IMMUNOLOGY

INTRODUCTIONMeasles, symptoms (rash and fever) appear after 8-14 days of infectionIn most cases, anyone surviving this disease will never suffer from it again IMMUNEWhy? while suffering, our body has developed defence mechanism immune system

INTRODUCTION: DiseasesHealth can be defined as a persons physical, mental and social condition. Good health means good physical, mental and social condition Disease is a disorder or malfunction of the mind or body, which destroys good health.Infectious diseases (caused by pathogens) and non infectious diseases (physical, nutrition, inherited, mental etc.)

INTRODUCTION: Infectious DiseasesPathogens are organisms living in or on our bodies, causing disease such as viruses, bacteria, fungi, protoctists, worms and insects, which can be transmitted from person to person. Carriers are people who can transmit the pathogen but do not have the disease symptoms.

Defences against DiseasesPhysical (skin), Chemical (exp: HCl in Stomach) and Cellular (exp: Blood cells) defence mechanismsImmune System is made up of cells that work with the bodys physical and chemical barriers. It helps prevent any pathogen (disease-causing organism) entering your body, and becoming infected

Immune responseOn the surface of all cells are chemical markers (for example, proteins) called antigens. Your body recognises the antigens on your cells as your own (self); anything with different antigens to you (non-self) stimulates an immune response.Pathogens may induce our immune system through pathogens antigens

First Line of DefenceNon specific responses: the same responses for any pathogensPhysical bariers e.g. Skin, Nose, throat and digestive tract Chemical bariers e.g. Eyes: tears, Ear: wax, Stomach: HCl, Sweat: acidic liquid

2nd Line of DefenceNon specific responsesIt is a 3-Steps attack on any microbes that have survived the first line of defence1. Inflammation2. Phagocytes 3. Macrophage and Interferon

2nd Line of Defence : 1. InflammationIt happens because cells damaged by invading pathogens and particular white blood cells release alarm chemicals which makes blood vessels enlarge (vasodilate) and the capillaries more leaky, and thus:1. >> blood (>> White Blood Cells) in site of infection2. WBCs let out into affected tissue, >> Blood = red, swollen, hot, painful

2nd Line of Defence : 2. PhagocytesInflammation attracts WBCs to the area.Neutrophils and macrophages are WBCs which are able to engulf and digest offending pathogens, and thus also called phagocytesPhagocytes are produced and stored in the bone marrow (scavenger, removing any dead cells & invasive phatogens)

2nd Line of Defence : 2. PhagocytesNeutrophils are form about 60 % of WBCs, function to patrol the tissue through capillaries and released during infection (short-lived cells)Neutrophils destroy pathogens by phagocytosis. Infected cells as well as pathogens can release chemicals which attract passing neutrophils to the site (such as Histamin by the infected cells)Dead neutrophils often collect in the site of infection to form Pus

PhagocytosisAttraction (chemotaxis)Recognition: direct attachment or through antibody receptors (surface of neutrophils membrane) for marked pathogens (marked by antibodies)Engulfing (endocytosis) forming phagocytic vacuoleDigesting by fusion of phagocytic vacuole with lisosome (contain hydrolytic enzymes) Killing pathogens

Neutrophils attack the pathogens in this way

2nd Line of Defence : 3. Macrophages and Interferon Other than direct hand-to-hand combat, some killing is done at a distance macrophagesMacrophages : phagocytes, larger than neutrophils, rather than remaining in the blood (as monocytes), they tend to be found in organs e.g. lungs, liver, spleen, kidney and lymph (macrophages)Long-lived cells, initiating immune respones

2nd Line of Defence : 3. Macrophages and Interferon Macrophages make proteins that act in two ways: They can punch holes in the bacteria and parasites so that they die.Or the proteins can stick to the outside of the bacteria to make them more appealing (display its antigens) for the phagocytes to eat!Interferon is chemicals made by infected cells to ultimately prevents that cell from making molecules that the pathogen would need to survive.

2nd Line of Defence : WeaknessesIt cant deal completely with any one particular micro-organism (some pathogens will nearly always survive this attack).It can not remember past infections.This is why a 3rd line of defence is needed

3rd Line of Defence: Lymphocytes Depend on Lymphocytes, made in bone marrow2 Basic Types of lymphocytes (your level):1. B cells ( B Bone marrow), migrate to and then mature in either the bone marrow or in the foetal liver or spleen 2. T cells (T Thymus), mature after migrated from the bone marrow to the thymus glandOnce mature, they patrol around the blood and body, hunting for foreign antigens.

3rd Line of Defence: Lymphocytes 2 Kind of immune response:B cells are involved in the humoral response T cells are involved in the cell-mediated responseOnly mature lymphocytes can carry out immune response. The maturation of lymphocytes is a development process of many different types of B- and T- which is specialized to respond to specific and only one antigen

Humoral immune response it involves substances found in the humours, or body fluids The principal function of B cells in the humoral immune response is to make antibodies against soluble antigens Matured B-cell has a unique receptor protein on the plasma membrane referred as B-Cell Receptor (BCR) that will bind to one particular antigen

Humoral immune response When pathogen invades our body, some of them will be taken up by the marophages to make it more appeal for the appropriate B-lymphocytesOnce BCR bound to this antigen, the development of B-lymphocytes begins as follow:...

