Lectures 1 & 2 The immune system Overview
Jan 17, 2016
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