II. Acquired (specific or adaptive)
immunity
•The adaptive immune system is
composed of highly specialized,
systemic cells...
• The adaptive immune response has
the ability to recognize and
remember specific pathogens (to
generate immunity), and to...
Antigen or Immunogens
•Antigen is a foreign substance of
high molecular weight that
induces a specific immunological
respo...
Molecules

differ
in
their
effectiveness in stimulating Ab
production
as
proteins
&
polysaccharides are generally
good an...
Epitope:

is a part of antigen
recognized by the immune system
(antibody).
Any given antigen may have several
epitopes.
...
Ags are large molecules ( high M.W).
Hapten: partial antigen, specific non
protein substance which does not itself
elicit ...
Origin of Antigens
1. Exogenous Antigens: Ags that
have entered the body from the
outside by inhalation, ingestion,
or inj...
2. Endogenous Antigens:
Ags generated within the cell, as a
result of normal cell metabolism,
or because of viral or intra...
3. AutoAntigens:
Is usually a normal protein that is
recognized by the immune system
of patients suffering from a
specifi...
Types of antigen
A.Heterologous antigen:
is an Ag derived from one species
and is capable of stimulating an
immune respons...
B. Homologous Antigen:
is an Ag in an individual of one
species which is capable of
eliciting an immune response in
geneti...
C. Heterophile Antigens(common
to more than one species):
Antigens share the antigenic
determinants & the Antibody
formed ...
a. Human heart valve tissue &
certain Antigen found in
Steptococcus pyogenes.
b. Forssman Antigen: glycopeptide
heterophile protein found in
certain animals as dog, horse, cat,
sheep
(RBCs),
pneumococ...
Antibody structure
Antibody structure
Monomer:
A flexible Y-shaped
molecule with four protein chains:
2
identical light chains (L)
polypept...
These

two chains are held
together by disulfide bonds.
Ab molecules combined with
large Ag molecules form different
ang...


Constant Regions:
Stem of
monomer & lower parts of Y arms.
The constant regions for all
molecules of the same antibody
...
Variable Regions: Two sections at
the end of Y’s arms. Contain the
antigen binding sites (Fab).
Identical on the same anti...
Ab Binding Sites
Typically, an Ab molecule has two
identical binding sites, one at the end
of each arm of the Y.
Ag-Ab r...
1.Van der Waal's forces:
attract all molecules through their
electron clouds.
2.Hydrogen bonding:
electromagnetic interact...
3. Electrostatic: attraction between
Ab & Ag molecules due to
electrically charged particles.
4. Hydrophobic regions: attr...
Immunoglobulin Classes
Immunoglobulin isotype Heavy chain
IgM
IgA

m
a

IgG

g

IgE
IgD

e
d
I. IgM
 Structure: Pentamer
 Percentage serum antibodies: 5-10%
 Location: Blood, lymph, B cell surface.
 Half-life in...
II. IgA (2 subclasses, IgA1-2)
 Structure: Dimer
 Percentage serum antibodies: 10-15%
 Location: Secretions (tears, sal...


Half-life in serum: 6 days
 Complement Fixation: No
 Placental Transfer: No
 Known Functions: Localized protection o...
III. IgG (4 subclasses, IgG1-4)
 Structure:
Monomer, has 2 epitopebinding sites.
 Percentage serum antibodies: 80%
 Loc...
IV. IgE
 Structure: Monomer
 Percentage serum antibodies: 0.002%
 Location: Bound to mast cells and
basophils
 Half-li...
V. IgD
 Structure: Monomer
 Percentage serum antibodies: 0.2%
 Location: B-cell surface, blood, and lymph
 Half-life i...
Consequences of AntigenAntibody Binding
1. Agglutination: Antibodies cause antigens
(microbes) to clump together.
2.

