K3 - Konsep Dasar Imunologi

Basic concepts in immunology

Evy Sulistyoningrum

Introduction

Immune system & components

Immune response

Immunological regulation

Immunity

Immunological memory

Defects in immunity

Outlines

Immunology: the study of the body’s defense against infection

To protect individual from infectious agents and damage they cause

Introduction

Edward Jenner discovered in 1796 that cowpox, or vaccinia, induced protection against human smallpox vaccination

The eradication of smallpox by vaccination.After a period of 3 years in which no cases of smallpox were recorded, the World Health Organization was able to announce in 1979 that smallpox had been eradicated.

History of Immunology

Robert Koch (1843–1910) proved that infectious diseases are caused by microorganisms

History of Immunology

Louis Pasteur (1822–1895) devised a vaccine against cholera in chickens, and developed a rabies vaccine that proved a success upon its first trial in a boy bitten by a rabid dog

Shibasaburo Kitasato (1892–1931) in collaboration with Emil von Behring (1854–1917) discovered specific antitoxin activity against tetanus and diphtheria in serum

Elie Metchnikoff (1845–1916) :central role of phagocytes in host defense.

Variety of organs, tissues, cells, molecules that performed immune response and produce immunity

Cellular components

Immune cells

Lymphoid tissue or organs

Humoral components

Soluble protein: complements, antibody

Physical, mechanical, chemical barriers

Non-immune system “inherent component”

Performed by other structure not specific to immune system but acts as first line defense againts pathogen

Immune system

Immune system: barrier

Cells of the immune system

Origin: Pluripotential hematopoietic stem cells

Located within the bone marrow, fetal liver and yolk sac of the fetus

Stem cells differentiate into 2 types of “committed” stem cells

produce platelets, erythrocytes (red blood cells), monocytes or granulocytes (myeloid progenitor)

produces cells of the lymphoid line (lymphoid progenitor)

Myeloid cells

3 subsets :

B lymphocytes

T lymphocytes

NK cell

Functions:

B & T cell : adaptive immune response

NK cell : innate immune response

Distributions:

Circulation

Lymphoid organs

Lymphocytes

T Lymphocytes (T cells)

Derived from stem cells in the bone marrow.

Leave bone marrow and travel to the Thymus to mature

Have T Cell Receptor (CD3)

Can be found in circulation and lymphoid tissues

Approximately 75 to 80% of lymphocytes are T cells

Subsets: Th : helper

Tc : killer

Tsup : suppressor

Treg: regulator

B lymphocytes (B cells)

Derived from stem cells and become mature in the Bone marrow in human / Bursa of fabricius in birds

Have BCR (B cell receptor) (CD19/CD20)

Can be found in circulation and lymphoid tissues

Transform into plasma cells and produce antibodies (immunoglobulins)

Undergo a process called clonal expansion

Derived from stem cells in the bone marrow

Circulate in the blood

No TCR and BCR null cell

Large cells, contain cytolytic granules kill cell targets

Important in the defense from certain tumor cell andfrom virally infected cells.

Innate immune response

Act without prior activation

NK cells

Reticuloendothelial System

Lymphocytes are produced in bone marrow

Mature in the bone marrow and thymus (primary /central

lymphoid organs) => mature naive lymphocyte

Congregate in lymphoid tissues throughout the

body to be exposured by antigen

(secondary/ peripheral lymphoid organs)

Tissue and organs of the immune system

Tissue and organs of the immune system

Circulation

Primary lymphoid organs: development & maturation

Bone marrow: B cell maturation

Primary lymphoid organs: development & maturation

Thymus: T cell maturation

Circulating lymphocytes encounter antigen in peripheral lymphoid organs(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)

Lymph node

Secondary lymphoid organs: antigen processing

Circulating lymphocytes encounter antigen in peripheral lymphoid organs(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)

Spleen

Secondary lymphoid organs: antigen processing

Circulating lymphocytes encounter antigen in peripheral lymphoid organs(lymph node, spleen, Mucosal-Associated Lymphoid Tissue)

MALT

Secondary lymphoid organs: antigen processing

Humoral component Plasma soluble protein

Complement system

Protein secreted by cells, complementary effect to antibody

Natural immune response

Acute phase protein

Protein secreted by cells, released due to immune response in early phase

Natural immune response

Antibody

Secreted by plasma cells, bind to antigen, first known has protective effect, various mechanism

