Immune System 4410
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This 13 page Class Notes was uploaded by LilBe Notetaker on Thursday June 16, 2016. The Class Notes belongs to 4410 at Nova Southeastern University taught by in Summer 2016. Since its upload, it has received 10 views. For similar materials see Physiology and Pathophysiology in SCCP - SC College of Pharmacy at Nova Southeastern University.
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Date Created: 06/16/16
ADAPTIVE IMMUNITY Recognizes and targets only particular pathogens or SPECIFIC foreign substances. Immunocompetance each lymphocyte recognizes its one specific antigen by binding to it. SYSTEMIC Immunity is not restricted to the initial infection site. “MEMORY” After an initial exposure, it recognizes and mounts even stronger attacks on previously encountered pathogens. The DUAL Nature of the Adaptive Immune System The adaptive immune system is divided into two parts, each responsible for dealing with pathogens in different ways. Antibody- mediated immunity Directed at freely circulating pathogens. HUMORAL B cells Involves antibodies. The recognition of different antigens depends on receptors to the antigens that coat the surface of the B cell. Cell- mediated immunity Directed at intracellular pathogens. CELLULAR T cells Eliminate intracellular pathogens. Reject foreign tissue recognized as nonself. Destroy tumor cells. Antigen- presenting They don’t respond to specific antigens, but they APCs cells play auxiliary roles. B cells T cells Type of immune response Humoral Cellular Antibody secretion YES NO EXTRACELLULAR INTRACELLULAR pathogens pathogens Primary targets bacteria, virus-infected cells fungi, cancer cells parasites (in extracellular fluid) Origin Red bone marrow Red bone marrow Maturation Red bone marrow Thymus Effector cells Helper T cells HT ) Plasma cells Cytotoxic T cellsC(T ) Regulatory T cellsReg) Memory formation YES YES Elimination process Clonal deletion Thymic selection Specificity Coating of immunoglobulins TCRs (T-cell receptors) Response Antibodies Antigen presentation (B cells exposed to antigens) Effector cells the cells that do the work of fighting infection. Memory cells the cells that are able to respond quickly after any subsequent encounter with the same antigen. ANTIGENS Antigens (Ag) (Immunogen) any substance that causes antibody formation. They are substances that can mobilize the adaptive defenses and provoke an immune response. Antigens provoke a highly specific immune response that results in the production of antibodies that are capable of recognizing the antigen that gave rise to them. Antigenic compounds: capsules, cell walls, flagella, fimbriae, toxins of bacteria. ANTIGENIC DETERMINANTS Immunogenic A specific region on the surface of an antigen that interacts EPITOPES with antibody. They can be recognized by the host by means of receptors and serve as warning flags of an invading organism. Each antigen carries more than one epitope. Each Y-shaped antibody molecule has at least two binding sites that can attach to a specific epitope on an antigen. INCOMPLETE ANTIGEN Reactive butNOT Immunogenic A substance of low molecular weight that doesn’t cause the formation HAPTENS of antibodies itself but does so when combined with a carrier molecule. Once an antibody against the hapten has been formed, the antibody will react with the hapten independent of the carrier molecule. Penicillin not antigenic itself, but some people develop an allergic reaction to it. Self- Antigens MHC proteins Self- antigens are not foreign or antigenic to you, but they are strongly antigenic to other individuals. MHC proteins the cell surface proteins that identify a cell as self. MHC Major Histocompatibility Comples Antigen- Presenting Cells (APCs) Antigen-presenting cells (APCs) engulf antigens and then present fragments of them, like signal flags, on their own surface where T cells can recognize them. Antigen fragment (Ag) +MHC class II on APC surface. Naive T cells can only be activated by antigens that are presented to them on MHC proteins by APCs. ONLY MHC class II are present on Antigen- Presenting Cells (APCs). Long extensions dendrites. Dendritic cells Important in the activation of CD4 T cells and in developing their effector functions. They present antigens to T cells to be activated themselves. Macrophages Effector T cells release chemicals that activate macrophages. B cells They present antigens to helper T cells. ANTIBODIES Antibodies (Immunoglobulins, Ig) are gamma globulin proteins made in response to an antigen and can recognize and bind to the antigen. Monomer- is the simplest antibody with 2 identical halves. 