NATURAL IMMUNITY

1
NATURAL IMMUNITY

• Mechanisms
• Phagocytosis
• Complement activation
• Inflammation

2
Ligand (identity unknown)
Class I MHC
Nucleated cell
"Balance" no cytolysis
aka KAR (protein name NKR-P1) aka KIR
(protein name Ly49)
3
Ligand
Class I MHC (-) nucleated cell
Cytolysis
4
Natural Killer Cells and Antibody-Dependent
Cell-Mediated Cytotoxicity (ADCC)
5
Other Mediators and Molecules

• Phagocytes
• Toxic oxygen radicals
• Peroxides
• Nitric oxide (NO)
• Lipid mediators of inflammation
• Prostaglandins
• LTB4
• Platelet activating factor
• Complement component C5a
• Stimulates mast cells to release histamine,
  serotonin and LTB4
• IL-1, IL-6 and TNF-a
• Induce acute-phase response in liver
• Induce fever
• IL-1 and IL-18 signaling pathways activate NF-kB,
  important in innate immunity

6
Dendritic cell (sentinel)
7
Innate vs. Adaptive Immunity
8
TLR Microbs or its DNA,
Lipoprotein, Polysacarid
- MHCPeptide
- Costimulatory Molecules (B7)
- Pro-inflamatory cytokines (IL-12,
TNF-?)
9
Protective Role of Antibodies Against Pathogens

• Toxin neutralization
• Opsonization/enhancement of phagocytosis
• Sensitization for killing by NK cells
• Sensitization of mast cells
• Activation of complement system

10
Toxin Neutralization
11
Preventing Bacterial Adherence
12
Virus-blocking Antibodies
13
Antibody functions

• neutralizing
• opsonization
• complement activation
• sensitizing for NK cell killing (ADCC), or for
  granulocyte activation
• mast cell sensitizing

IgG, IgA IgG IgM, IgG3 gtG1gtG2,IgA IgG IgE
14
Functions of B lymphocytes
15
The Initial Stages of Signal Transduction by an
Activated B Cell ReceptorSignal 1

16
(No Transcript)
17
Inhibitory Co-receptors

18
T cell recognition of Ag The T cell receptor
(TCR)
T cells

• express a TCR consisting of a covalent,
  disulphide-linked heterodimer
• of 2 polypeptide chains (type I TM proteins)
  ab or gd

19
T cell recognition of Ag The TCR/CD3 complex

• the TCR is non-covalently associated with the
  CD3 signaling complex
• CD3gdeezz (analogous to Igab complex in the BCR)

20
CD40 L
CD40
21
(No Transcript)
22
(No Transcript)
23

• Role of Costimulatory Molecules
• - Increase in mRNA life span
• - Increase in cell survival
• - Induction of membrane movement
• - Activation of other signal transduction

24

• Events after signal transduction
• After 24h cell growth, lymphoblast, IL-2
  secretion( growth factor)
• After 48h DNA synthesis
• After 72h TCD4 activation and proliferation

25

• Other activation pathways
• Polyclonal Activators
• Super Ag
• Mitogen
• Anti-CD3
• LipidsCD1

26
DC
IL-12
Naive CD4
IL-4, IL-5
IFN?
IL-4
Th1
Th2
Viruses and Bact.
Th1 Alegena and Parasites Th2
27
T helper Cell Differentiation

• Type 1 response( Cell-medited)
• (NK,TCD8, Mac.)
• Immunity to intracellular Bact.
• Inflammation

IFNg TNFa,? IL2,3 GM-CSF

• Type 2 response(Humoral)
• IgE antibody responses
• Immunity to some parasites
• allergic diseases

IL4,5,6 IL10,13 IL3 GM-CSF
28
Bcell Tcell Interaction
29
Bcell Tcell Interaction
30
ITAMs

• Fc?RIIb(CD32) IgAg
  Inhibitory Signal (ITIM)
• Ti-1Mitogen in high concentration (LPS,
  H.influenza capsule)
• Ti-2Non Mitotic (Ficole, Dextrane, Pneumococal
  polysacarides)

31
Th1 CELL AS AN EFFECTOR CELL MULTIPLE CELLS
ACTIVATED
32
(No Transcript)
33
(No Transcript)
34
CD8 Cell Function
35
(No Transcript)
36
, INF-?, TNF-?
37
Cytotoxic T Lymphocyte Killing of Targets

• 2 pathways
• FasL
• Perforin/Granzyme

Perforin
TCR
Ag
CTL
MHC
Granzyme (serine protease)
Fas
FasL
Perforin
38
CD8 Cell Function
39
Effector T Cells - Summary
40
AICD (Activation Induced Cell Death)