MCMP 422: Immunology• Class MWF 11:30-12:20• Instructors

– Dr. Geahlen– Dr. Harrison– Dr. Hazbun (RHPH 406D, 496-8228,

thazbun@purdue.edu)

• Objectives• Course Policies• Grading

The Immune System

Second Edition

Chapter 1

Elements of the Immune Systemand their Roles in Defense

Copyright © 2005 by Garland Science Publishing

Peter Parham

Chapter 1Summarizes all of immunology

Get a good Foundation

Before class: Read the textbook in general and try to understand all the terminologies in bold.

During class: Take good notes because I will be adding information that will be tested

After class: Review material to commit to long-term memory

What components make up the immune system?Cells, organs, cytokines and molecules involved in the

immune system

What is the goal of the immune system?To clear pathogens and cancer cells 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

Lecture Concepts

• 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

2. Cells

3. Blood borne 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

Part of body BacteriaHead (scalp) 1,000,000 /cm2Surface of skin 1000 /cm2Saliva 100,000,000 /gNose mucus 10,000,000 /gFaeces over 100,000,000 /g

How Clean are You?

• Four Classes

• Opportunistic pathogens

• Pathogen-Host relationship

Diversity of Pathogens

Defenses against Pathogens

Physical Defenses1. Skin

2. Mucosal surfaces

Immune Defenses1. Innate2. Adaptive

Figure 1-4

Pathogen Recognition

Signal

Effector mechanisms

Effector Cells Complement

Innate immunity - “naïve” everyday immunity Acquired immunity - “specialized” immunity

Immunity: Basic Parts

(Binding event)(Foreign)

(Self)

Immunedisorders

Figure 1-5 part 1 of 2

ComplementEffector cellEndocytosis

One way Immunity Works

Figure 1-5 part 2 of 2

Figure 1-6

CytokinesInflammationPhagocytosisInflammatory cells

Innate Immunity

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

Figure 1-7Characteristics of Innate vs Adaptive Immunity

Lymphocytes - white blood cells that increase the immune response to ongoing infection

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

Figure 1-11 part 1 of 2Flowchart of Hematopoiesis

Figure 1-11Flowchart of Hematopoiesis

Myeloid Lineage

Figure 1-9 part 3 of 6Neutrophils:Most abundantPhagocyteEffector cells of Innate ImmunityShort-lived - Pus

Eosinophils:Worms/intestinal parasitesAmplify inflammationBind IgEVery Toxic - Pathogen and hostChronic asthma

Basophils:RareUnknown functionBind to IgE

Granulocytes (Myeloid progenitor)Polymorphonuclear leukocytes (PMLs)

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

Figure 1-11 part 2 of 2Lymphoid Myeloid Erythroid

Figure 1-12

Figure 1-14

Figure 1-15

Sites of Lymphoid Tissue

Primary and SecondaryGALT, BALT, MALTLymphRecirculation

Figure 1-16

Draining Lymph nodeEdemaAfferent and Efferent

Figure 1-17 part 1 of 2

B-cell area(follicle)

Figure 1-19Anatomy of immune function in the Spleen

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 like to bind to a structure

B-cellsBCR is Immunoglobulin (Ig)Plasma cells - effector cells that secrete Ab

T-cellsTc = cytotoxic (CD8+)

TH = helper T-cells (CD4+)Th1 (inflammation)Th2 (help B-cells make AB)

Small lymphocyte sub-types

Recognition modules of Adaptive immunity

B cells T cells

B-cells T-cell

Figure 1-25

Intracellularpathogens

Extracellular pathogens

Figure 1-26MHC class I communicates with Tc cells

Figure 1-27MHC class II communicates with TH cells

Parasite +

Mast cell

Inflammation

Mast cell activated

Expel and/or destroy

pathogen

• Neutralization• Opsonization1. Inflammation

Parasitic infection

Principles of Adaptive Immunity

DiversitySpecificityMemorySelf-tolerance

Gene Rearrangement is the source of Diversity

Germline configuration

Diversity1. Alternative combinations2. Imprecise joints3. Different types of chains4. B-cells - somatic hypermutation

In the absence of antigen

Clonal Selection

1. Each cell = one receptor2. Millions of lymphocytes

are generated3. Small subset will

recognize a pathogen4. Proliferation and

differentiation5. Acquired immunity - the

adaptive immunity provided by immunological memory

Figure 1-22

Figure 1-30

Figure 1-31

Figure 1-28

Mechanism of Self-tolerance

Immunodeficiencies

Inherited deficiencies

Stress induced

Pathogen caused deficiencies

Figure 1-32IgGCD4 TH1CD8 CTL

Figure 1-33Insulin-Dependent Diabetes Mellitus

Figure 1-34

Figure 1-10

Figure 1-29 part 1 of 2

Figure 1-29 part 2 of 2

Figure 1-31 part 1 of 3

Figure 1-31 part 2 of 3

Figure 1-31 part 3 of 3