LECOM-Pharmacy SchoolImmunology 01

Overview of the Immune System Dr. Saber Hussein

Reading & Goal

• Read Chapter 1, Abbas & Lichtman: Basic Immunology functions and Disorders of the Immune System; Saunders, 2nd Editions 2004– If you have1st Edition 2001 that is o.k.

• Or Chapter 1, Immunology A Short Course, Benjamini et al

• The goal of this lecture is to introduce to you some of the subjects studied under the umbrella of Immunology. It is not meant to teach you the whole Immunology in one hour

Why immunology for pharmacists?• Pharmacists as healthcare providers must

understand the human body and what keeps it healthy and what causes its disease

• Pharmacists might provide vaccines. Therefore you must know how immunization works

• Immunology helps understand mechanisms of action of some drugs such as: – monoclonal antibodies– cytokine analogs or antagonists– immunosuppressants– immune modulating drugs

Overview of the Immune System1. Innate immunity

2. Adaptive immunity: 1. Humoral and

2. cell-mediated immunity

3. Properties of adaptive immunity: 1. Specificity and

2. memory

4. Phases of the immune response

5. Cells of the immune system: Lymphocytes, antigen-presenting cells, effector cells

6. Tissues and organs of the immune system: Peripheral lymphoid organs, lymphocyte circulation

Learning Objectives1. Know the protective role of the immune system2. Differentiate between the adaptive (acquired) and the

innate immunity3. Know the fundamental role of the discrimination between

self and nonself in the work of the immune system4. Know the major branches of the immune system: the

humoral and the cell-mediated immune response5. Have an idea about the benefits and the harmful effects of

the immune system6. Recognize genetic recombination as a basis of the

diversity of the immune response7. Know that the immune system is usually regulated up

and down

Protective role of the immune system

• Immune system evolved to protect us against:– Intra- and extracellular bacterial infections– Viral infections: Always intracellular– Fungal infections: Extracellular– Parasitic infestation: Some unicellular protozoa such

as malarial parasites, Plasmodium species, are intracellular but most are large, extracellular and even lumen dweller

– Malignant cells

• Intracellular pathogens live inside host’s (patient’s) cells

• Extracellular pathogens live outside host’s cells

Innate Immunity• Synonyms:

– Natural – None-adaptive– Nonspecific

• Cells involved:– All white blood cells except B and T lymphocytes– Phagocytes

• Monocytes (mono[nuclear leuko]cytes)/macrophages• PMN (polymorphonuclear) neutrophils

– Natural killer (NK) cells• Humoral or soluble components

– Complement system• Exterior defenses

– Skin, Stomach acidity, Mucus, Cilia, Microflora, Lysozyme in tears, Flushing of urinary tract by urination

Exterior Innate Defenses

Adaptive (Acquired) Immunity• Develops in response to microorganisms and

other foreign antigens (Ags)

• Anamnesis– Improves after each encounter with the Ag has a

memory

• Antibodies (Abs) = Immunoglobulins (Ig):– IgA, IgG, IgM, IgE, IgD

• Lymphocytes: – B cells– T cells

Antibody: A flexible adaptor

• Abs specific binding sites of the Fab region bind Ags– As with microbe 1

• No specific Ag No binding – As with microbe 2

• The Fc region of the Ab binds Fc receptors on some cells such as phagocytes

• The Ag-Ab complex can activate the complement system via the Fc of the Ab

L chain

H chainPapain

V

C

Ag

Phases of the Immune Response• Recognition of Ag:

– Naïve B lymphocytes recognize certain types of Ags– Naïve T lymphocytes recognize peptides presented by Ag

presenting cells (APC)– Clonal expansion

• Activation phase– Differentiation:

• B cell Ab producing cell• T cell Effector T cell

• Effector phase– Elimination of Ags by:

• Humoral immunity• Cell-mediated immunity

• Decline (homeostasis) Apoptosis• Memory Surviving memory cells

Active & Passive Immunization• Active immunization

– is acquired in response to Ag administration

• All vaccinations

• Passive immunization – acquired through administration of Ab from immunized individual

