2. Objectives
•Define immunity
•List down the functions of immune system
•Discuss the components of immune response
•Discuss innate and acquire immunity
•Describe humeral versus cell mediated
immunity
•Discuss Antigen processing ,presentation and
recognition
3. •IMMUNITY: The defense mechanisms of the
body against micro-organisms, toxins and other
foreign particle which are harmful for the body.
or
•Resistance to disease by means of antibodies.
or
•The human body capacity to resist almost all
type of organism and toxins which tend to
damage tissue or organs.
IMMUNE RESPONSE: interaction between
antibody & antigen which result in the antigen
being eliminated from the body
6. Components of immune system
•Lymphocytes
•Neutrophils
•Macrophages
•Lymphoid tissues ( thymus, spleen, bone
marrow, tonsils )
•Immunoglobulin's (antibodies)
7. Lymphocytes
•Lymphocytes are small white blood cells that play a
role in the body’s immune response (that is, in the
body’s fight against germs and diseases).
•Once they recognize foreign material in the body, they
produce chemicals (cytokines) to destroy that material.
•Two types of lymphocyte are produced in the bone
marrow.
B lymphocytes (B cells) :- They stay within the bone
marrow until they are mature. Once mature, they spread
throughout the body and concentrate in the spleen and
lymph nodes.
T lymphocytes(T cells):- They leave the bone marrow
and mature in the thymus, a gland found in the chest.
There are four types of t cell.
8. Types of t-lymphocytes:
Cytotoxic or killer T cells do their work
by releasing lymphotoxins, which cause
cell lysis
Cytotoxic T cells, sometimes called killer
T cells, destroy tumor cells and cells infected
by viruses.
They are also called CD8+ (CD8 positive)
cells because they have the CD8 protein on
their surface membrane.
Helper T cells serve as
9. Activation of Helper T Cells
•Cells called phagocytes surround and
engulf invaders, a process called
phagocytosis.
•Once certain phagocytes have “eaten” a
pathogen such as a virus or bacterium, they
travel to a lymph node or to the spleen,
which are sites where mature T cells
assemble.
• The phagocytes digest the pathogen and
then send a piece of the pathogen’s body to
their cell membrane, where it acts as an
antigen
10. •A phagocyte, which is now known as an
antigen-presenting cell, “presents” its newlyacquired antigen to helper T cells.
•A helper T cell with the correct receptor
joins to the antigen.
• This begins the process of helper T cell
activation.
•The activated T cell releases proteins called
cytokines which trigger B cells, cytotoxic T
cells and other white blood cells to become
active and start attacking the pathogens.
13. Antigen:
•Antigen is any chemical substance that
when introduced into the body is
recognized as foreigner.
Characteristics of antigen
1.Immunogenicity
2.Reactivity
Immunogenicity:
•The ability to provoke an immune
response i.e to stimulate the production of
antibodies or proliferation of T cell or both.
Reactivity:
14. Chemical nature of antigen:
Chemically antigen are large complex
molecules, most often they are protein such as
•nucleoprotein (nucleic acid +protein),
•Lipoprotein (Lipid + Protein)
•Glycoprotein (carbohydrate + Protein)
T cell respond only to antigen that include
protein
B cell respond to antigenic proteins, certain
lipid carbohydrate and nucleic acid
15. Complete antigen:
•Substance having molecular weight 10000
or more and having both the characteristics
of antigen are called complete antigen.
Partial antigen:
•Smaller substance which have reactivity but
not immunogenicity are called heptens.
•Heptans can stimulate immune response
when it binds to larger carrier molecules
Example penicillin may combine with protein
and the complex become immuogenic.
16. Antigenic determinant:
•Specific region of antigen molecule which
trigger the immune response is called antigenic
determinant or epitopes.
•Most antigens have many antigenic
determinant each of which induces production
of different types of antibodies or T cells
17. Major histocompatibility complex (MHC):
•MHC are the glycoprotein on the surface of
cells.
•MHC are also called HLA because it was 1st
identified on the surface of WBCs
•There are two categories of MHC antigens
Class I and Class II.
•Class I MHC molecules are built into the
plasma membrane of all body cell except
RBCs.
•Class II MHC molecule appear only on the
surface of antigen presenting cell i.e Dendritic
cells, macrophages and B cells.
18. Innate immunity:
•The immunity result from general processes
directed at specific pathogen is called innate
immunity.
It include
•Phagocytosis
•Destruction of pathogens by acid and other
digestive enzymes
•Resistance of skin to invasion of pathogens
19. •Chemical compound in blood that
destroyed pathogens i.e lysozyme, basic
polypeptides, complement protein, natural
killer cells (lympocytes that kill the tumor and
infected cells)
•Innate immunity produce resistance to the
diseases like viral such as cholera, cattle
plague,
20. Acquire immunity:
•The type of immunity in which the powerfull
response against the pathogens like virus
,bacteria and toxin are produced. Acquire
immunity is caused by Antibodies and
activated lymphocyte.
