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Humoral immunity
1) The document discusses humoral immunity and the mechanisms of antibody diversity. It describes how antibodies are produced through gene rearrangement of immunoglobulin genes, resulting in a huge variety of possible antibody structures. 2) Gene rearrangement of the heavy and light chain gene segments, along with junctional diversity and somatic hypermutation, allow for millions of different antibody combinations to be produced. This ensures antibodies can recognize a wide range of pathogens. 3) The key mechanisms that generate antibody diversity are combinatorial diversity through rearrangement of variable gene segments, junctional diversity through additions/deletions at gene junctions, and somatic hypermutation of rearranged genes in mature B cells.
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Humoral immunity
- 1. Humoral Immunity R. C.Gupta M.D. (Biochemistry) Jaipur, India
- 2. We are exposedto a huge variety of micro-organisms The micro-organisms include bacteria, viruses, parasites etc Many of these are harmless; some are even useful
- 3. There are manymicro-organisms that can cause disease These are known as pathogenic micro- organisms (or pathogens) Diseases caused by them can be serious, even fatal
- 4. Nature has equippedus with very competent defense mechanisms These mechanisms help us to deal with the foreign invaders
- 5.
- 6. This is amechanism that we are born with Skin and mucous membranes act as physical barriers They prevent the entry of pathogens in our body Innate immunity
- 7. Skin and mucousmembranes are covered with some secretions These secretions create an inhospitable environment for pathogens
- 8. If a pathogencrosses the physical barriers, it is challenged by phagocytes Phagocytes include macrophages, neutrophils etc Phagocytes engulf and destroy the micro-organisms
- 9. Besides phagocytes, someproteins also help in fighting against pathogens These include complement proteins, acute phase proteins, interferons etc
- 10. The second componentof the defence mechanism is adaptive immunity Unlike innate immunity, adaptive immunity is acquired after birth Adaptive immunity is also known as acquired immunity
- 11. Innate immunity Doesn’t recognize antigens Isnon-specific Doesn’t improve on repeated exposure to the same pathogen Acquired immunity Recognizes antigens Is specific Improves on repeated exposure to the same pathogen
- 12. Acquired immunity isprovided by some cells and molecules These cells and molecules recognize chemicals called antigens A given immune cell or molecule can recognize only one antigen Acquired immunity
- 13.
- 14. Humoral immunity Operates through proteins called antibodies Acts against extracellular antigens Cell-mediated immunity Operates through activated lymphocytes Actsagainst intracellular antigens Acquired immunity comprises:
- 15. Foreign chemicals havinghigh molecular weight May be proteins, polysaccharides, nucleic acids, synthetic chemicals Have complex structure May enter as free molecules or as components of some cell Antigens
- 16. Antigens can evokean immune response Immune response may be humoral or cellular or both A small part of the antigen is recognized by the immune system This part is known as epitope or antigenic determinant
- 17. Low molecular weightcompounds Cannot evoke an immune response by themselves Can evoke an immune response when combined with some other large molecule Haptens
- 18. Once immune responsedevelops, the free hapten can be recognized by the immune system Some drugs act as haptens in some individuals
- 19.
