Transcript Document

MCMP422
Immunology and Biologics
• Immunology is important personally and
professionally!
• Learn the language - use the glossary and index
• RNR - Reading, Note taking, Reviewing
• All materials in Chapters 1-3 are examinable
(with exceptions) plus extra material from class
Chapter 1
Elements of the Immune System
and their Roles in Defense
Summarizes all of immunology
Foundation for the rest of the course
The rest is all details
Chapter 1 Concepts
What components make up the immune system?
Cells, organs, cytokines and other molecules involved in the
immune system
What is the goal of the immune system?
To clear pathogens in our body
How do we classify immune responses?
Innate and adaptive immune responses
What are the side effects of the immune system?
Autoimmune diseases, Allergies, Transplantation Rejection
•
Immunology: the science of how the body responds to
foreign organisms (e.g. pathogens) or substances (e.g.
allergen)
•
Immune system: the organs, cells and molecules that
defend and respond to pathogens/allergens
1. Tissues/organs
bone marrow, thymus, spleen, lymph nodes
2. Cells
lymphocytes, dendritic cells, macrophages, natural killer
cells, granulocytes (neutrophils, basophils, eosinophils),
mast cells
3. Blood borne proteins
complement and mannose-binding proteins
Origin of Immunology - individuals who survived a disease seemed
to be untouched upon re-exposure
Vaccination/Immunization - procedure where disease is prevented
by deliberate exposure to infectious agent that cannot cause
disease.
Figure 1-2
Diversity of Pathogens
• Four Classes
• Opportunistic pathogens
Pneumocystis carinii
• Pathogen-Host relationship
How Clean are You?
Part of body
Head (scalp)
Surface of skin
Saliva
Nose mucus
Faeces
Bacteria
1,000,000 /cm2
1000 /cm2
100,000,000 /g
10,000,000 /g
over 100,000,000 /g
Defenses against Pathogens
Physical Defenses
1. Skin
- Tough water-proof Barrier
- Pathogen Penetration is difficult
- Breached by wounds/mosquito
2. Mucosal surfaces
- line body cavities
- epithelial cells covered with mucus
- e.g. mucus in lungs traps pathogens
Immune Defenses
1. Innate
2. Adaptive
Physical Barriers
Figure 1-4
Innate and Adaptive responses
Innate
Adaptive
 Pathogen independent
 Immediate (hours)
 Pathogen-dependent
 Slower (days)
Neutrophils
NK cells
Macrophages
Mast cells
Eosinophils
Basophils
Dendritic cells
B cells
T cells (CD4 or CD8)
Both systems “talk” to each other to modulate response
Immunity: Three Basic Parts
Recognition
(Binding event)
Pathogen
(Foreign)
Immune
disorders
(Self)
Signal
Effector mechanisms
Effector Cells
Complement
Innate immunity - “naïve”, immediate, everyday immunity
Acquired immunity - “specialized”, late, immunity
One way Immunity Works
Figure 1-5 part 1 of 2
Complement
Effector cell
Endocytosis
Figure 1-5 part 2 of 2
Innate Immunity
Figure 1-6
Cytokines
Inflammation
Phagocytosis
Inflammatory cells
Inflammation
•
Inflammation - local accumulation of fluid and cells involved in
the immune response
- State of Inflammation is induced - increased swelling, pain,
heat and redness.
1.
Blood capillary dilation = heat = redness
2. Vascular dilation = swelling = pain
3.
Extravasation - change in adhesiveness of the endothelial tissue
allowing immune cells to attach and migrate into the connective
tissue
What if Innate Immunity is not Enough?
