Immune System

Overview of Vertebrate Defenses INNATE IMMUNITY Rapid responses to a broad range of microbes ADAPTIVE (ACQUIRED) IMMUNITY Slower responses to specific microbes External defenses Internal defenses Skin Mucous membranes Secretions Phagocytic cells Antimicrobial proteins Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Invading microbes (pathogens) non specific all plants and animals pathogen-specific only in vertebrates involves B and T cells

Innate Immunity ______________________

Avenues of Attack Attack from Outside Attack from inside animals are a tasty nutrient- & vitamin-packed meal cells are packages of macromolecules animals must defend themselves against invaders (pathogens) viruses HIV, flu, cold, measles, chicken pox bacteria pneumonia, meningitis, tuberculosis, Lyme disease Fungi yeast (athlete’s foot) Protists amoeba, malaria Attack from inside cancers = abnormal body cells

Innate Immunity Cellular innate defenses involve specific toll- like receptors: Recognize molecules common to a set of pathogens calling phagocytic white blood cells (WBC) to engulf recognized pathogen.

Innate Immunity 1st Line: Non Specific Barriers Barrier skin Traps mucous membranes, cilia, hair, earwax Elimination coughing, sneezing, urination, diarrhea Unfavorable pH stomach acid pH 2, sweat, saliva, urine Lysozyme enzyme digests bacterial cell walls tears, sweat

Bacteria being engulfed Macrophage destroying yeast Innate Immunity 2nd Line: Non – specific patrolling cells and proteins attack pathogens, but don’t “remember” for next time 1. leukocytes phagocytic white blood cells macrophages, neutrophils, natural killer (NK) cells 2. complement system proteins that destroy cells 3. inflammatory response increase in body temp. increase capillary permeability attract macrophages Bacteria being engulfed Macrophage destroying yeast 3m

Innate Immunity 2nd Line: Non – specific patrolling cells and proteins 1. Leukocytes: Phagocytic WBCs attracted by chemical signals released by damaged cells ingest pathogens digest in lysosomes Neutrophils most abundant WBC (~70%) ~ 3 day lifespan Macrophages “big eater”, long-lived

Innate Immunity 2nd Line: Non – specific patrolling cells and proteins Natural Killer Cells (NK) destroy virus- infected cells and cancer cells recognize abnormal surface roteins on virus infected or cancerous cells perforate cells release perforin protein and insert into membrane of target cell forms pore allowing fluid to flow in and out of cell cell ruptures (lysis) NK cell Perforin Cell membrane Virus infected cell

Innate Immunity 2nd Line: Non – specific patrolling cells and proteins 2. Complement System: anti-microbial proteins ~20 proteins circulating in blood plasma attack bacterial & fungal cells form a membrane attack complex perforate target cell apoptosis cell lysis complement proteins form cellular lesion bacterial cell

Innate Immunity 2nd Line: Non – specific patrolling cells and proteins Inflammatory Response- triggered by tissue damage releases chemical signals: histamines & prostaglandins capillaries dilate, become more permeable (leaky) delivers macrophages, RBCs, platelets, clotting factors increases temperature (inhibits bacterial growth, stimulates phagocytosis, speeds up repair of tissues) fever: if local response is ineffective, system wide response - inhibits bacterial growth and stimulates phagocytois

Adaptive (Acquired) Immunity Lymphatic System : involved in adaptive immunity Body's drainage system Composed of a network of vessels and small structures called lymph nodes Lymph vessels convey excess fluid collected from all over the body back into the blood circulation. These fluids are forced to percolate through the lymph nodes so that they can be filtered. Harmful organisms are trapped and destroyed by the specialized white blood cells (lymphocytes) that are present in these nodes. Lymphocytes are also added to the lymph that flows out of nodes and back to the bloodstream.

Adaptive Immunity Specific defense with memory lymphocytes B cells Lymphatic System Specific defense with memory lymphocytes B cells T cells antibodies Responds to antigens specific pathogens specific toxins abnormal body cells (cancer)

Adaptive Immunity: Lymphatic System

Adaptive Immunity Antigens: substance that elicits lymphocyte response “self” antigens no response from WBCs “foreign” antigens response from WBCs pathogens: viruses, bacteria, protozoa, parasitic worms, fungi, toxins non-pathogens: cancer cells, transplanted tissue, pollen epitope (antigenic determinant) - specific piece of the antigen to which an antibody binds - 5-6 amino acids long

cells learn to distinguish between Adaptive Immunity Uses specialized lymphocytes (WBC) produced by stem cells in bone marrow B cell lymphocytes stay and mature in bone marrow humoral response system “Shumors” = body fluids plasma cells  antibodies attack pathogens still circulating in blood and lymph T cell lymphocytes migrate to and mature in thymus gland (neck) cellular mediated response system attack invaded cells (soldiers who search out and destroy the targeted invaders) Maturation cells learn to distinguish between “self” and “ non-self”

Adaptive Immunity Proliferation of B and T Cells In the body there are few lymphocytes with antigen receptors for any particular epitope In the lymph nodes, an antigen is exposed to a steady stream of lymphocytes until a match is made Binding of a mature lymphocyte to an antigen activates the lymphocyte Once activated, a B or T cell undergoes multiple cell divisions This proliferation of lymphocytes is called clonal selection Two types of clones are produced: effector cells- short lived act immediately against the antigen memory cells- long lived give rise to effector cells if the same antigen is encountered again

