8/13/2019 Kuliah 1. Humoral Effector Mechanism
1/97
Tonang Dwi Ardyanto
FK UMS Mei 2009
8/13/2019 Kuliah 1. Humoral Effector Mechanism
2/97
Plus tumor cells
8/13/2019 Kuliah 1. Humoral Effector Mechanism
3/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
4/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
5/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
6/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
7/97
The Immune System is the Third Line of
Defense Against Infection
8/13/2019 Kuliah 1. Humoral Effector Mechanism
8/97
Figure 1-7Innate (immediate) and
adaptive (late but antigen-specific) immune responses
8/13/2019 Kuliah 1. Humoral Effector Mechanism
9/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
10/97
Immune cell recognition of pathogensfollowed by destruction
8/13/2019 Kuliah 1. Humoral Effector Mechanism
11/97
Infection induces inflammation torecruit more immune cells
8/13/2019 Kuliah 1. Humoral Effector Mechanism
12/97
Hematopoiesis
generates immune
cells
Immune cells = Soldiers
8/13/2019 Kuliah 1. Humoral Effector Mechanism
13/97
The common myeloid progenitor:most of the cells of the innate immune system:
Macrophagegranulocytes (polymorphonuclear leukocytes)
mast cellsdendritic cells
The lymphoid progenitor:
T cellB cellNK cell
8/13/2019 Kuliah 1. Humoral Effector Mechanism
14/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
15/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
16/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
17/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
18/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
19/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
20/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
21/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
22/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
23/97
APC
8/13/2019 Kuliah 1. Humoral Effector Mechanism
24/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
25/97
h lf b d d
8/13/2019 Kuliah 1. Humoral Effector Mechanism
26/97
Figure 1-14
Macrophages engulf bacteria and produceinflammatory cytokines
8/13/2019 Kuliah 1. Humoral Effector Mechanism
27/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
28/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
29/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
30/97
Humoral Effector
Mechanism
8/13/2019 Kuliah 1. Humoral Effector Mechanism
31/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
32/97
Consequences of Antigen-AntibodyBindingAntigen-Antibody Complex: Formed when an antibody
binds to an antigen it recognizes.
Affinity: A measure of binding strength.
1. Agglutination: Antibodies cause antigens (microbes)to clump together. IgM (decavalent) is more effective that IgG (bivalent).
Hemagglutination: Agglutination of red blood cells. Usedto determine ABO blood types and to detect influenza andmeasles viruses.
2. Opsonization: Antigen (microbe) is covered withantibodies that enhances its ingestion and lysis byphagocytic cells.
8/13/2019 Kuliah 1. Humoral Effector Mechanism
33/97
Humoral Immunity (Continued)3. Neutralization: IgG inactivates viruses by binding totheir surface and neutralize toxins by blocking theiractive sites.
4. Antibody-dependent cell-mediated cytotoxicity:Used to destroy large organisms (e.g.: worms). Targetorganism is coated with antibodies and bombardedwith chemicals from nonspecific immune cells.
5. Complement Activation: Both IgG and IgM triggerthe complement system which results in cell lysis andinflammation.
C f A ib d Bi di
8/13/2019 Kuliah 1. Humoral Effector Mechanism
34/97
Consequences of Antibody Binding
C f A ib d Bi di
8/13/2019 Kuliah 1. Humoral Effector Mechanism
35/97
Consequences of Antibody Binding
Eff t F ti f A tib di
8/13/2019 Kuliah 1. Humoral Effector Mechanism
36/97
Effector Functions of Antibodies
8/13/2019 Kuliah 1. Humoral Effector Mechanism
37/97
Neutralization of Microbes by Antibodies
8/13/2019 Kuliah 1. Humoral Effector Mechanism
38/97
Neutralization of Toxins by Antibodies
8/13/2019 Kuliah 1. Humoral Effector Mechanism
39/97
Antibody-Dependent Cellular Cytotoxicity (ADCC)
F ti f C l t
8/13/2019 Kuliah 1. Humoral Effector Mechanism
40/97
Functions of Complement
8/13/2019 Kuliah 1. Humoral Effector Mechanism
41/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
42/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
43/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
44/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
45/97
A tib d R Aft E t A ti
8/13/2019 Kuliah 1. Humoral Effector Mechanism
46/97
Antibody Response After Exposure to Antigen
8/13/2019 Kuliah 1. Humoral Effector Mechanism
47/97
Kuliah ke 2
8/13/2019 Kuliah 1. Humoral Effector Mechanism
48/97
Cellular Effector
Mechanism
8/13/2019 Kuliah 1. Humoral Effector Mechanism
49/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
50/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
51/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
52/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
53/97
Cell Mediated Immunity General responses by CMI, include: Facilitate innate immune response to
bacteriaAnti-viral
Anti-fungal
Anti-tumor Transplantationrejection
8/13/2019 Kuliah 1. Humoral Effector Mechanism
54/97
Cell Mediated Immunity Many microbes have developed mechanisms thatenable them to survive and even replicate withinphagocytes, so the innate immunity is unable to
eradicate infections by such microbes. In CMI against phagocytosed microbes, the specificity
of the response is due to T cells but the actualeffector function is mediated by the phagocytes.
