Immunology

Immunity
 Immunity
 Learning objectives
 Definitions
 Types of immunity
 Innate immunity
 Immunity
 Micro-organisms are ubiquitous
 In air we breathe, in/on food eat
 Epithelial surfaces (skin, respiratory tract,
gastro-intestinal tract, genitourinary tract) -
continuously exposed to micro-organisms
 Disease occurs when micro-organisms invade
epithelial surfaces
 Inspite of constant exposure - long infection-
free periods - is surprising
 Infections are exception rather than rule.
 Immunity
 Immunity: latin - free of burden. Development of
resistance to a foreign substance or infectious
agent.
 Immune: exempted or protected
 Immune response: series of defensive actions
 Immunology: study of immune responses to antigen
and its biological, physical and chemical aspects.
 Structure & function of immune system
 Immunity to disease
 Hypersensitivity
 Immunization
 Transplantation,
 Tumor immunity
 Immuno-deficiency
 Immunity
 Two categories Innate and Acquired
 Innate (natural) immunity
 non specific resistance (immunity) existing in body

prior to exposure to antigens

 Include physical, chemical and genetic barriers like

epithelial surfaces, cells, proteins, IFN,

complement, lysozyme, inflammation, phagocytosis.
 Acquired immunity
 Development of specific response to agents like

antigens, infections
 that improves on repeated exposure

 Prevents entry of micro-organisms into tissues or once

entered, eliminates them prior to the occurrence of
disease
 Innate Immunity
 Characteristics
 Present from birth.
 Non-specific - acts on many organisms
 Does not become more efficient on
subsequent exposure to same
organisms
 Acute phase response e.g. C reactive
protein, Mannose binding proteins from
liver
 Innate Immunity
 Prevention of entry of organisms
 Non-specific elimination of micro-organism

 Prevention of entry of organisms

 Mechanical barriers at body surfaces, skin, mucous
membranes - disruption leads to infection
 Antibacterial substances in secretions, lysozyme,
lactoferrin, low pH of stomach and vagina
 Prevention of stasis - Peristalsis, Flow of urine,
defecation
 Flushing by secretions
 Flora, mucociliary blanket, nasal hair
 Reflexes of cough, sneezing
Innate Immunity (Natural Barriers)
 Innate Immunity
 Non-specific elimination of micro-
organism
 Phagocytosis - ingestion and killing of
micro-organisms by specialized cells
(phagocytes) e.g. polymorphonuclear
leukocytes (neutrophils) & mononuclear
phagocytes (monocytes, macrophages).
 Opsonization - the process of coating
micro-organisms with proteins to
promote phagocytosis
 Innate Immunity
 Acute phase response
 Plasma proteins produced by liver in response to
IL1 & 6, TNF (Pro-inflammatory cytokines)
 C reactive protein
 Mannose binding lectin MBL
 bind to bacterial surface- activate
complement – kill bacteria
 MBL also act as opsonin
Innate Immunity (Acute Phase Proteins
 Innate Immunity
 Defensins:
 Cationic peptide create pores in
membranes of bacterial. α in neutrophils in
intestines. β in respiratory tract
 Interferons
 Glycoproteins ( cytokines) inhibit growth of