Opsonization: Antigen (microbe) is
covered with antibodies that enhances
its ingestion & lysis by phagocytic cells.
3. Neutralization: IgG inactivates pathogen
by binding to their surface & neutralize
toxins by blocking their active sites...
4.Antibody-dependent cell-mediated
cytotoxicity: Used to destroy large
organisms (e.g.: worms). Target
organism is coated ...
5. Complement Activation: Both IgG & IgM
trigger complement system which results in cell
lysis.
Pattern of Antibody Levels During
Infection
Primary Response:
– After initial exposure to antigen, no
antibodies are found...
Secondary Response:
 Subsequent exposure to the same
antigen displays a faster & more
intense antibody response.
 A seco...
Antibody Response After Exposure to Antigen

IgG

IgM

Class switch
Three important feature of the
immunological response
1. Specificity. An Ab or reactive T-cell will
react specifically wit...
3. Tolerance. An animal generally does not
undergo an immunological response to its
own (potentially-antigenic) components...
Types of T-cell
1. Helper T (Th) Cells:
Helper T cells are named for their
ability to help other cells in the
immune
syste...
2. Cytotoxic T (Tc) Cells:
•Cytotoxic T cells kill cells that
have been infected with viruses,
and some tumor cells.
•The ...
3. Regulatory T (Treg) Cells or
suppressor T-cell:
 Shutting down the immune response
after they have successfully elimin...
Possible mechanisms of this action
1. Inhibit conversion of B-cells to plasma
cells & suppress the activity of some
of the...
4. Delayed Hypersensitivity T (TD)
Cells:
Participate
in
cell-mediated
reactions but do not interact with
B-cells.
TD ce...
TS

and TC cells recognize Ag
fragments associated with MHC
class I molecules.
TH and TD cells recognize Ag
associated w...
Cytokines
1. IL-1 & IL-2:
Macrophages secrete a potent
cytokine known as IL-1, which
acts on several different cell types...
 IL-1

is a key component of the immune
response because Th cells are one of its
main targets.

 During

this activation...
 IL-2

secreted by Th cells acts with
other cytokines such as IL-4 to
stimulate Ag-activated B-cells to
proliferate & pro...
 2.

interferon (IFN-α and IFN-ɤ)
 Named interferon because it interfere with
viral replication.
 Produced by leukocyte...
The complement system
It is a biochemical cascade which
helps clear pathogens from an
organism.
It is part of the larger...
 Over

25 proteins & protein fragments make
up the complement system.
 These proteins are synthesized mainly in
the live...
 The

end result of this activation
cascade is massive amplification of the
response & activation of the cell-killing
mem...
Membrane attack complex or Lytic complex
Three biochemical pathways activate
the complement system:
1.
The
classical
complement
pathway.
2. The alternative complem...
1- Classical pathway (adaptive immunity)
 Activation of the C1-complex (C1q, C1r,
and C1s), which occurs when C1q binds t...
2- Alternative pathway (innate
immunity)
 The alternative pathway is triggered
by C3 hydrolysis directly on the
surface o...
3- Lectin pathway (Mannose-binding
lectin or MBL) (innate immunity)
 The lectin pathway is homologous to
the classical pa...
 MASP-1

& MASP-2 very similar to C1r &
C1s respectively), which can split C4 & then
C2 produce C2a & C4b.
 C2a & C4b bi...
Complement System
The Biological Effects of Complement
1.Opsonization: The C3b molecules are
opsonins which are any molecules
enhance phagoc...
2. Inflammation: The C5a and C3a
fragments are important inflammatory
activators
inducing
vascular
permeability
&
activati...
Immunization
 Immunization:

is the process by
which an individual's immune system
becomes fortified against an agent
(kn...
Types of Immunization
1. Naturally Acquired Immunity: Obtained
in the course of daily life.

A. Naturally Acquired Active ...
B.
Naturally
Acquired
Passive
Immunity:
– Antibodies pass from mother to fetus
via placenta or breast feeding.
– No immune...
2.

Artificially
Acquired
Immunity
(vaccination):
Obtained by receiving a vaccine or immune
serum.
A. Artificially Acquire...
B.
Artificially
Immunity:

Acquired

Passive

– Preformed antibodies are introduced

into body by injection.
– Immunity is...
Who should not be vaccinated?
 Women who are pregnant (or plan a
pregnancy in the near future).
 People

with weakened i...
How are vaccines made?
 •Vaccines are made in several
different ways.
 1. Inactivate (killed vaccine, 3 doses):
grown in...
2. Attenuated (weakened live vaccine,
one dose):
 Bacterial: BCG against T.B.
 Viral: measles vaccine.
 Immunity from a...
Immune tolerance
 Specific non reactivity of the immune
system to a particular antigen.
1.Innate tolerance
 Innate toler...
2. Acquired tolerance
 Acquired or induced tolerance is the
immune system's tolerance for
external Ags.


