ADAPTIVE IMMUNITY

1. MATEEN IRFANSHA
ADAPTIVE IMMUNITY

2. Adaptive immunity :-
Adaptive immunity is induced as a response against a specific
antigen, after the collaboration among phagocytic cells,T and B
lymphocytes and the production of immunoglobulins and
lymphokines (IL).
Q. Differences bitween Innate immunity & Adaptive immunity?
• Present at birth • developed afterbirth

3. •Types of adaptive immunity :-
1. Humoral immunity .
2. Cell-mediated immunity.

4. • Humoral immunity :-
immunity that is mediated by secreted antibodies produced in the B cells . B Cells
(with co-stimulation) transform into plasma cells which secrete antibodies. Humoral
immunity is so named because it involves substances found in the humours, or
body fluids.
•(Humoral immunity block extrtracellular microbes)
Exogenous antigens

5. Cell-mediated immunity :-
Cell mediated immunity is an immune response that does not
involve antibodies but rather involves the activation of phagocytes ,
natural killer cells (NK), antigen-specific cytotoxic T-lymphocytes, and
the release of various cytokines in response to an antigen.
•Cell mediated immunity block intracellular microbes:-
1. By activate macrophages to kill phagocytosed microbes i.e by
Helper T lymphocytes . &
2. By killing infected cell (e.g viruses within infected cells) i.e by
cytotoxic T lymphocytes.

6. T cell activation :-
Endogenous antigens
Th2 :-release of Interleukin 4,
which results in the activation of
B-cells to make neutralizing
(killing) antibodies, leading to
humoral immunity.
Exogenous antigens Endogenous antigens

7. Phases of adaptive immune responses
•peripheral lymphoid organs
contain a mixture of B and T
cells in at least three stages of
differentiation:
•naive cells that have
matured, left the bone
marrow or thymus, have
entered the lymphatic
system, but that have yet to
encounter their cognate
antigen,
•effector cells that have
been activated by their
cognate antigen, and are
actively involved in
eliminating a pathogen.
•memory cells – the long-
lived survivors of past
infections

8. Passive memory :-• Active Memory &

9. Active and passive immunity
Active immunity: long-lasting protection (memory),
multiple effector mechanisms activated, lag time
Passive immunity: rapid protection, short duration
Abbas, Lichtman and Pillai. Cellular and Molecular Immunology, 7th edition, 2011

10. •Properties of adaptive immune responses :-

11. humoral immune response :-
is the aspect of immunity that is mediated by
secreted antibodies produced in the cells of
the B lymphocyte lineage (B cell).

12. •B Cells (with co-stimulation) transform into plasma
cells which secrete antibodies.
•This entire process is aided by CD4+ T-helper 2 cells,
which provide co-stimulation.
• Secreted antibodies bind to antigens on the surfaces of
invading microbes (such as viruses or bacteria), which
flags them for destruction.
•Humoral immunity is so named because it involves
substances found in the humours, or body fluids.

13. Function…
•Antibody production and the accessory processes that
accompany it.
• Th2 activation and cytokine production.
•Germinal center formation and isotype switching, affinity
maturation and memory cell generation.
•Classical complement activation, and
•Opsonin promotion of phagocytosis and pathogen
elimination

14. •COMPLEMENT SYSTEM :-
Complement System is special part of immune system which
consists of a number of serum proteins
(C1,C2,C3,C4,C5,C6,C7,C8 & C9) which exist in the serum in an
inactive form.basically these protein are pro-enzymes.
Q.WHAT ARE THE FUNCTIONS OF THESE PROTEIN ?
These proteins basically complement or augment the immune
system & complement inflammatory reactions .
Q.WHERE THESE PROTEINS ARE PRODUCED ?
Major source of protein is liver. But Complement protein C1
Mainly produced by GIT mucosa. & some complementory protein
also produced by macrophages. Anyways all are present in blood.

15. Q.HOW THIS PROTEINS WORKS?
These proteins can be workes/activated in a cascade-like fashion
by
•(1) Antigen-antibody complexes in the Classical pathway.
• (2) Alternative pathway.
• (3) Mannan binding lectin pathway.

16. Once activated, complement can:
•(1) Destroy all cells (even host cells) in the activation area,
•(2) Cause inflammation (complement is an anaphylatoxin),
•(3) Opsonize microbial cells (complement is an opsonin) and
•(4) Attract leukocytes to the area (complement is a chemotaxin).