• Innate immunity keeps us healthy most of the time
• Some pathogens escape the innate immune process
• Need a specific system to adapt to a specific pathogen
• Adaptive immune response
Characteristics of Innate vs Adaptive Immunity
Figure 1-7
Lymphocytes - white blood cells that increase the
immune response to ongoing infection
INNATE
ADAPTIVE
Genes are constant
Genes rearrange
NO Longterm immunity
Longterm immunity
Innate vs Adaptive Molecular Recognition
• Most important difference: Receptors used to recognize
pathogens
• Innate immunity: Receptors recognize conserved structures
present in many pathogens
Pathogen-associated Molecular Patterns: LPS,
peptidoglycan, lipids, mannose, bacterial DNA and viral RNA
• Adaptive immunity: Receptors recognize a specific structure
unique to that pathogen
Flowchart of Hematopoiesis
Figure 1-11 part 1 of 2
Flowchart of Hematopoiesis
Figure 1-11
Myeloid Lineage
Granulocytes (Myeloid progenitor)
Polymorphonuclear leukocytes (PMLs)
Figure 1-9 Neutrophils:
partMost
3 abundant
of 6
Phagocyte
Effector cells of Innate Immunity
Short-lived - Pus
Eosinophils:
Worms/intestinal parasites
Amplify inflammation
Bind IgE
Very Toxic - Pathogen and host
Chronic asthma
Basophils:
Rare
Unknown function
Bind to IgE
Figure 1-9 part 5 of 6
Figure 1-13
Lymphoid Lineage Cells
Figure 1-9 part 2 of 6
Lymp
Figure 1-9 part 1 of 6
Erythroid Lineage
Figure 1-9 part 6 of 6
Lymphoid
Myeloid part 2 of 2
Erythroid
Figure 1-11
Figure 1-12
Figure 1-14
Sites of Lymphoid Tissue
Figure 1-15
Primary and Secondary
GALT, BALT, MALT
Lymph
Recirculation
Figure 1-16
Draining Lymph node
Edema
Afferent and Efferent
Figure 1-17 part 1 of 2
B-cell area
(follicle)
Anatomy of immune function in the Spleen
Figure 1-19
Figure 1-19 part 1 of 2
Figure 1-19 part 2 of 2
Figure 1-20
Adaptive Immunity
1. Vertebrates only
2. Specificity
- recognition modules - BCR, Ab and TCR
- gene rearrangement is the source of diversity
- clonal selection
3. Small lymphocytes
- types and sub-types
- functions
Recognition concept
Receptor or Antibody molecule
Antigen - structure recognized by an Ab, BCR or TCR
Epitope - particular sub-structure of the Ag that is bound
Affinity - how much a molecule likes to bind to a structure
Small lymphocyte sub-types
B-cells
BCR is Immunoglobulin (Ig)
Plasma cells - effector cells that secrete Ab
T-cells
Tc = cytotoxic (CD8+)
TH = helper T-cells (CD4+)
Th1 (inflammation)
Th2 (help B-cells make AB)
Recognition modules of Adaptive immunity
B cells
T cells
B-cells
T-cell
Figure 1-25
Intracellular
pathogens
Extracellular
pathogens
Figure 1-26
MHC class I communicates with Tc cells
MHC class II communicates with TH cells
Figure 1-27
Parasitic infection
Parasite
+
Mast cell
Inflammation
Mast cell
activated
Expel
and/or
destroy
pathogen
• Neutralization
• Opsonization
1. Inflammation
Principles of Adaptive Immunity
Diversity
Specificity
Memory
Self-tolerance
Gene Rearrangement is the source of Diversity
Germline configuration
Diversity
1. Alternative combinations
2. Imprecise joints
3. Different types of chains
4. B-cells - somatic hypermutation
In the absence of antigen
Clonal Selection
1. Each cell = one receptor
2. Millions of lymphocytes
are generated
3. Small subset will
recognize a pathogen
4. Proliferation and
differentiation
5. Acquired immunity - the
adaptive immunity
provided by
immunological memory
Figure 1-22
Figure 1-30
Polio Vaccine - Inactive vs Oral “live” version
Figure 1-28
Mechanism of Self-tolerance
Immunodeficiencies
Inherited deficiencies
Stress induced
Pathogen caused deficiencies
Cells and molecules
involved in
Hypersensitivity Diseases
Figure 1-32
• IgE
• IgG
• CD4 TH1
• CD8 CTL
Insulin-Dependent Diabetes Mellitus
Figure 1-33
Figure 1-34