•Acquire immunity give full protection to the
body. For example protection from certain
toxin such as paralytic botolinum occur in
high dose with immunity but without
immunity that dose become lethal .
21. Types of acquire immunity:
•There are two types of acquire immunity
•Cell mediated immunity ( immunity due to
cytotoxic T lymphocytes)
•Humeral immunity ( immunity due to
antibodies)
•Both types of immunity are initiated by
antigens
22. Cell mediated immunity:
•Cellular immunity is directed against
intracellular pathogen.
•T cell do not recognize free antigen but do
recognize antigen combine with an MHC
protein.
•Cytotoxic T cells are activated CD8 cells they
attack our own cells if they have become
infected by an intracellular pathogen or they
have become cancerous.
•Cytotoxic T cells circulated through the body
crawling over cells to examine the self antigen
on their surface.
23. •Only a few kinds of cells have Class II MHC
protein these are Antigen Presenting Cell
(Dendritic cells, Macrophages and B cells)
•These cells communicate with CD4 cells
which are destined to become or have already
become helper T cells.
•The antigen that are presented on class II
MHC protein are exogenous antigen they
originate from out side the cells.
24. •Steps
Pathogen ( Bacteria)
↓
Ingested by Dendritic cell
↓
Intracellularly bacteria is surrounded by
phagosome
↓
Phagosome fuse with lysosome
↓
Bacteria is digested into small fragment and
the product is presented on the cell surface
25. Humeral Immunity:
•The humoral immune system involves
antibodies that are dissolved in extracellular
fluids,such as blood plasma, lymph, and
mucus secretions known as humors.
•This system uses B cells to produce
antibodies that are specifically directed against
the antigens.
•The humoral immune response defends
mostly against bacteria, bacterial toxins, and
viruses in the body’s fluids.
26. Anti bodies:
•Antibodies belong to a class of proteins called
immunoglobulins (Ig).
• Another term used with antibodies is
antiserum.
•Antiserum is a generic term for fluids
containing antibodies.
• The antibody rich serum component is called
gamma
globulin.
•These proteins can recognize, bind to, and
help cause the destruction of antigens.
Antibodies can only interact with one antigenic
determinant on an antigen.
27.
28. Structure of Immunoglobulin
1.Four (4) polypeptide chains:
•2 identical LIGHT chains and 2 identical HEAVY
chains.
2.Both light and heavy chains are
• held together by COVALENT DISULFIDE BONDS.
3.Heavy chains are interconnected by DISULFIDE
LINKAGES in the HINGE region.
4.Ig has 2 terminal regions:
constant region : with constant amino acid
sequence
variable region with varying antibody specificity.
29. Immunoglobulin
A protein produced by lymphocytes in
response to the entry of an antigen into the
body.
Or
Protein produced by the body in response to
foreign antigens
30. I.IgG
•Structure: Monomer
•Molecular weight 160000
•Make up 75-80% of serum antibodies
•Location: distributed in intra vascular and extra
vascular areas
•Half-life in serum: 23 days
•Placental Transfer: Yes
• Can be broken down by proteolytic enzymes
•Rate of synthesis 2g/day
•Serum concentration 800-900mg/dl
31. Functions:
•Opsonize (coating) the bacteria
•Enhances phagocytosis
•neutralizes bacterial toxins and viruses.
•Fix the complement with enhance
bacteria killing.
32. II. IgM
•Structure: Pentamer
•Molecular weight 9-10 lac
•Percentage serum antibodies: 8-10%
•Serum concentration 30-130mg/dl
•Rate of synthesis .1mg/dl
•Location: restricted to blood because of large
molecular weight and size
•More effective then IgG
•Half-life in serum: 5 days
•Placental Transfer: No
33. Functions:
• First antibodies produced during an
infection.
•Produce in primary response to an
antigen.
•Fixes the complement
34. III. IgA
•Structure: Dimer
•Percentage serum antibodies: 15-20%
•Serum concentration 50-190 mg/dl
•Rate of synthesis 1.5 mg/day
•Location: Secretions
(tears, saliva, intestine, milk), blood and lymph.
•Half-life in serum: 6 days
•Placental Transfer: No
36. IV. IgD
•Structure: Monomer
•Percentage serum antibodies: 1.0%
•Rate of synthesis .02g/day
•Serum concentration .02mg/dl
•Location: B-cell surface
•Half-life in serum: 2 days
•Placental Transfer: No
•Known Functions: In serum function is unknown.
37. V. IgE
•Structure: Monomer
•Percentage serum antibodies: 0.005%
•Rate of synthesis is unknown
•Serum concentration is .05mg/dl
•Location: Bound to mast cells and basophils
throughout body.