Adaptive immune response

Cytokine

Soluble protein regulating other cell’s activity

Natural & Adaptive immune response

Response against pathogen infection

Distinguish self vs non-self

Resulted in immunity (an immune condition)

Classification :

Innate immune response

Adaptive immune response

Immune response

4 main tasks:

Immunological recognition

Immune effector function

Immune regulation

Immunological memory only in adaptive immune response

Immune response

Innate/Natural/Native Adaptive /Acquired

Characteristics

Time Immediate (0-4 hours) Delayed (>96 hours)

Specificity Non-specific : Certain structure of all pathogens

Specific : Specific parts of the specific pathogen (antigen)

Diversity Limited Large range

Memory (-) (+)

Components

Cellular & chemical barriers

Skin, mucosal epithelia,Antimicrobial chemicals

Lymphocytes in epithelia,antibodies in epithelial surfaces

Humoral Complements, acute phase protein, cytokines

Antibodies , cytokines

Cellular Phagocytes, NK cell Lymphocytes (B & T)

Innate vs Adaptive

Innate & adaptive immune response

Innate immunity

May prevent

establishment of

infection?

Immunological recognition

Innate

PAMPS (Pathogen-associated molecular patterns) Certain sugar residue

Anionic polymers

LPS

PRR (Pattern recognition receptors) MBL

Macrophage mannose receptor

TLRs, etc

Adaptive

Antigen: specific part of the specific pathogen with epitope (special site that can bound to its specific receptor)

Antigen receptors

T cell receptor MHC molecules

B cell receptor

Examples of PRR: TLRs

Antigen recognition by lymphocytes

Actions of immune system to combat pathogen elimination of pathogen

Innate effector actions

Phagocytosis or other killing mechanisms

Inflammatory reactions

Cytokines release

Adaptive effector actions

T cell : Cellular-mediated mechanism

B cell :Antibody-mediated mechanism humoral

Cytokines release

Immunological effector phase

Ability of immune system to self regulate

Mantain adequate response to dangerous agent & prevent excessive response that can damage the body

Failure in regultion: autoimmunity, allergy

T reg: regulatory T cell

Produce cytokines that regulate development & activity of other cells

Immunological regulation

Immunological regulation

Immunological regulation

Specific feature of adaptive immune response

Protective immunity against reinfection against the same pathogen

Memory cells

Memory-associated immune response classification:

Primary immune response

Secondary immune response

Immunological memory

Immunological memory

Application of Immunological Memory

Immunization• Introduction of a pathogen, which allows are

body to do its primary immune response without the risk of actual sickness

• Active immunization• Passive immunization • Result in immunity of an immune person

Infectious pathogen

Mechanical barriers

Tissue resident cells – pathogen

Elimination of pathogen

Inflammatory reaction

Chemokine & cytokine

Complement system

Inflammatory cells

Induction adaptive immune response

Activation of adaptive immune response

Effector phase of adaptive immune response

Interaction between innate & adaptive immune response

Recognition by innate immune system

PAMPs - PRRs

Activation of cells in innate immunne response Pathogen killing

Release of cytokine & chemokine

Inflammatory process

Activation of complement system

Release of Acute Phase Protein

Engulfing activity digestion

Large particles, ex: bacteria

Performed by phagocytes Macrophage

Neutrophil, eosinophil (little effect)

Receptor – Ligand

Engulfing phagosome formation fuse with lysosome

Digestion mechanism: O2 dependent

O2 independent

Opsonization by opsonins

Phagocytosis

Phagocytes

Phagocytosis

Killing mechanism performed by NK cell

Viruses, tumor cell, intracellular bacteria

Recognition by NK cell Activating (NKARs) & inhibitory receptors (NKIRs)

Release granules that kills pathogen Perforin

Granzymes

Granulysin

(= Tcytotoxic cell)

Induce apoptosis of cell targets

ADCC

NK cell killing

NK cell

NK cell

Inflammatory process

Inflammation

Cardinal signs of inflammation

Rubor

Kalor

Tumor

Dolor

Functiolaesa

Organ + -”itis”

Leucocyte migration to infection site: role of chemokine & cellular adhesion molecules

