Lecture 14 + 15 PDF

Lecture #14: Constitutive Defense and the Complement:  The deeper-layer living keratinocytes secrete cytokines such as interleukin 8 (IL-8) and tumor necrosis factor (TNF) if they are Inna...

Lecture #14: Constitutive Defense and the Complement:  The deeper-layer living keratinocytes secrete cytokines such as interleukin 8 (IL-8) and tumor necrosis factor (TNF) if they are Innate immune system consists of a number of physical barriers (skin , damaged in any way. These cytokines are responsible for the PH, cilia) as well as molecular barriers (interferons and complement inflammation system)  Skin also contains Langerhans cells which phagocytose Infections that break through the body’s physical barriers activate the microorganisms and migrate to the local lymph node to present molecular barriers of the innate immune system antigen to T cells b) Gastrointestinal Tract:  The low pH of the stomach is one of the main defenses against infection of the gut. (For example, patients who are unable to secret gastric acid have a high risk for infection like Salmonella.  The colon is colonized by trillions of endogenous bacteria, which are normally harmless and inhibit the growth of pathogenic bacteria.  The gut epithelium also secretes transformation growth factor beta (TGF-β) that induces T-regulatory cells (Tregs), which help the host immune system tolerate the presence of harmless commensal bacteria c) Respiratory Tract:  The Upper Airway (from nose to bronchioles) is protected by the Mucociliary Escalator.  Mucus secreted by goblet cells that lines the airway and traps microorganisms & Cilia waft the mucus toward the mouth and nose where it’s cleared by sneezing or coughing.  Mucus secretion is abnormal in cystic fibrosis patients and cilia are defective in primary ciliary dyskinesia. So, Patients with these conditions have recurrent respiratory tract infections.  Physical barriers of innate immunity:  In The Lower Respiratory Tract (terminal bronchioles and a) Skin: alveoli) the main defenses here are SURFACTANTS secreted by  The dense outer layer of dead keratinocytes prevents penetration type II pneumocytes. of organisms that live on skin surface into deeper tissues   Surfactants are a mixture of proteins and phospholipids that  Type I IFNs have a range of actions: prevent alveoli from collapsing during expiration. Surfactant - inhibit viral replication on neighboring cells (paracrine effect) by also contains pathogen-binding proteins, which are members of activation of two intracellular enzyme pathways that degrade the the Collectin Family. viral genome and inhibit transcription of viral messenger RNA  The collectins have : (mRNA) - Globular lectin heads: that can bind - stimulate activity of TAP and proteasomes and increased to sugars on microorganisms expression of (MHC) class I- antigen complex to promote the - Long collagen-like tails: that bind to effects of CD8+ T cells phagocytes or complement. - activate macrophages and natural killer (NK) cells - The collectin family includes surfactant proteins and mannan- binding lectin - These molecules have a pattern recognition role.  Both segments of the respiratory tract are also reliant on secretory IgA immunoglobulins  Extracellular Molecules of the Innate Immune System: a) Interferons: b) The Complement System:  interfere with viral replication  an enzyme cascade of plasma proteins called the complement proteins that help antibodies to clear  The antiviral effects are most potent with type I IFN (IFN-α and pathogens IFN-β) and less with type 2 IFN (like IFN-γ)  It is comprised of 30 different proteins produced from  IFN-γ is more potent at activating the TH1 arm of the adaptive liver, including serum proteins, serosal proteins, and cell immune response than at inhibiting viral replication membrane receptors  the most efficient producers of type I IFNs are a type of antigen-  An important part of the innate immune system as well as presenting cell (APC) called plasmacytoid dendritic cells, which the acquired immune system secrete IFNs in response to infection  Some complement proteins bind to immunoglobulins or to  Double-stranded RNA is not present in mammalian cells but is membrane