Lectures 1 & 2The immune system

Overview

Grading:Exam I 25%Exam II 25% State Exam 35%Lecture highlight 5%Final oral report 10%

Textbook

Core

LCME 514 Lectures

Oral reports: A student each lecture will take turn to summarize the last lecture’s highlights for 5 minutes, and take questions from other students

Experts in Clinical Immunology

On 4/19/05, each student should present for 5 minutes as if he or she is an expert immunologist on the disease. This presentation accounts for 10% of the final grade.

The students should include following components in their presentation:

1. What is the immunological mechanism of the disease? Describe the major immune components (cells, cytokines or molecules) and their functions in each disease.

2. What are the diagnosis criteria?3. What are the therapy options?

Before lecture

Read the textbook and try to understand all the terminologies in bold.

These are building blocks so that we can build a “nice house of Immunology” in the class.

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

Innate and adaptive immune responses

Humoral Immunuty and Cell-Mediated Immunity

What are the side effects of the immune system?Autoimmune diseases, Allergies, Transplantation Rejection

Lecture objectives

Figure 1-2

goal of the immune system

The goal of the immune system

Plus tumor cells

Figure 1-3 part 1 of 4

Figure 1-3 part 2 of 4

Figure 1-3 part 3 of 4

Figure 1-3 part 4 of 4

Figure 1-4

The territory to defend by the immune system: the physical barriers

The immune system =The defense system of the body

Figure 1-7

Innate (immediate) and adaptive (late but antigen-specific) immune responses

Innate and adaptive responses work together

Innate

Antigen independent Immediate (hours)

Neutrophils NK cells Macrophages

Adaptive

Antigen-dependentSlower (days)

T cells

B cells

Dendritic cells

*Innate immune responses help form adaptive immune responses, and Adaptive immune responses utilize the machinery of innate immunity for effector function

Cells of Innate Immunity

NeutrophilsNK cellsMacrophagesMast cellsEosinophilsBasophils

Cells of Adaptive Immunity

Dendritic cellsB cellsT cells (CD4 or CD8)

Figure 1-5Immune cell recognition of pathogens followed by destruction

Figure 1-6Infection induces inflammation to recruit more immune cells

Hematopoiesis generates immune cells

Stem cells: 1. Self renewal 2. Totipotency

They are in bone marrow after fetal development.

They make all myeloid and Lymphoid blood/immune cells

T cell progenitors migrate to thymus and generate T cells

B cell progenitors reside in bone marrow to make naïve B cells

Immune cells = Soldiers

Figure 1-10

Hematopoiesis occurs in the adult bone marrow

Myeloid vs. Lymphoid cells

Stem cells

T cells: T cell antigen receptorB cells: B cell antigen receptorNK cells: no antigen-specific receptor

Myeloid cells

Lymphoid cells

Monocytes: Macrophage precursors Origin : bone marrow Antigen receptors: No

Function: to become macrophages Present in blood circulation

Neutrophils: Phagocytes

Origin and maturation: Bone marrow Antigen receptors: No Function: Phagocytosis and killing of microorganisms Where: in blood circulation Sites of function: infection sites Short life span

NK cells: natural killers Origin : many (bone marrow and thymus)

Antigen receptors: No

Function: Kill tumor and virus-infected cells

Effector machinery (=weapons): perforins and granzymes

Macrophages: Phagocytosis and antigen presentation Origin : bone marrow Antigen receptors: No

Function: phagocytosis of microorganisms and antigen presentation to T cells

Present in various tissues in various forms(Kupffer cells, intraglomerular, alveolar, serosal, microglia,

spleen sinus and lymph node sinus macrophages)

Dendritic cells (DC): transport antigens and activate T cells

Origin : bone marrow Antigen receptors: No

Function: antigen presentation to T cells

Mechanisms: phagocytosis, cytokines (IL-4, IL-10, IL-12) and antigen-presentation through MHC molecules

