Immune Defenses Against Disease

Chapter 15 (innate immunity)

Chapter 16 (adaptive/acquired immunity)
Chapter 17 (passive vs active immunization – pp 505-512)

Health lies in the balance

your immune system achieves
in its response to different
antigens

Response vs Tolerance

Modulation of response

Immune Defenses 1
What are the two main arms of
the immune defense system?

1. ‘Innate’ defenses against infection

(antigen-nonspecific)

‘Barriers’ to infection

Normal microbiota

Cellular / enzymatic responses

2. ‘Acquired’ defenses against infection

antigen-specific

humoral & cell-mediated systems

These systems interact in many ways

Immune Defenses 2
What are the types of
Innate Immunity?

I. Non-induced mechanisms
“Barriers to infection”
-- 1st line of defense

Anatomical
Mechanical

Cilia and mucus

Skin wounding

Immune Defenses 3
Innate Immunity…

II. Cellular responses

Physiological, e.g., fever
Cellular , e.g., phagocytosis
Enzymatic, e.g., complement

Receptor-mediated
Broadly specific
-- recognize “danger signals”
-- molecules shared by
many pathogens
“PAMPs”

Responses
pathogen killing (intra- & extra-cellular)
activation of acquired immune responses

http://lpi.oregonstate.edu/infocenter/phagocytosis.html

Immune Defenses 4
What are the cells
of the Immune System?

Innate
granulocytes

monocytes, etc

Acquired
lymphocytes

‘Cytokines’ coordinate activities

Immune Defenses 5
Organs of the Immune system
Primary Lymphoid organs

Bone marrow

Thymus

Secondary lymphoid organs

Spleen

lymph nodes

etc.

B-cells and T-cells circulate

Immune Defenses 6
What are 4 characteristics of the
Adaptive Immune system?
Specificity
Diversity
Memory
Self/nonself discrimination

What are the two branches?

Humoral Response:
Attack free antigens via antibodies
B-cell lymphocytes
“B-cell receptors” (BCR)

Cell-mediated Response:
Hormonal regulation
Attack infected cells
T-cell lymphocytes
“T-cell receptor” (TCR)
AG on MHC proteins

Immune Defenses 7
Acquired Immune system recognizes antigens
…What is an antigen?
Complex macromolecules (e.g., proteins)
-- distinctive to a pathogen (+/-)

Perceived as “foreign”
-- ‘self ‘ vs ‘non-self’

B-cell antigens (antibodies)

-- on pathogen surface

T-cell antigens
-- from intracellular pathogens

Immune Defenses 8
What is an epitope?
Actual part of the antigen recognized

By antibody or T-cell Receptor

Immune Defenses 9
What is an antibody?

Functional regions
antigen binding sites

constant region
-- triggers response

hinge region

What are the 5 types of antibodies

and their functions?
IgG – primary serum Ig

IgA – secretory Ig

IgM – B-cell receptor

IgE – eukaryotic Ags

IgD – membrane associated

Immune Defenses 10
How does the Humoral System
respond to an infection?

“Clonal Selection”

‘Naïve’ B-cells

Activation (AG selection)

+ TH cell stimulation

Plasma cells
“Antibody” factories

Memory cells
create acquired defense

(T-cell response is similar)

Immune Defenses 11
Clinical Manifestation of Immunity
Primary vs Secondary responses

Differences in:
lag time
Ab Titer
memory cells

Immune Defenses 12
How do antibodies trigger
an immune response?

Blocking of receptors

Toxin neutralization

Antigen clearing

Enhanced phagocytosis

Activation of complement

Immune Defenses 13
How does the Cell-mediated
system respond to infections?

MHC proteins
-- antigen “presentation”

Professional AG-presenting cells

-- macrophages, dentritic cells
vs Normal body cells

T-Helper cells  MHC-II

-- release cytokines
-- interferons, interleukins, etc

T-Killer cells  MHC-I

-- are first “licensed” to kill
-- attack infected body cells
--trigger cell lysis, apoptosis

Immune Defenses 14
How can our bodies produce millions of
different types of B-cells and T-cells?

Each B- or T-cell can recognize

only a specific antigen

Antibody/TCR genes are

randomly “rearranged”

Why don’t B and T-cells act against “self”

antigens?
-- Cells “tested” in bone marrow and thymus
Immune Defenses 15
How is MHC different?
-- 100s of different MHC among humans
-- We each possess only 12-18
-- inherited from parents

Cause predispositions

-- Disease susceptibility

-- Allergies

-- Autoimmune disorders

Is basis of Transplant Compatibility

Immune Defenses 16
Types of tolerance

Central vs Peripheral

Types of peripheral tolerance

1. Missing signals, e.g.,

-- no TH help for B-cells or Tc cells

2. Treg cells
-- Immunosuppressive cytokines

3. Tolerogenic DC cells
-- induced by missing danger signals

Immune Defenses 17
Overview of Acquire immune responses

Cell meditated

TH activated by AG presented on P-APC

-- cytokines needed for
TC and B-cell activation

TC activated by DC cells &

AG presented on infected cell
-- kill target cells

Humoral

B-cells activated by free AG

Ab bind to pathogens
-- induce phagocytosis
-- activates “complement”
-- etc

Immune Defenses 18
Immunization

Passive Immunotherapy

maternal antibodies

anti-toxins

Active Immunotherapy
(i.e., vaccination)

Types of vaccines

dead cells

attenuated cells

molecular components

Vaccine production

Immune Defenses 19
Autoimmune disorders
Examples

Type I diabetes
-- B-cells of pancreas

Rheumatoid arthritis
-- cartilage of joints

Myasthenia Gravis
-- acetylcholine receptors

Multiple sclerosis
-- myelin sheath

Immune Defenses 20
How can microbes trigger
Autoimmune disorders?
Examples
Type I diabetes -- B-cells of pancreas
Rheumatoid arthritis -- cartilage of joints
Myasthenia Gravis -- acetylcholine receptors
Multiple sclerosis -- myelin sheath

Possible examples of “Molecular Mimicry”

Immune Defenses 21
What causes Allergies
Two steps

Sensitization
B-cells ----> IgE

mast cells

Triggering
mast cell activation

histamine

inflammation

IgE and Allergy

Immune Defenses 22