viruses by blocking translation of viral

proteins, bacteria, cancer cells and
protozoa. 3 groups - α, β, γ from
leukocytes, fibroblast, lymphocytes
Innate Immunity (Interferons)
 Innate Immunity
 Inflammation
 Opening up of junctions between
endothelial cells to allow plasma proteins
to escape
 Adhesion of leukocytes to endothelial cells
of post-capillary venule, followed by
emigration of phagocytes into tissues
 Functions of innate immunity
Getting rid of invader
Activation of acquired immunity
 Pattern-recognition receptors”
 Innate arm recognize what is foreign by
these receptors, recognize molecular
pattern present on surface of many
microbes that is not present on human cells
pathogen associated molecular pattern
PAMP (Carbohydrates, Lipids)
 Innate arm recognize self and non-self
proteins.
 ”Pattern-recognition receptors
 Type of receptor activated determine type of
acquired response
 Toll Like Receptors TLR: family of 10 receptors
on surface of macrophages, dendritic and mast
cells. Activate synthesis of Pro-inflammatory
cytokines which initiate immune response
appropriate to type of microbe. E.g. LPS – LPS
binding protein – CD14 on macrophage – TLR-4 –
induce cytokine production
 NOD protein: present in cytoplasm of human cells
recognize a part of peptidoglycan in intracellular
bacteria
 Acquired, Adaptive or Specific
Immunity
 “Specific Immune Response” mounted
after exposure to an agent, improves after
repeated exposure. The responsible cells
have long term memory.
 An immune response must:
 Recognize a micro-organism as foreign (non-
self) as distinct from self.
 Respond by production of specific antibodies
& specific lymphocytes.
 Mediate elimination of micro-organisms
 Acquired, Adaptive or Specific Immunity
 Two Components
 Cell Mediated Immunity
 T Lymphocytes (Helper and Cytotoxic)
 Antibody Mediated Immunity
 Neutralize toxins and viruses
 Opsonize bacteria (Phagocytosis
 3 features
 Diversity
 Long memory
 Specificity
 Acquired, Adaptive or Specific
Immunity
 occurs in response to infection
 The immune system must adapt itself to
previously unseen molecules
 Following recovery from infection with a
particular micro-organism, an individual
is protected against the micro-organism.
 This form of protection is called
“Immunity"
 individual is said to be “Immunized”
against that organism.
Immunity (Response to Infection)
 Acquired, Adaptive or Specific
Immunity
 Active Immunity: The induction of immunity after
contact with foreign antigen e.g. microbial
infection, live or killed vaccines or microbial
products (toxins , toxoids). long term resistance,
Slow onset
 “Passive Immunity” is conferred by preformed
“Antibodies” and “Lymphocytes”. Neutralize
toxins. Maternal antibodies via placenta (IgG)
and milk (IgA). Short term, prompt availability
 Acquired, Adaptive or Specific
Immunity
 The immune system responds to micro-
organisms but not to its own cells
 The system knows that the body has been
infected previously with a particular organism
 Immunological recognition
 Self/non-self discrimination
 Immunological specificity
 Immunological memory
Acquired Immunity (Immunological Memory)
 Innate and Acquired Immunity
 Main Features

Cell-mediated Humoral
immunity Immunity

Macrophages Complement Innate Immunity

Natural Killer Neutrophils
cells
Helper T cells B-cells Acquired
Cytotoxic T cells Plasma cells Immunity
Immunity (Integrated Defense Mechanisms)
 Antigens
 Immunogen: molecules which induce an
immune response
 Antigen: molecules which react with
antibody
 Haptens small univalent molecules not
immunogenic but can react with specific
antibody. They have to combine with carrier
proteins to be immunogenic eg. penicillin,
poison ivy.
 Haptens can not bind with MHC Class II
molecules but carrier protein can
 Antigens
 Antigen antobody reaction is highly specific
 Bind with weak forces such as hydrogen
bonds and vander Waals forces
 The affinity (strength of binding) depends
upon the fit of antigen at binding site and
ability to form more bonds. Affinity increases
with subsequent exposure.
 Features of molecule that
determine Immunogenicity
 Foreignness: non self
 Molecular weight : high above 100000
 Chemical Structural complexity
 Antigenic Determinants (Epitopes): small
chemical groups on antigen molecules, 5
amino acids or sugars multivalent which can
elicit or react with the antibody
 Dosage, Route and Timing of Antigen
Administration
 Effect of age
 New born has poor immune response because
 less effective T cell function
 Maternal antibodies decay over 3-6 months
 IgA in colostrum
 Good response to protein than polysaccharide
antigen
 More infectious diseases
 Immunity declines in old age
 Reduced IgG response to some antigens
 Fewer T cells
 Reduced delayed hypersensitivity
 More autoimmune diseases