This document discusses antigen, antibody, and complement systems and types of immune responses and hypersensitivity reactions. It provides an overview of innate and adaptive immunity, cells involved in the immune system including B cells, T cells, and macrophages. It describes the properties of antigens and antibodies as well as the components, functions, and activation pathways of the complement system. The document also discusses the four types of hypersensitivity reactions (type I-IV) and provides examples of conditions that fall under each type of hypersensitivity.
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ANTIGEN, ANTIBODY AND COMPLEMENTS. TYPES OF IMMUNE RESPONSES AND HYPERSENSITIVITY REACTIONS
1. ANTIGEN, ANTIBODY AND COMPLEMENTS.
TYPES OF IMMUNE RESPONSES AND
HYPERSENSITIVITY REACTIONS.
Raju Kaiti
Optometrist, Dhulikhel Hospital-Kathmandu University Hospital
2. REFERENCES
ī§ Short text book of medical microbiology, 6th
edition,
Satish Gupte
ī§ Lippincottâs microbiology
ī§ Robbinâs pathology
ī§ Immunopathology of the eye by A. H. S. Rahi and A.
Garner
ī§ Ocular Pathology by Myron Yanoff and Ben S. Fine
ī§ Internet
ī§ Class notes
3. IMMUNITY
ī§ Greek word
Immunis:- Free from burden
Sequence of cellular and molecular events
designed to rid the host of an offending
stimulus
Pathogenic organismtoxic
substancescellular debris neoplastic cells
4. Immunology
ī§ Science which deals with the bodyâs response
to antigenic challenge.
ī§ Deals with the vital immune system.
ī§ Immune system is an interacting set of
specialized cells and proteins designed to
identify and destroy foreign invaders or
abnormal substances before they damage
the body.
5. Two arms of immune system
1.Innate (or natural) immune system
a. Non specific
īē Physical barrier: skin, mucus
īē Proteins in serum and in tissues: Lysozyme, interferon,
complements. (eg. In tearsâĻâĻ.)
b. Specific
īē Antibody mediated
īē Cell mediated
2.Adaptive(or acquired)specific immune system
6. Active Passive
1.Produced actively by the
immune system of host
1.Received passively by the host and the
immune system doesnât participate.
2.Induced by infection or
by contact with
immunogen.
2.Conferred by introducing ready made
antibody.
3. Immune response-
durable and effective
3. Immune response-short lived and less
effective
4.Immunity develops only
after a lag period.
4.Immunity effective immediately.
5.Immunological memory
presumed.
5.No immunological memory.
6.Serves no purpose in
immunodeficient host.
6.Applicable in immuno-deficient host.
7.No inheritance of
immunity.
7.May be acquired from mother
10. Adaptive Immunity
ī§ Humoral
īē B cells
īē Antibodies
īē Complements
ī§ Cell-mediated
īē Antigen Presenting Cells
īē T cells
Characteristics:
Specific response
Late response
11. Cells of Immune system
ī§ T-Lymphocytes
īē Thymus derived lymphocytes
īē Role in cellular or cell-mediated immunity.
īē Constitutes 60-70% of peripheral lymphocytes
īē Differentiation of T-cells
Helper T cells
īē Essential to the differentiation of B-cells into plasma
cells and their subsequent secretion of Antibodies.
īē Each helper T-cell is capable of activating hundreds of
specific B-cells
12. Suppressor T-cells :
ī§ inhibit the development of B-cells in to
plasma cells
ī§ regulate the activity of killer T-cells and
ī§ suppress the productionof Abs when they
become excessive.
ī§ Also suppress auto-immune responses.
13. Killer T-cells
ī§ Have specific receptor for antigenic determinants.
ī§ Killer T-cell migrate from lymphoid tissue to the site of
foreign cell invasion where they secrete small protein,
lymphokines.
ī§ Prevent the reproduction of invading micro-organisms,
infected host cells or viruses inside host cells.
