Introduction

of

Immunology
 Immunology

• Immunity : means protection against infections

• Immune system: collection of cells and molecules

that defend us against microbes

• Immune deficiencies → infections

• Immune excesses → autoimmune diseases

 Immunology Overview
• Types of immunity: Innate and Adaptive
Immunity
• 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
Innate and Adaptive Immunity
 Innate (Natural) Immunity

• Always present (innate); doesn’t change over time

• First line of defense

• Major components:
• Epithelial barriers (skin, GI, respiratory)
• NK cells
• Complement
 Adaptive (Acquired) Immunity

• 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)
 Cells and Tissues of the Immune System
• Lymphocytes
• Antigen-presenting cells
• Effector cells
• Lymphoid tissues
White blood cells
 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!
 T- lymphocytes
• 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
The T-Cell Receptor
The T-Cell Receptor

T cell
 T- lymphocytes
 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
CD8+ T cells surrounding tumor cell
MHC (Major Histo-Compatipility) complex
• 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)
 class II MHC genes class III MHC genes class I MHC genes

class II MHC molecule class I MHC molecule

 Class I MHC molecules

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

viral antigens) to CD8+ T cells.

• Present on all nucleated cells!

 Class II MHC molecules

• Display extracellular antigens (e.g., bacterial

antigens the cell has eaten) to CD4+ T cells

• Present mainly on antigen presenting cells, like

macrophages!
 B - lymphocytes
• 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 (don’t have to be bound to

MHCs or displayed by other cells to be recognized!)
The B-Cell Receptor
 Natural Killer Cells

• Belong to innate immunity system

• Main job: recognize and kill damaged or infected

cells

• Antigens don’t have to be bound to MHCs or

displayed by other cells!
Natural killer cell
Natural killer cell (top) killing infected cell (bottom)
 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 T
cells, which tell macrophages to kill microbe
• B- cells present antigens to helper T cells, which tell B
cells to make antibodies
dendritic cells APCs
 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)
 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
 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
 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
 Cell-mediated immunity
How does the process work?
• T cells are activated by antigen and co-stimulators in
lymph nodes…

• …then they proliferate and differentiate into effector

cells 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

Cell-5Mediated Immunity
 What are cytokines?
• 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 γ

 Types of effector T cells
• 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 to
secrete 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.
Cell-Mediated Immunity
 Humoral immunity
How does the process work?

• 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.

Plasma cell
 What is an antibody?
• Y-shaped glycoprotein
• 2 light chains
• 2 heavy chains
• Constant regions of heavy chain form the
Fc fragment
• binds to APCs
• defines isotype (immunoglobulin
class: IgA, IgE, etc.)
• Variable regions of both chains form the
Fab fragments
• binds to antigen
• defines idiotype
 What do antibodies do?

• Bind to – and “neutralize” – microbes, so they can’t

infect cells.

• Coat (“opsonize”) microbes, making them tasty to

macrophages and neutrophils (which have receptors
for the Fc portion of IgG!

• Activate complement.
 The complement

• It’s 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,
Humoral Immunity
 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 naïve cells
• vaccines depend on these cells
Summary of the Adaptive Immune Response
 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.

 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.
 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.

 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.

Fish mouth Mitral stenosis:
 Asthma
• Hypersensitivity – Allergy , Type I

• Narrowing of airways of lungs - Bronchi

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

• Inflammation of airways – Bronchitis.

• Causes: Genetic, Environmental, Race, Age.

• High in industrial cities

• Increasing incidence in smokers

Pathogenesis - Atopic Asthma:
Asthma Mechanism:

• Allergy
• Inflammation Of Bronchi
• Obstruction
• Mucous Plugs
 INFLAMMATION
INDUCERS
Allergens,pollutants
Airway
Hyperresponsiveness
Genetic*

TRIGGERS
Exercise Airflow Limitation
Cold Air, diseases,
 Epidemiology/pathology

Normal Asthma

Barnes PJ
Lung in Asthma with Mucous plugs
Mucous plug in asthma:
Asthma Microscopic Pathology

Obstructed
Inflammed
Bronchi
 Systemic Lupus Erythromatosis (SLE)

• Typical patient: young woman with butterfly rash

• Symptoms unpredictable (relapsing/remitting)

• Multisystem (skin, kidneys, joints, heart)

• Antinuclear antibodies
 Etiology
• Autoantibodies!
• Antinuclear Ab present in all patients with SLE... but
found in other autoimmune diseases too
• Anti-RBC, -lymphocyte, -platelet, or –phospholipid
antibodies may be present.
• Underlying cause unclear
• Genetic predisposition…
• …plus triggers (UV radiation, drugs)
What’s so bad about having these autoantibodies?

• 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)
 Clinical presentation of SLE

• Young woman with polyarthritis and a butterfly (or

other) skin rash

• Sensitivity to sunlight

• Headaches, seizures, or psychiatric problems

• Unexplained fever
 Prognosis of SLE

• 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