- 20. Are the keycells of immune system Are formed from stem cells in bone marrow Differentiate into B and T lymphocytes Lymphocytes:
- 21. B lymphocytes (Bcells) are processed in bone marrow B lymphocytes synthesize antibodies that provide humoral immunity T lymphocytes (T cells) are processed in thymus T lymphocytes provide cell-mediated immunity
- 22. Both B lymphocytesand T lymphocytes are capable of recognizing antigens A given B cell or T cell can recognize only one particular antigen
- 23. Operates against extracellularantigens Operates through antibodies Antibodies are plasma proteins belonging to g-globulin fraction They are also known as immunoglobulins Humoral immunity
- 24. One light chainis joined to one heavy chain by disulphide bonds Heavy chains are joined to each other by disulphide bonds Two light chainsTwo heavy chains Basic unit of an immunoglobulin (Ig) molecule consists of:
- 26. Immunoglobulin light chains Lightchains are smaller than heavy chains Their molecular weight is about 23,000 They are of two types - k (kappa) and l (lambda)
- 27. One Ig hasonly one type of light chains In one type of light chain (k or l): C-terminal half has a constant amino acid sequence (constant region) N-terminal half has a variable amino acid sequence (variable region)
- 28. Heavy chains havea molecular weight of 50,000-70,000 They are of five types - a (alpha), d (delta), e (epsilon), l (gamma) and m (mu) Immunoglobulin heavy chains
- 29. One Ig hasonly one type of heavy chains In one type of heavy chain: C-terminal three-fourth has a constant amino acid sequence N-terminal one-fourth has a variable amino acid sequence
- 30. C-Terminal three-fourth ofheavy chain is known as its constant region N-Terminal one-fourth of heavy chain is known as its variable region
- 32. The light chainsand heavy chains are folded to form some globular domains The variable regions of light and heavy chains come together to form antigen- binding sites
- 34. Variable regions oflight and heavy chains have three hypervariable (HV) regions Amino acid sequence is extremely variable in hypervariable regions HV regions constitute the antigen-binding sites
- 35. HV regions arealso called comple- mentarity determining regions (CDRs) They determine the complementarity between the antigen and the antibody
- 37. Only a smallregion of the antigen, known as epitope, is recognized by the antibody The region of antibody that contacts the epitope is known as paratope
- 38. Action of papain Theproteolytic enzyme, papain cleaves the antibody molecule The molecule is broken up into: Two identical Fab fragments One Fc fragment
- 39. Each Fab fragmentcan bind antigen (Fragment antigen binding) Fc fragment can be easily crystallized (Fragment crystallizable) Papain treatment has thus shown the functions of different regions of antibody
- 40. Fab fragments Fc fragment Antigenbinding sites Papain cleavage Antibody
- 41. Antigen-antibody interaction The antibodybinds the comple- mentary epitope of an antigen by: Hydrogen bonds Electrostatic bonds Hydrophobic interactions van der walls forces
- 42. Antigen-antibody binding isnon-covalent and reversible After antigen binding, the constant (Fc) region of the antibody performs the effector functions
- 43. Effector mechanisms Antibodies defendthe organism by a number of effector mechanisms The important mechanisms are: Neutralization Opsonization Complement activation
- 44. Antibodies coat theantigens present on the surface of pathogens and prevent their entry in cells Antibodies also coat the toxins released by pathogens and prevent their toxic effects Neutralization
- 45.
- 46. Antibodies coat thesurface of pathogens They facilitate phagocytosis by attracting phagocytes Opsonization
- 47.
- 48. Antibodies also attractnatural killer (NK) cells NK cells cause antibody-dependent cell- mediated cytotoxicity (ADCC) which kills the pathogens
- 49. Binding of antibodiesto antigens on the surface of pathogens can activate the complement system Complement system either destroys the pathogens directly or facilitates their destruction by phagocytes Complement activation
- 50.
- 51. Classification of immunoglobulins Immunoglobulinsare classified on the basis of their heavy chains According to the type of heavy chains, they are divided into five classes
- 52. Immuno- globulin class Type of heavy chains Type of light chains IgAa k or l IgG g k or l IgD d k or l IgE e k or l IgM m k or l
- 53. IgA is dividedinto two subclasses – IgA1 and IgA2 IgG has four subclasses – IgG1, IgG2, IgG3 and IgG4 Subclasses
- 54. Most abundant Igin plasma Longest half-life Performs all the effector functions Can cross placental barrier Maternal IgG provides immunity to the newborn in the first few weeks of life IgG
- 55.
- 56. IgA is presentin plasma as well as in exocrine secretions IgA present in exocrine secretions is known as secretory IgA Plasma IgA is a monomer while secretory IgA is a dimer IgA
- 57.
