introduction

1. Introduction &
Innate immunity

2. Learning Objectives
 Define immunity and its types and innate immunity
 Classify types of immunity according to their function especially innate
immunity
 List the components of immune system
 Discuss the functions of immune system
 Discuss the role of T cells, B cells, natural killer cells, macrophages in immunity
 Discuss the specificity of the immune response and properties, component and
pattern of recognition receptors
 Discuss properties, components & pattern recognition receptors.

3. 1.1. Definition of terms
Immunology
The study of immune system or immunity
the study of all aspects of host defense against
infection and of adverse consequences of immune
responses.
The study of the physiological mechanisms which
enable the body to recognize materials as foreign and
to neutralize, metabolize or eliminate them without
injury to the host tissue.

4. Immunity: State of protection from infectious
diseases OR Defined as resistance to disease
specifically infectious disease.
 Immune system: the collection of cells, tissues
and molecules that mediate resistance to
infections.

5. How do these specific protective
mechanisms originate?
 The process by which these host defenses
originate can be summarized by three actions:
(1) the recognition of the foreign organism by
specific immune cells,
(2) the activation of these immune cells to
produce a specific response (e.g., antibodies),
(3) the response that specifically targets the
organism for destruction.

6. Types of immunity
Immune
System
Innate
(Nonspecific)
Cellular
Components
Humoral
Components
Adaptive
(Specific)
Cell-
Mediated
Humoral
(Ab)

7. Innate immunity
 Innate immunity (also called natural, or native,
immunity) refers to intrinsic mechanisms that are
poised to react immediately, and thus
constitute the first line of defense.
 Mediated by cells and molecules that recognize
products of microbes and dead cells and induce
rapid protective host reactions.

8. Innate immunity: Properties
 Non – specific i.e., same response to the range of
pathogens
 Always present, ready to provide immediate defense
 has no memory i.e., same response after repeated
exposure
 Relies on already formed components
 Based on genetic makeup

9. Innate immunity: Functions
1. Initial most response to microbes
2. Eliminate damaged cells and initiate the process
of tissue repair
3. Stimulates adaptive immune response

10. Innate immunity: Components
 Physical (Epithelial barrier)
 Cellular mechanisms {phagocytic cells (mainly
neutrophils and macrophages), dendritic cells,
natural killer cells etc.}
 Humoral mechanisms {antibodies, complement
proteins, antimicrobial peptides etc.}

11. Lines of defenses in immune system
 Innate defense system has two lines of
defense
 First - external body membranes (skin and mucosae)
 Second - antimicrobial proteins, phagocytes, and
other cells
 Inhibit spread of invaders
 Inflammation most important mechanism
 Adaptive defense system
 Third line of defense attacks particular foreign
substances
 Takes longer to react than innate system

12.  Prevent entrance:
 Structural barriers – effective with most microorganisms
 Skin - epidermis = layers of tightly packed epithelial
cells. Outer layer is dead cells and keratin,
waterproofing protein
 Inner layer skin - dermis = blood vessels, hair
follicles, sweat glands, and sebaceous glands that
produce an oily secretion called sebum
 Cilia and cough reflex – helps expel microbe
containing mucous
 Sneeze
Innate Defense: Physical barriers

13.  Mucus membranes - conjunctivae, alimentary,
respiratory, and urogenital tracts
• saliva, tears, and mucous secretions wash away
invaders and contain antibacterial or antiviral
substances.
• acidity (pH 5.6) of sweat, sebaceous glands, vagina
(pH 5) and stomach (pH 1) – unfriendly to many
microorganisms
 enzymes present in the skin and stomach, tears
 Normal flora - out compete pathogens for attachment sites
on the epithelial cell surface and for necessary nutrients.
Innate Defense: Physical barriers

14. Innate Defense: Cellular & Humoral
mechanisms
 To prevent expansion of penetration
 Recognize carbohydrates not normally present on
cells such as mannose
 May cause nonspecific activation of white cells
 Phagocytosis – by neutrophils, eosinophils,
basophils, or macrophages, mast cells, and
dendritic cells
 Clotting mechanism which entraps organisms in
fibrin clots
 Complement System can lyse cells or enhance
phagocytosis

15. Phagocytes: engulf bacteria, release toxic
chemicals, present antigens
Residue is exocytosed
Phagolysosome
destroys infectious
agent
Phagosome
Lysosome
Macrophage
Infectious agent
engulfed
Neutrophil, macrophage, eosinophil: Phagocytic cells
Originally WBCs – they migrate into connective tissue
The “clean-up crew”: phagocytose debris and digest via lysosomes
Neutrophils enter first then macrophages (derived from monocytes)
Eosinophils involved with parasitic infections and Ag-Ab complexes
Also an APC

