Physiology Lecture 007 Immunity PDF
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University of Northern Philippines
Dr. Marsha Michelle Cabuena
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This document is a lecture outline for a course covering immunity. It provides an overview of innate and acquired immunity, including basic types, lymphocytes, antibodies, classical pathways, T-lymphocytes, and immunizations. It also touches on allergies and hypersensitivity reactions.
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(007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 OUTLINE caused by a special immune system that forms antibodies...
(007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 OUTLINE caused by a special immune system that forms antibodies and/or activated lymphocytes that attack and destroy I. INNATE IMMUNITY the specific invading organism or toxin II. AQUIRED IMMUNITY bestows extreme protection A. BASIC TYPES basis for immunization formed in the lymphoid tissues of the body B. LYMPHOCYTES both types are initiated by antigens (must have a high C. ANTIBODY molecular weight >/= 8000); D. CLASSICAL PATHWAY o Epitopes (regularly recurring molecular groups) E. T – LYMPHOCYTES on the surface of the large molecule; proteins and large polysaccharides are almost always F. IMMUNIZATION antigenic III. ALLERGY AND HYPERSENSITIVITY o Antigen: anything that generates antibody A. TYPES OF ALLERGIC REACTION production and activates lymphocytes. Not all antigens are antigenic product of the body's lymphocytes (T and B Lymphocytes) recognition of self vs. non-self (each toxin or each type of IMMUNITY- the ability to resist almost all types of organisms or organism almost always contains one or more specific toxins that tend to damage the tissues and organs. This capability is chemical compounds in its makeup that are different from called immunity. Much of immunity is acquired immunity that does all other compounds) not develop until after the body is first attacked by a bacterium, virus, o important to prevent destruction of self antigens or toxin, often requiring weeks or months to develop the immunity. o before T or B lymphocytes are sent to destroy the invader, they are first trained to recognize self 2 TYPES: from non-self antigens 1. ACQUIRED o a lymphocyte attaches to specific bacteria 2. INNATE depending on chemical compound on its surface. I. INNATE IMMUNITY A. Basic Types of Acquired Immunity An additional portion of immunity results from general 1 1. HUMORAL process, rather than from processes directed at specific -develops circulating antibodies; B-cell immunity (because B disease organisms. This is called innate immunity. It lymphocytes produce the antibodies) includes the following: - B cells are preprocessed in the Bursa of Fabricius 1. Phagocytosis of bacteria and other invaders by white blood 2. CELL-MEDIATED cells and cells of the tissue macrophage system -activated T lymphocytes; crafted in the lymph nodes; - during infection, initial responses are: increased T-cell immunity (because the activated lymphocytes are T production and release from the bone marrow lymphocytes) and lymphatic tissues, and effective function of -T cells are preprocessed in thymus WBCs; engulfment and lysis of bacteria and other o React highly specifically with only one specific type of antigen invaders by the WBCs occur o An antigen (antibody generations - proteins or large poly- 2. Destruction of swallowed organisms by the acid secretions of saccharides that initiate the acquired immunity) activates only the stomach and the digestive enzymes. the lymphocytes that have cell surface receptors that are 3. Resistance of the skin to invasion by organisms. complementary and recognize a surface antigen - intact skin confers resistance (e.g. popping a blister welcomes bacteria for invasion) 4. Presence in the blood of certain chemical compounds that attach to foreign organisms or toxins and destroy them. B. Lymphocytes a. Lysozyme = a mucolytic polysaccharide that attacks bacteria and causes them to dissolute Responsible for acquired immunity b. Basic polypeptides = react with and inactivate certain Located most extensively in the lymph nodes types of gram-positive bacteria Special lymphoid tissues: c. Complement complex = a system of about 20 proteins o Spleen = circulating blood that can be activated in various ways to destroy bacteria o Submucosal areas of the gastrointestinal tract d. Natural killer lymphocytes= can recognize and destroy o Thymus = circulating blood foreign cells, tumor cells, and even some infected cells o Bone marrow = circulating blood o Tonsils, adenoids = upper respiratory tract II. ACQUIRED IMUNITY