- 58. Secretory IgA isformed beneath the baso-lateral surface of epithelial cells It binds to an Ig receptor present on epithelial cells A part of the Ig receptor detaches from the cell It attaches to IgA dimer as secretory component Secretory IgA
- 60. Secretory IgA traversesthe cell to reach the mucosal surface It acts mainly by neutralization Secretory IgA present in breast milk enters the gut of the newborn It binds to mucosa and protects the baby against gastro-intestinal pathogens
- 61. The largest Ig Thefirst Ig to be secreted upon entry of any antigen Acts mainly by complement activation Weak neutralizing and opsonizing activity IgM
- 63. Bound to mastcells and basophils Parasitic antigens bind to IgE on mast cells Mast cells release chemical mediators that destroy the parasite Also mediates allergic reactions IgE
- 64.
- 65.
- 66. Important features ofIg classes Class of Ig Plasma conc (mg/dl) Half-life (days) Active against Bacteria and viruses Strongly antiviral, weakly antibacterial Strongly antibacterial, weakly antiviral Anti-parasitic, mediates allergic reactions Function not known IgG IgA IgM IgE IgD 700-1,500 60-500 40-200 0.01-0.1 0.3-40 23 5-6 5-6 2-3 2-3
- 67. Variants of thebasic immunoglobulin structure are: Idiotypes Isotypes Allotypes Variants of immunoglobulins
- 68. The variable regionof an Ig forms a typical three-dimensional structure This is complementary to the antigenic determinant of a particular antigen This typical antigen-recognition structure constitutes an idiotype Idiotypes
- 69.
- 70. Immunoglobulins are dividedinto five classes viz. IgA, IgD, IgE, IgG and IgM IgA is further divided into IgA1 and IgA2 subclasses IgG is further divided into IgG1, IgG2, IgG3 and IgG4 subclasses Isotypes
- 71. These variants (theclasses and the subclasses) are known as isotypes Isotypic variations are due to differences in amino acid sequence in the constant region of heavy chains
- 72.
- 73. Allotypes are immunoglobulinsof the same class differing slightly in amino acid sequence in the constant region These are formed by mutations substituting one or two amino acids in the constant region Allotypes are inherited from parents Allotypes
- 74.
- 75. Our immune systemcan produce a vast range of antibodies having different antigen specificities These antibodies can recognize virtually every actual and potential antigen that we may come across Antibody diversity
- 76. Every antibody hasa unique antigen- binding site This is due to a unique amino acid sequence in the variable region Amino acid sequence of each protein is encoded by a specific gene
- 77. Human beings cansynthesize millions of unique antibodies So, we need millions of genes to encode the huge repertoire of antibodies However, the number of antibody genes in human genome is less than 200 Every protein is encoded by a particular gene
- 78. How a smallnumber of genes can produce a vast range of antibodies remained a mystery for long Tonegawa solved this mystery by showing that antibody diversity arises from gene re- arrangement
- 79. Genes for lightchains and heavy chains are present on different chromosomes In genomic DNA, light chain and heavy chain genes are not complete genes The genes are split into segments The segments are brought together when a new B cell is being formed Gene re-arrangement
- 80. Light chain genere-arrangement A light chain gene is made up of three segments: Variable (V) segment Joining (J) segment Constant (C) segment
- 81. Genes for V,J & C segments are present in 3 different clusters on two chromosomes The genes for k light chains are present on chromosome 2 The genes for l light chains are present on chromosome 22
- 82. For k lightchains, there are: 40 genes in V cluster 5 genes in J cluster One gene in C cluster
- 83. For l lightchains, there are: 30 genes in V cluster 4 genes in J cluster 4 genes in C cluster
- 84. The V segmentand J segment genes encode the variable region of the light chains The C segment genes encode the constant region of the light chains
- 85. When a Bcell differentiates, one of the V segment genes joins one of the J segment genes The intervening DNA is deleted This is known as V-J joining
