Introduction to Immunology

Science of Immunity How we are Protected

Dr.T.V.Rao MD

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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Dr.T.V.Rao MD

Dr.T.V.Rao MD

Immunology
Contains Basic science Clinical Application Host defense reactions to foreign Antigen Substance is not self Antigen recognizing Cell Mediated Host defense functions
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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 Dr.T.V.Rao MD 6 and molecules of the immune system

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)

Jenner - Smallpox vaccine

Noticed that milkmaids 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

Emil von Behring

S. Kitasato

1880s- 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?

Elie Metchnikoff

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Dr.T.V.Rao MD

Louis Pasteur watching as Joseph Meister receives attenuated rabies vaccine (1885)

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Subjects In Immunology
Cell mediated host defense functions Antibody related defense mechanisms Hypersensitivity reactions ( Including Allergy ) Auto Immunity Immunodeficiency Transplantation
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Protect against pathogens

Eliminate damaged or malignant cells

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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 Dr.T.V.Rao MD 15 one cell determines one antigenic determinant

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 longlived memory to provide protection upon re-infection
Second line of defense Generation of Ag-specific effector cells Early (4-96 hours) Late (>96 hours)Dr.T.V.Rao MD

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THE EVOLUTION OF IMMUNITY

Immunity
Non-specific Immediate onset Specific Delay onset

Innate immunity

Acquired immunity

Humoral Immune Response

Antibodies production

Cellular Immune Response

T-cell activation
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Basic classification of Immunity

Designed by 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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The immune system

Immune system
Innate (non-specific) immunity
Anatomic barriers (Skin, mucous membranes) Physiological barriers (temperature, pH) Phagocytic Barriers (cells that eat invaders) Inflammatory barriers (redness, swelling, heat and pain)

Adaptive (specific) immunity

Antigen specificity Diversity Immunological memory Self/nonself recognition

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Innate, Surface Defenses

Skin
physical barrier to microbes Keratin resistant to most bacterial enzymes & toxins secretions are acidic pH 3-5

Mucosa
physical barrier & produces a variety of protective chemicals

Gastric mucosa
very acidic & produces proteolytic enzymes

Saliva & lacrimal fluid contain lysozyme Mucous

traps bacteria & moves them away from epithelial surface

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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

It is Dependent on
Species Race ( Racial ) Individual

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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 Dr.T.V.Rao MD

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Immunity In Adults
Polio infection , and Chickenpox highly severe in adults. Enlargement of prostate lead to UTI
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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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Nutrition Some protection in some diseases

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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
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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 Dr.T.V.Rao MD pyogenic infections

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 Cilia in Respiratory tract Propel the foreign particles

Respiratory secretion contain
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Oral Cavity
Saliva Stomach HCl Large intestine large number of bacteria
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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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Innate, Internal Defenses

Phagocytes
Macrophages: derived from monocytes
Free Macrophages: roam through tissues Fixed Macrophages: Kupffer cells (liver) & microglia (brain) Ingest cellular debris, foreign material, bacteria, fungi

Neutrophils: ingest pathogens Eosinophils: weakly phagocytic of pathogens. Attack parasites (degranulation) Mast Cells: phagocytic of various bacteria

Antibacterial Substances
May be present Blood as Complement Antibacterial substances in Blood Betalysin, Leukin Lactoperoxidase 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 tumour 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 Bacteroides make up a large percentage of the inhabitants. These organisms contribute to our existence in Dr.T.V.Rao MD 47 several ways

Other Normal Flora

Streptococcus and Bacteroides 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. Bacteroides) 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

Metchnikoff 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, chemokine's, complement) Systemic response- fever, acute-phase proteins C-reactive protein

Interferon and Function

Anti-Viral Interferons
IFN and IFN made by virusinfected 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
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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.
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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
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Plasma cell (Derived from B-lymphocyte, 72 produces antibodies)

Cell-mediated immune response

1.T-cell
recognizes peptide antigen on macrophage in association with major histocompatibility 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 Dr.T.V.Rao MD kill infected cells

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Primary response

Cell mediated immune 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 77

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
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 Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World

Email [email protected]

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