17. How do phagocytes invade the area of
infection or injury?
- Inflammatory factors –
released by mast cells, etc.
- Vasodilation – capillaries
become permeable
- Margination – WBCs slow
down & align on the vessel wall
-Diapedesis – blood cells leave
vessels & enter the CT
-Chemotaxis – blood cells follow
a chemical gradient (move
toward the source ie., bacteria)

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(b)
Venule
Eicosanoids
Histamine
Basophil
Arteriole
Basophil and mast cell: Proinflammatory chemical-secreting cells
Heparin
Vasodilation
Increases capillary
permeability Capillary
Anticoagulant
Increases inflamation
Basophils open up vessels & increase blood
flow

20. Eosinophils: Parasite-Destroying Cells
Eosinophil
Parasitic worm
Cytotoxic chemicals
Eosinophils: Parasite-destroying cells
(d)
Eosinophils also phagocytose antigen-antibody complexes

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Recognizes unhealthy cell (usually expressing abnormal proteins or viral proteins – uses
perforins (make a hole in the membrane) and granzymes; cells that lack "self" cell-surface
receptor
Induce apoptosis in cancer cells and virus-infected cells
Apoptosis
Unhealthy or
unwanted cell
NK cell
Granzymes
enter
pore, causing
apoptosis of cell
Perforin forms a
transmembrane pore
Perforin and
granzyme
NK cell: Apoptosis-initiating cells
Immunological surveillance: NK cells

23. Complement Proteins
C
C
Elimination of
immune complexes
Antigen
Antibody
Complement
Erythrocyte
Complement (C) cross-links
immune (antigen-antibody)
complexes to erythrocyte and
transports to liver and spleen.
Complement proteins create
MAC to lyse cell.
Complement activates and attracts various cells of
innate immunity.
Complement (C) binds to
pathogen; acts as opsonin
Macrophage
Pathogen
Complement
Inflammation
Opsonization Cytolysis
Complement
MAC
protein
Pathogen
Inflammation
Macrophage
Neutrophil
Basophil
Mast cell
 A series of ~20 enzymes normally circulating in an inactive form
• May be activated by the classical or alternate pathways
• Can result in lysis or enhanced phagocytosis of cells
Thus, helps or “complements” the ability of
antibodies and phagocytic cells to clear pathogens
from an organism.

24.  Binds receptors of neighboring cells:
 Promotes macrophage function and apoptosis of infected cell
 Triggers synthesis of enzymes destroying viral RNA or DNA
 Triggers synthesis of enzymes that inhibit synthesis of viral proteins
Interferons – signaling molecule
(cytokine) released by viral-infected cells

25. Reactions of Innate Immunity
 The innate immune system provides host
defense by two main reactions.
1. Inflammation.
2. Antiviral defense.

26. Reactions of Innate Immunity: Inflammation
 Overall non-specific reaction of body to injury or invasion
– starts immediately with infection or trauma
 Reactants may initiate, expand, or sustain the
response
 Can be acute (short duration) or become chronic
(prolonged duration)
 Has 4 cardinal signs: heat, pain, redness, loss of
function.

27. Reactions of Innate Immunity: Antiviral
defense
 Type I interferons produced in response to
viruses act on infected and uninfected cells and
activate enzymes that degrade viral nucleic
acids and inhibit viral replication, inducing what
has been called an antiviral state.
 NK cells recognize virus-infected cells

28. Reactions of Innate Immunity: Antiviral
defense

30. Microbial pattern recognition by
innate immunity
 Cells that participate in innate immunity are
capable of recognizing components shared by
microbes and molecules released by injured and
necrotic cells through their pattern
recognition receptors (PRR).

31. Microbial pattern recognition by innate
immunity

32. Pattern recognition receptors (PRR) expressed
mainly
 By immune cells such as dendritic cells,
macrophages, monocytes, neutrophils, as well as
 By non-immune cells e.g., Epithelial cells
Function of pattern recognition receptors
(PRR)
1. Opsonization
2. Phagocytosis
3. Activation of complement
4. Activation of proinflammatory pathways
5. Induction of apoptosis

33. Location of pattern
recognition receptors
(PRR)
 Plasma membrane
receptors detect
extracellular
microbes,
 Endosomal
receptors detect
ingested microbes,
and
 Cytosolic
receptors detect
microbes in the
cytoplasm

34. Classes of Pattern recognition receptors
(PRR)
1. Extracellular PRR (Binding activate proinflamm. Activity)
 Toll-like receptors (TLRs)
 C-type lectin receptors (CLRs)
2. Endosomal PRR (Mediate microbial uptake by phagocytes)
 Toll-like receptors (TLRs)
3. Cytosolic PRR (Activate complement proteins)
 NOD-like receptors (NLRs) and the inflammasome
 RIG-I-like receptors (RLRs)

35. Thank you