Lymphoid tissue is distributed advantageously in the body to intercept invading organisms or toxins before they can develops after the body is first attacked by a bacterium, spread too widely virus, or toxin, often requiring weeks or months to develop the immunity - Entry into blood allows invading organisms to widely spread in immunity that is developed once a person is exposed to the body the invader (bacteria, virus, toxin) - Before the bacteria can enter lungs, they must be intercepted by tonsils and adenoids in the upper respiratory tract PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D. (007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 - Before the bacteria are absorbed into the blood, they must be - The thymus makes certain that any T lymphocyte leaving the intercepted by lymphocytes in submucosal areas and the thymus will not react against the proteins or other antigens present different chemicals secreted in GIT in the body tissue (to recognize self from non-self) - Prolonged intake of omeprazole decreases secretion of HCl in - The thymus selects which T lymphocytes should be released by the GIT and allows bacteria to gain more access for absorption first, mixing them with antigens in the body. If a T lymphocyte reacts into the blood with self antigen, it is destroyed or phagocytized, instead of being - Tonsillectomy decreases immunity and the ability to intercept released. The only cells that are finally released are those that are invading organisms nonreactive to the body’s own antigens. Invading agent first enters the tissue fluids and then is carried Antigen by lymph vessels to the lymph node or other lymphoid tissue Preprocessing of the T and B Lymphocytes Macrophages phagocytize and partially digest the antigen Pass these antigens by cell-to-cell contact directly to the lymphocytes Activation of the specified lymphocytic clones Secrete interleukin-1 (activating substance), promotes further growth and reproduction of the specific lymphocytes Forms helper cells, secrete specific substances (collectively called lymphokines) that activate the specific B lymphocytes Activation of B lymphocytes (enlarge) -before lymphocytes are released to the lymphoid tissues, they will wait until they are exposed to antigen. They will be preprocessed Lymphoblast first by either thymus or the Bursa -both types of lymphocytes are derived originally from the hematopoietic stem cells in the embryo, forming the common Plasma blasts lymphoid progenitor cells (first offspring) that will later differentiate into T or B lymphocytes -preprocessing in the following ways: Mature plasma cell then produces gamma globulin antibodies 1.) Lymphoid progenitor cells migrate and are preprocessed in the thymus. Thus, they are called T lymphocytes to designate the role of thymus. They are responsible for cell-mediated Antibodies are secreted into the lymph and carried to the immunity circulating blood 2.) Hematopoietic stem cells are formed into common lymphoid progenitor cells which develop into B lymphocytes. B Memory Cells lymphocytes are preprocessed in the liver during mid-fetal life B-cell population of the specifically activated clone or in the bone marrow during the late fetal life and even after becomes greatly enhanced, and the new B lymphocytes birth (this population of cells was discovered in birds that have are added to the original lymphocytes of the same clone special preprocessing organ called Bursa of Fabricius. Hence, Circulate throughout the body to populate all the lymphoid the name ‘B lymphocyte’ to designate the role of Bursa, tissue responsible for humoral immunity) Remain dormant until activated once again by a new - once they have been preprocessed, they will start to be released quantity of the same antigen to the lymphoid tissue. Almost all the types of lymphocytes Subsequent exposure to the same antigen will cause a eventually end up in the lymphoid tissue. But, before doing so, they much more rapid and much more potent antibody are further differentiated or preprocessed either in the thymus or response this second time around Bursa Explains why there is immunization -there is a need for preprocessing in the thymus or bursa to render the T and B lymphocytes nonreactive to cells, for them not to destroy the body’s own tissues. -One lymphocyte develops specific reactivity against one antigen. The next lymphocyte develops specificity against another antigen. The process continues, thousands of lymphocytes develop specific reactivity against thousands of different antigens. - The preprocessed T lymphocytes now leave the thymus and spread by way of the blood all throughout the body to lodge into lymphoid tissue, where