1. Overview of the Immune System
Zoran Galic Ph.D.
Division of Hematology/Oncology
David Geffen School of Medicine UCLA
August 11, 2015

2. The Immune System Outline: Introduction to the Immune System:
Innate vs Acquired Immunity
Cells and Organs of the Immune System
How Does it Work?
Closing Comments

3. 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.

4. Innate vs adaptive immunity
In response to pathogens, vertebrate immune systems use two interconnected systems:
Innate immunity
Adaptive immunity

5. Overview of Innate Immune Response
There are multiple barriers to infection:
1. Mechanical: Tight junctions of epithelial cells form a physical barrier
(Bio)Chemical: Antibacterial peptides, enzymes, and low pH environment
Cellular: Macrophages, Neutrophils, Natural Killer cells (NKs),
Dendritic cells

6. Skin and other epithelial barriers to infection

7. The major cells of innate immunity
Big eaters/Always hungry
Antigen presentation
Phagocytosis
PHAGOCYTOSIS:
A process by which
 a white blood cell
 envelopes and 
digests debris and 
microorganisms to 
remove them from 
the blood
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.

8. Phagocytosis of antigen
Fusion of lysosome and
phagosome
3) Enzymes start to
degrade antigen
4) Antigen is broken into
small fragments/peptides
5) Peptides are presented
on APC surface (MHC
class II)
6) Leftover fragments are
released by exocytosis

9. Adaptive Immunity (Acquired, Specific)
The antigenic universe is incredibly diverse/this diversity must
be overcome by the immune response
Antigen (Ag)- the molecule or structure against which the immune response is directed
Adaptive immune response 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 is different than HIV)
Characterized by more rapid, stronger memory response

10. Adaptive immunity: humoral and cellular responses
CD4 (helper) T cell
CD8 (killer) T cell
T cell receptors only recognize antigens
presented on MHC molecules

12. 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

13. 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.

14. 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)

15. Initiation of an immune response

16. Adaptive immune response

17. Memory is the hallmark of adaptive immunity
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

18. 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