The Immune System Chapter 43 ~

Lines of Defense Nonspecific Defense Mechanisms……

PCA: List the organs involved in the immune sytem:

Innate Immunity: Specialized phagocytic white blood cells Antimicrobial proteins Inflammatory response

Innate Immunity: 5 types of Leukocytes Neutrophils 60-70% WBCs; engulf and destroy microbes at infected tissue Short lived Monocytes 5% WBCs; develop into…. Macrophages 1)phagocytosis 2)lysosomal enzymes destroy microbes Dendritic cells: Stimulate development of the acquired immune system

Innate Immunity: 5 types of Leukocytes Eosinophils 1.5% WBCs; destroy large parasitic invaders Enzymatic action- no phagocytosis Natural killer (NK) cells destroy virus-infected body cells & abnormal cells apoptosis

Antimicrobial Proteins: Complement system- group of 30 proteins Once activated can cause invading cells to lyse – burst Interferons (α, β and γ) Immune response to viruses Activates macrophages

The Inflammatory Response Tissue injury; release of chemical signals~ • histamine (basophils/mast cells): causes Step 2... • prostaglandins: increases blood flow & vessel permeability Dilation and increased permeability of capillary~ chemokines: secreted by blood vessel endothelial cells mediates phagocytotic migration of WBCs Phagocytosis of pathogens~ • fever: leukocyte-released molecules increase body temperature

Acquired Immunity: Lymphocyctes •pluripotent stem cells... • B Cells (bone marrow) • T Cells (thymus) Antigen: a foreign molecule that elicits a response by lymphocytes (virus, bacteria, fungus, protozoa, parasitic worms) Antibodies: antigen-binding immunoglobulin, produced by B cells Antigen receptors: plasma membrane receptors on B and T cells

Acquired Immunity: Epitope- antigenic determinant Small area on antigen recognize by lymphcyte

T cell receptors and MHC: Major Histocompatibility Complex (MHC) Antigen presentation- bind to fragments and bring them towards the cell surface Two classes: Class I MHC Class II MHC

MHC Class I MHC(nucleated body cells): recognizes antigen fragments in the cell, binds to them and displays them at the cell surface Cytotoxic T cells will bind and destroy fragments Class II MHC: recognizes antigen fragments in the cell, binds to them and displays them at the cell surface Helper T cells will bind and initiate a process to destroy fragments

Cytotoxic T cell mechanism Destroy cells infected by intracellular pathogens and cancer cells Activity enhanced by CD8 surface protein present on most cytotoxic T cells (similar to CD4 and class II MHC) cell lysis and pathogen exposure to circulating antibodies

Cytotoxic T cell mechanism: the activated cytotoxic T cells release: perforins which form pores in the target cell membrane and proteolytic enzymes which enter the cell via endocytosis and initiate apoptosis Cytotoxic T cell becomes first activated by the secretion of cytokines from helper T cells

Cytotoxic T cell mechanism

Helper T cell mechanism: Function in both humoral & cell-mediated immunity Stimulated by antigen presenting cells T cell surface protein CD4 enhances activation(similar to CD8 of class II MHC) Cytokines secreted (stimulate other lymphocytes): a) interleukin-2 (IL-2): activates B cells and cytotoxic T cells b) interleukin-1 (IL-1): activates helper T cell to produce IL-2

Helper T cell mechanism: a helper T cell recognizes the complex becomes activated with the aid of cytokines secreted by the macrophage forming a clone of activated helper T cells an activated T cell binds to the B cell B cell becomes activated with the help of cytokines

Helper T cell mechanism

Clonal Selection: 1. antigen binds to antigen receptors of a specific lymphocyte 2. the selected lymphocyte proliferates forming a clone of identical cells bearing the same receptors 3. some of the proliferated cells develop into short- lived effector cell(plasma cell if B lymphocyte, helper T cell or cytotoxic T cell if T lymphocyte) that secrete antibodies specific for the antigen or destroy the antigen 4. some proliferated cells develop into long lived memory cells that can respond rapidly upon exposure of the same antigen

Clonal Selection

Induction of Immune Responses primary immune response- the selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to a particular antigen (10-17 days) secondary immune response- if individual is exposed again to the same antigen, the response is faster( 2- 7 days)- immunological memory

Induction of Immune Responses

Types of immune responses Cell-mediated immunity T cell activation Binds to and/or lyses cells Defend against intracellular pathogens such as bacteria, viruses, fungi, protozoa, and parasite s; and cancer cells Humoral immunity B cell activation Production of antibodies Defend against bacteria, toxins, and viruses free in the lymph and blood plasma

Humoral response: B cells Stimulated by T-dependent antigens (help from TH cells) Macrophage (APCs) with class II MHC proteins Helper T cell (CD4 protein) Activated T cell secretes IL-2 (cytokines) that activate B cell B cell differentiates into memory and plasma cells (antibodies)

Antibody Structure & Function Epitope: region on antigen surface recognized by antibodies 2 heavy chains and 2 light chains joined by disulfide bridges Antigen-binding site (variable region)

5 classes of Immunoglobins IgM: 1st to circulate; indicates infection; too large to cross placenta IgG: most abundant; crosses walls of blood vessels and placenta; protects against bacteria, viruses, & toxins; activates complement IgA: produced by cells in mucous membranes; prevent attachment of viruses/bacteria to epithelial surfaces; also found in saliva, tears, and perspiration IgD: do not activate complement and cannot cross placenta; found on surfaces of B cells; probably help differentiation of B cells into plasma and memory cells IgE: very large; small quantity; releases histamines-allergic reaction

Antibody-mediated Antigen Disposal Opsonization: antibody binds to and blocks antigen activity-coats antigen surface enhancing macrophage activity Agglutination: antigen clumping- antibodies contain at least two antigen binding sites Precipitation: cross-linking of soluble antigens- forms immobile aggregates that are disposed of by phagocytosis Viral Neutralization: antibodies bind to certain proteins on the surface of a virus blocking its ability to infect a host cell

Immunity in Health & Disease Active immunity natural: conferred immunity by recovering from disease artificial: immunization and vaccination; produces a primary response Passive immunity: transfer of immunity from one individual to another natural: mother to fetus; breast milk artificial: rabies Transfer of antibodies from rabid(immune) animal to non-rabid (non-immune) animal

Self/Nonself Recognition Self-tolerance: capacity to distinguish self from non-self Autoimmune diseases: failure of self-tolerance; multiple sclerosis, lupus, rheumatoid arthritis, insulin-dependent diabetes mellitus

Blood Group and Transfusions: See PCA: Explain why blood type AB is considered the universal recipient and blood type O is considered the universal donor?

Abnormal immune function Allergies (anaphylactic shock): hypersensitive responses to environmental antigens (allergens); causes dilation and blood vessel permeability Allergy symptoms can be diminished with antihistamines The hormone epinephrine counter acts this allergic reaction Autoimmune disease: Immunodeficiency disease: SCIDS (bubble-boy); A.I.D.S.

Essay: 10pts. 1. Describe the main role of the following cells types: helper T cells, cytotoxic T cells and B cells. 2. What is responsible for the activation of these molecules? 3. What deficiencies, if any would result from an individual born without a Thymus?