• Hepatitis A

• Anti-rabies treatment

• Anti-tetanus

• Adoptive transfer: – Transfer of immunity by transplantation of immunocompetent

cells

• E.g. bone marrow transplant

Self and Nonself

• Discrimination between self and nonself Ags is fundamental for the function and evolution of the immune system

• This is the basis of immune response against pathogens and transplant rejection

• Self fanaticism– Reacting against foreign Ag because it is

foreign – Not based on beneficial or harmful Ag

Humoral and Cell-mediated Immunity• Acquired humoral (soluble) immunity is based on Abs

made by B cells• Complement and cytokines may be considered part of

the humoral immunity• Acquired cell-mediated immunity depends on T

helper cells (TH) and cytotoxic T cells (Tc), or cytolytic T lymphocytes (CTLs)

• Other leukocytes are part of the cellular immunity, including: – Phagocytes, – macrophages, – natural killer cells (NK)

Complement Functions

• Complement is a system of serum proteins that interact with one another and with other molecules to generate important effects

1. Lysis• The complement system has an

intrinsic ability to lyse the cell membranes of many bacterial species

2. Chemotaxis • Complement products released in this

reaction attract phagocytes to the site of the reaction

3. Opsonization • Complement components coat the

bacterial surface allowing the phagocytes to recognize the bacteria and engulf them

Cells of the Immune System

• Lymphocytes– T helper cells (TH) – Cytotoxic T cells (Tc)– B cells– NK

• PMNs– Neutrophil – Basophil & Mast cells– Eosinophil

• Monocytes– Dendritic cells – Macrophages

Cells involved in the immune response

Hematopoiesis

Functions of Lymphocytes

NK( )

Major histocompatibility complex (MHC)

• MHC is called HLA or human lymphocytes Ag

• Two classes: I & II

• Important in presenting Ags to the TH and TC cells– MHC I presents Ag peptides to TC

– MHC II presents Ag peptides to TH

Cytokines• Small peptides, synthesized by different cells involved in

the immune system• They are regulators: activate cells or inhibit cell

functions• Major means of communication among cells of the

immune system and between them and others• Examples:

– Interleukins• IL-2• IL-4

– Interferons• IFNα• IFNγ

Clonal Selection Theory

1. T and B cells exist with almost unlimited specificities before any contact with foreign Ags

2. Ag-specific receptors that recognize foreign Ags: 1. Abs are the B cell receptors on the surface of B cell & 2. T-cell receptor (TCR) on T cell

3. Each lymphocyte has a single specificity4. The antigenic determinant (epitope) on the Ag binds

with lymphocyte (B or T) and triggers their differentiation and proliferation

5. Negative selection by self Ags shut off cells that recognize them during maturation

Clonal Selection

Epitopes2, 103, 821

No specialized receptor

Epitopes2, 103, 821

Benefits of the Immune System

• Immunization and defense against infectious disease

• Cancer detection and management

A benefit of immunology (application):

– Organ transplantation and blood transfusion

Harmful Effects of the Immune System• Hypersensitivity or allergic reactions:

– Type I, immediate hypersensitivity– Type II, cytotoxic Ab-mediated reactions– Type III,immune complex Ab-mediated – Type IV, delayed-type cell-mediated

• Autoimmune diseases– The immune system attacks body’s own Ags causing diseases

like rheumatoid arthritis, diabetes mellitus and systemic lupus erythematosus

• Immunodeficiencies– Occur when one or more components of the immune system fail

to function properly– This can be result of genetic defect (SCID) or acquired (AIDS)

• Graft rejection– Occurs because of immune response against transplant’s Ags

Genetic Recombination & Immune Response Diversity

• 106-107 of antigenic specificities might exist• If 1 gene = 1 response, are 107 genes needed?

– No

• Genetic recombination “within “ a gene that encodes the Ig proteins is the answer

• So, the basic Ab is composed of 2 types of polypeptides: H-chain, L-chain and each chain has a variable domain

• This mechanism generates Ab & T cell receptor (TCR) specificity

Regulation of the immune system

• Why regulation?• Immune response proliferation and increased

synthesis of specific molecules that will not be useful after their job is finished (infection response cure)

• Homeostasis or equilibrium must be established by shutting down the system

• Deregulation of the immune system has severe consequences

• Immune response to self Ags Autoimmunity