Pathology Immunity Hanouts by Mam Wardah Naeem

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    Pathology By Dr. Wardah NaeemLecture: Immunity

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    IMMUNITY

    Prior Concepts: 5th semester do read about topics like leucocytes, White blood cells,neutrophils, basophils, eosinophils etc

    IMMUNITY: The ability of human body to resist almost all kinds of organisms and toxins thattends to damage the tissues and organs is called immunity.

    Immunity is the bodys ability to fight off harmful micro-organismPATHOGENSthatinvade it.

    Fungi, Protozoans, Bacteria and viruses are all potential pathogens.IMMUNE SYSTEM: It refers to a system composed of specialized cells that fight againstdisease producing bacteria and toxins.

    The immune system produces antibiotics or cells that can deactivate pathogens. The immune system includes all parts of the body that help in the recognition and

    destruction of foreign materials. White blood cells, phagocytes and lymphocytes, bonemarrow, lymph nodes, tonsils, thymus and your spleen are all part of the immune system.

    TYPES OF IMMUNITY

    According to ability of body to develop immunity, it is classified into two types:

    Active immunity Passive immunity

    Active immunity is further divided into two types with respect to bodys ability to develop

    specific or non-specific immunity.

    Immunity

    Passive immunity Active immunity

    Innate immunity Acquired immunity

    Antibody mediatedimmunity

    Cell mediatedimmunity

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    1) PASSIVE IMMUNITY: occurs the antibodies come from some other source. This type ofimmunity is short term.

    Breast milk: milk form a mothers breast contains antibodies. The body is acquiringpassive immunity. These antibodies will only last several weeks.

    Gamma globulin: A gamma globulin shot is pure an injection of antibodies to providetemporary immunity. You might receive a gamma globulin shot if you travel outside ofthe country.

    2) ACTIVE IMMUNITY: occurs when one makes his / her own antibodies. This type ofimmunity is long term.

    Getting the disease: if you get an infectious disease (like chicken pox), often times thatstimulates the production of MEMORY CELLS which are then stored to prevent theinfection in the future.

    VACCINATION: is an injection of a weakened form of the actual antigen that causes thedisease. The injection is too weak to make you sick but your B-lymphocytes willrecognize the antigen and react as if it were the real thing. Thus, you produceMEMORY CELLS for long term immunity.

    a) INNATE IMMUNITY (non-specific): the natural resistance of the body to variousbacteria, toxins and other foreign agents without any specific immune process is calledinnate immunity. Bodys first line defenses (physical and chemical barriers)

    Innate immunity can be obtained by:

    Cellular components: phagocytosis of bacteria and other invaders by white blood cellsand tissue macrophage system.

    Non-cellular components:Destruction by the acid secretions of stomach and by the digestive enzymes of

    organisms swallowed into stomach.Resistance of skin to invasion by organisms.Presence in the blood of certain chemical compounds that attach to foreign organisms

    or toxins and destroy them e.g. lysozymes, basic polypeptide, complement complex.Other examples include tears, saliva, mucous, sweat etc.

    b) ACQUIRED IMMUNITY (specific): human body has ability to develop extremelypowerful specific immunity against invading agents and this is called the acquiredimmunity. Acquired immunity is of 2-types:

    i.HUMORAL (ANTIBODY-MEDIATED) IMMUNITY: in this type of immunity, bodydevelops circulating antibodies which are globulin molecules and are capable ofattacking the invading agents. This type of immunity is composed of specific antibodiessynthesized by plasma cells derived from B-lymphocytes.

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    ii.CELL-MEDIATED IMMUNITY: in this type of immunity body develops large numberof lymphocytes which are specifically activated against foreign agent. These activated orsensitized lymphocytes have the ability to attach to a foreign agent and to destroy it.This type immunity is composed of sensitized T-lymphocytes.

    Acquired immunity is the second line defense of the body. If a pathogen is able to get pastthe bodys first line of defense and an infection starts, the body can rely on its second line ofdefense. The results in what is called an inflammatory response which cause:

    Redness and heat: due to capillary dilation resulting in increased blood flow. Swelling: due to passage of plasma from the blood stream into the damaged tissue. Pain: due mainly to tissue destruction and to a lesser extent swelling.

    ANTIGEN: any invading agent like foreign proteins, organisms, or toxins that can produce animmune response is called an antigen. OR a substance usually protein in nature which whenintroduced into the tissue, stimulate antibody production.

    ANTIBODY: (Immunoglobulin) the specific globulin protein formed in the blood plasma ass a

    reaction to antigen is called antibody. Blood contain three types of globulin: alpha, beta and

    gamma. Antibodies are gamma globulins.

    The antibodies that circulate in the blood stream are called as immunoglobulins (Ig)

    Each antibody is composed of two light chains and two heavy chains. Each chain has a constant

    and variable portion.

    1- Variable portion (Fab fragment) attaches specifically to a particular type of antigen. Itdetermines antigen binding specificity.

    2- Constant portion (Fc fragment) has receptors for attachment to complement complex. Itdetermines physical properties.

    TYPES OF IMMUNOGLOBULIN: (acronym: GAMED)

    IgG:

    It is the most abundant type of immunoglobulin present in serum. It is main antibody in secondary response (while IgM in primary response) It provides an important defense against bacteria and viruses. It is the only antibody that can cross placenta. It is the most abundant immunoglobulin in newborn. It activates complement (IgM also) It acts as opsonin and therefore enhances phagocytosis.

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    IgA:

    It is the main immunoglobulin in secretions such as colostrum, saliva, tears andrespiratory, intestinal and genital tract secretions.

    It prevents attachment of microorganism to mucus membrane. It cannot cross placenta and does not activate complement.

