Immunology Basics Dr.T.V.Rao MD

1 Dr.T.V.Rao MD

Immunology

• Immunology is the study of our protection from foreign macromolecules or invading organisms and our responses to them.

• Host – e.g. me!!!!

• Foreign macromolecule, antigen – e.g. virus protein, worm, parasite (Everything that should not be in my body)

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Immunology

• Contains Basic science

• Clinical Application

Host defense reactions to foreign Antigen

Substance is not self

Antigen recognizing Cell Mediated

Host defense functions 4 Dr.T.V.Rao MD

Definitions • Immune system = cells, tissues, and

molecules that mediate resistance to

infections

• Immunology = study of structure and

function of the immune system

• Immunity = resistance of a host to pathogens

and their toxic effects

• Immune response = collective and coordinated

response to the introduction of foreign

substances in an individual mediated by the cells

and molecules of the immune system 5 Dr.T.V.Rao MD

Role of the immune system

• Defense against microbes

• Defense against the growth of tumor

cells

– kills the growth of tumor cells

• Homeostasis

– destruction of abnormal or dead cells

(e.g. dead red or white blood cells,

antigen-antibody complex)

Bacteria Tubercule bacillus

Staphylococci

Fungi Candida albicans

Viruses Influenza

Polio mellitus

Parasites Tapeworms

Malaria

Helminths

Role of the immune system

is to protect from:

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March towards modern

times…

1718- Lady Montague became aware of a practice, called variolation or inoculation, and introduced it to Britain after first having her own children treated.

1774 – Benjamin Justy 1776- Geo. Washington

1798 –Edward Jenner noticed immunity bestowed to milkmaids – injected fluid from cowpox blister into skin of patient (orphan or prisoner)

1989- WHO announced smallpox was eradicated from the world

Lady Mary Wortley Montague (1689-1762)

War on smallpox…

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Jenner - Smallpox vaccine

• Noticed that milkmades that had contracted cowpox did NOT get smallpox

• Test on an 8 year old boy, injected cowpox into him (NOT very nice……)

• Follwed by exposure to smallpox

• Vaccine was invented (latin vacca means ”cow”)

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First insights into mechanics of immunity…

1880’s- Metchnikoff discovered phagocytic cells that ingest microbes and particles

cells conferred immunity

1890- von Behring and Kitasato discovered blood sera could transfer immunity

liquid of blood conferred immunity

Q: Which confers immunity… cells or serum?

Emil von Behring

S. Kitasato

Elie Metchnikoff 10 Dr.T.V.Rao MD

Subjects In Immunology

• Cell mediated host defense functions

• Antibody related defense mechanisms

• Hypersensitivity reactions ( Including Allergy )

• Auto Immunity

• Immunodeficiency

• Transplantation

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What is Response to Infection

• Immunity can

be Innate ( Nonadapative )

• Adaptive -

Acquired.

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Immunology is a Complex

Subject

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Two types of immunity

1. Innate (non-adaptive)

– first line of immune response

– relies on mechanisms that exist before

infection

2. Acquired (adaptive)

– Second line of response (if innate fails)

– relies on mechanisms that adapt after

infection

– handled by T- and B- lymphocytes

– one cell determines one antigenic determinant 14 Dr.T.V.Rao MD

Distinction Between Innate and

Adaptive Immune Responses

• Innate immunity is non-adaptive and helps to initiate adaptive immune responses (= first line of defense – but LIMITED) – Immediate (0-4 hours)

• Adaptive immunity provides a more universal line of defense and has long-lived memory to provide protection upon re-infection – Second line of defense

– Generation of Ag-specific effector cells

– Early (4-96 hours)

– Late (>96 hours) 15 Dr.T.V.Rao MD

THE EVOLUTION OF

IMMUNITY

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Immunity

Innate immunity Acquired immunity

Non-specific Specific Immediate onset Delay onset

Humoral

Immune Response

Cellular

Immune Response

Antibodies production T-cell activation Dr.T.V.Rao MD

The immune system

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Immune system

•Anatomic barriers (Skin, mucous membranes) •Physiological barriers (temperature, pH) •Phagocytic Barriers (cells that eat invaders) •Inflammatory barriers (redness, swelling, heat and pain)

