Requirements for protective immune response• be able to detect foreign object• prevent host from being killed by foreign object• limit replication of foreign object in host• limit damage to host by foreign object and immune system
Types of Infectious Agents• 5 groups 1. Viruses 2. Bacteria 3. Fungi 4. Protozoans 5. Helminths
Physiological Barriers• Defecation and Vomiting-expel microbes• pH‐Stomach, vagina, and skin• Normal microflora of GI tract, skin• Chemical Mediators – Hydrolytic enzymes of Saliva – Lysozyme in tears
• Inflammatory Barriers• injured cells release a protein called HISTAMINE, which starts the a series of changes called the Inflammatory Response Histamine increases blood flow to the injured area and increases the permeability of the surrounding capillaries, as a result, Fluid and White Blood Cells (WBC) leak from blood vessels into nearby tissue.• fever– Fever is an abnormally high body temperature. It occurs during infection and inflammation. Elevated temp. intensifies effects of interferons, inhibits growth of microbes and speeds up body reactions that aid repair.
organismuse preformed produce specificcomponents to componentsnon-specifically directed againstclear the agent the agent
Components of the Immune Components of the Immune System System Nonspecific Specific innate adaptive Humorall Cellular Humoral Cellular macrophages, T cells; otherinterferon, neutrophils antibodies effectors cells NK cell
Characteristics of Innate and Adaptive Characteristics of Innate and Adaptive Immunity ImmunityInnate Immunity Adaptive ImmunityAntigen independent Antigen dependentNo time lag A lag periodNot antigen specific Antigen specific No Immunologic Development memory of memory
Non specific cellular• Macrophages• Neutrophiles• Natural killer cells
NEUTROPHIL• The most common Phagocyte, 50 to 70 percent of the White Blood Cells in the body.• circulate freely through blood vessels.• They then engulf and destroy any pathogens they encounter
MACROPHAGE (big eaters)• they consume and destroy any pathogens they encounter,• Macrophages present pathogen antigen to cells
NATURAL KILLER CELLS• are large white blood cells• attack cells that have been infected by pathogens, Not the Pathogen Themselves.• They are particularly effective in killing Cancer Cells and Cells Infected with Viruses.• A Natural Killer Cell punctures the cell membrane of its target cell, allowing water to rush into the cell, causing the cell to burst• NK cells are Activated by IFN- alpha/beta
IFN• Interferons are proteins produced by cells infected with viruses,• protect other cells against virus infection or decrease drastically the virus yield from such cells.• Interferon itself is not directly the anti-viral agent, but it is the inducer of one or many anti-viral mechanisms
Activities of interferon Antiviral actionsInterferon initiate an antiviral state in cellsInterferons block viral protein synthesisInferons inhibit cell growth Immunomodulatory actionsInterferons-alpha and IFN-beta activate NK cellsInterferon activates macrophagesInterferon regulate the activities of T cells Other actionsInterferons regulate inflammatory processesInterferon regulate tumor growth
Mechanism of action• Release from an initial infected cell occurs• IFN binds to a specific cell surface receptor on an other cell• IFN induces the “antiviral state” :• Inhibition of viral and cellular protein synthesis occurs
Interferon “priming” Interferons are produced in response toa viral infection and spread to the nearby cells where they activateinterferon-stimulated genes (ISGs), which are responsible for theestablishment of an “antiviral state” by preventing viral replication andalso alert the immune system.
The Complement System heat-labile antibacterial substance in immune serum kills bacterianon immune (normal) serum……………noimmune serum……………………….….. Yesheated* immune serum…………………. noheated immune serum plusnon-immune serum………………….…. yes 560C for 30 minutes or 600C for 5 minutes
complements• Conclusion: Two components are needed for bacterial inactivation: a heat-stable immune component (antibody)• and a heat-labile non immune component (complement).
But if all that is not enough …IF A PATHOGEN IS ABLE TO GET PAST THE BODYS NONSPECIFIC DEFENSES, THE IMMUNE SYSTEM REACTS WITH A SERIES OF SPECIFIC DEFENSES THAT ATTACK THE DISEASE CAUSING AGENT.This is called the IMMUNE RESPONSEA SUBSTANCE THAT TRIGGERS THE SPECIFIC DEFENSES OF THE IMMUNE SYSTEM IS KNOWN AS AN ANTIGEN.AN ANTIGEN IS A SUBSTANCE THAT A MACROPHAGE (WBC) IDENTIFIES AS NOT BELONGING TO THE BODY.