14. Memory T-cells
ī§ The T-cells that remain potentially active and viable even
after the antigen has been inactivated.
ī§ Upon 2nd
encounter memory cells proliferate,
differentiate into plasma cells and secrete Abs so rapidly
that the symptoms of the disease may not even be
observed.
16. Antigens
īŧ Basically Exogenous
īŧ Occasionally may be derived from bodyâs own tissues
īŧ Protein molecules or part which have specific AA
sequence folded in tertiary shapes.
īŧ Substances that stimulate Ab production when they
react.
īŧ Molecular wt. : 8000 or more
18. īļHapten e.g lipid,nucleic acid
Two types:
īļComplex hapten and
īļSimple hapten
Immunogen Vs antigen
īŧ All immunogens are antigens but not all the
antigens are immunogens.
19. Antibody
o Specific glycoprotein molecules generated by
à âcells in response to antigens.
o Also called immunoglobulins.
o Humoral substance found in serum,lymphs and other
body fluids.
o Highly specific in nature.
20. Organs producing Antibodies
ī§ Spleen, lymphnodes and bone marrow
ī§ Tissues like peyerâs patches, appendix, thymus
ī§ These structures contains lymphocytes macrophages
and plasma cells
21. FUNCTIONS
ī§ Neutralization of toxins.
ī§ Activation of complement (results in improved
opsonisation)
ī§ Lysis of invading microorganisms.
22. Immunoglobulin
ī§ Immunoglobulins are synthesized by plasma
cells and also by lymphocytes.
ī§ All antibodies are Immunoglobulins but all
Immunoglobulins may not be antibodies.
ī§ Immunoglobulin is the structural and chemical
concept while antibody is biological and
functional concept.
23. Classification:
# Types based on Size, Carbohydrate
content and amino acid analysis:
ī§ IgG
ī§ IgM
ī§ IgA
ī§ IgD
ī§ IgE
24. Immunoglobulin
ī§ IgG:
īē comprises 70% of total Ig.
īē Shortest half life of 21 days
īē Lowest mol. Wt. and found in highest concn in body.
īē crosses placenta and provides much of maternal antibody.
īē Responsible for late immune response.
īē Bivalent in structure.
īē Four sub classes: IgG1, IgG2, IgG3, IgG4.
25. IgA:
âĸIn body secretion like milk, tears, saliva, urine etc.
âĸAlso called secretory immunoglobulins
âĸAntibacterial and antiviral
âĸPresent as either monomer or dimer
âĸMajorly generated in bone marrow
26. ī§ IgM:
īē Highest mol.wt
īē Present in serum as pentamer
īē Constitute only 10% of serum immunoglobin
īē Canât cross transplacental barrier.
īē Responsible for early immune response.
27. ī§ IgE:
īē Play role in parasitic and allergic disease.
īē Shortest half life.
īē Present in small quantities.
28. ContdâĻ
ī§ IgD:
īē Present in the surface
of the lymphocytes.
īē Least abundant of all.
īē Mainly intravascular
distribution.
29.
30.
31.
32. Chemistry of
immunoglobulins
ī§ All immunoglobulins composed of same basic units.
ī§ Consists two light (L) and two heavy (H) chains.
ī§ L chains and H chains linked together by a disulphide
bond.
ī§ Two H chains linked similarly.
33. ī§ Enzyme action breaks the structure into three.
ī§ Two identical Fab fragments
ī§ Third Fc fragment
ī§ Two classes of L chains â Kappa (k) and Lamda (Îģ)
ī§ Five classes of H chains
ī§ Âĩ- IgM
ī§ Îą- IgA
ī§ Îŗ- IgG
ī§ δ- IgD
ī§ Îĩ- IgE
34. Different regions
ī§ Constant region âCâ
ī§ Variable region âVâ
ī§ Adjuvants are substances which enhance the
immune response
ī§ Weak antigens also evoke high order of
antibody production
35.
