DEPARTMENT OF MICROBIOLOGY

(II B.Sc Microbiology )

Course Title :IMMUNOLOGY

Course CODE: 18BSU02
Unit - I (Class – 02)
Introduction to cytokines and its properties

1
SNAP TALK
NEWS READING
ATTENDANCE
 TOPIC
Innate Immune Response And Its Role In
Protection

5
 CONTENTS
• Immune system
• Innate vs adaptive
• Innate
• Defenses
• Protection
 Immune System
• functional system
rather than organ
system
– Hematopoetic
– Vasculature
– Lymphatic

Fig 21.1
 Innate vs. Adaptive Immune System –
Introduction
• Innate: structural defenses; responds to
nonspecific foreign substances
– First line: external surface epithelium & membranes
– Second line: inflammatory processes – antimicrobial
proteins, phagocytes, etc.

Fig 21.1
 Innate
immunity
 Barriers in innate immunity
• Physical barriers and Chemical barriers.
• https://www.youtube.com/watch?v=4fxtyWM
npj8
•
 Innate vs. Adaptive Immune System –
Introduction
• Adaptive: responds to specific foreign substances

Fig 21.1

• Innate & adaptive mechanisms work together

 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
 Innate, Internal Defenses
• Based on recognition of surface carbohydrates
(glycocalyx)
– Glycocalyx is recognized as “self” or “non-self”

Figure 3.3
 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
 Innate, Internal Defenses
• Phagocytic mechanisms:
– Adherence: cell binds to invader
• Aided by opsonization (a chemical process that enhances binding
via complement & antibodies)

– Ingestion: formation of phagolysosomes

• Respiratory Bursts: merge phagosome with lysosome & flood
phagolysosome with free radicals (macrophage)
• Defensins: proteins that crystallize out of solution & pierce
pathogen membranes (neutrophils)
Mechanism of Phagocytosis

Figure 21.2
 Innate, Internal Defenses
• Natural Killer Cells:
– Small population of large granular lymphocytes
– Non specific for “non-self”
– Not phagocytic: attack is by release of perforins that
perforate the target cell plasma membrane.
• Shortly after perforation the target nucleus disintegrates.
– Release chemicals that enhance the inflammatory
response
Innate, Internal Defenses: Inflammation

• tissue response to injury

• Triggered by injury – trauma, heat, chemical
irritation, infection, etc.
• Beneficial effects
– Prevents spread of injury
– Disposes of cellular debris & pathogens
– Promotes repair
Innate, Internal Defenses: Inflammation

• cardinal signs of inflammation

– Redness
– Heat
– Swelling
– Pain
– (functional impairment Rigor)
Innate, Internal Defenses: Inflammation

• Inflammatory response: signs are associated

with vasodilation & increased vascular
permeability
– Dilation: redness, heat
– Permeability: edema, (increased pressure) pain
– Pain also associated with bacterial toxins &
some mediators (kinins, PGs)
Innate, Internal Defenses: Inflammatory
Response
• Mechanisms causing vasodilation & vascular
permeability
– Injured cells release inflammatory mediators
• Histamines
• Kinins
• Prostaglandins
• Complement
• Cytokines (also activated by receptors on macrophages in
response to microbial glycocalyx)
Innate, Internal Defenses: Inflammatory
Response
• Edema
– Dilutes harmful substances
– Provides nutrients (& O2) for repair
– Enhances entry of clotting protein
• Epithelial breaches also stimulate -defensin
release from epithelial cells
 Events in
Inflammation

Figure 21.3
Innate, Internal Defenses: Inflammatory
Response
• Phagocyte mobilization: infiltration of damaged
area by neutrophils & macrophages
Innate, Internal Defenses: Inflammatory
Response
• Leukocytosis: leukocytosis inducing factors
released by injured cells promote rapid release of
WBCs from marrow
• Margination: increased vascular permeability
causes decreased fluid in vessels; blood flow
slows & neutrophils are able to move to vessel
margins. Here endothelial markers (CAMs) allow
neutrophils to cling to vessel walls (pavementing).
Innate, Internal Defenses: Inflammatory
Response
• Diapedesis: neutrophils migrate through capillary
walls
• Chemotaxis – inflammatory chemicals attract
neutrophils to move up the chemical concentration
gradient (neutrophils respond first)
• As the process continues, monocytes diapedes into
the area & become macrophages. With chronic
inflammation, macrophages predominate
Inflammatory Response:
Phagocytic Mobilization

Figure 21.4
Innate, Internal Defenses: Inflammatory
Response
• Macrophages clean up cellular debris & pathogens
• If pathogens were associated with the injury,
activation of the complement cascade occurs &
elements of adaptive immunity join the process
 Innate, Internal Defenses
• Viral replication – (viruses lack metabolic
processes) Viruses release nucleic acid (RNA or
DNA) into cytoplasm. The information on the
nucleic acid is incorporated into the cell’s DNA.
Normal cellular mechanisms then produce viral
structural components. Multiple new viral
particles are produced & released from the cell
(sometimes killing the cell)
 Innate, Internal Defenses
• Antiviral proteins: interferon & complement
• Interferon: some cells produce & release
interferons (IFNs) when invaded by virus
• Released interferons stimulate nearby cells to
produce proteins (PKR) that interfere with viral
replication by disrupting protein synthesis & the
ribosome
• Not virus specific.
Interferon (IFN)

Figure 21.5
 Innate, Internal Defenses
• Complement – a group of plasma proteins (20) that
are activated in the presence of foreign substances
• Complement activation enhances & amplifies
inflammation
• Bacteria & some other cell types are lysed by
complement activation
• Complement activation enhances both innate &
adaptive defenses
 Innate, Internal Defenses
• Complement activation pathways
– Classical pathway: requires antibodies
• Antibodies bind to target (antigen)
• Complement protein C1 binds to the antibody-
antigen complex (complement fixation)
– Alternative pathway: complement factors interact with
microorganism glycocalyx
• Both pathways lead to a cascade of protein activation,
leading to activation of C3
 Innate, Internal Defenses
• C3 is the start of the; Final Common Pathway
– C3 cleaves to form C3a & C3b
– C3a (& C5a) enhance inflammation by increasing
histamine release, increasing vascular permeability &
stimulating chemotaxis
– C3b coats bacterial membrane supplying adhesion
points (opsonization)
– C3b initiates the cascade forming the membrane attack
complex (MAC)
– The MAC forms a hole in the cell membrane &
enhances Ca2+ influx  cell lysis
Innate, Internal
Defenses;
Complement

Figure 21.6
 Innate, Internal Defenses
• C-reactive proteins (CRP) produced by the liver in
response to inflammatory molecules can activate
the classical pathway by binding to membrane &
activating C1. Also participates in opsonization.

• Fever – a systemic response to infection.

Leukocytes & macrophages release pyrogens that
raise the hypothalamic “set point” for temperature
 KEYWORDS
• Histamines
• Kinins
• Prostaglandins
• Complement
• Cytokine
POINTS TO PONDER????????

• INNATE IMMUNE SYSTEM

• TYPES OF DEFENSES
• ROLE OF PROTECTION THROUGH
DEFENSES
MCQ’S