they will end up. PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D. (007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 Disulfide bonds makes the attachments of chain to one another very strong. Variable region: site of antigen attachment Five general classes of antibodies: Ig stands for immunoglobulin, and the other five respective letters designate the respective classes IgM (primary response) - Recent exposure (for example in Dengue Duo Rapid Test). - These antibodies have 10 binding sites that make them exceedingly effective in protecting the body against invaders, even though there are not many IgM antibodies Primary Response: IgG (75%) 1-week delay or more - a bivalent antibody and the most abundant ~ weak potency constitutes about 75 per cent of the antibodies of the short life normal person when the body is first exposed to an antigen, production of - it is the only type of antibody that can cross the antibodies and activation of T lymphocytes occur (very placenta in a pregnant woman to help protect her slow) baby. down sloping: it goes down immediately after a few days - responsible for the secondary response (short-lived response) - have had exposure, exposed before (Dengue Duo) Secondary response: IgA begins rapidly after exposure to the antigen the second - it constitutes a small percentage of antibodies but is time around (often within hours) specially involve in allergy. far more potent, quicker, more rapid IgD forms antibodies for many months rather than for only a - signals B- cell to be activated in order for them to few weeks participate in the immune defense down sloping: it goes down slowly because antibodies and IgE (allergy) T lymphocytes stay longer in the blood - Has a strong propensity to attach to mast cells and basis for immunization, once a person is immunized to basophils. A single mast cell or basophil can bind as antigens, the body develops its memory cells. many as half a million molecules of IgE. if both IgM and IgGisa positive, the patient had been C. Antibody infected before and indicates an ongoing infection at the same time. Structure of an Antibody Mechanism of Action of Antibodies 2 Actions: 1. Direct attack on the invader Agglutination = multiple large particles with antigens on their surfaces, such as bacteria or red cells, are bound together into a clump Precipitation = the molecular complex of soluble antigen (such as tetanus toxin) and antibody becomes so large that it is rendered insoluble and precipitates - Dehydrates the bacteria and renders it insoluble Neutralization = cover the toxic sites of the antigenic agent Lysis = directly attacking membranes of cellular agents and thereby causes rupture of the agent 2. Activation of the "complement system" that then has multiple means of its own for destroying the invader Nature of Antibodies Gamma globulins called immunoglobulins Constitute about 20 percent of all the plasma proteins Composed of combinations of light and heavy polypeptide chains Combination of two light and two heavy chains PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D. (007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 - Initial complex formation is needed for complement phagocytes to migrate into the tissue area adjacent to the activation to take place. antigenic agent. 6. Activation of mast cells and basophils: Fragments C3a, C4a, and C5a activate mast cells and basophils, causing them to release histamine, heparin, and several other substances into the local fluids o increased local blood flow, increased leakage of fluid and plasma protein into the tissue, and other local tissue reactions that help inactivate or immobilize the antigenic agent 7. Inflammatory effects: the already increased blood flow to increase still further the capillary leakage of proteins to be increased the interstitial fluid proteins to coagulate in the tissue spaces, thus preventing movement of the invading organism through the tissues C3b5 – opsonization of bacteria C3a, C4a, C5a: activate mast cells symptoms of allergy C5 activation chemotaxis of WBC mechanism on how the antibodies carry out their function on attacking the invader is just the same with Direct and Indirect mechanism. Both will agglutinate, precipitate, neutralize, and lyse Complement the foreign invader. Collective term that describes a system of about 20proteins, many of which are enzyme precursors Principal actors in this system are 11 proteins designated C1through C9, B, and D E. T - Lymphocytes The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway T lymphocytes respond to antigens only when they are bound to specific molecules called MHC proteins (major histocompatibility complex) on the surface of antigen- D. Classical Pathway presenting cells in the lymphoid tissue MHC proteins, bind peptide fragments of antigen proteins Initiated by Antigen-Antibody complex formation. which are degraded in APC and transported to the cell surface 1. Opsonization and phagocytosis: C3b, strongly activates phagocytosis by both neutrophils and macrophages o engulf the bacteria to which the antigen-antibody complexes are attached (opsonization) and enhances the number of bacteria that can be destroyed by many hundredfold. 