Download Overview of the Immune System Zoran Galic Ph.D.

Overview of the Immune System
Zoran Galic Ph.D.
Division of Hematology/Oncology
David Geffen School of Medicine UCLA
[email protected]
August 18, 2014
The Immune Response
Outline:
 Introduction to Immune Response
Innate Vs Acquired Immunity
 Cells and Organs of the Immune Response
 How Does it Work?
 Closing Comments
Introduction to the Immune Response
 The central problem that the immune system deals with is invasion
by microbial pathogens
 The task of the immune system is to distinguish self from non-self.
 It must not attack and destroy self, but it has to eliminate microbial threats:
1. Whole organisms (bacteria, fungi, parasites,etc);
2. Intracellular pathogens (viruses).
 Immune responses are tailored to the type of organism involved.
Innate vs adaptive immunity
In response to pathogens, vertebrate immune systems
use two interconnected systems:
•
•
Innate immunity
Adaptive immunity
Overview of Innate Immune Response
There are multiple barriers to infection:
1. Mechanical: Tight junctions of epithelial cells form a physical barrier.
2. (Bio)Chemical: Antibacterial peptides, enzymes,
and low pH environment.
3. Cellular: Macrophages, Neutrophils, Natural Killer cells (NK),
Dendritic cells
Skin and other epithelial barriers to infection
The major cells of innate immunity
Big eaters/Always hungry
Antigen presentation
Phagocytosis
Antigen Presenting Cells (APCs)
Proteins eaten by APCs are broken down to small pieces (peptides),
which are loaded on special receptors (MHCs) and transported to the
cell surface. Peptide+MHC complex can be recognized by a T cell and
that interaction can lead to an adaptive immune response.
Acquired Immunity
(Adaptive, Specific)
The antigenic universe is incredibly diverse
This diversity must be overcome by the immune response
First appears in evolution in cartilaginous fishes (sharks, sting rays, etc)
Can detect subtle changes in proteins, carbohydrates (sugars), and lipids
This response is specific
It must detect self versus non-self
It must differentiate different forms of non-self (flu virus looks different than HIV)
Antigen (Ag)- the molecule or structure against which the immune response is directed
The immune response only sees bio-organic molecules (proteins, sugars, fats, etc)
Characterized by more rapid, stronger memory response
Adaptive immunity: humoral and cellular responses
CD4 (helper) T cell
CD8 (killer) T cell
T cell receptors only recognize antigens
presented on MHC molecules
How do B and T cells work?
B cells see soluble (free) Ag
Antibody (Ab) is released, binds Ag, removes it
T cells need to see Ag on the surface of cells
Pieces of Ag are “presented” in molecules called MHC molecules
APC take up (eat/engulf) Ag
Ag is digested (processed)
Pieces of Ag get caught in MHC molecules, these go to the cell surface
CD4 T cells see Ag in MHC-II molecules.
They proliferate
They secrete “helper factors” which help B cells and CD8 cells
CD8 T cells see Ag in MHC-I molecules on infected cells
They get help from CD4 T cells
They proliferate
They kill infected cells
Organs of the Immune System
Red-primary lymphoid organs
Blue-secondary lymphoid organs
T cells are generated
in the thymus
The bone marrow contains
blood-forming Stem cells,
and makes B cells, innate
cells, and all other blood
cell types, except T cells.
Immune cells localize in secondary
lymphoid organs, such as the spleen,
lymph nodes, etc.
Lymphatic System
Fluid in blood leaks out of capillaries
must be returned to circulation
pressure in vessels too great to diffuse back
Lymphoid system recovers fluid
picked up in capillary sinuses,
which coalesce into larger lymphatic
vessels and ducts.
Fluid returned to subclavian vein
Pumped by action of adjacent muscles
Drains every part of body
Lymph nodes screen for pathogens
Nodes packed with leukocytes
(lymphocytes, APCs, no granulocytes)
Initiation of an immune response
Innate Immune Response: The Cellular Response
Steps in phagocytosis of a bacterium
Macrophage activation leads to:
- Cytokine secretion
- Induction of co-stimulatory molecules
- Antigen processing and presentation (MHCII)
….hence…. Adaptive Response Can Be Activated Too!
Adaptive immune response
Important concepts for understanding the mammalian immune response
• Memory is the hallmark of adaptive immunity
– Primary response is initiated upon first exposure to an
antigen
• Memory lymphocytes are left
behind after antigen is cleared
– A second exposure to the
same antigen re-stimulates
memory lymphocytes
• Reactivation yields faster,
more significant, better response
– Memory is NOT present in
innate immunity
Closing Comments
 APCs, B cells, CD4 and CD8 T cells work together to fight infection
 HIV perturbs APC function, and kills CD4 T cells
 This allows secondary “opportunistic” infections to occur,
leading to disease/death
 Vaccines have the potential to halt HIV infection, but thus far
an efficacious vaccine strategy has proven elusive
 A vaccine approach that takes into account all aspects of the immune
response will likely have the best chance of success