Such as medica...
Immunodeficiency
 In medicine, immunodeficiency (or
immune deficiency) is a state in which
the immune system's ability to...
Primary immune deficiency diseases:
The

World Health Organization
(WHO) recognizes over 100
primary
immune
deficiency
di...
1. X-Linked Agammaglobulinemia
(XLA)
 Congenital.
 Low or absent IgG due to failure of Blymphocyte precursors to mature ...
2. Common Variable Immunodeficiency
(CVID)
 Normal B cell but with low levels of
antibody production.
 It is a relativel...
3. The X-Linked Hyper IgM Syndrome
 Patients with the disease have an
inability to switch their Ab production
from IgM to...
4. Selective IgA Deficiency
 Individuals
with
Selective
IgA
Deficiency lack IgA, but usually have
normal amounts of the o...
5. IgG Subclass Deficiency
 The IgG class of immunoglobulins is itself
composed of four different subtypes of
IgG molecul...
6. Severe Combined Immunodeficiency
(SCID)
 Severe Combined Immunodeficiency is an
uncommon primary immunodeficiency in
w...
7. The Wiskott Aldrich Syndrome
 Primary

immunodeficiency disease
involving both T- and B-lymphocytes.
 Platelets are a...
8. The DiGeorge Syndrome
 Developmental defect in the thymus
gland & T-lymphocyte production
may be impaired, resulting i...
9. Ataxia-Telangiectasia (neurologic
abnormalities)
 Variable immunodeficiency involving
both cellular (T-lymphocyte) &
h...
10. Chediak-Higashi Syndrome
 Hereditary fatal disease results from
the slow fusion of the lysozymes to
the phagosomes & ...
Acquired immunodeficiency
 Immune deficiency as a result of
particular external processes or
diseases"secondary“
immunode...
Many specific diseases:
 1. cancer with bone marrow &
blood cells.
 2.
acquired immunodeficiency
syndrome (AIDS), caused...
Hypersensitivity
 Nearly

40 years ago Gell and
Coombs proposed a classification
scheme which defined 4 types of
hypersensitivity reaction...
I.Type I Hypersensitivity (anaphylactic
reaction)
 Immediate hyper sensitivity reaction to
exogenous antigen mediated by ...
 Eczema:

pruritic dermatitis characterized
by erythema, edema, serous exudate in
the epidermis.
 Asthma: chronic inflam...
 The

high affinity IgE receptors are found
on mast cells & basophils. Each cell has a
high density of these receptors (4...
 These

mediators cause all the normal
consequences of an acute inflammatory
reaction, increased vascular permeability,
g...
Allergens
 Ags that trigger allergic reactions &
provoke IgE-mediated responses.
 Typical allergen sources include
polle...
 There

are two types of allergic
reaction according to mode of entry
of the allergen:
1. Local (atopic) allergy
 Occurs...
2. Systemic anaphylaxis
 The consequences of a generalized
reaction are potentially fatal.
 Ingestion of nuts or seafood...
 Death

in such cases is due to systemic
release of vasoactive mediators
leading to general vasodilation &
smooth muscle ...
Diagnostic tests for immediate
hypersensitivity
 Include skin (prick & intradermal) tests
measurement of total IgE & spec...
Symptomatic treatment
 Antihistamines:
block
histamine
receptors.
 Chromoglycate

(mast cell stabilizer):
prevent the re...
Thank You
Immunology lecture 2 (2)
Immunology lecture 2 (2)
Immunology lecture 2 (2)
Immunology lecture 2 (2)
Immunology lecture 2 (2)
Immunology lecture 2 (2)
Immunology lecture 2 (2)
Immunology lecture 2 (2)
Immunology lecture 2 (2)
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Immunology lecture 2 (2)