•Antigen specificity •Diversity •Immunological memory

•Self/nonself recognition

Innate (non-specific) immunity Adaptive (specific) immunity

Dr.T.V.Rao MD

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Different types of Immunity

A - Non specific

1 Species

2 Racial

3 Individual

B Specific

1.Species

2 Racial

3 Individual

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Types of Immunity

Acquired Immunity A Active

Natural

Artificial

B Passive

Natural

Artificial

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Resistance to Infectious Disease

• Innate immunity (nonspecific

resistance) protects us against all

pathogens: “over-the-counter

defenses”

• Adaptive immunity (specific

resistance) is defenses against

specific pathogens: “prescription

defenses”

Innate Immunity

Innate Immunity is resistance that is preexisting and is not acquired through contact with a foreign substance known as antigen

Individual has innate Immunity by genetic or constitutional Make Up

Non related to prior contact with Microorganisms or Immunization

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Physical and Chemical Barriers

• Skin, mucus membranes

• Cilia, mucus, reflexes

• pH, lysozyme, fatty

acids, defensins

• Normal flora

• Genetic resistance

– species differences

– individual differences

Species and Immunity

• Immunity refers to total resistance to a Pathogen by all members of the species

• Eg Human do not get plant diseases

• Humans do not get some animal diseases

• Dependent on Human configuration physiology ? Biochemical difference

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Race - Immunity

• Genetic resistance

Plasmodium

falciparum malaria

resistance in Africa

• In sickle cell

anemia immune to

malaria

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Individual - Immunity

• Twins homozygous

twins exhibit similar

resistance

• Susceptibility similar

in Leprosy

• Tuberculosis similar

resistance

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Factors Influencing Innate Immunity

• Placenta prevent

infection

• But still can

infected with

Toxoplasmosis,

Rubella, CMV and

Herpes infection.

• Can produce

congenital

malformations

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Hormonal Influence on Immunity

• Diabetes mellitus

• Hypothyroidism in

adults

• Adrenal

dysfunction

• Stress increases

steroids

predisposes to

Infection

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Mechanism's of Immunity

• Epithelial surfaces

Skin and Epithelial surfaces cover the

body and protects the individuals

Healthy skin poses bactericidal

influence, salt, drying sweat , Long

fatty acids

Wet hand predisposes to Mycotic and

pyogenic infections 29 Dr.T.V.Rao MD

Mucous Membranes

• Respiratory

tract

Shape of

Nose,

Nasal

orifice

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Mechanism's of Immunity

• Epithelial surfaces

Skin and Epithelial surfaces cover

the body and protects the

individuals

Healthy skin poses bactericidal

influence, salt, drying sweat , Long

fatty acids

Wet hand predisposes to Mycotic and

pyogenic infections 31 Dr.T.V.Rao MD

Respiratory tract barrier to

prevent Infections

• Cilia in

Respiratory

tract

• Propel the

foreign

particles

• Respiratory

secretion contain 32 Dr.T

.V.Rao MD

Oral Cavity

• Saliva

• Stomach HCl

• Large

intestine large

number of

bacteria 33 Dr.T.V.Rao MD

Conjunctiva

• Contain lachrymal

secretions

• Tears contains

antibacterial

substances

• Lysozyme present

except in CSF,

Sweat, Urine

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Other Mechanisms

• Flushing action of urination

drives out Microbes in the

Urethra

• Spermine in Semen

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Antibacterial Substances

• May be present Blood as

Complement

• Antibacterial substances in Blood

Betalysin,

Leukin

Lacto peroxidase in Milk

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Interferon's in Immunity

• Interferon's (IFNs) are natural proteins produced by the cells of the immune system of most vertebrates in response to challenges by foreign agents such as viruses, parasites and tumor cells. Interferon's belong to the large class of glycoproteins known as cytokines