T C ll d C ll M di t d
8/13/2019 Kuliah 1. Humoral Effector Mechanism
55/97
Types of T cells1. T Helper (TH) Cells: Central role in immune response
Most are CD4+
Recognize antigen on the surface of antigen presenting cells(e.g.: macrophage).
Activate macrophages
Induce formation of cytotoxic T cells
Stimulate B cells to produce antibodies.
T Cells and Cell MediatedImmunity
8/13/2019 Kuliah 1. Humoral Effector Mechanism
56/97
Subpopulations of Th Cells
Subpopulations basedon cytokine profiles Th0 Th1
Th2 Differentiation
determined bycytokines Influenced by antigen
IL-4 - Th2 cells IL-12 Th1cells
8/13/2019 Kuliah 1. Humoral Effector Mechanism
57/97
Subpopulations of Th Cells
Th1 cell cytokines Activate macrophages
Generation of Tc
Th2 cell cytokines Activate of B cells
Activate granulocytes
8/13/2019 Kuliah 1. Humoral Effector Mechanism
58/97
RegulationAntigen
INF-inhibits
proliferation of Th2cells
IL-10 inhibitsproduction of INF-
8/13/2019 Kuliah 1. Humoral Effector Mechanism
59/97
Central Role of Helper T Cells
8/13/2019 Kuliah 1. Humoral Effector Mechanism
60/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
61/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
62/97
ANTIGEN RECOGNITION BY NAVE T CELLS IN
ABSENCE OF CO-STIMULATION Nave T cell only activated by professional APC carrying
specific peptide:MHC complex and co-stimulatorymolecule
T cell beomes anergic when it encounters APC carryingspecific peptide:MHC complex without co-stimulatorymolecule
No effect on T cell which encounters APC carrying nospecific peptide:MHC complex but has co-stimulatorymolecule
8/13/2019 Kuliah 1. Humoral Effector Mechanism
63/97
TH1 T CELLS AND MACROPHAGE
ACTIVATION Macrophage activation
Enhancement of macrophage function againstintracellular pathogens by TH1 cells
Phagosome fused more efficiently with lysosome
Important with Mycobacteria
Activation of macrophages requires 2 signals providedby TH1 cells
Interferon-gamma
CD40 ligand
8/13/2019 Kuliah 1. Humoral Effector Mechanism
64/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
65/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
66/97
EFFECTOR OPTIONS OF CD8 AND
CD4 T CELLS FOLLOWING ANTIGEN ACTIVATION CD8 committed to becoming cytotoxic effector cells
CD4 T cells can differentiate along two pathways
TH1 or TH2
Mechanisms of differentiation not well understood
Most immune responses involve both TH1 and TH2
CD4 TH1 cells help with cell-mediated immune
response CD4 TH2 cells help with humoral immune response
8/13/2019 Kuliah 1. Humoral Effector Mechanism
67/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
68/97
TH1 and TH2 The control of TH polarization is through thedendritic cell.
DC1 polarizes TH1 through IL-12
DC2 polarizes TH2 through IL-4 DC1 function appears to be through Toll-like receptors
that bind bacterial DNA motifs (reviewed p 282-283).
DC2 function appears to be though increased levels of
cAMP.
Bacterial antigen presentation to Th1 or
8/13/2019 Kuliah 1. Humoral Effector Mechanism
69/97
Figure 1-27Bacterial antigen presentation to Th1 or
Th2 CD4+cells
8/13/2019 Kuliah 1. Humoral Effector Mechanism
70/97
TH1
vsTH2
8/13/2019 Kuliah 1. Humoral Effector Mechanism
71/97
CD4 T CELL RESPONSE TO
MYCOBACTERIUM LEPRAE Mycobacterium leprae is an intracellular pathogen, agentof leprosy and directs either TH1 or TH2 response
Most effective immune response is mediated by TH1 cells
Immune response mediated by TH1 cells results in Tuberculoid leprosy
Immune response mediated by TH2 cells results in Lepromatous leprosy
8/13/2019 Kuliah 1. Humoral Effector Mechanism
72/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
73/97
T Cells Only Recognize Antigen Associated
8/13/2019 Kuliah 1. Humoral Effector Mechanism
74/97
T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
8/13/2019 Kuliah 1. Humoral Effector Mechanism
75/97
Types of T cells (Continued)2. Cytotoxic T (Tc) Cells: Destroy target cells.
Most are CD4 negative (CD4-).
Recognize antigens on the surface of all cells:
Kill host cells that are infected with viruses or bacteria.
Recognize and kill cancer cells. Recognize and destroy transplanted tissue.
