7- Introduction of Immunology

8/8/2019 7- Introduction of Immunology

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Introduction

of

Immunology


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Immunology

Immunity : means protection against infections

Immune system: collection of cells and moleculesthat defend us against microbes

Immune deficiencies infections

Immune excesses autoimmune diseases


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Immunology Overview

Types of immunity: Innate and AdaptiveImmunity

Cells and Tissues of the Immune System

Lymphocytes Effector cells

Antigen-presenting cells Lymphoid tissues

Normal Immune Responses

The innate immune response

Capturing and displaying antigens Cell-mediated immunity

Humoral immunity

Immunologic memory


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Innate and Adaptive Immunity


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Innate (Natural) Immunity

Always present (innate); doesnt change over time

First line of defense

Major components:

Epithelial barriers (skin, GI, respiratory) NK cells

Complement


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Second line of defense

More specific (adaptive) and powerful than innate

Major components:

Lymphocytes

Lymphocyte products

Two types of adaptive immunity: Humoral immunity (mediated by antibodies)

Cellular immunity (mediated by T cells)

Adaptive (Acquired) Immunity


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Cells and Tissues of the Immune System

Lymphocytes

Antigen-presenting cells

Effector cells

Lymphoid tissues


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Lymphocytes

Present in blood and in lymphoid organs

Groups

T-lymphocytes (grow up in thymus)

B-lymphocytes (grow up in bone marrow)

Each one has receptors for a specific antigen

Recognize millions of different antigens!


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Live in blood, bone marrow, lymphoid tissues

Two basic functions:

kill stuff

help other cells do their jobs

T-cell receptor (TCR) complex recognizes antigens

binds antigen

sends signals to the T cell

Antigens must be:

displayed by other cells and bound to an MHC(Major Histo-Compatipility) receptor

T- lymphocytes


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The T-Cell Receptor


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The T-Cell Receptor

T cell


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Helper T cells

CD4+ (and CD8-)

help B-cells make antibodies

help macrophages

decreased in patients with AIDS

Cytotoxic T cells

CD8+ (and CD4-)

kill virus-infected cells and tumor cells

T- lymphocytes


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CD8+ T cells surrounding tumor cell


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Collection of genes on chromosome 6

Three types: class I, class II, class III

Highly polymorphic!

Gene products:

class I molecules

class II molecules

class III molecules (and other stuff)

MHC (Major Histo-Compatipility) complex


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class I MHC moleculeclass II MHC molecule

class II MHC genes class I MHC genesclass III MHC genes


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Display antigens from within the cell (e.g.,

viral antigens) to CD8+ T cells.

Present on all nucleated cells!

Class I MHC molecules


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Display extracellular antigens (e.g., bacterial

antigens the cell has eaten) to CD4+ T cells

Present mainly on antigen presenting cells, like

macrophages!

Class II MHC molecules


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Live in blood, bone marrow, lymphoid tissues

Basic function: make antibodies (Immunoglobulins)

B-cell receptor complex recognizes antigens

binds antigen

sends signals to T cells

Antigens can be free and circulating (dont have to be bound to

MHCs or displayed by other cells to be recognized!)

B - lymphocytes


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The B-Cell Receptor


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Belong to innate immunity system

Main job: recognize and kill damaged or infected

cells

Antigens dont have to be bound to MHCs or

displayed by other cells!

Natural Killer Cells


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Natural killer cell


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Natural killer cell (top) killing infected cell (bottom)


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Antigen-presenting cells

Main job: catch antigens and display them to lymphocytes

Dendritic cells

Have fine cytoplasmic projections

Present all over body: skin, lymph nodes, other organs

Capture microbial antigens, display to B and T cells

Other APCs

Macrophages eat microbe and present antigens to Tcells, which tell macrophages to kill microbe

B- cells present antigens to helper T cells, which tell B

cells to make antibodies


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dendritic cells APCs


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Effector cells

These cells carry out the ultimate immune system function:eliminate infection.

Types of effector cells

NK cells

Plasma cells

T cells (both CD4+ and CD8+)

Macrophages

Other leukocytes (e.g., neutrophils)


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Lymphoid tissues

Lymphocytes grow up in primary organs, then travel

to secondary organs, searching for antigens.

Primary organs

Thymus bone marrow

Secondary organs

lymph nodes spleen

Mucosal and Cutaneous lymphoid tissues


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The Innate Immune Response

Main barriers: skin, mucosa

If microbes go through epithelium, they encounter

innate immune system

What happens in the innate immune system?

Phagocytes eat microbes, kill them

Cytokines are released

Complement is activated

The adaptive immune system is activated


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Capturing and displaying antigens

Dendritic cells in epithelium capture microbe antigens,transport them to lymph nodes

APCs in lymph nodes eat antigens, display them to T-cells

B-cells in lymph nodes also recognize antigens

Antigens and molecules produced during innate immune

response trigger proliferation and differentiation of B and T

cells


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Cell-mediated immunity

T cells are activated by antigen and co-stimulators in

lymph nodes

then they proliferate and differentiate into effectorcells that go find the antigen.

CD4+ T cells help macrophages eat microbes

CD8+ T cells kill infected cells directly

All these steps are dependent upon cytokines

How does the process work?