• Interferon's are more useful than Antibodies

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Microbial Antagonists Normal flora Help us

• Normal Microbial flora

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Normal flora Helps Us • we harbour near 1014 bacteria. This group

of organisms, traditionally referred to as

"normal flora" (although they are not

plants) is composed of a fairly stable set of

genera, mostly anaerobes. While each

person has a relatively unique set of

normal flora, members of the

Streptococcus and Bactericides make up a

large percentage of the inhabitants. These

organisms contribute to our existence in

several ways’ 39 Dr.T.V.Rao MD

Other Normal Flora

• Streptococcus and Bactericides make up a

large percentage of the inhabitants. These

organisms contribute to our existence in

several ways’

• Help us by competing with pathogens

such as Salmonella • Help us by providing vitamins or eliminating toxins (e.g.

Bactericides)

• Harm us by promoting disease (e.g. dental caries)

• Cause neither help nor harm (e.g. "commensals").

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Normal Bacterial Flora of

Conjunctiva

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Cellular Factors in Innate Immunity

• Metichinkoff 1883

• Cells called as Phagocytic cells

Microphages,

Macrophages

Microphages Polymorph nuclear neutrophils

Macrophages Histiocytes wandering Amoeboid cells

Monocytes in Blood

Cells in Reticuloendothelial System

These cells remove foreign particles

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Phagocytes

• Phagocytes = eating cells

–Neutrophils (PMNs) are present in

the highest numbers in blood

–Macrophages (“big eaters”) in the

tissues encounter the pathogen first

• Secrete cytokines --->

inflammation, systemic responses

How Phagocytes act

• Phagocytic cells

reach the site o

Inflammation

• Attracted by

Chemo tactic

substances

• Ingest particle

material

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Cellular and Inflammatory

Components of Innate Immunity

• Cellular

–Phagocytic

cells

• Inflammatory

–Vasodilation

–Capillary

permeability

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Phagocytosis

Capsule In Innate immunity

• Some bacteria have capsules

• Streptococcus pneumonia

• Klebsiella pneumonia

• Bacteria with capsules are not ingested by Phagocytes unless in the presence of opsonins

• Bacteria are fixed against fixed surface such as alveoli

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Mechanism of Phagocytosis

• Bacteria are

phagocycosed into

vacuole (Phagosome)

• Forms

phagolysosome

• Lytic enzymes

destroy the Bacteria

• Brucella and Leprosy

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Natural Killer cells

NK cells

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Mediators of inflammation Vasodilation, smooth muscle contraction

Increased vascular permeability

Edema, extravasation

(histamines, prostaglandins, kinins)

Extravasation

Chemo taxis

(cytokines, chemokines, complement)

Systemic response- fever, acute-phase

proteins

C-reactive protein

Interferon and Function

Anti-Viral Interferon's

• IFN and IFN made by virus-

infected cells

• Not virus-specific

• Bind neighboring host cells

and induce synthesis of anti-

viral proteins to block virus

replication

Natural Killer Cells

• All nucleated cells in body have membrane MHC = tissue typing antigens

• In virus-infected cells, MHC is reduced in amount or contains virus peptides

• NK cells recognize this ‘altered’ MHC and kill virus-infected cells (also tumor cells)

Role of Natural killer Cells

• Natural killer cells (or NK cells) are a

type of cytotoxic lymphocyte that

constitute a major component of the Innate

immune system. NK cells play a major role

in the rejection of tumours and cells

infected by viruses. The cells kill by

releasing small cytoplasmic granules of

proteins called perforin and granzyme that

cause the target cell to die by apoptosis

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Inflammation

• Tissue Injury

• Irritation

• Arterioles constrict initially and then

dilate

• Slow the Blood flow and Margi nation

of Leucocytes

• Escape into tissues by diapedesis

and accumulate in large numbers 56 Dr.T.V.Rao MD

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Inflammation

• Outpour plasma,

and dilute the toxic

material

• Produce fibrin

barrier and

localized the

infection

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Fever

• Natural defense

Mechanisms

• Destroy infectious

agents

• Therapeutic –

Trepanoma palladium

• Production of

Interferon's

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Antibacterial substances in

Blood and Tissues

• The complement system possess bacterial

activity and plays role in the bactericidal

activity and destroys the pathogenic

bacteria

• Betalysin – anthrax

• Leukins and Plakins

• Lactic acid found in muscles

• Lacto peroxidase in milk

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Acute Phase proteins too play

