Immunology

Immunity – First Line of Defense (Keeping pathogens from getting in) Skin and mucous membranes Epithelium traps pathogen – swallow or expel them from the body Secrete oil and sweat – kills pathogens with a pH of 3-5 Lysozyme is produced by eyes and upper respiratory tract – digests cell walls so kills bacteria

Immunity – Internal White Blood Cells/Proteins Non-Specific Cells (develop in bone marrow) Neutrophils Eosinophils Basophils Moncytes Natural Killer Cells Proteins Specific B-cells originate from bone marrow Make anti-bodies – destroy soluble pathogens T-cells Originate in bone marrow and then go to thymus T-killer – kill tumor cells and infected cells T-helper – activate T and B cells

Non-Specific Immunity Quick, short-lived, activated specific immunity Activated by damaged cells releasing chemical attractants or break in skin Limits the spread of pathogens

Non-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 continued Eosinophils (1.5% of WBC’s) – release granules of enzymes to kill parasites Natural Killer Cells – destroy infected cells and tumor cells by breaking open their cell membranes with a secreted enyzme Basophils and Mast Cells – release histamine in response to physical damage or damage by microorganisms – Causes an inflammatory response

Inflammation Histamine increases blood flow to an area by dilating the pre-capillary arteries and constricting the venules Increases the permeability of bv so immune cells can get into the tissue Blood leaks into the area causing redness and swelling Clotting factors activate and complement attracts macrophages Pus – dead WBC’s and fluid leaked from the bv. Widespread inflammation – causes low blood pressure and high fever (some inflammatory cells release pyrogens that reset the brain’s thermostat) – can die of septic shock

Non-Specific Immunity - Proteins Chemokines or Cytokines – released from damaged cells or other immune cells Bind to receptors on immune cells – attract them to the area or activate them Cause neutrophils to be released from the bone marrow Cause monocytes to produce NO Cause basophils to produce histamine Etc.

Proteins Continued Complement – 20 proteins (both specific and non-specific) Non-specific – attracts phagocytes, coats bacteria making it easier to phagocytize, binds to basophils and mast cells causing release of histamine and inflammation Specific - Binds to 2 Ab bond to antigen and causes lysis of invaders Interferon – produced by virus infected cells – makes nearby cells resistant to virus infection Interleukins – activate other immune cells

Specific Immunity Uses Specific Antigens Activity Immunity – your own immune system responds Pasive Immunity – transfer of antibodies Rabies Treatment Mother’s Milk Humoral – antibodies (proteins) – can only attack free pathogens in the blood Cell Mediated – can only attack cells infected with pathogens and cancer cells

General Information about Specific Cell Mediated Immunity Primary response – takes 5-10 days for a maximum response against a specific antigen Secondary response – takes 3-5 days for a maximum response (due to memory cells which divide faster and survive longer) What happens when a T helper cells binds to an antigen on an APC? The cell makes cytokines that cause specific T killer and B cells to multiply What happens when a B cell binds to an antigen on a free pathogen? B cell secretes soluble antibodies and undergoes mitosis to make more of that B cell What happens when a T killer cells binds to an antigen on an infected? It makes clones of the T cell and secretes perforin to kill the infected cell

MHC MHC = major histocompatibility complex Marker proteins on the cell’s surface for immune recognition 200 MHC molecules Class I MHC – on all cells Class 2 MHC – on macrophages, B and T cells

T cells T - Helper cells CD4 cells (part of receptor) Recognizes antigen and MHC class II (APC’s) When binds to APC, makes cytokines that act on B and T cells (causes them to multiply and activate) T – Killer cells (cytotoxic T cells) – Steps of Activation 1. Pathogen is eaten by a macrophage (Antigen Presenting Cell or APC) 2. APC digests the pathogen and displays antigens on MHC class II 3. T-helper binds and get activated – makes cytokines to activate T killer cells – only activates T killer as shown below 4. CD8 cells (part of receptor) Recognizes infected or cancerous cells because they are displaying antigen on MHC class I (binds to the infected cells) Releases enzymes that punch holes in the infected cell’s membrane Cell explodes releasing pathogens Pathogen no longer has a place to reproduce – antibodies pick it up or macrophages eat it Immunology You Tube Video

Infected Cell

Steps of B cell activation B cells Has antibodies embedded in membrane as receptors / secretes Ab in soluble form when activated Steps of B cell activation Pathogen is eaten by a macrophage (Antigen Presenting Cell or APC) APC digests the pathogen and displays antigens on MHC class II T-helper binds and get activated – makes cytokines to activate B cells B cells bind to antigens on free pathogens that match the shape of their receptor (membrane antibodies) Only the B cells that bind to antigen get activated by the cytokines – become plasma cells (make 2000 Ab/sec and memory cells (can multiply faster the second time)

Antibody Structure Variable Region makes different 3-D binding sites It is made up of three differerent regions: Variable region – 400 different choices Diverse region – 15 different choices Joining region – 4 different choices 1 billion different shaped antibodies

B cells also become APC’s when activated and further activate T helpers which produce more cytokines to activate the B cells more

Antibody Functions Bind to antigen (neutralization) – may block the activity (block virus from binding to a host cell, etc.) Clumping or coating bacteria (opsonization) – makes it easier for macrophage to engulf Activates complement which punches holes in the cell membrane of bacteria