2. Lysis: One of the most important of all the products of the complement cascade = lytic complex = C5b6789. This has a direct effect of rupturing the cell membranes of bacteria or other invading organisms. 3. Agglutination: The complement products also change the surfaces of the invading organisms, causing them to adhere to one another, thus promoting agglutination 4. Neutralization of viruses: The complement enzymes and other complement products can attack the structures of some viruses and thereby render them nonvirulent. 5. Chemotaxis: Fragment C5a initiates chemotaxis of neutrophils and macrophages, thus causing large numbers of these PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D. (007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 IL4, IL5, IL6- B-cell stimulating factors or B- Three Major Types of Antigen-Presenting Cells cell growth factors - should possess MHC proteins on their surface to be able to interact with T cells - the MHC proteins peptide fragments of antigen proteins are degraded inside antigen-presenting cells and then transport them to the cell surface. 1. Macrophages 2. B lymphocytes 3. Dendritic cells o most potent of the antigen-presenting cells o located throughout the body o their only known function is to present antigens to T cells MHC 1. MHC I proteins - present antigens to cytotoxic T cells 2. MHC II proteins - present antigens to T helper cells Types of T Cells 1. Helper T Cells most numerous of the T cells (3/4) Important in immunity, a significant decrease in this T cell population could be very fatal. Attacked by the Human Immunodeficiency Virus (HIV), rendering the patient very immunocompromised. Activate fully the Cytotoxic and Suppressor T cells Involved in formation and production of Plasma Cells that are responsible in production of Ab major regulator of virtually all immune functions by forming a series of protein mediators, called lymphokines: o Interleukin-2: special strong stimulatory effect in causing growth and proliferation of both Cytotoxic and Suppressor T cell o Interleukin-3 o Interleukin-4 o Interleukin-5 o Interleukin-6 o Granulocyte-monocyte colony- 2. Cytotoxic T Cells stimulating factor - direct-attack cell that is capable of killing micro- o Interferon-γ organisms and even own cells. For this reason, these cells are called killer cells secretes hole-forming proteins, called perforins, that literally punch round holes in the membrane of the attacked cell and they delivered cytotoxic substances and then move on to kill more cells. These cytotoxic killer cells can pull away from the victims’ cell fluid flows rapidly into the cell from the interstitial space swells dissolves PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D. (007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 Active vs Passive Immunity ACITVE the person's own body develops either antibodies or activated T cells in response to invasion of the body by a foreign antigen PASSIVE transfusion of antibodies or T lymphocytes to confer immunity Antibodies last in the body of the recipient for two to three weeks, during that time the person is protected against invading disease. ex. Rabies vaccine, we don’t wait for a delay since the response is primary during an initial infection and it will take a longer period of time for a person to generate antibody on its own (7-14 days), we inject Anti-Rabies Immunoglobulin right away instead which is readily available. 3. Suppressor T Cells III. ALLERGY AND HYPERSENSITIVITY Regulatory T cells - An important undesirable side effect of immunity is the Suppress the function of cytotoxic and T helper cell to development, under some conditions, of allergy or other prevent the cytotoxic cells from causing excessive types of immune hypersensitivity immune reactions that might be damaging to the body's own tissues - immune tolerance ALLERGEN Prevents the Cytotoxic T cells from attacking self an antigen that reacts specifically with a specific type of antigens IgE reagin antibody An antibody will only react on specific antigen that has on F. Immunization by Injection of Antigens its surface a specific immuno compound. For IgE or Reagin it only acts with an