  1. 1. II. Acquired (specific or adaptive) immunity •The adaptive immune system is composed of highly specialized, systemic cells & processes that eliminate or prevent pathogenic challenges.
  2. 2. • The adaptive immune response has the ability to recognize and remember specific pathogens (to generate immunity), and to mount stronger attacks each time the pathogen is encountered. •It is adaptive immunity because the body's immune system prepares itself for future challenges.
  3. 3. Antigen or Immunogens •Antigen is a foreign substance of high molecular weight that induces a specific immunological response in the form of antibody mediated immunity (AMI), or cell-mediated immunity (CMI) or both. Ag: antibody generator.
  4. 4. Molecules differ in their effectiveness in stimulating Ab production as proteins & polysaccharides are generally good antigens, whereas lipids & DNA are rarely antigenic.
  5. 5. Epitope: is a part of antigen recognized by the immune system (antibody). Any given antigen may have several epitopes. Each epitope is recognized by a different antibody.
  6. 6. Ags are large molecules ( high M.W). Hapten: partial antigen, specific non protein substance which does not itself elicit antibody formation but elicit the immune response when coupled with carrier protein. As Penicillin: has low M. W. & by itself is not an antigen, in body changed by enzyme result in molecule that can combine with large protein carrier to form antigenic hapten carrier complex.
  7. 7. Origin of Antigens 1. Exogenous Antigens: Ags that have entered the body from the outside by inhalation, ingestion, or injection.
  8. 8. 2. Endogenous Antigens: Ags generated within the cell, as a result of normal cell metabolism, or because of viral or intracellular bacterial infection.
  9. 9. 3. AutoAntigens: Is usually a normal protein that is recognized by the immune system of patients suffering from a specific autoimmune disease. These antigens under normal conditions, not be the target of the immune system.
  10. 10. Types of antigen A.Heterologous antigen: is an Ag derived from one species and is capable of stimulating an immune response in another species.
  11. 11. B. Homologous Antigen: is an Ag in an individual of one species which is capable of eliciting an immune response in genetically different individual of the same species e.g. RBCs & tissue Antigens.
  12. 12. C. Heterophile Antigens(common to more than one species): Antigens share the antigenic determinants & the Antibody formed to any of them could react with the other (cross reaction). Cross reactivity: reaction between antibody & antigen that differ from the immunogen.
  13. 13. a. Human heart valve tissue & certain Antigen found in Steptococcus pyogenes.
  14. 14. b. Forssman Antigen: glycopeptide heterophile protein found in certain animals as dog, horse, cat, sheep (RBCs), pneumococci which valuable in determining infection with mononucleosis; antibody formed in human react with Forssman antigen on sheep RBCs & make hemolysis of the blood.
  15. 15. Antibody structure
  16. 16. Antibody structure Monomer: A flexible Y-shaped molecule with four protein chains: 2 identical light chains (L) polypeptide chain of about 200 amino acids. 2 identical heavy chains (H) polypeptide chain of about 450 amino acids.
  17. 17. These two chains are held together by disulfide bonds. Ab molecules combined with large Ag molecules form different angles around this flexible area, & the arms of the Y rotate to bring the variable regions of the molecule into contact with the Ag.
  18. 18.  Constant Regions: Stem of monomer & lower parts of Y arms. The constant regions for all molecules of the same antibody class have the same amino acid sequence & determines the mechanism used to destroy antigen. Fc region: Stem of monomer only important because they can bind to complement or cells.
  19. 19. Variable Regions: Two sections at the end of Y’s arms. Contain the antigen binding sites (Fab). Identical on the same antibody, but vary from one antibody to another.
  20. 20. Ab Binding Sites Typically, an Ab molecule has two identical binding sites, one at the end of each arm of the Y. Ag-Ab relationships like lock & Key. •In order for an Ag-Ab reaction to be triggered, there must be a close physical & chemical complementary fit between the two.
  21. 21. 1.Van der Waal's forces: attract all molecules through their electron clouds. 2.Hydrogen bonding: electromagnetic interaction between polar molecules in which hydrogen is bound to a highly electronegative atom as (N) or (O), strong than van der waal’s
  22. 22. 3. Electrostatic: attraction between Ab & Ag molecules due to electrically charged particles. 4. Hydrophobic regions: attracted in an aqueous environment; this is probably the strongest force between them. Affinity: the measure of binding strength of antigen antibody interaction.