Humoral immune response 1. the selected B-cell divide by mitosis2. some daughter cells develop into plasma cells others into memory cells3. plasma cell has main function to secrete antibodies molecules. They are sometimes referred to as antibody factories.4. memory cells are able to live for a long time, and can respond quickly following a second exposure to the same antigen.

AntibodiesImmunoglobulinsSpecificity for certain antigens depend on the variability of amino acids sequences forming the variable regionAntibodies class.: see p. 187 (Cambridge A/AS Level)

AntibodiesThis antibodies action means that:1. The pathogens clumping together make them more vulnerable to phagocytes and reducing the spread throughout the body. 2. The antibody tags the bacteria when it is stuck to it, making it more easily recognisable to phagocytes.3. Together with other molecules, some antibodies punch holes in the cell walls of pathogen causing cell lyses 4. Any antigens acting as toxins in your body are neutralised when the antibody sticks to it, i. e antibodies can act as antitoxins. In a similar way, if a virus has an antibody attached to it, it will no longer be able to attach or enter a host cell.

Infeksi 1st Defence survive 2nd Inflamation Phagocytes (Neutrophils) survive macrophages tagging (marker) Phagocytes (Neut.) survive/ unrecognisable 3rd defence humoral immune response BCR (marker) (primary response) & Memory cell (secondary response) killed antibodies survive/unrecognisable cell mediated immune response

Cell-mediated Immune ResponseT-cell posses special receptor on their cell surface called the T cell receptor (TCR) which has a similar structure to atibodies and specific to 1 antigen.T cells are activated when they meet antigen in contact with another host cell, for example:a. exposed antigen by macrophagesb. help signal on the plasma membrane of pathogen invaded body cellsIf an antigen is presented to a T cell with a complementary shaped receptor, the T cell is stimulated, increases in size and starts to divide (activation T-cell differentiation).

Cell-mediated Immune ResponseT cells differentiation forming 4 groups of specialised T cells:Killer T cells Helper T cells Suppressor T cellsMemory cells

Cell-mediated Immune ResponseHelper T cells: co-operate with B cells in antibody production by producing cytokines that help B-cell to develop into plasma cell. They also activate macrophages (also by cytokines) and promote inflammation.

Cell-mediated Immune ResponseKiller T cells: combine with the antigens on the surface of any invading cell and release a powerful group of chemicals called lymphokines. Some lymphokines kill the pathogens as well as its host cell directly, others stimulate other lymphocytes to become active, and still others increase the inflammation so that there are more macrophages. Suppressor T cells: keep the immune system in check so that once the antigens have been dealt with, the system is switched offMemory T cells: remain after the pathogens have been killed to stop re-infection and activate immune system very quickly in the secondary response

3rd Line of Defence: LymphocytesTypical recognition markers for lymphocytes

LYMPHOCYTE CLASSFUNCTION OF LYMPHOCYTEPROPORTIONPHENOTYPIC MARKER(S)NK cellsLysis of virally infected cells and tumour cells7% (2-13%)CD16 CD56 but not CD3Helper T cellsRelease cytokines and growth factors that regulate other immune cells46% (28-59%)TCR, CD3 and CD4Cytotoxic T cellsLysis of virally infected cells, tumour cells and allografts19% (13-32%)TCR, CD3 and CD8 T cellsImmunoregulation and cytotoxicityTCR and CD3B cellsSecretion of antibodies23% (18-47%)MHC class II, CD19 and CD21

Memory of our immune systemalthough the first infection was dealt with in a few days to a few weeks by the primary response, the secondary response to re-infection is much quicker and much more powerful. Because of this clever system, even if you are re-infected, you may not even know about it because no symptoms show! The infecting organism does not have the chance to cause disease. This is why many diseases can only infect you once.

Memory of our immune systemThis is not infallible though. There are some diseases that come in a variety of guises, for example the common cold and influenza (flu).Although each time you get a cold you have a similar set of symptoms, each new cold is in fact caused by a slightly different virus with slightly different antigens (high rate of mutation in some microorganisms).

Active Immunity Active Immunity occurs naturally during an infection: natural active immunity (activation by infection) artificial active immunity (artificially activated, exp: vaccination)Vaccine small quantities of the antigen attached to the offending organism. To reduce the risk involved when taking the vaccine, the disease itself may have been artificially weakened by taking the disease cell and altering it (as in polio, smallpox and measles vaccines), killing it (as in whooping cough and typhoid vaccines), or by using altered toxins (as in the tetanus vaccine).

Passive Immunity Passive Immunity no activation process, immunity process does not develop by its own body but it is given and thus, short term immunity natural passive immunity (exp: immune system of newborn infants (from their mother), Colostrums) artificial passive immunity (An injection of antitoxin during treatment of tetanus which contains human antibodies taken from blood donors who have recently been vaccinated against tetanus).