Migration: From tissue infection sites to 2o lymphoid tissues

Mast cells: parasite killers Origin : bone marrow Antigen receptors: No

Function: to kill parasites Sensor: IgE receptor Effector machinery:cytotoxic granules, lipid mediators,

cytokines and chemokines Present in connective tissues

Eosinophils: worm (parasites) killers Origin : bone marrow Antigen receptors: No

Function: killing of antibody-coated parasites through release of killing mix (granule contents)

Effector machinery:cytotoxic granules, lipid mediators, cytokines and chemokines

Basophils: relatives of mast cells and eosinophils Origin : bone marrow Antigen receptors: No

Function: important effector cells in allergic disorders and immune responses to parasites

Sensor: IgE receptor Effector machinery:cytotoxic granules, lipid mediators,

cytokines and chemokines

T lymphocytes: master regulators of the immune system

Origin: Bone marrow Maturation: Thymus Differentiation to effector cells: secondary lymphoid tissues

(Lymph nodes, spleen, Peyer’s patch, and tonsils)

Antigen receptors: Yes Function: regulates humoral and cell-mediated immune

responses Mechanisms: cytokines, cell surface molecules,

granules (cytotoxic T cells)

B lymphocytes: antibody producers

Origin and maturation: Bone marrow Differentiation to plasma B cells: secondary lymphoid

tissues (Lymph nodes, spleen, Peyer’s patch, and tonsils)

Antigen receptors: B cell receptor (cell surface immunoglobulins)

Function: Production of antibodies (IgM, IgE, IgA, and IgG) Regulated by T cells

Antigens+ T cell help

B lymphocytes

Figure 1-12

Circulating blood cells

Figure 1-13

Neutrophils: disposable phagocytes to clear pathogens

Figure 1-14

Macrophages engulf bacteria and produce inflammatory cytokines

Figure 1-15

The lymphatic system

Figure 1-16

Naïve lymphocytes encounter pathogens’ antigens in lymph nodes

Activates lymphocytesBeginning of adaptive response

Figure 1-17Antigens+DCs T cells

B cells undergo differentiation to PC

Figure 1-18

Figure 1-19

Spleen does not haveAfferent Lymphatics

Spleen filters blood to search for antigens

Figure 1-20

Figure 1-21

Antigen receptors of B cells and T cells

Figure 1-22

Antibodies neutralize pathogens in an antigen-specific manner

Figure 1-23Gene rearrangement to form antigen receptors on lymphocytes

(immunoglobulins and T cell receptors)

Figure 1-24Antibodies (B cells) bind whole proteins while TCR (T cells) binds small peptides

Figure 1-25

Peptides are presented to TCR by MHC class I or II molecules on APC (antigen presenting cells: B cells, dendritic cells and macrophages)

Figure 1-26Viral antigen presentation to CD8+ T cells via MHC class I molecules

Figure 1-27

Bacterial antigen presentation to Th1 or Th2 CD4+ cells

Figure 1-8

Selection and expansion of antigen specific T and B cells

Figure 1-28

Generation and selection of T cells

The thymic selection processes are to generate T cells with functional TCRs that are not autoreactive.

Figure 1-29 part 1 of 2

Antibodies neutralize and opsonize

Figure 1-29 part 2 of 2

Typical time course of adaptive immune responses

Primary response

Slow (2 weeks)Weak

Secondary

Fast (several days)Vigorous

The impact of vaccination

Unwanted immune response: allergies

Unwanted immune response: autoimmune diseases

Immunity[Pathogens]= 0[tumor cells]= 0

The goal of a balanced immune system

Allergy and hypersensitivities

Immune response to allergens

[Pathogens]= 0[tumor cells]= 0

Cancer

[tumor cells] >> 0

Immune response to tumor cells

Autoimmune diseases

[Pathogens]= 0[tumor cells]= 0

Immune response to self antigens

Immunodeficiency

Immunity to pathogens and cancer cells

[Pathogens] >> 0

[tumor cells] >> 0

e.g. AIDS patients

Figure 1-34

Immune responses can be both beneficial and harmful