  23. 23. Immunoglobulin Classes Immunoglobulin isotype Heavy chain IgM IgA m a IgG g IgE IgD e d
  24. 24. I. IgM  Structure: Pentamer  Percentage serum antibodies: 5-10%  Location: Blood, lymph, B cell surface.  Half-life in serum: 5 days  Complement Fixation: Yes  Placental Transfer: No  Known Functions: First antibodies produced during an infection.
  25. 25. II. IgA (2 subclasses, IgA1-2)  Structure: Dimer  Percentage serum antibodies: 10-15%  Location: Secretions (tears, saliva, intestine, milk), blood & lymph.  Vibrio cholerae, Streptococcus mutans, and Neisseria gonorrhoeae will not bind to cell surfaces in the presence of secretory IgA.  Some pathogenic bacteria produce an enzyme splits the secretory IgA (IgA protease).
  26. 26.  Half-life in serum: 6 days  Complement Fixation: No  Placental Transfer: No  Known Functions: Localized protection of mucosal surfaces.
  27. 27. III. IgG (4 subclasses, IgG1-4)  Structure: Monomer, has 2 epitopebinding sites.  Percentage serum antibodies: 80%  Location: Blood, lymph, intestine  Half-life in serum: 23 days  Complement Fixation: Yes  Placental Transfer: Yes  Known Functions: Enhances phagocytosis, neutralizes toxins & viruses, protects fetus & newborn.
  28. 28. IV. IgE  Structure: Monomer  Percentage serum antibodies: 0.002%  Location: Bound to mast cells and basophils  Half-life in serum: 2 days  Complement Fixation: No  Placental Transfer: No  Known Functions: Allergic reactions. Possibly lysis of worms.
  29. 29. V. IgD  Structure: Monomer  Percentage serum antibodies: 0.2%  Location: B-cell surface, blood, and lymph  Half-life in serum: 3 days  Complement Fixation: No  Placental Transfer: No  Known Functions: initiate immune response.
  30. 30. Consequences of AntigenAntibody Binding
  31. 31. 1. Agglutination: Antibodies cause antigens (microbes) to clump together.
  32. 32. 2. Opsonization: Antigen (microbe) is covered with antibodies that enhances its ingestion & lysis by phagocytic cells.
  33. 33. 3. Neutralization: IgG inactivates pathogen by binding to their surface & neutralize toxins by blocking their active sites.
  34. 34. 4.Antibody-dependent cell-mediated cytotoxicity: Used to destroy large organisms (e.g.: worms). Target organism is coated with antibodies & bombarded with chemicals from nonspecific immune cells.
  35. 35. 5. Complement Activation: Both IgG & IgM trigger complement system which results in cell lysis.
  36. 36. Pattern of Antibody Levels During Infection Primary Response: – After initial exposure to antigen, no antibodies are found in serum for several days. – A gradual increase in antibody, first IgM is observed. – Gradual decline of antibodies follows.
  37. 37. Secondary Response:  Subsequent exposure to the same antigen displays a faster & more intense antibody response.  A secondary response usually involves a change in Ab class, often from IgM to IgG.  This is known as class switching and is mediated by IL-4 produced by the Th cell that activates the memory B-cell.
  38. 38. Antibody Response After Exposure to Antigen IgG IgM Class switch
  39. 39. Three important feature of the immunological response 1. Specificity. An Ab or reactive T-cell will react specifically with Ag that induced its formation; it will not react with other Ags. 2. Memory. Once the immunological response has reacted to produce a specific type of Ab or reactive T-cell, it is capable of producing more of the Ab or activated Tcells rapidly & in larger amounts.
  40. 40. 3. Tolerance. An animal generally does not undergo an immunological response to its own (potentially-antigenic) components. The animal is said to be tolerant to selfAgs.  This ensures that under normal conditions, an immune response to "self" Ags (called an autoimmune response) does not occur.  Autoimmune responses are potentially harmful to the host.
  41. 41. Types of T-cell 1. Helper T (Th) Cells: Helper T cells are named for their ability to help other cells in the immune system achieve maximum efficiency.
  42. 42. 2. Cytotoxic T (Tc) Cells: •Cytotoxic T cells kill cells that have been infected with viruses, and some tumor cells. •The cytotoxic T cell secretes a protein called perforin, which makes a hole in the cell membrane, causing the cell to lyse and die.
  43. 43. 3. Regulatory T (Treg) Cells or suppressor T-cell:  Shutting down the immune response after they have successfully eliminated invading organisms.  Maintain the tolerance to the self antigen.  Modulation of Treg can treat autoimmune disease, cancer & facilitate organ transplantation.