Specific (adaptive) immunity Antigen Specific: Immune response specific to component of pathogenHumoral Active/passive Cellularantibodies T cells
Sites Occupied By Pathogens• Extracellular - site of most bacteria - elicits antibody (humoral) response• Intracellular - site of viruses, ,some bacteria, fungi, rickettsiae and protozoa - elicits cell-mediated response
HUMORAL IMMUNITY• The production of antibody molecules in response to an antigen; mediated by B- lymphocytes.
This message activates T-helper cells and triggers theimmune response. Once the T cell has read the antigens, itwill send out messages to activate other cells, known as Bcells
The activated B cell will then produce millions of antibodiesThe antibody is a protein that will bind to an antigen. Eachantibody is unique and specific; for example, a measlesantibody will only bind to a measles virus. We produceantibodies because, given the high concentration of infectiousagent that is needed to cause disease, our macrophages couldnot go after the invaders alone. However, antibodies canoutnumber the invaders and help us get rid of them.
How do the antibodies bind to the infectious agent? Theantibody resembles the mirror image of the antigen (like a keyand a lock), usually providing such a close fit that, if they bumpinto each other, the antibody will grab the antigen and hang onOnce an antibody has "caught" an invader, it will broadcast asignal that says "eat me and
A macrophage will in turn get themessage and will devour theantibody-antigen complex and ridthe body of the infectious agent
Eventually, as this process continues,the number of infectious agents willdecrease and the body will need to stopthe battle. However, all the cells arestill activated and the immune systemneeds to put them to rest. Another kindof T cell, the T-suppressor cell (or T8cell), will send out messages to theother cells and "de-activate" them).Without the T-suppressor cells, thebody would continue trying to fight offa disease that no longer exists (andeventually would end up fighting itsown cells).
Antibodies• also called immunoglobulins or Igs• constitute the gamma globulin part of the blood proteins.• They are soluble proteins secreted by the plasma offspring (clones) of primed B cells.• The antibodies inactivate antigens by, – (a) complement fixation (proteins attach to antigen surface and cause holes to form, i.e., cell lysis), – (b) neutralization (binding to specific sites to prevent attachment—this is the same as taking their parking space), – (c) agglutination (clumping), – (d) precipitation (forcing insolubility and settling out of solution),
Cell mediated immunity• Mediated by T lymphocytes.• An immune response against intracellular microbes,such as viruses and some bacteria, survive and proliferate inside phagocytes and other host cells, where they are inaccessible to circulating antibodies.• Promotes destruction of microbes within phagocytes or killing of infected cells.
CELL-MEDIATED IMMUNITY• The production of cytotoxic T-lymphocytes and cytokines in response to an antigen; mediated by T-lymphocytes.
T cell• Cytotoxic or killer T cells (CD8+) – do their work by releasing lymphotoxins, which cause cell lysis.• Helper T cells (CD4+) – serve as managers, directing the immune response. They secrete chemicals called lymphokines that stimulate cytotoxic T cells and B cells to grow and divide, attract neutrophils, and enhance the ability of macrophages to engulf and destroy microbes.• Suppressor T cells – inhibit the production of cytotoxic T cells once they are unneeded, lest they cause more damage than necessary.• Memory T cells – are programmed to recognize and respond to a pathogen once it has invaded and been repelled.
CYTOKINES• A wide variety of intercellular regulatory proteins produced by many different cells in the body which ultimately control every aspect of body defense.• Cytokines activate and deactivate phagocytes and immune defense cells,• increase or decrease the functions of the different immune defense cells, and promote or inhibit a variety of nonspecific body defenses.
Cellular Immunity Infected cells Pathogen engulfed by Perforin Foreign antigen Infected cell lyses Macrophage Cytotoxic T cellDisplays antigenson surface and Attacks infected cellstimulates T cell Stimulates Helper T cell Cytotoxic T cell