Pathology By Dr.

Wardah Naeem
Lecture: Immunity IMMUNITY

Compiled By >>>

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 that tends to damage the tissues and organs is called immunity. Immunity is the bodys ability to fight off harmful micro-organism PATHOGENS that invade it. Fungi, Protozoans, Bacteria and viruses are all potential pathogens.

IMMUNE SYSTEM: It refers to a system composed of specialized cells that fight against disease 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, bone marrow, 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 mediated immunity

Cell mediated immunity

Pathology By Dr. Wardah Naeem

Lecture: Immunity

Compiled By >>>

1) PASSIVE IMMUNITY: occurs the antibodies come from some other source. This type of immunity is short term. Breast milk: milk form a mothers breast contains antibodies. The body is acquiring passive immunity. These antibodies will only last several weeks. Gamma globulin: A gamma globulin shot is pure an injection of antibodies to provide temporary immunity. You might receive a gamma globulin shot if you travel outside of the country. 2) ACTIVE IMMUNITY: occurs when one makes his / her own antibodies. This type of immunity is long term. Getting the disease: if you get an infectious disease (like chicken pox), often times that stimulates the production of MEMORY CELLS which are then stored to prevent the infection in the future. VACCINATION: is an injection of a weakened form of the actual antigen that causes the disease. The injection is too weak to make you sick but your B-lymphocytes will recognize the antigen and react as if it were the real thing. Thus, you produce MEMORY CELLS for long term immunity. a) INNATE IMMUNITY (non-specific): the natural resistance of the body to various bacteria, toxins and other foreign agents without any specific immune process is called innate 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 cells and 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 extremely powerful specific immunity against invading agents and this is called the acquired immunity. Acquired immunity is of 2-types: i. HUMORAL (ANTIBODY-MEDIATED) IMMUNITY: in this type of immunity, body develops circulating antibodies which are globulin molecules and are capable of attacking the invading agents. This type of immunity is composed of specific antibodies synthesized by plasma cells derived from B-lymphocytes.

Pathology By Dr. Wardah Naeem

Lecture: Immunity

Compiled By >>>

ii. CELL-MEDIATED IMMUNITY: in this type of immunity body develops large number of lymphocytes which are specifically activated against foreign agent. These activated or sensitized 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 past the bodys first line of defense and an infection starts, the body can rely on its second line of defense. 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 an immune response is called an antigen. OR a substance usually protein in nature which when introduced 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. It determines antigen binding specificity. 2- Constant portion (Fc fragment) has receptors for attachment to complement complex. It determines 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.

Pathology By Dr. Wardah Naeem

Lecture: Immunity
IgA: IgM: IgE: IgD: It occurs in B cell surface.

Compiled By >>>

It is the main immunoglobulin in secretions such as colostrum, saliva, tears and respiratory, intestinal and genital tract secretions. It prevents attachment of microorganism to mucus membrane. It cannot cross placenta and does not activate complement.

It is also known as monomeric IgM on B cell 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.

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.

ROLE OF LYMPHOID TISSUE IN ACQUIRED IMMUNITY

Acquired immunity is the product of bodys lymphoid tissue. There are two types of lymphoid tissue. a- Central lymphoid tissue b- Peripheral lymphoid tissue CENTRAL LYMPHOID TISSUE: Thymus, bone marrow

Pathology By Dr. Wardah Naeem

Lecture: Immunity

Compiled By >>>

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 Tlymphocytes. Mature T lymphocytes circulate in the blood and pass to peripheral lymphoid tissue. e.g. a- Paracortical areas of lymph nodes b- 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 antigens presented to them by macrophages, dendritic and Langerhans cells. T CELL SURFACE MOLECULES: T Cell Receptor (TCR): binds to Antigen presented by macrophages and Langerhans cells.

Pathology By Dr. Wardah Naeem

Lecture: Immunity

Compiled By >>>

CD3 molecular complex: they dont bind to antigens but transduct signals to T cells after it has bound to antigen. (CD = Cell Differentiation) CD4 molecules: are expressed on 60% of mature CD3 + T cells. During antigen presentation 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 is 2:1) During antigen presentation they bind to class I MHC molecules on antigen presenting cells.

TYPES OF T - LYMPHOCYTES: 1- Helper T cell (CD4+) subdivided into a- Helper inducer T cells b- 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 Blymphocytes 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

Pathology By Dr. Wardah Naeem

Lecture: Immunity

Compiled By >>>

NONPOLYMORPHIC MOLECULES ON B LYMPHOCYTES: CD17 & CD20 are two nonpolymorphic molecules present on B cell surface. They are of practical value in classification of lymphoid molecules. (CD = Cell Differentiation)

MACROPHAGES: are the large, mononuclear highly phagocytic cells, occurring in the walls of blood vessels (adventitial cells) and in loose connective tissue (histocytes). They are usually fix but when stimulated by inflammation they become mobile. Functions of Macrophages: They present antigens to immunocompetent T cells. (they process and present antigens to CD$ + T cells which recognize antigen by binding to class II MHC molecules on macrophages. Note: T cells cant recognize free unprocessed antigen) In addition to phagocytosis, macrophages also produce cytokines/monokines: interleukin 1 (IL-1) which promotes the differentiation of both T &B lymphocytes and TNF- (Tissue Necroting Factor) is also produced which is a pro-inflammatory. Macrophages produce CytokinesIL-1enhanced activity of helper T cells Macrophages produce TNF inflammatory response i.e., swelling, redness, pain and edema They lyse tumor cells by secreting toxic metabolites and proteolytic enzymes thus play a role in immunosurveillance. They act as powerful effector cells in certain forms of cell-mediated immunity, such as the delayed hypersensitivity reactions (type IV). NATURAL KILLER CELLS: are large granular lymphocytes because they contain azurophilic cytoplasmic granules. They are peripheral blood lymphocytes (10-15%). They differ from T and B cell function and are also larger than B&T cells. They are lymphocytes in nature but do not pass through thymus for maturation. NK cells are devoid of cell surface immunoglobulins. They do not have immunological memory and dont have T cell receptors. NK cells have a basic role in innate immunity and are considered to provide first line of defense against tumors and virus infections. Surface molecules on NK cells are CD2 CD16 (Fc receptor for IgG) CD56

Pathology By Dr. Wardah Naeem

Lecture: Immunity
Functions of NK - cells:

Compiled By >>>

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 processes 2- 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.