  44. 44. Possible mechanisms of this action 1. Inhibit conversion of B-cells to plasma cells & suppress the activity of some of the T cells. 2. Absorption of essential cytokines thus preventing the division of other lymphocytes. 3.Release of nonspecific immunosuppressive molecules.
  45. 45. 4. Delayed Hypersensitivity T (TD) Cells: Participate in cell-mediated reactions but do not interact with B-cells. TD cells are responsible for recruiting & activating phagocytes.
  46. 46. TS and TC cells recognize Ag fragments associated with MHC class I molecules. TH and TD cells recognize Ag associated with MHC class II molecules.
  47. 47. Cytokines 1. IL-1 & IL-2: Macrophages secrete a potent cytokine known as IL-1, which acts on several different cell types.  IL1 binding by IL-1 receptors (IL-1R) on the Th cell acts as an activation signal & causes Th cell to divide, producing clonal copies.
  48. 48.  IL-1 is a key component of the immune response because Th cells are one of its main targets.  During this activation stage, the stimulated Th cells begin to make IL-2, which in turn stimulates other Th & Tc precursors to form active Tc cells.
  49. 49.  IL-2 secreted by Th cells acts with other cytokines such as IL-4 to stimulate Ag-activated B-cells to proliferate & produce antibody forming plasma cells.  The end result is stimulation of several cells through the actions of IL-1 & IL2, resulting in both humoral & cellmediated immune responses.
  50. 50.  2. interferon (IFN-α and IFN-ɤ)  Named interferon because it interfere with viral replication.  Produced by leukocytes & inhibits viral replication in virtually any cell in the body.  3.Tumor necrosis factors (TNF-α & TNF-β) Capable of destroying a variety of tumors provided that TNF-producing cells have access to the tumor.
  51. 51. The complement system It is a biochemical cascade which helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system.
  52. 52.  Over 25 proteins & protein fragments make up the complement system.  These proteins are synthesized mainly in the liver, and they account for about 5% of the globulin fraction of blood serum.  Circulate in the blood as inactive components.  •When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines & initiate an amplifying cascade of further cleavages.
  53. 53.  The end result of this activation cascade is massive amplification of the response & activation of the cell-killing membrane attack complex.  Membrane attack complex: typically formed on the surface of pathogenic bacterial cell as a result of complement system & forms transmembrane channels which disrupt the phospholipid bilayer of the target cell lead to cell lysis.
  54. 54. Membrane attack complex or Lytic complex
  55. 55. Three biochemical pathways activate the complement system: 1. The classical complement pathway. 2. The alternative complement pathway. 3. Mannose-binding lectin pathway.
  56. 56. 1- Classical pathway (adaptive immunity)  Activation of the C1-complex (C1q, C1r, and C1s), which occurs when C1q binds to IgM or IgG complexed with Ags.  C1 bind & split C4 & then C2 produce C2a & C4b.  C2a & C4b bind to C3 convertase which promote clevage of C3 into C3a & C3b.  C3a & C3b bind to C2a & C4b to make C5 which enhance phagocytosis.
  57. 57. 2- Alternative pathway (innate immunity)  The alternative pathway is triggered by C3 hydrolysis directly on the surface of a pathogen.  It does not rely on a pathogen-binding protein like the other pathways.  C5a and C3a are known to trigger mast cell degranulation.
  58. 58. 3- Lectin pathway (Mannose-binding lectin or MBL) (innate immunity)  The lectin pathway is homologous to the classical pathway, but with the opsonin, mannose-binding lectin (MBL) & ficolins, instead of C1q.  This pathway is activated by binding mannose-binding lectin to mannose residues on the pathogen surface, which activates the MBL-associated serine proteases.
  59. 59.  MASP-1 & MASP-2 very similar to C1r & C1s respectively), which can split C4 & then C2 produce C2a & C4b.  C2a & C4b bind to C3 convertase which promote cleavage of C3 into C3a & C3b.  C3a & C3b bind to C2a & C4b to make C5 which enhance phagocytosis.  Ficolins (homologous to MBL): group of oligomeric lectin with subunits of fibrinogen like, collagen like molecules & lectin.
  60. 60. Complement System
  61. 61. The Biological Effects of Complement 1.Opsonization: The C3b molecules are opsonins which are any molecules enhance phagocytosis such as antibody or complement spilit .
  62. 62. 2. Inflammation: The C5a and C3a fragments are important inflammatory activators inducing vascular permeability & activation of phagocytes. 3. Lysis: C5b binds & recruits C6 & C7 to the target surface 4.Immune complex clearance: Complement has a very important role in solubilizing & causing removal from the circulation of immune complexes.