Types of Adaptive Response Humoral B Cells (antibodies) Cell Mediated T Cells

Adaptive Immunity Humoral Response (Antibody production) B Cells (lymphocytes) Attack, learn & remember pathogens circulating in blood & lymph Produce specific antibodies against specific antigen Types of B cells plasma cells immediate production of antibodies rapid response, short term release memory cells continued circulation in body long term immunity

Adaptive Immunity: Humoral Response Antibodies: Immunoglobulins (Ig) Made by B cells Proteins that bind to a specific antigen multi-chain binding region matches molecular shape of antigen epitope each antibody is unique & specific

Adaptive: Humoral Response Humoral = Antibodies B Cell Immune Response 10 – 17 days for full response

Adaptive Immunity: Humoral 1° vs 2° Response Memory B cells allow a rapid, amplified response with future exposure to pathogen

Adaptive Immunity: Humoral How Antibodies Work

Adaptive Immunity: Humoral Vaccinations immune system exposed to harmless version of pathogen stimulates B cell system to produce antibodies to pathogen “active immunity” rapid response on future exposure creates immunity without getting disease most successful against viruses Passive Immunity obtaining antibodies from another individual maternal immunity antibodies pass from mother to baby across placenta or in mother’s milk critical role of breastfeeding in infant health mother is creating antibodies against pathogens baby is being exposed to short-term immunity

Adaptive Immunity: Cell Mediated Self vs Non Self Major Histocompatability Complex (MHC) method by which immune system recognizes “self” Set of cell surface proteins essential for the acquired immune system to recognize foreign molecules unique arrangements of proteins on surface of cells (cellular “fingerprint”-different for each person) marks cells as “off limits” to immune system MHC proteins main function: to display foreign antigens on the cell surface for recognition constantly carry bits of cellular material from cytosol to cell surface give surface of cells unique label or “fingerprint”

Adaptive Immunity: Cell Mediated MHC I and MHC II B and T cells bind to MHC molecule in the adaptive response MHC I presents antigens from infected cells & cancer cells triggers cytotoxic T cells MHC II in phagocytic cells = antigen presenting cells present antigens from digested pathogens triggers helper T cells

Adaptive Immunity: Cell Mediated T Cells (thymus cells) activated if the attacker gets past B cells in blood and infects (hides in) cells learn and remember pathogens hiding in infected cells recognize “non self” antigens on cells actively destroy infected cells, as well as to signal other immune cells to participate in the immune response T cell attacking cancer cell

Adaptive Immunity: Cell Mediated Killer T cell binds to infected cell Types of T Cells Cytotoxic T cells (CD8+ T cells) killer cells attack virus infected or cancer cells contain protein (perforin)- punches holes in cells cause cell to burst open other proteins enter cell and trigger apoptosis Helper T cells (CD4+ T cells) alert rest of immune system stumulated by interleukin-1 released by APC activates other T cells activates B cells  humoral response HIV infects helper T cells and destroys them infected cell destroyed

Adaptive Immunity : Cell Mediated Types of T Cells (cont.) Memory T cell long term immunity stored in the lymph nodes and spleen can provide lifetime protection against specific antigens Natural Killer T (NKT) cells (not NK cells) have properties of both T cells and natural killer cells have T-cell receptors. distinguish infected or cancerous cells from normal body cells attack cells that do not contain body cell markers Regulatory T cells (suppressor T cells) suppress the response of B cells and other T cells to antigens stops immune response once it is no longer needed regulatory T cells defects can lead to autoimmune disease

Adaptive Immunity: Cell Mediated Antigen Presenting Cell (APC) APC: cell with foreign antigens on cell membrane (from MHC proteins that carry pieces to cell surface) T cells detect foreign antigens and destroy them. MHC I MHC II

Adaptive Immunity: Cell Mediated T Cell Response once the T-cell receptor binds to the MHC molecule, the antigen-presenting cell secretes cell signaling proteins called cytokines. cytokines signal the T cell to destroy the specific antigen, activating the T cell. activated T cell multiplies and differentiates into helper T cells. helper T cells initiate the production of cytotoxic T cells, B cells, macrophages, and other immune cells to terminate the antigen.

Adaptive Immunity: Cell Mediated Cytotoxic T Cells Attacking cytotoxic T cell attacking cancer cell

Adaptive Immunity B Cells vs T Cells Review humoral response (“in fluid”) defend against extracellular pathogens (invaders in body fluids) by binding to antigens, making pathogens easier targets for phagocytes T cells cell-mediated response defend against intracellular pathogens (invaders inside cells) & cancer cells by binding to & lysing infected cells or abnormal cells

Adaptive Immune Response Review

Immune System: HIV and AIDS Human Immunodeficiency Virus virus infects helper T cells helper T cells don’t activate rest of immune system: killer T cells & B cells also destroys helper T cells AIDS: Acquired ImmunoDeficiency Syndrome infections by opportunistic diseases death usually from “opportunistic” infections pneumonia, cancers

Immune System Malfunctions Auto-immune diseases immune system attacks own molecules & cells lupus antibodies against many molecules released by normal breakdown of cells rheumatoid arthritis antibodies causing damage to cartilage & bone diabetes beta-islet cells of pancreas attacked & destroyed multiple sclerosis T cells attack myelin sheath of brain & spinal cord nerves Allergies over-reaction to environmental antigens allergens - proteins on pollen, dust mites, in animal saliva stimulates release of histamine

Key Attributes of Immune System 4 attributes that characterize the immune system as a whole: 1. specificity antigen-antibody specificity 2. diversity react to millions of antigens 3. memory rapid 2° response 4. ability to distinguish self vs. non-self maturation & training process to reduce auto-immune disease

Immune System Generalized Overview