components of cells produced by viruses during intracellular infection of cells. So, Ds- RNA is a good example of a PAMP  Others are proenzymes that cleave other complement proteins when activated  Plasmacytoid dendritic cells recognize Ds-RNA using Toll-like receptor 3 & then secrete type I IFNs in response to it  End-result is formation of membrane attack complex (MAC) that kills cell or pathogen  The complement system has four major functions: 1) Classical pathway: 1) Lysis of infectious organisms (rupturing membranes of foreign  It is so named because it was discovered first cells)  This pathway is triggered by immune complexes of 2) Activation of inflammation. antibody and antigen 3) Opsonization (enhancing phagocytosis of antigens)  C1 is the initiating protein and it is able to recognize the Fc 4) Immune clearance portion of immunoglobulin (Ig) molecules when sufficient Fc portions are in sufficiently close proximity , that why  Overview of the Complement System: IgM is the most efficient complement activator  There are nine basic complement components, numbered C1  C1 is a large complex composed of (C1q, C1r, C1s & C1- to C9 , normally they are inactive until they are cleaved inhibitor)  Three different pathways used to activate key component (C3)  C1 binding to an Fc on an antigen-antibody complex causes a conformational change in the C1 molecule (C1 inhibitor falls off exposing C1s and C1r serine protease sites) this activates C1 to cleave C4 and C2 into (C4a and C4b) + (C2a and C2b) respectively  C2b4b will form “C3 convertase” which in turn activates multiple C3 molecules 2) The Alternative Pathway:  C3 is not a stable molecule, and it is constantly undergoing spontaneous low-level activation on cell surfaces  Stable C3b can bind complement protein B , Complement protein D clips B bound to C3b to Forms C3bBb = C3 convertase  Normal cells express surface complement inhibitors that prevent spontaneous C3 activation.  The surfaces of pathogens lack complement inhibitors, so the spontaneous activation of C3 can go ahead 3) The Lectin Pathway:  Mannan-binding lectin (MBL) is a collectin that is able to bind through its lectin portions, onto carbohydrates present on bacteria  after the lectin portions bind to bacteria, the MBL collagen- like domain indirectly activates the next complement components, C2 and C4, which produce C2b4b “C3 convertase” which activates several C3 molecules  Amplification Steps: 1) Anaphylatoxins:  once one component is activated it will activate downstream  C3a and C5a components  they have a low molecular weight and diffuse away from the site of  These molecules are activated by cleavage into small and large complement activation to cause the effects shown in the figure fragments. The large fragments may become enzymes themselves bellow and may cleave next molecule in the cascade.  These fragments may also interact with inhibitors that switch off the amplification steps.  The small fragments of C3 and C5 (C3A & C5A) are known as anaphylatoxins 2) Complement Receptors:  They bind early complement components (MBL, C1, and activated C4 and C3)  CRs serve the following functions: a) Opsonization (the process by which bacteria and other cells are made available for phagocytosis), the most important opsonin Is C3B and binds to different receptors present on a range of phagocytes. b) B-cell stimulation → Binding of C3 to the CR2 receptor on B 1 cells provides costimulation signal  Complement Effectors : CR2 is also used by the Epstein-Barr virus as its receptor c) Immune complex clearance → Immune complexes are  Activation of complement produces a number of effector molecules: insoluble lattices of antigen bound to antibody that can 1) The anaphylatoxins. form in tissues or in the blood. These can trigger 2) Complement fragments that bind and activate complement inflammation, and immune-complex disease if they are not receptors. removed 3) The membrane attack complex (MAC). 2  Complement helps to remove immune complexes in two ways:  The MAC complex in humans appears to be crucial for - Large insoluble complexes are particularly difficult to remove defenses against Neisseria , so patients with late complement from tissues; high numbers of activated C3 interrupt the lattice deficiency (C5-9) will have recurrent Neisserial infections of the immune complex, making them soluble - C4 and C3 present in solubilized immune complexes can bind to complement receptor CR1 on red cells, which transport the immune complexes to organs rich in fixed phagocytes, such as the liver and spleen to destroy them. The red cells are not harmed by this process Patients with complement deficiency are at high risk for immune complex disease, such as systemic lupus erythematosus(SLE)  Complement Inhibitors & Regulation of the Complement System:  Excessive complement activation is undesirable because it causes inflammation and widespread cell death  Therefore, activation of the complement system must be tightly regulated by complement inhibitors which are present at a higher concentration in the blood plasma than the complement proteins themselves.  At least 12 proteins are known involved in regulation of the complement system; Examples are: a- Factor H: removes Bb from the C3 convertase in the alternative pathway breaking the positive 3) Membrane Attack Complex (MAC): feedback loop.  Activated C3 activates the final part of the cascade of b- Factor I: inactivates C3b complement components C5 through C9. These components c- C1 inhibitor: binds to sites form the MAC on activated C1r and C1s  C5 and C6 have enzyme activity, which allows components C7, shutting down their C8, and C9 to insert themselves into the plasma membrane of proteolytic activity. the target cell. d- CD59, also known as  A group of 10 to 16 molecules of C9 form a ring, which creates protectin : inhibits C9 a pore in the plasma membrane.This allows free passage of polymerization during the water and solutes across the membrane, killing the cell. formation of the MAC  Acute phase response:  Clinical BOX Complement Deficiencies:  During infections, macrophages and other innate immune system  Deficiencies in the early lectin and classic pathways cause type III cells secrete cytokines such as IL-1, IL-6, and TNF. These cytokines hypersensitivity (immune complex disease) because immune activate the specific immune system and cause the acute-phase complexes cannot be solubilized or transported to phagocytes. response  Deficiency of early complement  These cytokines have a direct effect on the hypothalamus and components can cause autoimmune increase the body temperature (fever) & increase fat metabolism diseases due to imuune complex  They also stimulate the production of a series of proteins by the liver: deposition, For example: Systemic Lupus - Innate immune system molecules: C3, C4, and CRP. Erythematosus (SLE). - Damage-limiting proteins: α1-antitrypsin, haptoglobin.  Deficiencies of middle and late - Clotting factors: fibrinogen. complement components cause  Characteristics of an acute-phase response: recurrent bacterial (pyogenic) infection. 1) Elevated neutrophil count.  Deficiencies of the membrane attack 2) Raised C-reactive protein (CRP) complex (MAC) lead to a specific higher 3) Raised erythrocyte sedimentation rate (ESR) risk for infection with Neisseria species.  The most common congenital deficiency is C2 deficiency  DAF/CD55 deficiency causes PNH (Paroxysmal Nocturnal Hemoglobinuria)  C1 inhibitor deficiency causes Hereditary Angioedema - Hereditary angioedema is an autosomal-dominant disease caused by deficiency of C1 inhibitor, which is a member of serpins—serine protease inhibitors. - The deficiency of C1 inhibitor means that the early complement cascade is very easily activated.  Lecture #15: Phagocytes:  Tissue macrophages are large cells with specialized granules and Phagocytosis is the internalization of particulate matter by cells into cytoplasmic compartments, they are found in a wide range of cytoplasmic vesicles, when phagocytes recognize pathogens. sites. In some tissues these active macrophages are referred to as Phagocytes contain lysosomes (granules containing enzymes) that histiocytes. fuse with the vesicles and degrade the particulate matter. a- Giant and Epithelioid Cells: activation of a cascade of phagocyte enzymes leads to the  In sites of chronic inflammation, macrophages undergo production of toxic molecules, the oxidative burst, which is further maturation and become multinucleated giant cells necessary to kill phagocytosed organisms. or epithelioid cells under the influence of T-cell cytokines. Phagocytes also recognize dying cells and participate in the  Epithelioid and giant cells are characteristic of granuloma clearance of cellular debris. formation and participate in prolonging the inflammatory A second important role is that phagocytes can also produce response by: presenting antigen to T cells and secreting cytokines and cell-surface molecules, which alert the adaptive cytokines immune system to the presence of infection. b- Fixed Macrophages:  Phagocytic cell types:  These specialized phagocytes line sinusoids in the spleen 1- Neutrophils: and liver.  distinct appearance with multilobed nucleus  In the liver, these macrophages are referred to as Kupffer and their granules, which contain proteolytic cells. Their role is to phagocytose circulating particulate enzymes matter  the most numerous white cells in blood c- Alveolar Macrophages:  migrate rapidly into sites of infection  These contribute to the lung’s innate defenses.  neutrophils converts to pus cells after killing pathogens  They are involved in disease processes such as chronic  Pus formed at the site of infection is largely composed of dead obstructive pulmonary disease COPD neutrophils. d- Glial Cells :  play a crucial part in early defenses against bacterial infections  are long-lived macrophages resident in the nervous  patients with defective neutrophils or low levels of neutrophils system. (neutropenic) are at particular risk for serious bacterial infection  They are involved in clearing dead neuronal cells. e- Osteoclasts : 2- Monocytes/Macrophages:  specialized macrophages in bone, which participate in  Monocytes in the blood are immature cells migrating to their site regulating calcium metabolism by resorbing bone and of activity. releasing calcium into the blood  Monocytes migrate into tissues where they mature into macrophages and take on a number of specialized forms (  All macrophage forms have long life spans and survive in the tissue for months or years.   Phagocyte recruitment: Monocytes constantly migrate into healthy tissues and differentiate into the specialized macrophages Macrophages remain in a resting state unless they are stimulated by signals binding to their receptor Although neutrophils make up the majority of phagocytes circulating in the blood, they are absent from normal tissues and will migrate only into inflamed tissue Neutrophils are recruited to sites of inflammation by:  interleukin 17 (IL-17) secreted by T-helper 17 (TH17) cells  cytokines and chemokines secreted by resident macrophages recruit neutrophils and causes expression of adhesive molecules  Macrophages at the site of infection secrete chemokines such as IL-8 that modify neutrophil integrins to make the  phagocyte production: neutrophils more adherent to endothelium Neutrophils and monocytes are produced from the same stem cells  Anaphylatoxins (C3A,C5A) are also chemotactic for in the bone marrow phagocytes Many more neutrophils than monocytes are produced each day.  Chemotaxis is the directional migration of cells along a Production of these cells is stimulated by colony-stimulating factors gradient of chemokines to inflamed tissues (CSFs), which are produced by tissue macrophages as part of an acute-phase response. Recombinant granulocyte CSF (filgrastim) can be used to boost neutrophil numbers, such as after stem cell transplant  Receptors on Macrophages: Phagocytes use a variety of receptors on their cell membranes during their journey through the tissues and in their encounters with pathogens or damaged cells a- Receptors for Immunoglobulin :  Phagocytes can recognize IgG through their Fc receptors.  IgG acts as an opsonin and stimulates phagocytosis b- Receptors for Complement Components:  phagocytes can bind with Pathogens opsonized by complement components (like C3B)  Also they can bind immune complexes & Dead cells c- Lectin Receptors:  Lectins are sugar-binding proteins  Binding of C-lectin receptors activates the macrophages that lead to cytokines production.  C-lectin receptors capture pathogens and deliver them to  Drugs Based on Toll-Like Receptor Ligands: endocytic pathways. Stimulation of Toll-like receptors (TLRs) has potent activating effects d- Chemokine and cytokines receptors on many components of the immune system. e- Receptors for apoptotic cells. In clinical medicine, there are two areas where it is desirable to f- Toll-Like Receptors: increase the immune response: in cancer and vaccines  are a family of at least 10 different PAMPs , each of which unmethylated cytosine and guanosine sequences (CpG motifs) are recognizes different classes of pathogen molecules found in bacteria and absent in human cells. They stimulate  TLRs are found on macrophages and other APCs such as dendritic cells that express TLR-9 to secrete IL-12 which promotes dendritic cells and B cells as well as other cells, such as TH1 responses and boosts the subsequent production of both IgG epithelial cells that have a role in recognizing infection and cytotoxic T lymphocytes , used in vaccines & cancer drugs  On binding to the pathogen molecule, TLRs initiate an intracellular signal that leads to cytokine production Imiquimod is a synthetic drug that mimics single-stranded RNA and stimulates TLR-7 on macrophages and dendritic cells. These then secrete a wide range of cytokines with stimulatory effects on the innate and adaptive immune systems. Imiquimod is widely used to treat wart infections , skin tumors & in some vaccines  Actions of phagocytes: The main enzymes present are proteolytic and are able to digest Phagocytosis is most effectively bacteria in the acidic pH of the lysosomes triggered by pathogens that have The proteolytic enzymes are usually held in lysosomes. Enzymes that been opsonized by complement or leak out of phagocytes are usually prevented from damaging tissues IgG by serpins such as α1-antitrypsin A phagosome is formed by the Other substances released into the phagosome, including: ingestion of particulate matter  Defensins: low-molecular-weight peptides that punch holes in A number of pathogens have bacteria. developed defense mechanisms to  Lactoferrin binds to iron, depriving bacteria of this important avoid destruction by phagocytes nutrient After phagocytosis, three interrelated enzyme pathways are A third killing mechanism, used only by neutrophils, is the formation activated that produce toxic molecules (respiratory burst), which of NETs. further damage pathogens , These enzymes include :  This may be helpful when the pathogen is either too large or too 1- Hydrogen peroxide (by [NADPH] oxidase). numerous to be phagocytosed. 2- Hypochlorous acid (bleach by [myeloperoxidase]).  Upon activation, the neutrophil breaks down its own cell 3- nitric oxide (by inducible nitric oxide synthetase [macrophages membrane and extrudes chromatin (mixture of DNA and but not neutrophils]) histones)  The chromatin produce a trap that captures pathogens.  The toxic molecules and proteolytic enzymes are also restricted by the NETs, and so the pathogens are destroyed.  Presence of DNA in NETs may elicit an immune response against it & contribute to the development of systemic lupus erythematosus (SLE) with Anti-DsDNA.  Proteolytic Enzymes: Macrophages contain enzymes in lysosomes, which can be regenerated during the long life of these cells. In neutrophils, the proteolytic enzymes are contained in granules (after degranulation neutrophils die).  Inflammatory Signaling:  Clinical BOX :Chronic Granulomatous Disease: Neutrophils and macrophages produce inflammatory mediators  Primary immunodeficiency that affects neutrophil function. called prostaglandins and leukotrienes  It is caused by X-linked mutations in the genes for (NADPH) oxidase Although neutrophils secrete chemokines and nitric oxide, their short or its regulatory proteins life span prevents them from contributing to a stable, long-lasting  This disease is characterized by recurrent bacterial and fungal inflammatory response. Instead, a short-lived response is produced infections in the presence of neutrophilia (high # of neutrophils) with pyogenic (pus-forming) reaction  Although neutrophils are produced in abundance and are able to By comparison, macrophages have a key