  63. 63. Immunization  Immunization: is the process by which an individual's immune system becomes fortified against an agent (known as the immunogen).  Immunization can be done through vaccination. Vaccines against M.O.s that cause diseases can prepare the body's immune system, thus helping to fight or prevent an infection.
  64. 64. Types of Immunization 1. Naturally Acquired Immunity: Obtained in the course of daily life. A. Naturally Acquired Active Immunity: – Antigens or pathogens enter body naturally. – Body generates an immune response to antigens. – Immunity may be lifelong.
  65. 65. B. Naturally Acquired Passive Immunity: – Antibodies pass from mother to fetus via placenta or breast feeding. – No immune response to antigens. – Immunity is usually short-lived (weeks to months). – Protection until child’s immune system develops.
  66. 66. 2. Artificially Acquired Immunity (vaccination): Obtained by receiving a vaccine or immune serum. A. Artificially Acquired Active Immunity: – Antigens are introduced in vaccines (immunization). – Body generates an immune response to antigens. – Immunity can be lifelong (oral polio vaccine).
  67. 67. B. Artificially Immunity: Acquired Passive – Preformed antibodies are introduced into body by injection. – Immunity is short lived (half life three weeks). – Host immune system does not respond to antigens.
  68. 68. Who should not be vaccinated?  Women who are pregnant (or plan a pregnancy in the near future).  People with weakened immune systems should not get live virus vaccines.  People who have had a major allergic reaction to a specific vaccine or one of its components should avoid revaccination with that vaccine.
  69. 69. How are vaccines made?  •Vaccines are made in several different ways.  1. Inactivate (killed vaccine, 3 doses): grown in culture then killed using method such as formaldehyde.  Viral: polio.  Bacterial: diphtheria, pertusis, tetanus vaccines (DPT).
  70. 70. 2. Attenuated (weakened live vaccine, one dose):  Bacterial: BCG against T.B.  Viral: measles vaccine.  Immunity from a live virus vaccine is generally lifelong. However, these “live virus” vaccines should not be given to people who are immunocompromised, such as some people with cancer or AIDS.
  71. 71. Immune tolerance  Specific non reactivity of the immune system to a particular antigen. 1.Innate tolerance  Innate tolerance is the body's tolerance for its own Ags & proteins. When natural tolerance fails, or when the body does not properly recognize itself, an autoimmune disorder results.
  72. 72. 2. Acquired tolerance  Acquired or induced tolerance is the immune system's tolerance for external Ags.  Such as medication used to avoid transplant rejection.
  73. 73. Immunodeficiency  In medicine, immunodeficiency (or immune deficiency) is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. A person who has an immunodeficiency of any kind is said to be immunocompromised.
  74. 74. Primary immune deficiency diseases: The World Health Organization (WHO) recognizes over 100 primary immune deficiency diseases. The most common types of primary immune deficiency diseases:
  75. 75. 1. X-Linked Agammaglobulinemia (XLA)  Congenital.  Low or absent IgG due to failure of Blymphocyte precursors to mature into B-lymphocytes & plasma cells. Since they lack the cells responsible for producing antibodies.  The gene responsible for maturation found in X-chromosome, so the disease
  76. 76. 2. Common Variable Immunodeficiency (CVID)  Normal B cell but with low levels of antibody production.  It is a relatively common form of immunodeficiency, hence, the word “common.” The degree and type of deficiency of serum immunoglobulins, and the clinical course, varies from patient to patient, hence, the word “variable.”
  77. 77. 3. The X-Linked Hyper IgM Syndrome  Patients with the disease have an inability to switch their Ab production from IgM to IgG, IgA, and IgE.  As a result, patients have decreased levels of IgG & IgA & normal or elevated levels of IgM.  The most common form is inherited as an X-chromosome & affects only boys.
  78. 78. 4. Selective IgA Deficiency  Individuals with Selective IgA Deficiency lack IgA, but usually have normal amounts of the other types of immunoglobulins.  Most affected people have no illness as a result.  Others may develop a variety of significant clinical problems & increase risk of respiratory, GIT & urogential disorders.
  79. 79. 5. IgG Subclass Deficiency  The IgG class of immunoglobulins is itself composed of four different subtypes of IgG molecules called the IgG subclasses.  Patients who lack, or have very low levels of, one or two IgG subclasses, but whose other Ig levels are normal, are said to have a selective IgG subclass deficiency.  Defects occur in heavy chain genes in the regulation of isotypes.