1. A site that bind to epitopes. 2. V regions of the heavy and light chains combine. 3. It consists of: Antigen- binding site Heavy (H) chain Light (L) chain 4. The number of antigen-binding sites determines VALENCE of the antibody. Variable (V) region Constant (C) region The same in all antibodies of a given class. They are the effector regions of the antibody that dictate: The cells and chemicals of the body the antibody can bind to. Fc (stem) region It can attach to a host cell. How the antibody class functions to eliminate antigens. It can be bounded by macrophages. MECHANISM OF ANTIBODY ACTION Antibodies themselves cannot destroy antigens. They can inactivate antigens and tag them for destruction. 1. Antigen- antibody complex a) The combination of an antigen with the antibody that is specific for it. b) Characteristics: Affinity the strength of the bond between an antigen and an antibody. Specificity Outcomes of antigen- antibody reaction: IgG antibodies block specific sites on viruses or bacterial toxins. NEUTRALIZATION It blocks attachment to receptors on tissue cells. The process of causing clumping (agglutination). It is possible because each antibody has at least two antigen-binding sites. AGGLUTINATION IgM is a very effective agglutinating agent numerous binding sites (pentamer). Antigen is coated with antibodies that enhance its ingestion and lysis by phagocytic OPSONIZATION cells. Triggered bIgG or IgM Several antibodies bind close together on the same cell. the complement binding sites on their stem regions align. ACTIVATION OF This triggers complement fixation into the antigenic cell’s surface Cell lysis. COMPLEMENT Characteristics: o INFLAMMATION o Promote PHAGOCYTOSIS by opsonization Organisms that are too large to be phagocytized. ANTIBODY- ADCC is effective in destroying EUKARYOTIC PATHOGENS. Resembles opsonization, but destruction of the target cell is external DEPENDENT to the target cell. CELL-MIGRATED CYTOTOXICITY The pathogen is coated with antibodies. (ADCC) A variety of cells of the immune system biCd to the F regions of the antibodies. The target cell is lysed by substances secreted by the attacking cells. HUMORAL IMMUNITY Each B cell carries immunoglobulins on its surface that are part of its makeup. The majority are IgM and IgD. Clonal Selection of a B cell Clonal selection The development of clones of B and T cells against a specific antigen. Class switching Ability of a B cell to produce a different class of antibody against one antigen. Clonal deletion The elimination of B and T cells that react with self. Stem cells mutate and differentiate into B cells. Each B cell bears surface immunoglobulins specific for one antigen. B cells must be exposed to free or extracellular antigens. 1. ACTIVATION of a B cell B cell’s immunoglobulins bind to the epitope. B cells usually require the assistance of T helpHr cell (T ). Antigen contacts the surface immunoglobulins on the B cell. It is enzymatically processed within the B cell fragments of the antigen combines with MHC class II. T- dependent The combination of the antigenic fragments and the MHC II are displayed on antigen the B cell’s surface for the receptors on the T helper cells to identify. MHC class II is only found on the surface of APCs. TH cell in contact with the antigenic fragment on the surface of the B cell becomes activated and produces cytokines. Antigens that stimulate B cells directly without the help of T cells. Those antigens usually have repeating subunits (polysaccharides or T- independent lipopolysaccharides) and can bind to many B receptors. Characteristics: antigen Provoke a weaker immune response. Only IgM Memory cell are NOT generated. 2. CLONAL EXPANSION proliferation of activated B cells. Most of the clones differentiate into: PLASMA CELLS The antibody- secreting effector cells of the humoral response. MEMORY CELLS They can mount an immediate humoral response if they encounter the same antigen again in the future. IMMUNOLOGICAL MEMORY Antibody titer the relative amount of antibody in the serum. - Occurs on first exposure to a particular antigen. Primary response - Plasma antibody levels rise, reach peak levels (in about 10 days) and then decline. - IgM followed by IgG - Responses are faster, more prolonged, and more effective. Secondary response - Antibodies bind with greater affinity and their blood Memory (anamnestic) levels remain high after the infection. response - Produces more antibodies than the primary. - Reach peak in 2-7 days. - Cells involved: Memory B cell and Plasma Cells. Adaptive Immunity (Humoral Immunity) ACTIVE - Infection Naturally acquired - Contact with pathogen PASSIVE Antibodies passed from mother to fetus via placenta or to infant via the mother’s milk. ACTIVE - Vaccine Artificially acquired - Dead or attenuated pathogens PASIVE Antibodies (gamma globulin) in serum CELLULAR IMMUNITY 1. Cellular immunity depends on T cells to: Eliminate intracellular pathogens Reject foreign tissue recognized as nonself Destroy tumor cells 2. Thymic selection Elimination of T cells that don’t recognize self- molecules MHC. Clusters of differentiation (CD) cell differentiation glycoproteins. They play a role in interactions between T cells and other cells. Effector cells of cellular immunity: Helper T cells 1. Activate: (TH) B cells Regulatory T Other T cells CD4 cells Reg) MHC class II Macrophages 2. Direct the adaptive immune response. CD8 Cytotoxic T MHC class I cells (T ) C ANTIGEN PRESENTATION T cells can recognize and respond only to PROCESSED fragments of protein antigens displayed on surfaces of APCs and others. MHC proteins the cell surface proteins on which antigens are presented. MHC class I MHC class II APCs Displayed by All body cells Dendritic cells Macrophages B cells Naïve CD8 cells Naïve CD4 cells Recognized by Cytotoxic T cells CT ) Helper T cells ENDOGENOUS EXOGENOUS Fragments of proteins Phagocytized extracellular Antigens on MHC synthesized inside the cell. pathogens Cancerous cells MHC class I: Act as antigen holders “I belong to self, but have “I belong to self, but have captured a foreign invader. captured a foreign invader. This is what it looks like. KThis is what it looks like. Help any cell that displays it.” me mount a defense against Send a message to TC it.” “I belong to self, but have been invaded or become cancerous. Kill me!” ANTIGEN BINDING TCR T- cell receptors Cellular Immunity TLR Toll- like receptors Humoral Immunity TCR must perform DOUBLE RECOGNITION they must recognize both: MHC (self- antigen) The foreign antigen on MHC Activation of CD4 1. Dendritic cell engulfs an antigen, processes it into short peptides, and displays its fragments on MHC class II proteins. 2. BOTH TCR and CD4 bind to an antigen-MHC complex on the surface of an APC. ANTIGEN BINDING 3. TCR performs DOUBLE RECOGNITION Recognize both: MHC (self- antigen) The foreign antigen on MHC Co-STIMULATORY signals appear on the surfaces of APCs in tissues that are damaged or invaded by pathogens. 4. APCs produce co-stimulatory signals. C0- STIMULATION 5. Co-stimulation is crucial for T cell activation (that have not previously encountered antigen). 6. T cell are activated by: Antigen binding Co-stimulation 7. APCs or activatedHT cells produce cytokines. 8. Activated CD4 T cells proliferate (clone) and become: PROLIFERATION Memory cell and Effector cells DIFFERENTIATION 9. Period of apoptosis the activated T cells die off. IMORTANCE: T cells produce huge amounts of inflammatory cytokines. Cytokines may promote cancer in chronically inflamed tissue. 10. Cytokines are cell mediators that influence: Cell development CYTOKINES Differentiation Responses in the immune system 11. Cytokines include: interferons and interleukins. Helper T cells (T ) H 1. Mobilize both Humoral and Cellular immunity. 2. Activated H cells activate B and T cells and induce their proliferation. 3. Activation of B cells TH cells interact directly with B cells displaying antigen fragments bound to MHC II class. TH cells release interleukins as co-stimulatory signals to complete B cell activation. B cells divide as lonH as T stimulation is present. CYTOTOXIC T cells (T ) C 1. The ONLY T cells that can directly attack and kill other cells. 2. They circulate: Throughout the body in and out of the blood and lymph and Through lymphoid organs in search of body cells displaying antigens that the T can recognize. C 3. Two mechanisms of target cell killing: Perforin- creates large pores in the target cell’s Perforins and granzymes membrane. Granzymes- induce apoptosis, able to enter through the pores. Stimulate the target cell to undergo apoptosis REGULATORY T cells (T Reg ) Suppressor cells 1. Slows or stops activity of immune system. 2. Important in controlling autoimmune diseases.
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