a great role in Immunity

• Infection and Injury produces Acute phase proteins

• C- Reactive proteins CRP

• Mann in binding proteins

• CRP activates alternative pathway

• Increases host defenses

• Prevents issue injury

• Repair inflamed lesions. 61 Dr.T.V.Rao MD

Acute Phase proteins

• Infection and Injury produces Acute phase proteins

• C- Reactive proteins CRP

• Mann in binding proteins

• CRP activates alternative pathway

• Increases host defenses

• Prevents issue injury

• Repair inflamed lesions.

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Adaptive immunity:

second line of response

• Based upon resistance acquired during life

• Relies on genetic events and cellular growth

• Responds more slowly, over few days

• Is specific

– each cell responds to a single epitope on an antigen

• Has anamnestic memory

– repeated exposure leads to faster, stronger response

• Leads to clonal expansion

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Adaptive immunity:

mechanisms • Cell-mediated immune response (CMIR)

– T-lymphocytes

– eliminate intracellular microbes that survive

within phagocytes or other infected cells

• Humoral immune response (HIR)

– B-lymphocytes

– mediated by antibodies

– eliminate extra-cellular

microbes and their toxins Plasma cell

(Derived from B-lymphocyte, produces antibodies) 64 Dr.T.V.Rao MD

Cell-mediated immune response

1.T-cell – recognizes peptide

antigen on macrophage

in association with

major histo-

compatibility complex

(MHC) class

– identifies molecules on

cell surfaces

– helps body distinguish

self from non-self

2. T-cell goes into effectors

cells stage that is able to

kill infected cells

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Cell mediated immune

response Primary response

– production of specific clones of effector T cells

and memory clones

– develops in several days

– does not limit the infection

Secondary response

– more pronounced, faster

– more effective at limiting the infection

Example - cytotoxic reactions against intracellular parasites, delayed

hypersensitivity (e.g., Tuberculin test) and allograft rejection

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Humoral immune response 1. B lymphocytes recognize

specific antigens

– proliferate and

differentiate into

antibody-secreting

plasma cells

2. Antibodies bind to specific

antigens on microbes;

destroy microbes via

specific mechanisms

3. Some B lymphocytes

evolve into the resting state

- memory cells

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Antibodies (immunoglobulin's)

•Belong to the gamma-globulin

fraction of serum proteins

•Y-shaped or T-shaped polypeptides

– 2 identical heavy chains

– 2 identical light chains

• All immunoglobulin's are not

antibodies

•Five kinds of antibodies

– IgG, IgM, IgA, IgD, IgE

Measurement of Immunity

• It is not possible to measure the immunity

accurately

• Detection of antibodies

• Detected by agglutination tests,

Precipitation tests, complement fixation HI

ELISA

• Skin Tests, Schick test , Dick Tests

• Tuberculin Test – Delayed Hypersentivity

tests in Tuberculosis Dr.T.V.Rao MD 69

Local Immunity

• Can be produced by Oral Vaccines

• Sabin's vaccine for polio given orally X

Salk will not protect Local Immunity but

produces systemic Immunity

• Locally produced Antibodies IgA protect

the gut from entry of pathogens

• Local immunity antigen protects the

individuals

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Herd Immunity

• This indicates the overall level in the

community and important in control of

infections in the community (HERD )

• When Herd immunity is low epidemics

occur.

• Eradication of communicable diseases

depends on the development of high level

of herd immunity rather than high level of

Individual Immunity Dr.T.V.Rao MD 71

• Programme Created by

Dr.T.V.Rao MD for Medical and

Paramedical Students in the

Developing World

• Email

• doctortvrao@gmail.com

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