36. Complements
ī§ Protein substance involved in immune response
ī§ Synthesized by hepatocytes, blood monocytes, epithelial
cell of GI tract and tissue macrophages
ī§ Functions include opsonisation, target cytolysis,
inflamation and immune complex clearence with lysis of
bacterial cells
37. ī§ 2 pathway of complement activation.
complement system
classical alternate
Brought about by Ag-
Ab complex.
Involves activation of
nine major proteins
C1 to C9
Brought about by certain
bacterial polysaccharides,
endo-toxin
Activated by agregated
IgA
38. ContdâĻ
ī§ Refers to series of factors occuring in normal serum
activated by Ag-Ab interaction
ī§ Concentration is fairly constant for each species of
animal
ī§ 10% of human serum globulin.
ī§ Concentration decreased in acute glomerulo-nephritis,
serum sickness
ī§ Concentration increased in carcinomatosis, coronary
occlusion and rheumatic fever
39. Components of Complement
ī§ Known to have nine distinct components
ī§ One of which have three protein subunits
making total 11 proteins
ī§ C1: 3 proteins held by calcium ions.
40. Biosynthesis of Complement
ī§ C1 â synthesized in interstitial epithelium
ī§ C2 and C4 â macrophages
ī§ C5 and C8 â in spleen
ī§ C3, C6 and C9 â in liver
ī§ C7 â not known
41. Features of antigen antibody
reactions
ī§ Reactions highly specific
ī§ Entire molecules react and not fragment
ī§ No de-naturation of antigen or antibody during reaction
ī§ Combination is formed but reversible
ī§ Both Ag and Ab participate in formation of agglutinates
or precipitates
ī§ Ag and Ab may combine in varying proportion
42. ī§ Cross reactions
īē Particular antibody may react with other antigens
also
ī§ Heterophile antigens
īē Antigens those are cross reacting with other
antibodies
ī§ Heterophile antibodies
īē Antibodies those are cross reacting with or
antigens
ī§ Antibody title
īē highest dilution of patient serum where visible
antigen antibody reaction takes place
43. Factors influencing antibody
production
ī§ Age
ī§ Nutritional status
ī§ Root of adminstration
ī§ Size and no. of doses
īē Critical dose and immunological paralysis
ī§ Multiple antigens
ī§ Adjuvants
ī§ Immunosuperssive agents
45. Immune Response
ī§ Specific reactivity induced in host by
antigenic stimulus
Primary response Secondary response
Humoral
Cell-mediated
Slow, sluggish, short
lived with a long lag
phage and low
antibody production,
Predominantly IgM
Prompt, powerful,
prolonged with much
higher level of Ab
production
predominantly IgG
46. Ocular Immune Responses
Conjunctiva
īē Tear film:
ī Washes away debris and irritants
ī lysosyme, betalysin, lactoferrin, IgA
īē Well vascularized, Langerhans cells, dendritic
cells and macrophages
48. CORNEA
īē No localized immune processing
īē Immune Privilege: Normal limbal physiology,
avascularity, absence of APCs and lymphatics,
intact immunoregulatory systems of anterior
chamber
50. Failure of Immune system
Immune system
Hypersensitivity
(Overactive immune response)
Immunodeficiency
(ineffective immune
response)
Autoimmunity
(mistaken recognition of self
antigens)
51. Hypersensitivity
ī§ Term used to describe immune responses
that cause host tissue damage
ī§ Detrimental effect on hosts
īē Fever
īē shock
īē Inflammatory nature
īē Spasm of smooth muscle
īē Gastrointestinal and pulmonary disorders
īē Fatal circulatory collapse
52. Hypersensitivity
ī§ State in which the introduction of an
antigen into the body elicits an unduly
severe immunological reaction.
