Introduction to Immunology and the Immune System Assistant professor Dr. Aida R. Al-Derzi M.B.Ch.B; M.Sc; FICM/Path Dept. of Microbiology/College of Medicine/Baghdad University
Introduction to Immunology and the Immune System Objectives 1-Define immunity 2-Explain the components of the Innate (nonspecific) immune system & the Adaptive (specific) immune system 3-List the characteristics of innate & adaptive immunity 4-Summarize the main differences between active & passive immunity
5-Discuss the meaning of antigen &immunogen 6- List & Explain the criteria of immunogenicity 7-Discuss the Epitope 8-Define the Adjuvant & Hapten
Immunology IMMUNITY - State of increase resistance to disease - The sum of all naturally occurring defense mechanisms to protect human from infectious agents and their products IMMUNE---- IMMUNIS (Latin word)-------- Exempted from charges (expenses)
Defensive Mechanisms include: 1- Innate immunity (Natural or Non-Specific) 2- Acquired immunity ( Adaptive or Specific )
Innate immunity 1- Mechanical Barriers : a- Intact skin & Mucous membrane b- Mucous * Beating cilia of epithelium of R.T. * Coughing & Sneezing c- Shedding of cells (Mechanical Cleansing Action)
d- Flushing action of saliva, tears, urine.etc e- Vomiting, peristalsis, diarrhea..etc
2- Humoral (Chemical) Barriers Tears ----------- Lysozyme Saliva ---------- Enzymes Skin ---------- Sebaceous secretions Gastric acid Bile acids Trypsin Spermin Lactoferrin, Transferrin
Complement components-----(lytic) System Interferons (IFN) : proteins that are not anti-viral themselves, but induce an anti-viral state in uninfected cells. -Types of interferons: 1- Alpha-IFN-----Secreted by Macrophages 2- Beta-IFN------Secreted by Fibroblasts 3- Gamma-IFN Secreted by T-lymphocytes
Protective action of Interferons: 1- Anti viral proteins 2- Enhancing T- cell activity 3- Activating Macrophages 4- Increasing the cytotoxic action of Natural Killer cells (NK). 5- Enhancing the expression of MHC molecules on cell membrane.
3- Cellular Barriers: A- Phagocytes Specialized cells for capture, Ingestion and destruction of invading microorganisms Polymorphoniclear leucocytes, mainly neutrophils: granulocytes circulate in blood Mononuclear cells - Monocytes in blood------- Macrophages in tissue - Histocytes in connective tissues -Kupffer in liver - Splenocytes in spleen
B- Natural killer (NK) Definition: Large granular lymphocytes Innate cytotoxic lymphocytes Source : Bon marrow precursors Location : 10% or 15% of lymphocytes in peripheral blood 1% or 2% of lymphocytes in spleen Function : Cytotoxic for Tumor cells (immune surveillance) Viral infected cells Bacterial, fungal, parasitic infection Responsible for antibody dependent cell mediated cytotoxicity (ADCC)
Physical factors contribute to innate immunity: 1- Inflammatory process 2- Body temperature 3- Hormonal balance: -Increased susceptibility in endocrine disorders like DM. - Corticosteroids --- depress host s resistance (anti-inflammatory & anti phagocytic effect)
4- Age low levels of immunity at the 2 extremes of life. Fetus/ Neonates - immature immune system Old age - deteriorated immune system, physical abnormalities
Characteristics of NDM Pre-exist Non adaptive Non specific No Memory
Acquired (Adaptive) Immunity Adaptive (Specific) immunity is capable of Recognizing & Selectively eliminating of foreign microorganisms & molecules. TWO Interrelated & Interdependent Mechanisms: 1- Humoral Immunity - (antibody mediated response) - B-cells (Bone marrow derived) 2- Cellular Immunity - (cell mediated immunity) - T-cells (Thymus-derived)
Characteristics of Adaptive Immunity 1- Ability to distinguish self from foreign 2- Antigenic specificity 3- Immunologic memory 4- Diversity The human immune system is capable of producing a vast number of different antibody molecules, each with its own specificities.
Acquired immunities are not always protective Immune Response: Inappropriate------ Allergy (e.g. Hay fever) Directed against body s own constituents--- Autoimmune diseases (e.g. SLE, Rh. Arthritis)
Acquired or Adaptive immunity Active immunity is a resistance induced after contact with foreign antigen. Passive immunity is a resistance based on antibodies preformed in another host.
Active acquired immunity a-natural active acquired immunity : - Following clinical or subclinical infections Ex. measles or mumps, in which immunity is long lasting b- Artificial active acquired immunity : - Following vaccination with live or killed infectious agents or their products
Passive acquired immunity a-naturally passive acquired immunity Antibodies are passed through placenta to the fetus (IgG) b- Artificially passive acquired immunity The injection of already prepared antibodies, such as gamma globulin,antitoxin
Antigens & Immunogens Antigens are molecules that react with antibodies, whereas immunogens are molecules that induce an immune response. Immunogens have the capacity to stimulate the immune system to produce an immune elements & react specifically to it.
Criteria of immunogenicity: 1. Foreignness 2. Chemical structure 3. Molecular weight mol.wt. > 100000 dalton --- potent immunogen mol.wt. < 10000 dalton ----- weak immunoge 4. Dose, Route of Ag administration 5. Genetic constituents of host (HLA genes) 6. Antigenic determinants (Epitopes)
Immunogen or Antigen Possess unique cluster of chemical grouping that serve as the B- or T- cell stimulating sites in the molecule. These sites are called Epitopes. Epitope (Antigenic determinant) Is that portion of antigen with which antibodies and T- cell receptors react.
Epitope structure: Size: 4 5 amino acids(pr.), polysaccharide These are sites with which Ab combine Conformation: - Linear - conformational Site: - Topographic epitopes -Internal
Epitope Function: Epitopes determine the specificity of the antigen molecule. Antigens that share one or more identical or similar epitopes are cross-reactive antigens. Valence of an antigen is equal to the total no. of epitopes that the Ag possesses.
Adjuvants These are chemical substances that enhance the immune response to an immunogen. They act non-specifically by stimulating the immunoreactive cells or by releasing immunogen slowly. Ex. Some human vaccines contain adjuvants such as aluminum hydroxide or lipid.
Hapten: A small organic molecules that are non antigenic & non-immunogenic. Chemical coupling of a hapten to large protein (existing Ag), called carrier, yield an immunogenic hapten-carrier conjugate. Hapten can add a new epitope (i.e. a new specificity) when combined to an existing Ag.
SUMMARY The immune system has TWO arms, innate & adaptive. The innate arm is a barrier system consisting of Mechanical, Humoral, cellular, &physiological components. The innate arm is present intrinsically, has limited specificity & diversity, & is not enhanced by repeated exposure. The adaptive arm consists of T & B lymphocytes & antigen presenting cells.
Adaptive immune responses are specific, diverse, self-limiting, capable of self versus non-self recognition, & display memory. The innate & adaptive arms interact with & augment each other through soluble substances such as complements, antibodies, & cytokines. An antigen or immunogen is a substance capable of activating or generating an immune response. To be immunogenic, a substance must be recognized as foreign & have chemical complexity & sufficient size.
The portion of antigen that fit into an antigen receptor is called Epitope or Antigenic determinant. Haptens are single antigenic determinants that can only generate immune responses if they are linked to larger carrier proteins. Adjuvants increase immunogenicity nonspecifically.
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