- 86. The V-J combinationand a C segment gene are transcribed to form a hnRNA hnRNA is spliced to form mRNA for a light chain
- 87. Light chain genere-arrangement
- 88. There are 40genes for V segment and 5 genes for J segment of k light chains Therefore, 40x5 i.e. 200 different V-J combinations are possible
- 89. There are 30genes for V segment and 4 genes for J segment of l light chains Hence, 30x4 i.e. 120 V-J combinations are possible A given B cell has one particular V-J combination
- 90. Heavy chain genere-arrangement A heavy chain gene is made up of four segments: Variable (V) segment Diversity (D) segment Joining (J) segment Constant (C) segment
- 91. The heavy chaingenes are present in four different clusters on chromosome 14 V, D and J segments encode the variable region C segment encodes the constant region
- 92. For heavy chains,there are: 40 genes in V cluster 25 genes in D cluster 6 genes in J cluster 9 genes in C cluster
- 93. When a Bcell differentiates, one D segment gene joins one J segment gene The intervening DNA is deleted This is known as D-J joining
- 94. One V segmentgene joins the D-J combination The intervening DNA is deleted This is known as V-D-J joining V-D-J combination and the first C segment gene (Cm) are transcribed to form hnRNA
- 95. hnRNA is splicedto form heavy chain mRNA The V-D-J portion encodes the variable region Possible V-D-J combinations are 40x25x6 = 6,000 A given B cell has one particular combination
- 96.
- 97. Thus several hundreddifferent light chains can be formed Each has a unique amino acid sequence in its variable region Several thousand different heavy chains can be formed Each has a unique amino acid sequence in its variable region
- 98. When light chainscombine with heavy chains, millions of combinations are possible Each combination is specific for one antigen A given B cell has only one combination; it synthesizes only one specific antibody
- 99. Variable combination ofdifferent gene segments is the major mechanism of antibody diversity Antibody diversity, thus, generated is known as combinatorial diversity Nearly two million variable regions can be formed by combinatorial diversity Combinatorial diversity
- 100. Gene re-arrangement reactionsare catalyzed by: DNA repair enzymes RAG-1 and RAG-2 RAG-1 and RAG-2 are encoded by recombination activating genes 1 and 2
- 101. A second sourceof diversity is junctional diversity When different gene segments join, some nucleotides may be added to, or deleted from, the ends This creates new base sequences Junctional diversity
- 102. Nucleotides are addedby Terminal deoxyribonucleotidyl Transferase (TdT) Nucleotides are deleted by exonucleases
- 103. A final sourceof diversity is somatic hypermutation When a mature B cell encounters an antigen, a series of point mutations can occur in the variable region of the gene This results in further diversity Somatic hypermutation
- 104. Like other genes,the heavy chain genes are preceded by a promoter A regulator is present upstream of the promoter An enhancer element is present between V-D-J and C segments Re-arranged heavy chain gene
- 105. There are nineC (constant) segments The promoter is weak but gene expression is increased by the enhancer element Each C segment is preceded by a short repetitive sequence known as switch sequence
- 107. Among the nineC segments, the first is Cm IgM is the first immunoglobulin to be formed upon entry of any antigen After V-D-J joining, VDJ is transcribed with the first constant segment i.e. Cm
- 108. Different classes ofimmunoglobulins differ in their heavy chains and effector functions IgM is the first immunoglobulin to be formed However, Ig of a different class may be needed to deal with the same antigen Class switching
- 109. The new Igshould recognize the same antigen but perform a different effector function For this, the VDJ complex, already formed, joins a downstream constant segment The intervening DNA is deleted
- 110. Thus, an Igof a different class but having the same antigen specificity is formed This is known as class switching (isotype switching) Switch sequences preceding C segment genes facilitate class switching