ī§ 4 types: -
1. Anaphylaxis, atopic or Type I reaction.
2. Cytotoxic or Type II
3. Immune complex, Arthus-Type III
4. Delayed hypersensitivity Type IV
53. Hypersensitivity
ī§ Type I
īē Exaggerated IgE response to relatively harmless
environmental antigens
īē Genetic predisposition
īē Results in release of several active substances
including histamine, slow reacting substance and
an eosinophil chemo tactic factor
54. Type I
īē Eg:
ī Hay fever, atopic dermatitis, systemic anaphylaxis
ī Atopic conjunctivitis
īē Diagnosis:
ī In vivo skin testing with batteries of allergens
ī In vitro RAST test (quantitate specific IgE levels
56. Type II
īē Antibody mediated hypersensitivity against self
cells or receptors or membranes
īē Mediated by IgG or IgM antibodies against tissue
antigens, resulting in organ-specific antibody
production
57. Type II
īē Antibody binds to cells or tissues and causes local
complement activation, influx of leukocytes, and
tissue destruction by:
ī ADCC
ī Degranulation by phagocytes
ī Production of oxygen radicals
58. Type II
īē Diagnosis:
ī Detect immunoglobulins on affected cells
or tissues
ī Detect complement in affected tissue
ī Detect autoantibody or auto reactive T
cells
59. Type II
ī§ eg
Moorenâs ulcer
Hemolytic disease of the newborn
Goodpasture syndrome
Hyper acute graft rejection
60. Type III
īē Due to high levels of circulating, soluble immune
complexes overwhelming the ability of the
mononuclear phagocyte system to remove them
ī§ Damage is caused by antigen-antibody complex.
61. Type III
īē The excess complexes deposit in various tissues
and activate complement
īē Subsequent attempt by neutrophils to remove
them results in degranulation and tissue damage.
62. Type III
ī§ Can take one of two forms according to
whether the immune complex develops in
circulating blood or in tissues
ī§ Arthus reaction
īē Local manifestation in tissue
ī§ Serum sickness
ī Systemic form of type III hypersensitivity
63. Type III
īē Eg.
ī Arthus reaction, serum sickness, Lupus, Rheumatoid
arthritis, etc.
ī Immune ring formation in cornea in Herpes simplex
keratitis
īē Diagnosis:
ī very low levels of complements in blood, esp. c3 and
c4
66. Type IV
īē No role of antibody or complement
īē One aspect of cell mediated immunity
īē Antigen activates specifically macrophages
and sensitized T-lymphocytes leading to
secretions of lymphokines
īē Due to activity of thymus dependent
lymphocytes and clinically has a delayed
onset
īē Two types:
ī Classical or Tuberculin type
ī Granulomatous reactions
73. Antibody-mediated Diseases
ī§ Vernal conjunctivitis :
īē Mostly affects children & adolescents
īē Occurs only in warm season of year.
īē Produces giant papillae (cobblestone) of tarsal
conjunctiva.
75. ī§ Reiterâs diseases
īē males>females
īē C/F
ī Self limited papillary conjunctivitis
ī Acute iridocyclitis or both eyes occasionally with
hypopyn.
76. 76
Other antibody mediated
Diseases
ī§ Systemic lupus erythematosus
īē Occlusive vasculitis of nerve fiber layer of retina.
īē Infarcts results in cytoid bodies or cotton-wool spots in
retina.
ī§ Pemphigus vulgaris
īē Intraepithelial bullae of conjunctiva
77. Lens induced Uveitis
ī§ Rare condition
associated with
circulating Ab to
lens protein.
ī§ In individuals
whose lens capsule
is permeable to to
these protein as a
result of trauma or
other Diseases.
78. Cell mediated Diseases
ī§ Ocular sarcoidosis
īē Panuveitis with inflammatory involvement of
optic nerve and retinal blood vessels.
īē Acute iridocyclitis
īē Conjunctival erythema.
79. Sympathetic ophthalmitis
ī§ Inflammation of 2nd
eye after
the other has been damaged
by penetrating injury.
ī§ Symptoms
īē Floating spots
īē Loss of accommodative power.
īē Ultimately may lead to
Pappilloedema and 20
glaucoma