s (antigen presenting cells) to

specific immune cells

Non-Specific Cells continuedNon-Specific Cells continued• Eosinophils (1.5% of WBC’s) – release Eosinophils (1.5% of WBC’s) – release

granules of enzymes to kill parasitesgranules of enzymes to kill parasites

• Natural Killer Cells – destroy infected cells Natural Killer Cells – destroy infected cells and tumor cells by breaking open their cell and tumor cells by breaking open their cell membranes with a secreted enyzmemembranes with a secreted enyzme

• Basophils and Mast Cells – release Basophils and Mast Cells – release histamine in response to physical damage histamine in response to physical damage or damage by microorganisms – Causes or damage by microorganisms – Causes an inflammatory responsean inflammatory response

InflammationInflammation• Histamine increases blood flow to an area by Histamine increases blood flow to an area by

dilating the pre-capillary arteries and constricting dilating the pre-capillary arteries and constricting the venulesthe venules

• Increases the permeability of bv so immune cells Increases the permeability of bv so immune cells can get into the tissuecan get into the tissue

• Blood leaks into the area causing redness and Blood leaks into the area causing redness and swellingswelling

• Clotting factors activate and complement attracts Clotting factors activate and complement attracts macrophagesmacrophages

• Pus – dead WBC’s and fluid leaked from the bv.Pus – dead WBC’s and fluid leaked from the bv.• Widespread inflammation – causes low blood Widespread inflammation – causes low blood

pressure and high fever (some inflammatory pressure and high fever (some inflammatory cells release pyrogens that reset the brain’s cells release pyrogens that reset the brain’s thermostat) – can die of septic shockthermostat) – can die of septic shock

Non-Specific Immunity - ProteinsNon-Specific Immunity - Proteins

• Chemokines or Cytokines – released from Chemokines or Cytokines – released from damaged cells or other immune cellsdamaged cells or other immune cells– Bind to receptors on immune cells – attract Bind to receptors on immune cells – attract

them to the area or activate themthem to the area or activate them– Cause neutrophils to be released from the Cause neutrophils to be released from the

bone marrowbone marrow– Cause monocytes to produce NOCause monocytes to produce NO– Cause basophils to produce histamineCause basophils to produce histamine– Etc.Etc.

Proteins ContinuedProteins Continued• Complement – 20 proteins (both specific and Complement – 20 proteins (both specific and

non-specific)non-specific)– Non-specific – attracts phagocytes, coats bacteria Non-specific – attracts phagocytes, coats bacteria

making it easier to phagocytize, binds to basophils making it easier to phagocytize, binds to basophils and mast cells causing release of histamine and and mast cells causing release of histamine and inflammationinflammation

– Specific - Binds to 2 Ab bond to antigen and causes Specific - Binds to 2 Ab bond to antigen and causes lysis of invaderslysis of invaders

• Interferon – produced by virus infected cells – Interferon – produced by virus infected cells – makes nearby cells resistant to virus infectionmakes nearby cells resistant to virus infection

• Interleukins – activate other immune cellsInterleukins – activate other immune cells

Specific Immunity Specific Immunity Uses Specific AntigensUses Specific Antigens

• Activity Immunity – your own immune Activity Immunity – your own immune system respondssystem responds

• Pasive Immunity – transfer of antibodiesPasive Immunity – transfer of antibodies– Rabies TreatmentRabies Treatment– Mother’s MilkMother’s Milk

• Humoral – antibodies (proteins) – can only Humoral – antibodies (proteins) – can only attack free pathogens in the bloodattack free pathogens in the blood

• Cell Mediated – can only attack cells Cell Mediated – can only attack cells infected with pathogens and cancer cellsinfected with pathogens and cancer cells

General Information about General Information about Specific Cell Mediated ImmunitySpecific Cell Mediated Immunity

• Primary response – takes 5-10 days for a maximum Primary response – takes 5-10 days for a maximum response against a specific antigenresponse against a specific antigen

• Secondary response – takes 3-5 days for a maximum Secondary response – takes 3-5 days for a maximum response (due to memory cells which divide faster and response (due to memory cells which divide faster and survive longer)survive longer)

• What happens when a T helper cells binds to an antigen What happens when a T helper cells binds to an antigen on an APC?on an APC? The cell makes cytokines that cause The cell makes cytokines that cause specific T killer and B cells to multiplyspecific T killer and B cells to multiply

• What happens when a B cell binds to an antigen on a What happens when a B cell binds to an antigen on a free pathogen?free pathogen? B cell secretes soluble antibodies and B cell secretes soluble antibodies and undergoes mitosis to make more of that B cellundergoes mitosis to make more of that B cell

• What happens when a T killer cells binds to an antigen What happens when a T killer cells binds to an antigen on an infected?on an infected? It makes clones of the T cell and It makes clones of the T cell and secretes perforin to kill the infected cellsecretes perforin to kill the infected cell

MHCMHC

• MHC = major histocompatibility complexMHC = major histocompatibility complex

• Marker proteins on the cell’s surface for Marker proteins on the cell’s surface for immune recognitionimmune recognition

• 200 MHC molecules 200 MHC molecules

• Class I MHC – on all cellsClass I MHC – on all cells

• Class 2 MHC – on macrophages, B and T Class 2 MHC – on macrophages, B and T cellscells

T cellsT cells• T - Helper cellsT - Helper cells

– CD4 cells (part of receptor)CD4 cells (part of receptor)– Recognizes antigen and MHC class II (APC’s)Recognizes antigen and MHC class II (APC’s)– When binds to APC, makes cytokines that act on B and T cells (causes When binds to APC, makes cytokines that act on B and T cells (causes

them to multiply and activate)them to multiply and activate)

• T – Killer cells (cytotoxic T cells) – Steps of T – Killer cells (cytotoxic T cells) – Steps of ActivationActivation

1. Pathogen is eaten by a macrophage (Antigen Presenting Cell or 1. Pathogen is eaten by a macrophage (Antigen Presenting Cell or APC)APC)

2. APC digests the pathogen and displays antigens on MHC class II2. APC digests the pathogen and displays antigens on MHC class II3. T-helper binds and get activated – makes cytokines to activate T 3. T-helper binds and get activated – makes cytokines to activate T

killer cells – only activates T killer as shown belowkiller cells – only activates T killer as shown below4. CD8 cells (part of receptor)4. CD8 cells (part of receptor)

– Recognizes infected or cancerous cells because they are displaying Recognizes infected or cancerous cells because they are displaying antigen on MHC class I (binds to the infected cells)antigen on MHC class I (binds to the infected cells)

– Releases enzymes that punch holes in the infected cell’s membraneReleases enzymes that punch holes in the infected cell’s membrane– Cell explodes releasing pathogensCell explodes releasing pathogens– Pathogen no longer has a place to reproduce – antibodies pick it up or Pathogen no longer has a place to reproduce – antibodies pick it up or

macrophages eat itmacrophages eat it

Immunology You Tube Video

Infected Cell

B cellsB cells• Has antibodies embedded in membrane as receptors / Has antibodies embedded in membrane as receptors /

secretes Ab in soluble form when activatedsecretes Ab in soluble form when activated

Steps of B cell activationSteps of B cell activation• Pathogen is eaten by a macrophage (Antigen Presenting Pathogen is eaten by a macrophage (Antigen Presenting

Cell or APC)Cell or APC)• APC digests the pathogen and displays antigens on APC digests the pathogen and displays antigens on

MHC class IIMHC class II• T-helper binds and get activated – makes cytokines to T-helper binds and get activated – makes cytokines to

activate B cellsactivate B cells• B cells bind to antigens on free pathogens that match the B cells bind to antigens on free pathogens that match the

shape of their receptor (membrane antibodies)shape of their receptor (membrane antibodies)• Only the B cells that bind to antigen get activated by the Only the B cells that bind to antigen get activated by the

cytokines – become plasma cells (make 2000 Ab/sec cytokines – become plasma cells (make 2000 Ab/sec and memory cells (can multiply faster the second time)and memory cells (can multiply faster the second time)

Antibody StructureAntibody Structure

Variable Region makes Variable Region makes different 3-D binding different 3-D binding

sitessites

It is made up of three It is made up of three differerent regions:differerent regions:

Variable region – 400 Variable region – 400 different choicesdifferent choices

Diverse region – 15 Diverse region – 15 different choicesdifferent choices

Joining region – 4 Joining region – 4 different choicesdifferent choices

1 billion different 1 billion different shaped antibodiesshaped antibodies

B cells also B cells also become APC’s become APC’s when activated when activated

and further and further activate T activate T

helpers which helpers which produce more produce more cytokines to cytokines to

activate the B activate the B cells morecells more

Antibody FunctionsAntibody Functions• Bind to antigen (neutralization) – may block the Bind to antigen (neutralization) – may block the

activity (block virus from binding to a host cell, activity (block virus from binding to a host cell, etc.)etc.)

• Clumping or coating bacteria (opsonization) – Clumping or coating bacteria (opsonization) – makes it easier for macrophage to engulfmakes it easier for macrophage to engulf

• Activates complement which punches holes in Activates complement which punches holes in the cell membrane of bacteriathe cell membrane of bacteria