MAC = Membrane attack complex

Formation of a hole in the membrane → cell lysis

Cell lysis by complement system

Complement-Mediated Lysis of E. coli

Feature Functional significance

Specificity Ensures distinct antigens elicit specific response

Diversity Enables immune system to respond to a large variety of antigens

Memory Lead to enhanced responses to repeated exposures to same antigens

Clonal expansion Increases number of antigen-specific lymphocytes

Specialization General responses that are optimal for defense against different pathogens

Contraction and homeostasis

Allows immune system to respond to newly encountered antigens

Adaptive immune response

APC: Process & presents antigen to lymphocytes in secondary lymphoid organs

T cell activation

B cell activation

Proliferation Differentiation into effector cell

Cellular mechanism

Humoral mechanism

Immunological memory

Adaptive immune response

Induction of adaptive response

Activation of specialized antigen-presenting cells (APC) is a necessary first

step for induction of adaptive immunity

Induction of adaptive response

Antigen: substances that specificly bound to lymphocytes

Recognized by:

Antibody/B cell receptor

T cell receptor

Major histocompatibility Complex (MHC)

Antigen recognition

T cell & B cell activation

Active lymphocyte Lymphoblast

T cell differentiation effector T cell

Th cell ( CD4+)

Tc cell : CTLs (CD8+)

Proliferate in T cell region of 2nd lymphoid organs

B cell differentiation

Naive B cell plasma cell (producing antibody)

B cell proliferation:

B cell region of 2nd lymphoid organs

Effector B & T cell exits from 2nd lymphoid organs

Proliferation & Differentiation of T cell & B cell

Humoral

B cell antibody producing plasma cell

Neutralization

Opsonization

Complement activation

ADCC

Cellular

T cell

T cytotoxic/cytolitic : Destroy target cells

T helper:

Activate macrophages

Induce formation of cytotoxic T cells

Stimulate B cells to produce antibodies.

Effector mechanism of adaptive components

Innate immunity Pathogen recognition non specific effector &

inflammation elimination of pathogen

Antigen Presenting Cells (APC) Antigen processing and presentation

Adaptive immunity Antigen recognition activation of T & B cell specific

effector cells elimination of pathogen memory

Summary

Stop press

Active immunity vs passive immunity

Active Immunity

Body produce antibodies after exposed to the antigen in the past either through:

- Exposure to the actual disease

- Planned exposure to a form of the antigen that has been killed or weakened(immunization/vaccination)

How long does active immunity last?

Depends on the antigen Some pathogen develop

new forms of antigen body doesn’t recognize annual immunization

Some pathogen only induce low level of immunity booster/repeated immunization

Last for a lifetime

Passive Immunity

Body doesn’t produce the antibodies A mother will pass

immunities on to her baby during pregnancy

Antibodies will protect the baby for a short period of time

Lasts until antibodies die

Why doesn’t the mother just pass on the WBCs that

“remember” the antigens?

Stop press 2

CD molecules

Surface markers

Indicate: functional properties, maturation stage, and lineage identity

Detected by panel of monoclonal antibodies:

well documented: CD1 – CD247examples:

- CD4+: TH; CD8+: CTL (cytolytic T lymphocyte)- CD19+: B cell- CD56+: NK cell; CD16+ Fcg receptor on NK cell- CD14+: macrophage

CD (cluster of differentiation/cluster designation) molecules

CD molecules on B cell

CD molecules on T cell

Defects in immune system

Immune Disorders~Hipersensitivites or Allergies~

- Immune system mistakenly recognizes harmless foreign particles as serious threats

- Launches immune response, which causes allergic symptoms

- Anti-histamines block effect of histamines and bring relief to allergy sufferers

Aquired Immune Deficiency Syndrome

Caused by the Human Immunodeficiency Virus

Specifically targets and kills T-cells

- The HIV virus lowered immune system

- With immune system shutted down, common diseases that immune system normally could defeat become life-threatening

- No symptoms for several months all the way up to 10 years

AIDS

Transmitted by sexual contact, blood transfusions, contaminated needles

As of 2007, it affects an estimated 33.2 million people

Thank you very much….

Murphy K, Travers P, Walport M, Janeway’sImmunobiology, 7th ed

Abbas AK dan Lichtman AH, Pillai S, Cellular & Molecular Immnunology, 6th ed

Roitt, IM., Delves, PJ, Roitt’s Essential Immunology

Burmester, Colour Atlas of Immunology

References