17. The Classical Pathway
The binding of antibody to its antigen often triggers the
complement system through the so-called classical
pathway. It can occur when the antibodies have bound
to antigens on a cell surface.
•TYPES & STRUCTURE OF IMMUNOGLOBULINS :-

18. •ANTIGEN:-

19. The proteins of the classical pathway
C1
C1 exists in blood serum
•6 molecules of C1q
•2 molecules of C1r
•2 molecules of C1s
•The constant regions of mu chains (IgM) and some gamma chains
(IgG) contain a binding site for C1q. (A single molecule of IgM is
enough to initiate the pathway. IgG is far less efficient, requiring
many molecules to do so.)
Antibodies
Antigens
Bacterial
surface

20. •Binding of C1q to antibody activates C1r which cleaves &
activates the serine protease C1s.
•Activated C1s cleaves two serum proteins C4 &C2 :
C4 is cleaved into
oC4b, which binds covalently to sugar residues on cell-
surface glycoproteins, leaving behind an inactive
fragment of
oC4a
C4aC4b
C4

21. C2 is cleaved into
oC2b, which binds noncovalently to a site
on C4b, leaving an inactive fragment of
oC2a
The complex of C4b.2b is called "C3 convertase"
because it catalyzes the cleavage of C3.
C4bC2b/C3 convertase
C2a
C4bC2b

22. C3b
C3a
C4bC2bC3b/C5
Convertase
C3b
•C4b.2a cuts C3 into two major fragments:
C3b, which binds covalently to glycoproteins scattered across
the cell surface. Macrophages and neutrophils have receptors
for C3b and can bind the C3b-coated cell or particle
preparatory to phagocytosis . This effect qualifies C3b as
an opsonin.

23. C3a This small fragment is released into the surrounding fluids. It
can bind to receptors on basophils and mast cells triggering them
to release their vasoactive contents (e.g., histamine). Because of
the role of these materials in anaphylaxis, C3a is called
an anaphylatoxin .
•Some of the C3b binds directly to the molecules of C4b.2b producing
a trimolecular complex: C4b.2b.3b, which acts on C5; that is, it is a "C5
convertase".
C5
Cleavage of C5 by this C5 convertase initiates the assembly
of a set of complement proteins that make up the
membrane attack complex. (The membrane attack
complex can also be formed by another C5 convertase
produce by the "alternative pathway" .)

24. .
C5b
C5a
The Membrane Attack Complex :-
Cleavage of C5 by a C5 convertase, produces:
•C5a, which is released into the fluid surroundings
where it
is a potent anaphylatoxin(like C3a)
is a chemotactic attractant for neutrophils

25. •C5b which serves as the anchor for the
assembly of a single molecule each ofC6,C7 & C8
C5b
C6
C7
C8
C9
•The resulting complex C5b.6.7.8 guides the
polymerization of as many as 18 molecules
of C9 into a tube inserted into the lipid bilayer of
the plasma membrane.
C9

26. • This tube forms a channel allowing the passage of ions and
small molecules.
• Water enters the cell by osmosis and the cell lyses.
•These MACs can be imagined as ring-shaped structures
with a central pore; these structures are incorporated into
the lipid bilayer of cells and result in osmotic disruption of
the cell

27. Clinical significance:-
Q.Do you think MAC effect will be more on Gram +ve bacteria or
Gram –ve bacteria ? & why …………….? Endotoxins
Double lipid membrane
single lipid
membrane
• Gram +ve bacteria contain only 1 lipid membrane dat is inner
lipid membrane only… But Gram –ve bacteria contain 2 lipid
membrane (outer & inner membrane). So ,MAC effect will be
more on Gram –ve bacteria

28. Q. HOW THE GRAM +VE BACTERIA HANDLE ?
There are 2 ways to kill Gram +ve bacterias.
•By direct opsonisation.
•By indirect opsonisation.
•People who hav difficiency of terminal events proteins (i.e
C5b,C6,C7,C8 &C9) will hav difficiency of MAC effect so they are
highly vulnerable to Gram –ve bacterial infection more specially
NESIERRIAL Bateria ( Gonococci & meningococci)

29. Q.HOW ANTIBODY KILLS BACTERIAS?
• By direct opsonisation :-
•By indirect opsonisation:-
FC receptors
C3b receptors
Gram +ve bacteria
Antibody
Gram +ve bacteria
Antibody
Macrophages/
neutrophilis
Macrophages/
neutrophilis

30. •By activating complement system till MAC formation:-
MAC
Gram –ve bacteria
Antibody
C3 convertase
C5 convertase
C3a
C5a

31. An incompatible blood transfusion causes a transfusion
reaction, which is mediated by the humoral immune response.
This type of reaction, called an acute hemolytic reaction, results
in the rapid destruction (hemolysis) of the donor red blood cells
by host antibodies. The cause is usually a clerical error (i.e. the
wrong unit of blood being given to the wrong patient). The
symptoms are fever and chills, sometimes with back pain and
pink or red urine (hemoglobinuria). The major complication is
that hemoglobin released by the destruction of red blood cells
can cause acute renal failure.
Q. What is ABO incompatible blood transfusion?