Release protein calledperforinwhich forms a pore in targetcell, causing lysis of infected cells.
Undergo apoptosis when stimulating antigen is gone.
8/13/2019 Kuliah 1. Humoral Effector Mechanism
76/97
Cytotoxic T cells (CTLs) CTLs are not fully mature when they exit the thymus Have a TCR that recognizes antigen in association with
class I MHC molecules
Cannot kill Called pre-CTL
Must differentiate into fully active CTL
8/13/2019 Kuliah 1. Humoral Effector Mechanism
77/97
Generation of CTLs Differentiate in
response to twosignals Specific antigen
associated withclass I MHCmolecules
Cytokines producedby Th1 cells
8/13/2019 Kuliah 1. Humoral Effector Mechanism
78/97
Features of CTL KillingAntigen specific
Target cell must bear the same antigen associated withclass I MHC as did the pre-CTL
Requires cell contact
Ensures that nearby cells are not killed
CTLs are capable of killing many targets
CTLs are not injured when they kill a target
8/13/2019 Kuliah 1. Humoral Effector Mechanism
79/97
Steps in CTL Killing
Tc cell
1. Tc recognizes antigen on
target cellTarget cell
Tc cell
2. A lethal hit is delivered by
the Tc using agents such asgranzymes or TNF
Target cell
Tc cell
3. The Tc detaches
from the target cellTarget cell
4. Target cell dies
by apoptosis
Target cell
8/13/2019 Kuliah 1. Humoral Effector Mechanism
80/97
Mechanisms of CTL Killing Tc kill using a variety of mechanisms Direct cell-cell contact via surface molecules
Indirect signaling via cytokines
8/13/2019 Kuliah 1. Humoral Effector Mechanism
81/97
Mechanisms of CTL Killing Fas and TNF-mediated
killing Fas-L induced on CTL
interacting with Fas
receptor on target cell TNF secreted by CTL
interacting with TNFRon target cell
8/13/2019 Kuliah 1. Humoral Effector Mechanism
82/97
Mechanisms of CTL Killing Fas and TNF-mediated
killing Binding of ligand results
in tirmerization of thereceptor
Receptors with deathdomains activatecaspases resulting inapoptosis
8/13/2019 Kuliah 1. Humoral Effector Mechanism
83/97
Mechanisms of CTL KillingCTL granule-mediated killingGranules containing perforin and
granzymes are released by CTL
Perforin polymerizes and forms channelsin target cell membrane
Granzymes (serine proteases) enterthrough channels and activate caspasesresulting in apoptosis
8/13/2019 Kuliah 1. Humoral Effector Mechanism
84/97
Cytotoxic T Cells Lyse Infected Cells
8/13/2019 Kuliah 1. Humoral Effector Mechanism
85/97
CTL-Killing
8/13/2019 Kuliah 1. Humoral Effector Mechanism
86/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
87/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
88/97
Viral antigen presentation to CD8+ T cells via MHC class I molecules
8/13/2019 Kuliah 1. Humoral Effector Mechanism
89/97
Figure 1-26
CYTOTOXINS AND CYTOKINES OF T
8/13/2019 Kuliah 1. Humoral Effector Mechanism
90/97
CYTOTOXINS AND CYTOKINES OF T
CELLS T cells are distinguished by
Cytokines and cytotoxins produced and the effects onimmune response
CD4 T cells produce and act primarily through cytokines Macrophage stimulating (TH1)
B cell activating (TH2)
CD8 T cells produce and act primarily through cytotoxins Perforin and Granzymes
8/13/2019 Kuliah 1. Humoral Effector Mechanism
91/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
92/97
Relationship Between Cell-Mediated and Humoral Immunity
1. Antibody ProductionT-Dependent Antigens:
Antibody production requires assistance from T helper cells. A macrophage cells ingest antigen and presents it to THcell.
THcell stimulates B cells specific for antigen to become plasma cells.
Antigens are mainly proteins on viruses, bacteria, foreign red blood cells,and hapten-carrier molecules.
T-Independent Antigens: Antibody production does not require assistance from T cells. Antigens are mainly polysaccharides or lipopolysaccharides with
repeating subunits (bacterial capsules).
Weaker immune response than for T-dependent antigens.
Humoral Response to T Dependent Antigens
8/13/2019 Kuliah 1. Humoral Effector Mechanism
93/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
94/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
95/97
Relationship Between Cell-Mediated and HumoralImmunity
2. Antibody Dependent Cell MediatedCytotoxicity Target cell is covered with antibodies, leaving Fc portion
sticking outwards. Natural killer and other nonspecific cells that have
receptors for Fc region are stimulated to kill targetedcells.
Target organism is lysed by substances secreted byattacking cells.
Used to destroy large organisms that cannot bephagocytosed.
8/13/2019 Kuliah 1. Humoral Effector Mechanism
96/97
8/13/2019 Kuliah 1. Humoral Effector Mechanism
97/97
Top Related