acquired immune response
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Acquired Immune
Response
Sanjaya AdikariDepartment of Anatomy
Immune Response
Defense against foreign invaders or cancer cells
Immune Response
Innate Response Acquired Response
Antibody Response
Cell mediated Response
Innate Response
Adaptive Response
Cells of the immune system
Properties of Immune cells
Inactive/Naive Activated cellsEffector cells
Few surface molecules Many surface molecules
Becomes larger in size
Proliferate and produce more cells
Release peptides and lipids
Increased ability to migrate
Macrophage
epithelium
Macrophage
Common receptors for immune cells of many animals
Detect pathogen associated molecular patterns
Macrophages
Opsonization by Complement proteins
epithelium
Toll-like receptor
Toll-like receptors
Pathogen-associated molecular patterns
Phagosome Lysosomes
Phagolysosome
H2O2 O2-
NO
Activated macrophage
Prostaglandins, Leukotrienesand Platelet activating factor
Flow increasedVelocity reduced
Lipid mediators ofinflammation
Increased diameter
Increased permeability
Increased expression of adhesion molecules
Phagosome Lysosomes
Phagolysosome
H2O2 O2-
NO
Activated macrophage
ChemokinesCytokines
Cytokines
Proteins released by cells that affect the behavior of other cells that bear receptors for them
Chemokines
Proteins released by cells that attract other cells that bear receptors for them
A
A
Neutrophil
H2O2 O2- NO
Body tissue
Body tissue
Body tissue
activated
activated
activated
Cytokines
Mediators of
Chemokines Mediators of infl.
Cytokines
Chemokines
Cytokines
Cytokines
Cytokines
Chemokines
Pus cells
Pus cells
Natural Killer cells
Also called NK T cells
Larger than T and B cells
Activated during the innate response by macrophage derived cytokinesEg. IL-12 and Interferons
Produce IFN- when activated
Kills cells infected with intracellular pathogens
Mechanism of Killing is similar to that of cytotoxic T cells
Complement system
Augments the opsonization of bacteria by
antibodies. Hence, the name, meaning that
it complements the antibodies
Large number of plasma proteins that react
with each other following a trigger
Most of them are proteases that are
themselves activated by proteolytic
cleavage
Complement system….cont.
Precursor proteins are widely distributed in
body fluids and tissues
Only activated on the surface of the
pathogens
Once triggered it becomes a huge reaction
in its successive steps
Trigger
Innate immunity - summary
Immune cells identify the ‘pathogen-
associated molecular patterns’ on the
cell membrane of pathogens
Pathogen is immediately destroyed
Neutrophils and macrophages are key
players
Complement system plays an important
role
Activated dendritic cells present antigens
Kill
Body cells
Kill
Body cells
From Innate to Adaptive
Cells activated during the innate
immune response bridge the gap
between the innate and the adaptive
systems
Dendritic cells and Macrophages
Adaptive Immune Response
Dendritic cells
epithelium
TT
T
Antigen presentation
Antigen presenting cells(APC)
Toll-like receptors
T T
Dendritic cell or
macrophage
Clonal expansion of lymphocytes
Dendritic Cells (DC)
Most potent APC (>>> macrophages)
Designated as professional APC
Main function is to control T and B cells
through presentation of different
antigens
T BT BT B
MatureDC
TT
ImmatureDC
Circulation
TBT
BT B
TB
TB
T
B
Jefford et al., Lancet, June 2001
Surface molecules on DC and T cells
Cell-cell interaction molecules
Receptors for cytokines
Receptors for chemokines
Cell adhesion molecules