32. The Alternative Pathway:-
It is a part of innate immunity i.e first line of defence
there is a spontaneous conversion of C3 to C3b.
Ordinarily the C3b is quickly inactivated:
the C3b binds to inhibitory proteins and sialic acid present on the surface of body's
own cells, and the process is aborted.
However, bacteria and other foreign materials that may get into the body lack these
proteins and have little or no sialic acid.
So the C3b
•binds a protein called Factor B forming a complex of C3b.Bb.
•C3b.Bb is also a C3 convertase acting on more C3 to form:
C3b.Bb.C3b, which is a C5 convertase and can start the assembly of
the membrane attack complex.
C3 C3b C3b
B
Bb C3b Bb C3b
C3
C5 ConvertaseC3 Convertase

33. Clinical significans:-
Aggregation of IgA can cause activation of alternate pathway.
Diseases related with IgA aggregations are…..
1.IgA nephropathy/Buergers disease.
2.Dermititus Herpetiformus.
3.Henoshawlin Purpura.

34. Mannan-binding lectin pathway
• is similar in structure to the classical complement pathway in
that, after activation, it proceeds through the action of C4 and C2
to produce activated complement proteins further down the
cascade.
• it is not antibody-dependent.
• mannose-binding lectin binds to mannose, glucose or other sugars with 3-
and 4-OH groups placed in the equatorial plane, in terminal positions on
carbohydrate or glycoprotein components of microorganisms including
bacteria such as Salmonella, Listeria, and Neisseria strains.
•Fungal pathogens such as Candida albicans and Cryptococcus
neoformans as well as some viruses such as HIV-1 and Respiratory syncytial
virus (RSV) are bound by MBL

35. .
Mannan-binding lectin (MBL) is a protein belonging to
the collectin family that is produced by the liver and can initiate
the complement cascade by binding to pathogen surfaces.
MBL is a 6- to 18-headed molecule that forms a complex with
MASP-1 (Mannan-binding lectin-Associated Serine Protease),
MASP-2 and
MASP-3, two
protease zymogens.
The MASPs are very similar to C1r and C1s molecules of the
classical complement pathway, respectively
[
MASP-1(similar to C1r)
MASP-2 (similar to C1s)
MBL (6- 18headed molecule)
similar to C1q

36. •When the carbohydrate-recognising heads of MBL bind to
specifically arranged mannose residues on the surface of a
pathogen, MASP-1 and MASP-2 are activated to cleave
complement components C4 and C2 into C4a, C4b, C2a, and
C2b.
• In addition, two smaller MBL-associated proteins (MAps) are
found in complex with MBL. MBL-associated protein of 19 kDa
(MAp19) and MBL-associated protein of 44 kDa (Map44).
•MASP-1, MASP-3 and MAp44 are alternative splice products of
the MASP1 gene,
• while MASP-2 and MAp19 are alternative splice products of
the MASP-2 gene.
•

37. •C3 convertase :-
C4b and C2b combine on the surface of the pathogen to
form C3 convertase (C4bC2b).
while C4a and C2a act as chemoattractants.
•C5 convertase:-. C4bC2bC3b, which is a C5 convertase
and can start the assembly of the membrane attack
complex
Clinical significance :-
has been found that people deficient in MBL experience a
substantial increase in infections during the early years of
childhood.
•MAp44 has been suggested to act as a competitive inhibitor
of lectin pathway activation, by displacing MASP-2 from MBL,
hence preventing cleavage of C4 and C2

38. Regulation of Complement Activity:-
The explosive potential of the complement system requires that
it be kept under tight control.
At least 12 proteins are known that do this.
Three examples:
•Factor H removes Bb from the alternative pathway .
•Factor I inactivates C3b.
•C1 inhibitor (C1INH) binds to sites on activated C1r and C1s
shutting down their proteolytic activity. So when C1 is activated
by antigen-antibody complexes, there is only a brief interval
during which it can cleave C4 and C2 before it is deactivated by
C1INH.

39. Effector Functions of Complement :-
The complement system acts in several ways to mobilize defense
mechanisms.
•Opsonization by C3b targets foreign particles for phagocytosis.
•Chemotaxis by C5a attracts neutrophils/phagocytic cells to the site of
damage.
• anaphylatoxin This is aided by the increased permeability of the
capillary beds mediated by C3a and C5a.
•The early complement components are also important
for solubilizing antigen-antibody complexes assisting in their catabolism
and elimination from the body.

40. Disorders of the Complement System :-
With so many proteins involved, it is not surprising that inherited deficiencies of one
or another are sometimes encountered in humans.
examples:
•C3. An inherited deficiency of C3 predisposes the person to frequent bouts of
bacterial infections(streptococcus infection i.e Gram +ve)
•C2 & C4. Curiously, immune complex disorders, with a deficiency of C2 (or of one of
the other "early" components like C1q, C1r, C1s, or C4). This is frequently found in
patients with the immune complex disorders (autoimmune disorder) system lupus
erythematosus (SLE).
•Defficency of C5b,C6,C7,C8,C9 & lectin pathway lead to Gram –ve
infections (Nesierrial infection)

41. •C1INH. A deficiency of C1INH produces hereditary
angioneurotic edema (HANE). Patients are at risk of
occasional explosive triggering of the complement system.
• The massive release of anaphylatoxins (C3a, C5a) may
cause dangerous swelling (edema) of the airways, as well
as of the skin and intestine.