    IgM:

    It is also known as monomeric IgM on Bcell surface and constitutes antigenic receptor. It is the main immunoglobulin produced early in the primary response. It provides defense against bacteria and viruses. It can activate complement. It does not cross placenta.

    IgE:

    It is found in allergies and parasitic reactions. It mediates type I hypersensitivity reactions by causing release of mediators from mast

    cells and basophils upon exposure to antigen.

    It is the main host defense against helminth (worm) nfections such as ascaris, hook worm. It cannot cross placenta and does not activate complement. Its concentration in serum is very low but rises in allergy and helminth infections.

    IgD:

    It occurs in Bcell surface.ROLE OF LYMPHOID TISSUE IN ACQUIRED IMMUNITY

    Acquired immunity is the product ofbodys lymphoid tissue. There are two types of lymphoid

    tissue.

    a- Central lymphoid tissueb-

    Peripheral lymphoid tissue

    CENTRAL LYMPHOID TISSUE:

    Thymus, bone marrow

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    These are the tissues in which primitive lymphoid cells in the fetus are developed and get

    maturation.

    PERIPHERAL LYMPHOID TISSUE:

    Lymph node Spleen Tonsils Gut associated lymphoid tissue Peripheral blood

    These are the tissues in which mature lymphocytes reside and respond to antigenic stimuli.

    CELLS OF THE IMMUNE SYSTEM:

    LYMPHOCYTES: are cells derived from lymphoid stem cells in the bone marrow and develop

    in the fetal life. Lymphocytes may be classified on the basis of their site of development in the

    fetus.

    a- T lymphocytes: develop in thymus of the fetus. Then in adult life in bone marrow.b- B lymphocytes: develop in fetal liver or bone marrow.

    T-LYMPHOCYTES:

    They arise from the stem cells in the bone marrow. They are immature and are taken to the

    thymus for maturation during fetal life. About 80-90% of peripheral blood lymphocytes are T-lymphocytes. Mature T lymphocytes circulate in the blood and pass to peripheral lymphoid

    tissue. e.g.

    a- Paracortical areas of lymph nodesb- Periarteriolar lymphoid sheath in the white pulp of spleen.

    After stimulation or activation by specific antigen, T lymphocytes transform into large actively

    dividing cells known as transformed T- lymphocytes, which then divide to produce effector cells.

    These effector T-lymphocytes are also called sensitized, cytotoxic or killer T-cells.

    T lymphocytes cant be activated by free antigens. They are activated by processed antigenspresented to them by macrophages, dendritic and Langerhans cells.

    T CELL SURFACE MOLECULES:

    T Cell Receptor (TCR): binds to Antigen presented by macrophages and Langerhanscells.

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    CD3 molecular complex: they dont bind to antigens but transduct signals to T cells afterit has bound to antigen. (CD = Cell Differentiation)

    CD4 molecules: are expressed on 60% of mature CD3 + T cells. During antigenpresentation they bind to class II MHC molecules on antigen presenting cells.

    CD8 molecules: are expressed on 30% of mature CD3 + T cells. (So CD4/CD8 ratio is2:1) During antigen presentation they bind to class I MHC molecules on antigen

    presenting cells.

    TYPES OF T - LYMPHOCYTES:

    1- Helper T cell (CD4+) subdivided intoa- Helper inducer T cellsb- Helper suppressor T cells

    2- Suppressor T cells (CD8+)3- Cytotoxic/Killer T cells (CD8+)

    Functions of T - Lymhocytes:

    Cellular immune reaction: They are responsible for cell mediated immunity e.g. against foreign

    histocompatibility antigens, virus infected cells and some tumor cells.

    Regulatory function: They control the T & B cell mediated response through:

    1- T-helper cells which help in the production of T & B cells.2- T-suppressor cells which suppress T & B cell function.

    B - LYMPHOCYTES:

    They also arise from the stem cells in the bone marrow and are taken to some unknown part of

    the body possibly the fetal liver, bone marrow, GIT mucosa for maturation. Mature B-

    lymphocytes are taken to the peripheral lymphoid tissue e.g. lymph node (lymphoid follicles in

    superficial cortex), spleen (lymphoid follicles in white pulp) and Peyers patches of GIT. About

    10-20% of peripheral blood lymphocytes are B- cells.

    Functions of B - Lymphocytes:

    After stimulation by an antigen B cells differentiate into plasma cells that secrete

    immunoglobulins (antibodies).

    Specific antigenic stimulation B lymphocytes lymphoblast plasmoblast plasma cells

    specific antibodies directed against the antigen that caused antibody formation

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    Functions of NK - cells:

    THEY are capable of lysing a variety of tumor cells, virus-infected cells, and fungi without prior

    sensitization hence called natural killer cells. NK cells destroy tumor cells by secreting

    cytotoxins similar to T lymphocytes.

    NK cells have Fc receptors for IgG, so they can lyse IgG- coated target cells. (ADCC: Antibody

    dependent, cell mediated cytotoxicity).

    INTERFERONS:interferons are produced by NK cells that activate macrophages.

    NK cells interferons Macrophage activation

    Whereas, and interferones are produced by virus infected cells that activate NK cells.

    Virus in fected cells , interferons NK cell activation

    DENDRITIC AND LANGERHANS CELLS:

    Dendritic cells are found in lymphoid tissue whereas, Langerhans cells are located in epidermis.

    They have:

    1- Dendritic cytoplasmic processes2- Class II MHC molecules on surface

    Functions:

    These cells themselves are poorly phagocytic in nature. They process and present antigens to

    CD4 + T cells which recognize antigen by binding to class II MHC molecules on dendritic and

    Langerhans cells.

    Further see: difference between innate and acquired immunity, between passive and active

    immunity, between T and B lymphocytes etc.