B7= CD80 & CD86
MHC I
B-7
MHC II
Antigen presenting cell
Cell-cell interaction molecules on DC and T cells
TCR
CD8
CD28TCR
CD4
CD28
CD4+ helper T cell
CD8+cytotoxic T cell
MHC molecules Two types: MHC type I and MHC type II
MHC type I: Expressed in all body cells
MHC type II: Expressed in some immune
cells
Dendritic cells, macrophages and B cells
Human counterpart is called HLAMHC – Major histocompatibility complexHLA – Human leukocyte antigen
DC-T cell interaction
1st signal – determines antigen
specificity
2nd signal – triggers T cell proliferation
Dendritic cells send two signals to T cells
TCR
CD4+ helper T cell
CD4MHC II
immature DC
1st signal
TCR
CD4
CD28
B-7
Increase proliferation
MHC II
mature DC
2nd signal
CD4+ helper T cell
Secrete IL-2 (growth factor of T cells)
B7= CD80 & CD86
MHC I
B-7
MHC II
Antigen presenting cell
Cell-cell interaction molecules on DC and T cells
TCR
CD8
CD28TCR
CD4
CD28
CD4+ helper T cell
CD8+cytotoxic T cell
MHC IMHC II
APC
TCR
CD8
TCR
CD4
Vesicle Cytoplasm
Intravesicular pathogensExtracellular pathogensToxins
T helper cells(Th cells)
Th1 cells
Th2 cells
Th0 cells
Cytokines
Cytokines
Cytokines
Cytokines Cytokines
Cytokines
Th1 cells
IFN-
IFN-
IFN-IFN-
IFN-
Cytokines
Cytokines
Cytokines
Cytokines
Cytokines
Th2 cells
IL-4
IL-4IL-4
IL-5
IL-5
IL-10IL-10
IL-10
Macrophage Activation B cell Activation
Th1 cells
Produce IFN-, the main macrophage-activating cytokine.It inhibits B cells
Th2 cells
Produce IL-4, IL-5 that activates B cells and IL-10 that inhibits macrophages
Th0 cells
Produce both Th1 and Th2 cytokines and therefore have a mixed effect
Mycobacterium leprae grows in macrophage vesicles.
Clinical relevance of Th1 vs Th2To destroy bact. need to activate macrophages by Th1 cells
Th2 response is a waste
Th1 response
Tuberculoid leprosy- Few live bacteria
- Little Ab in serum
- Skin & PN damage due to Mac.
activation
- Slow disease, patient survives
Th2 response
Lepromatous leprosy- Numerous live bacteria
- Lot of Ab in serum
(ineffective)
- Gross tissue damage &
death
Humoral immune response
MHC II
B cell
BCR
MHC II
BCR
MHC II
BCR
MHC II
TCR
CD4
CD4+ T helper cell
B cell
IL-4IL-5IL-6
IL-10
Th2
B cellPlasma cell
Ab mediated response(Humoral immunity)
IL-4, IL-5, IL-10
MHC II
TCR
CD4
CD4+ T helper cell
B cell
IFN-IFN-
Th1
InhibitionInhibition
Cell mediated response
TCR
CD8+cytotoxic T cell
CD8MHC I
immature DC
1st signal
TCR
CD8
CD28
B-7
Increase proliferation
MHC I
mature DC
2nd signal
CD8+cytotoxic T cell
Secrete IL-2
TCR
CD8MHC I
mature DC
effectorCD8+cytotoxic T cell
Infected Tissue
Kill
IFN-
CD4 T cells
CD8 T cells
cytokines
chemokines
Kills virus or intracellular pathogen infected body cells
MHC I
MHC IMHC II
cytokines
chemokines
B cells
Cell mediated response
Antibody mediated response
Immunologicalmemmory
Immunological memory
The ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously
Both T cells and B cells are left behind as memory cells following the primary immune response
These are a distinct populations of long lived cells, without the need to getting exposed to residual antigen, in the body
Immunological memory…cont.
In the presence of memory T and B
cells, the naïve T and B cells are
not activated upon exposure to the
same antigen again (would be a
waste)
Adaptive immunity - summary
The immune cells need to
specifically identify the pathogen
Clonal expansion of specific immune
cells
Takes few days to build up
T and B lymphocytes are key players
Leaves behind memory cells
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