role in stimulating chronic migrate to sites of infection, they cannot produce superoxide inflammation radicals & they can’t kill pathogens. - Largely through secretion of soluble messengers with local and  Pathogens such as the fungus Aspergillus and the bacterium systemic effects. Staphylococcus, which would normally lead to short-lived pus- - Macrophages also process antigen, secrete cytokines, and forming infections, are not cleared and lead to the formation of express high levels of costimulatory molecules and MHC class II granulomatous chronic infection molecules  nitro blue tetrazolium test is carried out to diagnose the disease - If antigen is not cleared, the inflammation becomes chronic and and determine whether the neutrophils are capable of mounting a granuloma is the result an oxidative burst or not  Phagocyte defects: Primary disorders of phagocytes are rare but include important problems such as chronic granulomatous disease Secondary phagocyte defects are much more common. - The most important is neutropenia, in which neutrophils number is reduced, usually as a result of drug treatment - Diabetes. - Renal failure. - corticosteroid t.t  At the usual doses, corticosteroids act on phagocytes.  At higher doses, they act on lymphocytes. Questions: 5- The membrane attack complex of complement system consists of : a- C5B,6,7,8,9 1- The TLR9 pattern recognition receptor recognizes: b- C3B3bBb a- Flagella c- C1 , C3 ,C3A,C9 b- Gram + peptidoglycan d- C2,C4,C6 c- CpG motifs d- Gram – LPS 6- Which of the following is a function of the adaptive immune e- DsRNA system and NOT the innate immune system? a- Distinguishes self from non-self 2- During acute inflammation, there is a ‘burst’ of oxygen b- Has preformed or rapidly formed components consumption (respiratory burst) in neutrophils. This is an essential c- Responds within minutes to infection step for which of the following events? d- Has no specificity and responds to a range of pathogens a- Increased neutrophil production in the bone marrow e- Uses pattern-recognition molecules b- Attachment to the endothelial cells c- Opsonization of bacteria 7- What type of cells produce type I interferons (IFN-α and IFN-β)? d- Phagocytosis of bacteria a- Monocytes e- Generation of microbicidal activity b- Myeloid dendritic cells (mDC) c- Plasmacytoid dendritic cells (pDC) 3- Which of the following best describes the differences between the d- Plasma cells classic and alternative complement pathways: e- Goblet cells a- The classic pathway is more active than the alternative pathway b- The classic pathway results in the lysis of the target cell which is 8- Which of the following is recognized using a pattern-recognition not the case with the alternative pathway molecule called Toll-like receptor 3 TLR3 c- The alternative pathway requires antibody for initiation and the a- Single-stranded DNA classic pathway is antibody independent b- Double-stranded DNA d- The alternative pathway typically requires C3B for activation c- Single-stranded RNA while the classical pathway typically requires antigen-antibody d- Double-stranded RNA concentration e- None 9- In the lectin complement pathway, mannan-binding lecting (MBL) indirectly activated which of the following components? 4- Which of the following is true of neutrophils compared with A- C1 macrophages? B- C2 a- Respond to INF-gamma from the adaptive system C- C3 b- Found in healthy tissues D- C4 c- Rapid increase in production during acute response E- C2 & C4 d- Is long-lived e- Has different mature form 10- Which of the following is NOT true regarding interferon? 