antigen or allergy, so it will form allergen/reagin complex. The reagin is Produce acquired immunity against specific diseases actually the IgE antibody in the blood, so your allergen is Follows principle of Memory cells the trigger for your antigen, the antibody is called the Produce acquired immunity reagin or the immunoglobinity. Introduction(injection) of Antigen (microorganism) induces Ab production specific to the Antigen that caused its REAGIN/SENSITIZING ANTIBODIES production. IgE antibodies in the blood Secondary exposure of antigen (ex: virus) produces rapid Has a strong propensity to attach to mast cells and response, more potent antibody and longer duration and basophils. Indeed, a single mast cell or basophil can bind sustenance of immune response. as many as half a million molecules of IgE antibodies Responsible for the allergic symptoms. 1.Dead Organisms no longer capable of causing disease but that still have ALLERGIC REACTION some of their chemical antigens 1. Allergen + reagin complex E.g Typhoid fever, Whooping cough, Diphtheria 2. Attaches to a mast cell or basophil 3. Immediate change in 2. Toxins 4. The membrane have been treated with chemicals so that their toxic nature 5. Rapture and release of special agents has been destroyed even though their antigens for causing Histamine immunity are still intact Protease E.g. Tetanus, Botulism Slow-reacting substance of Anaphylaxis 3. Attenuated live organisms Eosinophil chemotactic substance grown in special culture media or have been passed neutrophil chemotactic Substance through a series of animals until they have mutated Heparin enough that they will not cause disease but do still carry Platelet activating factors specific antigens - This are all responsible for the signs and symptoms E.g. Smallpox, Yellow fever, Poliomyelitis, Measles of allergen reaction. PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D. (007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 A. Types of Allergic Reaction 2. URTICARIA -Results from antigen entering skin areas and causing 1. ANAPHYLAXIS- A widespread allergic reaction that occurs localized anaphylactoid reactions throughout the vascular system and closely associated tissues. a) Release of histamine Most deadly among the allergic reaction. A person who b) Vasodilation that induces an immediate red flare experience this reaction dies of circulatory shock within a few c) Increases local permeability of the capillaries minutes unless treated with epinephrine to oppose the effect of d) Local circumscribed areas of swelling of the skin histamine. A. a) Release of histamine into the circulation b) Widespread vasodilation and increased permeability of the capillaries c) Marked loss of plasma from the circulation Decrease of blood pressure of the patient d) The patient can have Circulatory shock very low blood pressure, tachycardia, the patient is also very pale which is because of the widespread marked of vasodilation. - If you have a patient with this symptoms and history of allergy or asthma or even slight allergy in the family history, and the patient on history for example has eaten peanut prior to the symptoms so - “Reverse skin” the peanut will be the cause of the allergen. It has activated the - Look like large mosquito bite that is scattered all reagin/allergen antibody that cause the release of histamine. You over the body, which is cause by the released of see that the patient is pale, with tachycardia, initially give the histamine, or allergen antibody or reagin. So patient anti-histamine and you must also give the patient remember that what is causing urticaria is epinephrine because the patient is already in a circulatory shock, Histamine. and there is the tendency that the patient may die in a few minutes because of circulatory shock. 3. HAY FEVER - called as sneezing syndrome; allergic rhinitis So even if your patient has a very mild symptoms admit them to (people who always have colds) prevent anaphylaxis (having very narrow airways or blocked airway cause by the release of leukotrienes and vasodilatation cause by a) Release of histamine the release of histamines). b) Local intranasal vascular dilation c) Increased permeability pressure and B. permeability a) Release of slow-reacting substance of anaphylaxis (leukotrienes) - Caused by the leakage of fluid in the nasal cavities b) Leukotrienes will cause Spasm of the smooth muscle and associated with colds or they usually have of the bronchioles (asthma-like attack) phlegm in their throat or nasal drip, also with swelling c) Suffocation in their nasal linings (red nose). If their nasal linings are irritated, it can cause mucus and they also constantly sneeze. All of