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Cell-5Mediated Immunity


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Polypeptides that do lots of different things:

help leukocytes grow and differentiate

activate T cells, B cells and macrophages

help leukocytes communicate

recruit neutrophils

Made by lymphocytes and macrophages

Examples: TNF, the interleukins, interferon

What are cytokines?


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CD4+ T cells differentiate into two kinds of effector

cells:

TH1 cells (activate macrophages, cause B cells to

secrete Ab)

TH2 cells (activate eosinophils, cause B cells tosecrete IgE)

These cells go to the site of infection, and with the

help of macrophages and cytokines, do their job.

CD8+ T cells differentiate into cytotoxic T cells

These cells kill cells that have microbes in their

cytoplasm.

Types of effector T cells

C ll M di t d I it


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Cell-Mediated Immunity


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Humoral immunity

B cells get activated by exposure to antigens

(sometimes with the help of CD4+ T cells)

B cells differentiate into plasma cells (that make

antibodies)

The antibodies do nasty things to microbes.

How does the process work?


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Plasma cell


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Y-shaped glycoprotein

2 light chains 2 heavy chains

Constant regions of heavy chain form theFc fragment

binds to APCs defines isotype (immunoglobulin

class: IgA, IgE, etc.)

Variable regions of both chains form theFab fragments

binds to antigen

defines idiotype

What is an antibody?


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What do antibodies do?

Bind to and neutralize microbes, so they cantinfect cells.

Coat (opsonize) microbes, making them tasty tomacrophages and neutrophils (which have receptors

for the Fc portion of IgG!

Activate complement.


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The complement

Its a bunch of proteins that poke holes in cells. Consists of about 20 plasma proteins (C1, C2, etc.)

Can be activated in a few different ways

by antigen-antibody complexes

by bacterial Lipo-proteins

End results:

cell lysis

chemotaxis

opsonization

Complement


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Complement,


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Humoral Immunity


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Immunologic memory

Most effector lymphocytes die after killing the

microbes.

A few memory cells live on for years.

expanded pool of antigen-specific lymphocytes

respond faster, better than nave cells

vaccines depend on these cells


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Summary of the Adaptive Immune Response


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Immune Disorders:

Immunodeficiency disorders

AIDS, antibody deficiency

Hypersensitivity Disorders (allergy)

Type-I (IgE), Type-II (IgG), Type-III

(Immunecomplex), Type-IV (Cell mediated).

Autoimmune disorders

SLE, Rhematoid, Rheumatic fever.


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Introduction

Immune response against self antigen resulting in Tissue

damage.

Single organ or systemic multi organ.

Common in females.

Normally immune system is tolerant to self antigens

(learns during fetal development).

Autoimmune disorders result from Defective tolerance,

cross reacting antibodies or antigenic mimicry.


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Rheumatic fever:

Autoimmune disorder.

Group A, streptococcal pharyngitis.

Antibody cross react with connective tissue in

susceptible individuals*

Inflammation - T lymphocytes, macrophages.

Affected organs: Heart, skin, brain & joints.

M h l


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Morphology:

Acute Rheumatic Fever

Acute Inflammatory Phase

Heart: Pancarditis

Skin: Erythema Marginatum

CNS: Sydenham Chorea

Joints: Migratory polyarthritis

Chronic Rheumatic Fever

Deforming fibrotic valvular disease.


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Fish mouth Mitral stenosis:


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Asthma

HypersensitivityAllergy , Type I

Narrowing of airways of lungs - Bronchi

Allergens in the air will stimulate mast cell - IgE antibody.

Inflammation of airwaysBronchitis.

Causes: Genetic, Environmental, Race, Age.

High in industrial cities

Increasing incidence in smokers


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Pathogenesis - Atopic Asthma:


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Asthma Mechanism:

Allergy

Inflammation Of Bronchi

Obstruction

Mucous Plugs


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INFLAMMATION

TRIGGERSExercise

Cold Air, diseases,

AirwayHyperresponsivenessGenetic*

INDUCERS

Allergens,pollutants

Airflow Limitation


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AsthmaNormal


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Lung in Asthma with Mucous plugs


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Mucous plug in asthma:


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Asthma Microscopic Pathology

Obstructed

Inflammed

Bronchi


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Systemic Lupus Erythromatosis (SLE)

Typical patient: young woman with butterfly rash

Symptoms unpredictable (relapsing/remitting)

Multisystem (skin, kidneys, joints, heart)

Antinuclear antibodies


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Autoantibodies!

Antinuclear Ab present in all patients with SLE... but

found in other autoimmune diseases too

Anti-RBC, -lymphocyte, -platelet, orphospholipidantibodies may be present.

Underlying cause unclear

Genetic predisposition

plus triggers (UV radiation, drugs)

Etiology


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They cause tissue injury!

Form immune complexes

Cause destruction, phagocytosis of cells

Multi-system effects:

Kidney (renal failure)

Skin (butterfly rash)

CNS (focal neurologic deficits) Joints (arthritis)

Heart (pericarditis, endocarditis)

Whats so bad about having these autoantibodies?


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Young woman with polyarthritis and a butterfly (or

other) skin rash

Sensitivity to sunlight

Headaches, seizures, or psychiatric problems

Unexplained fever

Clinical presentation of SLE


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Variable! Some have few symptoms, rare patients die within

months.

Most patients: relapses/remissions over many years.

Acute flare-ups controlled with steroids

80% 10-year survival

Most common cause of death: renal failure

Prognosis of SLE

7- Introduction of Immunology

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