14- Which of the following is NOT a major function of complement a- Interferon prevents infection spreading from cell to cell activation? b- NK cells are activated by interferon and lyse infected cells a- Opsonization c- Antigen-presenting cells are inactivated b- B-cell stimulation d- Interferon is viral specific, attacking viral protens c- T-cell stimulation e- Stimulation of activity of TAP (transporter-associated with d- Immune complex clearance antigen presentation) 15- To prevent inadvertent complement activation, eight inhibitors 11- In the classical complement pathway, which of the following exist. Which of the following is an inhibitor preventing activation components is the initiating protein(s)? of C2 and C4 a- C1 a- C1 inhibitor b- C2 b- C2 inhibitor c- C3 c- C3 inhibitor d- C4 d- C4 inhibitor e- C2 & C4 e- C2 & C4 inhibitor 12- In the alternative complement pathway, this component molecule 16- A deficiency in complement inhibitors could lead to which of the undergoes spontaneous activation following? a- C1 a- Meningitis b- C2 b- Leprosy c- C3 c- X-linked hyper-IgM syndrome d- C4 d- Hereditary angiodema e- C2 & C4 e- X-linked agammaglobulinemia 13- Anaphylatoxins are chemotaxins that stimulate phagocytosis and 17- Pus formed at the site of infection is largely composed of dead: degranulation. Which complement components is/are mainly a- Macrophages involved? b- Neutrophils a- C2 & C4 c- Eosinophils b- C3 d- Basophils c- C5 e- Lymphocytes d- C3 & C5 e- C5-C9 18- What is the primary response seen in acute-phase responses to 22- Which of the following immunodeficiency causes the patient to be infection? susceptible to Neisseria Organisms: a- Decreased blood pH a- B lymphocytes defect b- Decreased metabolic pH b- Early complement components defect c- Increased body temperature c- T lymphocytes defect d- Increased heart rate d- Late complement component defect e- Decreased blood pressure e- Phagocyte defect 19- A 4-year-old boy presents with chronic granulomatous disease 23- Flagella of bacteria is recognized by: (CGD), confirmed with a nitro blue tetrazolium (NBT) test. Which a- TLR-7 of the following pathogens could this child still mount a defense b- TLR-5 against? c- TLR-9 a- Staphylococcus d- TLR-2 b- Enterobacteria c- Aspergillus 24- LPS of gram-negative bacteria is recognized by: d- Streptococcus a- TLR-7 e- Pseudomonas b- TLR-4 c- TLR-3 20- Which of the following alerts the adaptive immune system to the d- TLR-2 presence of infection? a- IL-1 25- A child presents with a maculopapular rash on extremities and b- IL-6 trunk. Petechiae is found on the trunk and mucous membranes. c- IL-8 Lab tests show a Neisseria infection and the physician is concerned d- IL-12 about meningococcemia. Which of the following is the most likely? e- TNF a- C3 deficiency b- C5-C9 deficiency 21- Most cases of septic shock are caused by gram ____ organisms c- Leukocyte adhesion deficiency (LAD) with the ____ acting as the endotoxin in the disease. d- Hyper IgM syndrome a- Positive; Lipopolysaccharide (LPS) b- Negative; Lipopolysaccharide (LPS) c- Positive; Capsule d- Negative; Capsule 26- A patient presents in the winter months with swollen lips. 31- Deficiency of early complements (C3) causes: Uncontrolled activation of classical complement pathway is a- Systemic lupus erythematosus (SLE) responsible for the swelling. Records show the patient has C1 b- Hyper IgM syndrome inhibitor deficiency. Which of the following does this patient c- X-linked agammaglobulinemia have? d- Severe Combined Immunodeficiency (SCID) a- C5-C9 deficiency b- Hereditary angioedema 32- Complement receptor on RBCs for clearance of Ab-Ag complexes : c- Severe combined immunodeficiency disease (SCID) a- CR1 d- C3 deficiency b- CR2 c- CR3 27- Membrane attack complex (MAC) include all of the followings, d- CR4 except: a- C3 33- All of the followings are functions of complements, except: b- C6 a- Opsonization c- C7 b- Anaphylatoxin d- C8 c- Stimulate B cells by CR2 e- C9 d- Stimulate cytotoxic T cells by CR1 e- Clearance of immune complexes 28- Which one of the following cytokines is a chemokine: a- IL-6 34- Which of the followings represent the receptor for Epstein bar b- IL-1 virus (EBV): c- IL-8 a- Complement receptor 2 (CR2) “also called CD21” d- IL-2 b- CD1 c- TLR3 29- All of the followings are inhibitor\regulator of the complement d- CD80 system, except: a- Factor H & Factor I b- Factor D c- C1 inhibitor d- Decay-accelerating factor (DAF) Keys: 1)C 2)E 3)D 4)C 5)A 6)A 7)C 8)D 9)E 10) C 30- Deficiency of NADPH oxidase result in: 11)A 12)C 13)D 14) C 15)A 16)D 17)B 18) C 19) D 20) D a- Hyper IgM syndrome 21)B 22) D 23) B 24)B 25)B 26) B 27) A 28) C 29) B 30) D b- X-linked agammaglobulinemia 31) A 32)A 33) D 34)A c- Severe Combined Immunodeficiency (SCID) d- Chronic granulomatous disease (CGD)