  80. 80. 6. Severe Combined Immunodeficiency (SCID)  Severe Combined Immunodeficiency is an uncommon primary immunodeficiency in which there is combined absence of Tlymphocyte and B-lymphocyte function.  This condition is most serious of the primary immunodeficiencies.  bone marrow transplantation, exist that can cure the disorder and the future holds the promise of gene
  81. 81. 7. The Wiskott Aldrich Syndrome  Primary immunodeficiency disease involving both T- and B-lymphocytes.  Platelets are also affected lead to thrombocytopenia.
  82. 82. 8. The DiGeorge Syndrome  Developmental defect in the thymus gland & T-lymphocyte production may be impaired, resulting in recurrent infections.
  83. 83. 9. Ataxia-Telangiectasia (neurologic abnormalities)  Variable immunodeficiency involving both cellular (T-lymphocyte) & humoral (B-lymphocytes) immune responses.  Destroy parts of the motor control area of the brain leading to an unbalance (ataxia), dilated blood vessels (telangiectasia) of the eyes & skin.
  84. 84. 10. Chediak-Higashi Syndrome  Hereditary fatal disease results from the slow fusion of the lysozymes to the phagosomes & hence ingested bacteria are not destroyed.
  85. 85. Acquired immunodeficiency  Immune deficiency as a result of particular external processes or diseases"secondary“ immunodeficiency.  Common causes:  anti-rheumatic  Immunosuppressive drugs
  86. 86. Many specific diseases:  1. cancer with bone marrow & blood cells.  2. acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV).
  87. 87. Hypersensitivity
  88. 88.  Nearly 40 years ago Gell and Coombs proposed a classification scheme which defined 4 types of hypersensitivity reactions.  The first 3 are mediated by Ab, the fourth by T cells.
  89. 89. I.Type I Hypersensitivity (anaphylactic reaction)  Immediate hyper sensitivity reaction to exogenous antigen mediated by IgE.  Such as:  Hay fever (allergic rhinitis; allergic condition affect mucous membrane of the upper repiratory tract & eyes, characterized by nasal discharge, sneezing, itching, watery eyes caused by abnormal sensitivity to airborne pollen.),
  90. 90.  Eczema: pruritic dermatitis characterized by erythema, edema, serous exudate in the epidermis.  Asthma: chronic inflammatory disease of the airways, inflammation cause the air way to spasm & swell so the airway narrow.  Urticaria: a vascular reaction of the the skin marked by apprance of elevated red batches with severe itching.
  91. 91.  The high affinity IgE receptors are found on mast cells & basophils. Each cell has a high density of these receptors (40250,000 per cell) so that a wide spectrum of Ag specificities is represented.  Such cross-linking leads to rapid degranulation (60-300 secs) of the mast cells & the release of primary inflammatory mediators stored in the granules.
  92. 92.  These mediators cause all the normal consequences of an acute inflammatory reaction, increased vascular permeability, granulocyte chemotaxis.  Mast cell activation via IgE also leads to the production of two other types of mediators. These secondary mediators, unlike the stored granule contents, must be synthesized de novo & comprise arachadonic acid metabolites (essential fatty acid) (prostaglandins & leukotrienes).
  93. 93. Allergens  Ags that trigger allergic reactions & provoke IgE-mediated responses.  Typical allergen sources include pollens, food, insect venoms, fungal spores and the feces of the HDM (Human dust mite).
  94. 94.  There are two types of allergic reaction according to mode of entry of the allergen: 1. Local (atopic) allergy  Occurs after inhalation or ingestion of the allergen & causes a localized reaction such as asthma, hay fever.
  95. 95. 2. Systemic anaphylaxis  The consequences of a generalized reaction are potentially fatal.  Ingestion of nuts or seafood, insect bites (venom), & drug injection may all cause life-threatening reactions in highly sensitized individuals.
  96. 96.  Death in such cases is due to systemic release of vasoactive mediators leading to general vasodilation & smooth muscle contraction resulting in sudden loss of blood pressure, massive edema & severe bronchiole constriction (systemic anaphylaxis).
  97. 97. Diagnostic tests for immediate hypersensitivity  Include skin (prick & intradermal) tests measurement of total IgE & specific IgE antibodies against the suspected allergens.  Total IgE & specific IgE measured by a (ELISA).  Drop of allergy-producing substance on the skin & making breaks by lightly pricking the surface.
  98. 98. Symptomatic treatment  Antihistamines: block histamine receptors.  Chromoglycate (mast cell stabilizer): prevent the release of histamine.  Corticosteroids: anaphylxis. used mainly for local
  99. 99. Thank You

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