- 111. Class switching fromIgM to IgA2
- 112. There are millionsof B cells, each synthesizing one particular Ig The Ig molecules are inserted in the cell membrane of B cells These are known as antigen receptors The antigen-binding site is displayed on the cell surface Primary response
- 114. The antigens possessspecific epitopes Each epitope is recognized by a complementary antigen receptor
- 116. When an antigenenters for the first time, its epitope is recognized by some Ig molecule The Ig molecule binds the antigen This binding stimulates the B lymphocyte to divide and differentiate The B cell differentiates into a clone of plasma cells
- 118. The plasma cellsnot only synthesize but also secrete the antibody Antibody secretion upon first exposure to an antigen is called primary response Primary response is weak and short-lived
- 119. After first encounterwith an antigen, some B cells are converted into memory B cells If the same antigen enters again, memory B cells differentiate into plasma cells This is called secondary response Secondary response is quick, strong and long-lasting Secondary response
- 121. Immunoglobulins synthesized byB cells are inserted in their cell membrane B cells cannot secrete immunoglobulins into plasma Immunoglobulins displayed on the surface of B cells are known as antigen receptors Differentiation of B cells into plasma cells
- 123. The antigen receptorinserted in the membrane of B cells is IgM The CH4 domain of membrane-bound IgM is associated with two trans-membrane proteins These are Ig-a and Ig-b
- 124. Cytoplasmic portions ofIg-a and Ig-b possess immunoreceptor tyrosine-based activation motif (ITAM) ITAM is made up of two precisely spaced tyrosine residues that are 9-11 amino acid residues apart
- 125. When an antigenenters the body, its epitope finds a complementary antigen receptor The antigen binds to the receptor Antigen-binding causes oligomerization of neighbouring IgM molecules
- 126. Oligomerization activates anintracellular tyrosine kinase, Fyn Some other cytosolic tyrosine kinases (Lyn and Blk) may also be activated The activated Fyn phosphorylates the ITAMs of Ig-a and Ig-b
- 127. The phosphorylated ITAMsact as a docking site for a protein, Syk Syk, which is also a tyrosine kinase, is activated Active Syk phosphorylates the tyrosine residues of some other target proteins
- 129. The phosphorylated targetproteins generate some signals These signals stimulate the B cell to differentiate into a clone of plasma cells Plasma cells synthesize IgM of a different kind
- 130. IgM can beof two types - membrane-bound form and secreted form The two forms are synthesized from the same hnRNA by alternative splicing The splicing which occurs in B cells produces the membrane-bound form The splicing which occurs in plasma cells produces the secreted form
- 131. Immunization is aprocess by which active immunity against an infection is produced This is done by administering a vaccine Vaccine contains a small dose of an antigen belonging to the infectious agent Immunization
- 132. The antigen inthe vaccine produces a primary response The immune system retains the memory of the antigen
- 133. If the sameantigen enters again by way of natural infection, a quick secondary response develops The secondary response destroys the antigen (and the infectious agent) Immunization is used to prevent a variety of infectious diseases
- 134. The vaccine mayconsist of: • Killed micro-organisms e.g. typhoid vaccine, cholera vaccine, Salk’s polio vaccine etc • Live attenuated micro-organisms e.g. Sabine’s polio vaccine, BCG vaccine etc • Toxoids e.g. tetanus toxoid, diphtheria toxoid etc • Pure antigen e.g. Hepatitis B surface antigen in recombinant hepatitis B vaccine
- 135. Features of aneffective vaccine Safe The vaccine itself should not cause disease or death Protective Must protect against illness from exposure to live pathogen Sustained effect Protection should be long-lasting
- 136. Passive immunity Quick butshort-term protection against an infection can be provided by administering pre-formed antibodies These antibodies may be: Obtained from animals Obtained from human beings Synthesized in the laboratory