•Half-life in serum: 2 days
•Placental Transfer: No
42. Stages of Phagocytosis
1. Chemotaxis: Phagocytes are chemically
attracted to site of infection.
2. Adherence: Phagocyte plasma membrane
attaches to surface of pathogen or foreign
material.
Adherence can be inhibited by capsules (S.
pneumoniae) or M protein (S. pyogenes).
Opsonization: Coating process with opsonins
that facilitates attachment.
Opsonins include antibodies and complement proteins.
44. Stages of Phagocytosis (Continued)
3. Ingestion: Plasma membrane of phagocytes
extends projections (pseudopods) which engulf the
microbe. Microbe is enclosed in a sac called
phagosome.
4. Digestion: Inside the cell, phagosome fuses with
lysosome to form a phagolysosome.
Lysosomal enzymes kill most bacteria within 30
minutes and include:
Lysozyme: Destroys cell wall peptidoglycan
Lipases and Proteases
RNAses and DNAses
After digestion, residual body with undigestable
material is discharged.
46. Antimicrobial Substances:
I. Complement System: Large group of serum
proteins that participate in the lysis of foreign
cells, inflammation, and phagocytosis.
Two mechanisms of complement activation:
1. Classical Pathway: Initiated by an immune
reaction of antibodies.
2. Alternative Pathway: Initiated by direct
interaction of complement proteins with microbial
polysaccharides.
Both pathways cleave a complement protein
called C3, which triggers a series of events.
48. Both Classical and Alternative Complement
Pathways Trigger the Cleavage of C3
49. Consequences of Complement Activation:
1. Cytolysis: Due to the formation of a membrane
attack complex (MAC) which produces lesions in
microbial membranes.
2. Inflammation: Complement components (C3a)
trigger the release of histamine, which increases
vascular permeability.
3. Opsonization: Complement components (C3b) bind
to microbial surface and promote phagocytosis.
4. Inactivation of Complement: Regulatory proteins
limit damage to host cells that may be caused by
complement.
50. 5. Agglutination:
The complement products make the surface of the invading
organism sticky causing adherence of the cells which promote
agglutination.
6. Neutralization of virus:
The complement enzyme and product attack on the virus and change
its virulence factor.
7. Activation of mast cells and basophiles:
C3a C4a C5a activate mast cells and basophile which release of
histamine, heparin and other mediators which causes vasodilatation
, increase blood vessel permeability and emigration of WBCs.
51. Interferons: Antiviral proteins that interfere with viral
multiplication.
Small proteins (15,000 to 30,000 kDa)
Heat stable and resistant to low pH
Important in acute and short term infections.
Have no effect on infected cells.
Host specific, but not virus specific.
Interferon alpha and beta: Produced by virus infected cells
and diffuse to neighboring cells. Cause uninfected cells to
produce antiviral proteins (AVPs).
Interferon gamma: Produced by lymphocytes. Causes
neutrophils to kill bacteria.
52. Interleukins:
•interleukins are a group of cytokines that were
first seen to be expressed by white blood
cells (leukocytes).
•The term interleukin derives from (inter-) "as a
means of communication", and (-leukin) "deriving
from the fact that many of these proteins are
produced by leukocytes and act on leukocytes".
•The function of the immune system depends in a
large part on interleukins, and rare deficiencies of a
number of them have been described, all
53. Interleukin 1:
Source: macrophages, B cells, monocytes,
dendritic cells.
Target cells: T helper cells, B cells, NK cells
Function:
inflammation, small amounts induce acute phase
reaction, large amounts induce fever
54. Interleukin 2:
Source: Th1-cells
Target cells: Activated T cells and B cells, NK
cells,macrophages,oligodendrocytes
Function:
Stimulates growth and differentiation of T cell
response.
Can be used in immunotherapy to treat cancer or
suppressed for transplant patients
55. Interleukin 3:
Source: activated T helper cells, mast
cells, NK cells,
Target cells: hematopoietic stem cells
Function:
Differentiation and proliferation of myeloid
progenitor cells to
e.g. erythrocytes, granulocytes
56. Interleukin 4:
Source: Th2 cells, memory CD4+ cells, mast
cells,macrophages
Target cells:activated B cells, T cells
endothelium
Function:
proliferation and differentiation, IgG1 and IgE
synthesis. Important role in allergic response
(IgE)
57. Interleukin 5:
Source: Th2 cells, mast cells,eosinophils
Target cells: eosinophils, B cells
Function:
Differentiation, IgA production
58. Interleukin 6:
Source: macrophages, Th2 cells, B
cells, astrocytes, endothelium
Target cells: activated B cells, plasma cells,
hematopoietic stem cells.
Function:
•Differentiation into plasma cells
•Antibody secretion
•Differentiation