this is the cause of hay fever which is the result of release of histamine. - Use of anti-histamine can prevent the swelling reaction. However, other products of allergen-reagin reaction can still cause irritation of the nose, eliciting the typical sneezing syndrome. So as you can see the eyes of the child above, there is an edema with swollen tongue which is very dangerous. If it is swollen expect the bronchioles to be also swollen. There will be decrease in the caliber of your trachea or airway. The patient will report dyspnea or shortness of breath, cyanotic, and wheezing. It is more dangerous if you will not hear wheezing during auscultation 4. ASTHMA (allergen in the Bronchioles of lungs) because it means that there is no gas exchange happening in the - Often occurs in the allergic type of person airways, so anaphylaxis is a very dangerous allergic reaction. - If you have allergy you will develop asthma 95% or vice versa, that if you have asthma you will develop allergen. PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D. (007) IMMUNITY DR. MARSHA MICHELLE CABUENA | 03/11/2020 a) Asthma is a result of stimulation of Mast cells that release slow- 4. Which of the following is the final stage of B cell reacting substance of anaphylaxis maturation after activation by antigen? b) Spasm of the bronchiolar smooth muscle a. Large, granular lymphocyte c) Difficulty of breathing b. Plasma cell c. Reactive lymphocyte **Patient will report dyspnea, cyanotic and if auscultate the d. Immunoblast patient, you will hear wheezing, if you cannot hear wheezing or the lungs are silent it is dangerous for the patient as it means that 5. The following is unique to both B and T lymphocytes the airway is completely close. For the patient to reverse it give the patient antihistamine, epinephrine all at the same time, since and occurs during their early development it is swollen you also give anti-inflammatory and steroids all of a. Expression of surface antigens CD4 and CD8 the same time to reverse or save the life of your patient. b. Maturation in the thymus Administration of anti-histamine only has less effect on the course of asthma because histamine does not appear to be the c. Synthesis of immunoglobulins major affect eliciting asthmatic reaction. d. Rearrangement of antigen receptor genes So that is the 4 types of allergic reactions: 6. It is very important in immunity because a significant decrease in this cell population could be very fatal. 1. Anaphylaxis – most deadly 2. Urticaria a. Cytotoxic T-Cell 3. Hay fever b. Helper T-cell 4. Asthma c. Suppressor T cell d. Regulatory T cell ***For HIV patient or suspected patient with HIV: 7. It is a widespread allergic reaction that occurs -Even if the patient WBC is normal, you must still treat the patient throughout the vascular system and closely as a case of infection and you must start the patient with associated tissues. antibiotics. It is because, his/her WBC is not moving or the a. Asthma neutrophils is not working, it means that the patient is b. Anaphylaxis immunocompromised and you must start to treat it early on. c. Urticaria -Not all patient will show fever if they are immunocompromised, d.Hay Fever so look for other symptoms like loss of appetite and muscle weakness. 8. It is the result of stimulation of mast cells that release slow-reacting substance of anaphylaxis. TEST YOUR KNOWLEDGE a. Asthma 1. Which of the following cells are important in immune b. Anaphylaxis regulation, allergic inflammation, and destruction of c. Urticaria tissue invading helminths? d.Hay Fever a. Neutrophils and monocytes b. Eosinophils and basophils 9. It prevents the Cytotoxic T cells from attacking self antigens c. T and B lymphocytes a. Helper T-cell d. Macrophages and dendritic cells b. Suppressor T cell c. Regulatory T cell 2. Basophils and mast cells have high-affinity surface d. NK cell receptors for which immunoglobulin? a. A 10. Their only known function is to present antigens to T b. D cells a. Macrophages c. E b. B lymphocytes d. G c. Dendritic cell 3. Macrophages aid in adaptive immunity by: Answers: 1. b; 2. c; 3. a; 4. b; 5. d 6.b, 7.b 8. A 9. b 10. c a. Degrading antigen and presenting it to lymphocytes b. Ingesting and digesting organisms that neutrophils REFERENCE: cannot Rodak’s Hematology: Clinical Principles and Applications. 5thEdition c. Synthesizing complement components Guyton and Hall, Textbook of Medical Physiology, 11th Edition d. Storing iron from senescent red cells Hall, J. E., & Hall, M. E. (2016). In Guyton and Hall Text Book of Medical Physiology (13thed) PREPARED AND EDITED BY: MACARAEG, E., MACNI, K., MAPALO, D., MENDOZA, C., NITURA, A., PASCUA, C., PAYUMO, M., PINERO, D.