- 137. Monoclonal antibodies producedin laboratory by hybridoma technology are widely used for: Academic purposes Diagnostic purposes Therapeutic purposes
- 138. Monoclonal antibodies areclones of each other They are produced in the laboratory by hybridoma technology A hybridoma cell is a hybrid cell prepared by fusion of a B lymphocyte and a myeloma cell Production of monoclonal antibodies
- 139. B lymphocytes areantibody-forming cells A given B lymphocyte is dedicated to form one particular antibody Myeloma cells are immortal cancer cells Fusion of a B lymphocyte with a myeloma cell produces a hybridoma cell
- 140. Hybridoma cell possessesproperties of myeloma cells as well as B cells A hybridoma cell is immortal like a myeloma cell It synthesizes one particular antibody like a B cell
- 141. When the hybridomacell is put in a culture medium, it goes on: Dividing for ever Secreting the antibody for ever Since only one B-lymphocyte has fused with a myeloma cell, the hybridoma cell secretes a monoclonal antibody
- 142. A mouse isinoculated with an antigen B cells are taken from its spleen B cells and myeloma cells are fused in the presence of polyethylene glycol (PEG) Procedure
- 143. When B cellsand myeloma cells are put together in the presence of PEG: • Some B cells may fuse with B cells • Some myeloma cells may fuse with myeloma cells • Some B cells may fuse with myeloma cells • Some B cells and myeloma cells may remain unfused
- 144. Fusion of Bcells with myeloma cells produces hybridoma cells Hybridoma cells have to be selected from the other cells This is done by culturing the cells in Hypoxanthine-Aminopterin-Thymidine (HAT) medium
- 145. Production of monoclonalantibodies
- 146. Myeloma cells lackHGPRT Therefore, they cannot salvage hypo- xanthine (present in HAT medium) They are dependent on de novo synthesis for their purine requirement But de novo synthesis is blocked by aminopterin
- 147. Unfused B-lymphocytes diesoon when their life-span is over Unfused myeloma cells cannot survive because they are deprived of purines Only hybridoma cells survive as they have acquired HGPRT from B-lymphocytes In HAT medium:
- 148. Myeloma cells cannot salvagehypoxanthine as they lack HGPRT De novo synthesis of purine nucleotides and TMP is blocked by aminopterin PRPP AMP←IMP→GMP HGPRT Hypoxanthine ↓ ↓ ↓ ↓ ↓ UMP TMP ↓ ↓ ↓ ↓ ↓ Thymidine Thymidine kinase Production of monoclonal antibodies ‒‒
- 149. Complement system actsin concert with antibodies It complements the action of antibodies It consists of a group of proteins present in plasma Complement system
- 150. Complement proteins inplasma include: Complement components C1 – C9 Mannose-binding lectin MBL-associated serine protease Factors B, D, H, I etc
- 151. Complement components areinactive pro- enzymes These are converted into active enzymes by a cascade of reactions
- 152. During complement activation reactions: Onecomplement protein acts on the next A small peptide is split off from the second The pro-enzyme is converted into enzyme
- 153. The small peptidesplit off is denoted by suffix ‘a’ and the larger fragment by ‘b’ The enzymatically active fragment is shown by a horizontal bar on it X → Xā + Xb
- 154. There are threecomplement pathways: Classic complement cascade Lectin pathway Alternate complement pathway
- 155. The classic complementcascade is activated by antigen-antibody binding Lectin and alternate complement pathways don’t require antigen-antibody interaction
- 156. Classic complement cascade Theclassic complement cascade can be divided into three phases: Recognition phase Activation phase Membrane attack phase
- 157. Recognition phase A recognitionunit participates in this phase The recognition unit is made up of C1q, C1r and C1s
- 158. Activation phase An activationunit participates in this phase The activation unit is made up of C1, C2, C3 and C4
- 159. Membrane attack phase A membraneattack complex participates in this phase The membrane attack complex is made up of C5, C6, C7, C8 and C9
