Humoral Immune Response II 2024-2025 PDF

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer...

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor explanation Abbreviation Key information Book >> >> Fatimah Alrufayi Zinab Alabbad Student explaintion 221-222-223 notes References Deleted Humoral Immune Response II Dr. SayedA. Quadri 1. Functions of various classes immunoglobulins. 2. The role of NK cell in antibody dependent cellular (ADCC). 3. Cells bind IgEantibodies. cytotoxicity 4. Complement activation. Role of antibodies. 5. Function of the complement system. 6. IgA; role and mechanism of action. 7. Foetalprotection by maternal antibodies  Antibodies Protective antibodies are produced during the first (primary) response to a microbe and in larger amounts during subsequent (secondary) responses. Antibodies use Fab regions to bind to and block the harmful effects of microbes and toxins, and they use their Fc regions to activate diverse effector mechanisms that eliminate these microbes and toxins. 5 classes (Isotypes) of IgG, IgA, IgM, IgEand IgD. Antibody structure Antibody structure  complement pathway : 1- classical pathway 2- alternative pathway 3- lactic pathway one of these pathway activated by antibody which is classical pathway by IgG Maternal antibodies can pass across placenta and enter the fetus Q: which of the following class of immunoglobulin It’s abbreviated: ADCC confer neonatal immunity? IgG regulation of B lymphocytes activation Immunoglobulin functions Functions of Immunoglobulins Have two fundamental characteristics: 1- Specificity 2-Biologic Activity: Neutralization, Opsonization, Antibody dependent cellular cytotoxicity ADCC, Complement activation. especially classical pathway of complement activation  1-Neutralization Of Microbes & Microbial Toxins Antibody blocks penetration of microbe through immunoglobulin or antibodies against microbial epithelial barrier as GIT&RT. surface antigen which are involved in adhesion of microbes to the host cell the 1st step of infection : adhesion which specific binding of some microbial surface proteins with host Antibody blocks binding of microbe to host cell and so cell molecules on the host cell surface that determind the host specificity and tissue specificity prevent cells infection. of any organism so , if immunoglobulin formed against microbial Antibody blocks binding of toxin to cellular receptors. antigen on the surface of microbe this microbial antigen is involved in the adhesion of the microb to the host cell like epithelial cell , the binding will not take place because block by antibody so this is It was the idea of serum immunotherapy for diphtheria……. called neutralization of microbes 1stNobel prize in medicine. becterial toxins : exotoxins and endotoxins which becteria exotoxins are lethal ( serious consequences) ? tetani toxin is an exotoxin produced by a bacteria called as Clostridium tetani. This is a neurotoxin can produce paralysis, rigid paralysis of the skeletal muscles and leading to death. toxins can be neutralized by immunoglobulins or antibodies called antitoxins. So that they cannot produce the lethal action. So that's called as neutralization of toxins.  If there is a microbe that infects a particular cell, And it will produce the infection of the cell, of the tissue. for example, Microbacterium tuberculosis and antibody formed against Leishmania,Which is a parasite, the antigen that prevent not a bacteria. Leishmania. entry of microbes through Leishmania produces infection of epithelial surfaces macrophages. first step of infection is adhesion and then entry inside the cell and they multiply ultimately the cell ruptures. then they go to another cell. If there is antibodies formed against such organisms, it wouldn’t produce infection. Toxin also, they act through binding to the receptor for the toxin on the cell. And then they produce the effect. if there is an immunoglobulin antibody against the toxin, that will block the binding of the toxin to the receptor on the cell and this is called as neutralization..  2-Opsonization And Phagocytosis opsonization : enhanced phagocytosis Antibodies coat microbes and promote their ingestion by phagocytes (facilitated or enhanced). Opsonin is a moleculethat coat microbe to enhance its phagocytosis e.g IgG,C3b. Another mechanism of opsonization Substances produce opsonization called opsonin Antigen - Antibody complex → Classical complement activation C3b produce , one igG , another C3b (complement byproduct ) Pathway activation c3b deposit , the phagocytic cells have C3b deposit on the microb due to presence of Microbe presence → Alternative Pathways receptor for c3b through the receptor microb it will take alternative pathway activation they bind and enhance phagocytosis IgG1 and IgG3, their Fc regions bind to a high-affinity receptor for the Fc regionsof γheavy chains,calledFcγRI (CD64). A major mechanism of defense against encapsulated bacteria as pneumococci  Phagocytic cells : macrophages, neutrophils steps of phagocytosis 1st :binding of microbe to phagocytic cell to innate immune receptor like Toll like receptor this will lead to phagocytosis if there is microbial surface antigen against antibodies produced binding with those antigen this will enhance phagocytosis HOW ?? phagocytic cells has receptor Fc region for IgG called FcγR through FcγR is bound this will enhance and increase phagocytosis Antibody-mediated opsonization and phagocytosis of microbes 3-Antibody dependent cellular cytotoxicity (ADCC) ADCC mediated by natural killer cell Natural killer (NK) cells and other leukocytes may bind to antibody- coated cells and destroy these cells. NK cells express anFcγreceptor called FcγRIIIA(CD16) receptor for Fc, which is one of several kinds of NK cell–activating receptors. Activated NK cell discharge its granule proteins, which kill the opsonized cell. MCQ : which of the following cell are involved in antibody dependent cellular cytotoxicity? A. Macrophage B. Dendritic cell C. Neutrophil D. Natural killer cell ANS: D  ADCC important in: 1-Cells infected with enveloped viruses. 2-Therapeutic antibodies used to treat cancers we will not get through therapeutic application Don’t worry about the number and CD16 Microbe is coated with IgG→ NK Cell Fc Receptors bind IgG→ Release of Perforins and Granzymes→ lysis Cells ADCC 4- Ig E and Eosinophil/ Mast Cell-Mediated Reactions IgEantibodies activate mast cell and eosinophil reactions as they have Fc receptor for IgE(FcεRI). These reactions Against helminthic parasitesand allergic diseases. Eosinophil release content of the granulesthat can kill the worms also, mast cells secrete cytokines, including chemokines, that attract more leukocytes to destroy the helminths. IL-5secreted by Th2 cells enhances eosinophils to kill the helminths  how the immune system uses eosinophils to fight In infected organisms, against helminths (parasitic worms): helminthic parasites stimulate 1. Activation by Th2 cells: the production of IgE Specialized immune cells called Th2 cells release a signaling molecule called IL-5. antibodies. These antibodies IL-5 acts on eosinophils and activates them, bind to antigens on the preparing them to fight the infection. helminths. Eosinophils can bind 2. Eosinophil recognition of the parasite: to such IgE because they have a The worm (helminth) is coated with IgE antibodies receptor called FcεR (Fc epsilon (produced earlier by the immune system). Eosinophils have receptors called FcεRI that can receptor) for IgE. When this bind to these IgE antibodies, allowing eosinophils binding occurs, it leads to the to recognize and attach to the parasite. release of eosinophil granules 3. Granule release: containing certain proteins, Once eosinophils bind to the parasite, they such as major basic protein release toxic substances stored in their granules. These substances are specifically harmful to the (MBP) and cationic eosinophilic helminth, damaging its structure. protein. These proteins act on 4. Helminth death: the helminthic membrane, The toxic contents of the eosinophils kill the causing lysis and ultimately helminth, helping the immune system eliminate leading to the death of the the infection. parasite.  Functions of Immunoglobulins by make MAC :membrane attack complex Complement byproducts that increase inflammation, MCQ: like C3a and C5a, lead to an increase in which of the following neutrophils in the site of complement by product infection.which results produce inflammation? in increased C3a and c5a inflammation.  functions of immunoglobulins (antibodies) in fighting infections: 1. Neutralization: Antibodies block microbes and toxins, preventing them from entering or harming cells. Complement activation sequences 2. Opsonization and phagocytosis: Antibodies include opsonization, complement- coat microbes, making them easier for mediated cytolysis through the phagocytes (like macrophages) to engulf and formation of the membrane attack destroy. complex (MAC), and inflammation. 3. Antibody-dependent cellular cytotoxicity Components like C3a and C5a lead to (ADCC): Antibodies bind to infected cells or an increase in neutrophils at the site microbes, signaling natural killer (NK) cells to of infection, resulting in increased kill them. inflammation. 4. Complement activation: Lysis of microbes: Antibodies activate the complement system to form the Membrane Attack Complex (MAC), which creates holes in microbes and kills them. Phagocytosis with complement fragments: Complement proteins like C3b tag microbes for easier destruction by phagocytes. Inflammation: Complement components (like C3a and C5a) attract neutrophils to the infection site, increasing inflammation to fight the infection. 5-Complement Activation A collection of circulating and cell membrane proteins that play important roles in host defense against microbes and in antibody- mediated tissue injury. Complement refers to the ability of these proteins to assist, or complement, the activity of Ig in destroying microbes. Present in an inactive form, its activation involves sequential proteolytic protein cleavage. Complement proteins are inactive at first and are activated step by step through a process called proteolytic cleavage, where enzymes cut the proteins into active forms.  Three major pathways of activation: 1-Classical pathway:antibody dependent 2-Alternative pathway 3-Lectin pathway 1. Binding: The pathway starts when the complement protein C1 binds to an antibody (IgG or IgM) that is attached to a microbe. 2. Activation of C4 and C2: C1 cleaves C4 into C4a and C4b. C4b attaches to the microbe’s surface. C1 also cleaves C2 into C2a and C2b. C2a joins C4b, forming the C3 convertase. 3. Formation of C3 Convertase: The C3 convertase (C4b2a) cleaves C3 into C3a and C3b. C3b binds to the microbe, marking it for destruction. 4. Formation of C5 Convertase: Some C3b combines with the C3 convertase, forming C5 convertase (C4b2a3b). 5. C5 Activation: C5 convertase cleaves C5 into C5a (inflammatory signal) and C5b (starts the formation of the Membrane Attack Complex or MAC to kill the microbe). classic pathway of complement activation 1. Binding: The pathway begins when mannose-binding lectin (MBL) binds to sugar molecules (mannose) on the surface of a microbe. 2. Activation of C4 and C2: MBL activates C4, splitting it into C4a and C4b. C4b attaches to the microbe’s surface. MBL also activates C2, splitting it into C2a and C2b. C2a joins C4b to form C3 convertase. 3. Formation of C3 Convertase: The C3 convertase (C4b2a) cleaves C3 into C3a and C3b. C3b binds to the microbe, marking it for destruction. 4. Formation of C5 Convertase: Some C3b combines with the C3 convertase to form C5 convertase (C4b2a3b). 5. C5 Activation: C5 convertase cleaves C5 into C5a (promotes inflammation) and C5b (initiates the Membrane Attack Complex or MAC). Lectin pathway of complement activation 1. Spontaneous C3 Activation: The complement protein C3 is spontaneously hydrolyzed to C3b, which binds to the surface of microbes. 2. Formation of C3 Convertase: C3b binds with another complement protein called Factor B. Factor B is cleaved by Factor D to form C3bBb, which acts as a C3 convertase. 3. Cleavage of C3: The C3 convertase cleaves more C3 into C3a (inflammatory signal) and C3b. This amplifies the pathway. 4. Formation of C5 Convertase: Some of the newly formed C3b binds to the C3 convertase, forming C3bBbC3b, which acts as a C5 convertase. 5. C5 Activation: The C5 convertase cleaves C5 into C5a (promotes inflammation) and C5b (initiates the formation of the Membrane Attack Complex or MAC). Alternative pathway of complement activation Early steps of complement activation Late steps of complement activation 1. C5 Activation: C5 convertase splits C5 into C5a and C5b. C5a promotes inflammation by attracting immune cells. 2. C5b Binding: C5b binds to the microbial surface and initiates the assembly of the Membrane Attack Complex (MAC). 3. MAC Formation: C5b recruits other complement proteins: C6, C7, and C8. These proteins embed in the plasma membrane of the target cell. 4. C9 Polymerization: Multiple copies of C9 are added to form a pore-like structure called the MAC. 5. Cell Lysis: The MAC creates holes in the cell membrane, leading to leakage of contents and cell death.  Functions of the complement D- In addition to all antimicrobial effector functions , the complement system stimulate. B cell response and antibody production (C3d attached to the complement receptor 2 on the surface of B cell and activate it|).  team Wishes you the best