- 160. Binding of IgMor IgG to a bacterial antigen initiates the recognition phase One IgM or at least two (ideally six) IgG molecules are required for initiation Binding of IgM or IgG to the antigen attracts C1 Recognition phase
- 161. Complement system –Recognition phase
- 162. C1 is acomplex made up of C1q, C1r and C1s C1q consists of six identical subunits with globular heads and long tails The tails combine to bind two molecules each of C1r and C1s
- 164. C1 binds tothe constant region of the antibody This binding causes a conformational change in C1r As a result, C1r cleaves and activates C1s C1s → C1s
- 166. C6 + C7 C3b C5b C5b-6-7 C5C5a C8 C5b-6-7-8 Membrane attack phase C5b, C6, C7 and C8 combine to form the membrane attack unit C3b splits C5 into C5a and C5b The unit inserts in the cell membrane of the target cell and attracts C9
- 167. Several molecules ofC9 insert in the cell membrane of the target cell They are polymerized to form a trans- membrane annular pore Contents of the cell leak out through the pore leading to lysis of the target cell
- 169. The complement pathwaycan also be activated by mannose binding lectin (MBL) MBL is a protein synthesized by liver and secreted in circulation MBL binds to mannose (and some other carbohydrates) of microbes Lectin pathway
- 170. Binding of MBLto microbial carbohydrates activates MBL-associated serine protease (MASP) MASP activates complements C2 and C4 Rest of the pathway is identical with the classic complement pathway
- 171. Mannose on microbial surface Mannose-binding lectin (MBL) MBL-associated serineprotease MBL binds to mannose on the surface of microbe MBL-associated serine protease is activated MBL-associated serine protease splits C2 and C4
- 172. Active C2 andC4 split and activate C3
- 173. The alternate complementpathway does not involve antigen-antibody interaction It does not require C1, C2 and C4 It requires the rest of the complement components and Factor B and Factor D Alternate complement pathway
- 174. According to currentview, C3 is slowly hydrolysed when it contacts water This slow and spontaneous hydrolysis occurs continuously If a foreign cell is not present, active C3b binds to some self-cell
- 175. C3 is inactivatedby factors H and I present on the self-cell If a foreign cell is present, C3 binds to the foreign cell C3 remains active because the foreign cells lack factors H and I
- 176. A protein, FactorB binds to C3b to form a complex Factor D splits Factor B into Ba and Bb C3bBb splits C5 into C5a and C5b
- 177. Surface of self-cellSurface of foreign cell
- 178. After formation ofC5b, the pathway is similar to the classic complement cascade Membrane attack complex is formed The target cell is lysed
- 179. H2O C3 C3a C3b Factor B C3bB Factor DBa C3bBb C5C5a C5b Membrane attack complex Lysis of the target cell
- 180. Allergy is describedas a side effect of immunity It is an altered immune response to an otherwise innocuous antigen Antigens evoking an allergic response are called allergens Allergy
- 181. Allergens are smallmolecules present in: • Pollens • Molds (tiny fungi) • Dust mites • Animal dander (flecks of skin) • Insect sting • Drugs • Food
- 182. Allergens bind toIgE (Reaginic antibody) IgE is normally present in minute concentration Its function is to protect against parasites
- 183. Some persons havea relatively high concentration of IgE The concentration is influenced by genetic as well as environmental factors
- 184. Genetic susceptibility, inheritedfrom parents, can increase IgE concentration Very hygienic environment spares IgE as it doesn’t have to act against parasites
- 185. High-affinity receptors forIgE are present on mast cells Mast cells are present beneath mucosal cells and in connective tissue IgE binds to its receptors on the mast cells
- 186. When an allergenbinds to IgE, the mast cells release their stored granules The granules contain some chemical mediators
- 187. The chemical mediatorsinclude: Histamine Heparin Leukotrienes C4, D4 and E4 Platelet activating factor Eosinophil chemotactic factor
- 188. Increase in capillarypermeability Vasodilatation Itching Sneezing Bronchospasm Depending upon the site of release, chemical mediators cause: