Welcome to Core Biology 2

Semester 2
Disease and the Immune System

Reminder:
Press
Record!
 Plan for this week
Week 3

Lecture Seminar
• Pathogens
• Acquired Immunity
• Components of the Immune
• Humoral Response
System
• Cell Mediated Response
• Immune Defences in animals
• Immune System Disorders
• Innate Immunity
 Plan for today’s session
Objectives:
• Define Pathogens
• Define the immune system and its response
• Outline the 3 lines of immune defence
• Explain innate immunity
• Describe Phagocytosis
• Explain Inflammation & Fever
 cos
Pathogens
thirty
• Disease-causing organisms, when they colonize a host organism.
• Also known as infectious agents, as they cause infections.

pathogens
Can you name some?
Eat
• Pathogens can be classified as either primary pathogens or opportunistic

.
 Harmful Effects of Pathogens
• They overgrow and put pressure on specific membranes or cavities.

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• They produce toxins that can destroy our cells.

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• They parasitize cells and destroy their normal structure and function.
 Key Definitions
The Immune System
• A group of cells, tissues, organs and mechanisms that has the

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ability to
• recognise self from non-self defend, therefore
• protects against pathogens and other substances.

An Immune Response

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• A complex series of specific and non-specific processes involving
a range of cells and chemicals
 Organs of the Immune System
1. Primary lymphoid organs
- Bone marrow and thymus
2. Secondary lymphoid organs
- Spleen, ÉE
- Lymph nodes,
- Lymph vessels, and
- Mucosa associated lymphoid tissue (MALT)

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All immune cells originate in the bone marrow,
deriving from haematopoietic stem cells.
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Hematopoiesis - the formation of blood cellular components
e
 White blood cells classification

three main types

seven sub-types
 Immune System
• The immune system comprises both innate and adaptive (acquired)
immune responses.
• Innate immunity occurs naturally because of genetic factors or
physiology
• Adaptive immunity is an immunity
ÉÉE that occurs after exposure to an
antigen either from a pathogen or a vaccination.
• Innate and adaptive systems work in close cooperation
 Immune Response
The adaptive immune system relies upon the innate immune system to alert
it to potential targets, and shape its response to them.

antigent
 I M
Lines of Defence
Vertebrates have three levels of defences
1. The Integumentary System e
- Skin, mucous membranes and secretions innate
2. Nonspecific (innate) Immune System
e
- acts very rapidly after onset of infection
3. Specific (Acquired) Immune System adaptive
- Eliminates microbes that escaped the second line of defence

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 First line of defence
The Skin - the largest organ of the body
• Provides a nearly impenetrable barrier, reinforced with chemical weapons
- Oil & sweat glands give skin a pH of 3-5
- Lysozyme breaks bacterial cell FETT
walls
- Also contains many normal flora - Non-pathogenic microorganisms
that out-compete pathogenic ones
 First line of defence
e• Epidermis o
= Contains keratin, which
makes skin tough and water-resistant
• Dermis = Contains connective tissue
which is thicker than epidermis
- Provides structural support for
epidermis, and matrix for blood vessels,
muscles and nerve endings
The skin is composed of three layers
• Hypodermis = Contains mainly adipose
(fat) cells
- Acts as shock absorbers and insulators
 First line of defence
innate
Mucosal Epithelial Surfaces and Secretions non
specific
• The digestive, respiratory and urogenital tracts are lined by mucous
membranes
• Cells secrete mucus which traps microbes
• Digestive tract
- Salivary lysozyme; acidic stomach
• Respiratory tract
- Ciliary action - the driving force of the mucociliary escalator,
• Urogenital tract
- stratified epithelial cells, mucous, immune cells

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 Second line of defence
• The nonspecific or innate immune system provides the second line of
defence – Also called natural or native immunity
• The response is quite rapid
• It consists of cellular and chemical devices that respond to any microbial
infection: speactic cells
• Leukocytes y
cellrelease
fatthe
• Chemicals – Cytokines and Complement proteins
• Inflammation
• Fever
 Leukocytes of the Innate Immune System
1. Monocytes
– differentiate to Macrophages and Dendritic cells
presentantigent
– Kill microbes by phagocytosis

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– antigen-presenting cells located in tissues and surfaces exposed to initial
infection mm

2. Neutrophils
– The most abundant circulating leukocytes
– First to appear at site of damage/infection
– Kill microbes by phagocytosis 17
 Phagocytic cells: Neutrophil & Monocytes
eat bacteria, release toxic chemicals, present antigens
Phagocytes: engulf
The “clean-up crew”

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 Leukocytes of the Innate Immune System
3. Natural killer (NK) cells
- Lymphocytes that destroy pathogen-infected and cancer cells
- Produce perforins and granzymes leading to cell death
4. Eosinophils: granulocytes that target multicellular parasites.
- secrete a range of highly toxic proteins and free radicals that kill bacteria and
parasites.
5. Basophils: granulocytes that attack multicellular parasites.
- release histamine, much like mast cells.
6. Mast cells: found in mucous membranes and connective tissues,
- important for wound healing via the inflammatory response.
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 NK cells: Immunological surveillance
Recognizes unhealthy cells expressing abnormal proteins or viral proteins

NK cell: Apoptosis-initiating cells

Perforin and
granzyme

Perforin forms a
transmembrane pore
Granzymes
enter
NK cell pore, causing
apoptosis of cell
Unhealthy or
unwanted cell

Apoptosis
Eosinophils: Parasite-Destroying Cells
Eosinophils: Parasite-destroying cells

Cytotoxic chemicals
Parasitic worm

Eosinophil
Basophils open up vessels & increase blood flow

Basophil and mast cell: Proinflammatory chemical-secreting cells

Vasodilation
Basophil

Histamine
Increases capillary
permeability

Heparin
Anticoagulant
Eicosanoids
Increases inflamation
 Phagocytosis
Phagocytosis is the ingestion of extracellular particulate material such as
invading pathogens or dead/dying cells by phagocytic cells
engelvingbictaria followthy chemicals

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Step 1: Activation of Phagocytic cells & Chemotaxis

• Activated by inflammatory mediators

c
• Bacterial products
They squire

• Complement proteins
• Histamine typesof
• Prostaglandins signals
 Phagocytosis non speci fi
Step 2. Recognition and attachment
• Binding induces membrane protrusions, called pseudopodia, to extend around
the attached material and to ingest them.
• Phagocytic cells contain various receptors which help them to attach with
bacteria or viruses. Some of these receptors are:
• Pattern recognition receptors (PRR): recognize pathogen-associated
molecular patterns (PAMPs).
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• These include bacterial molecules such as peptidoglycan, lipopolysaccharide, and
flagellin.
• Complement receptors (CR1): Complement receptors present on the
phagocytic cells bind with complement proteins complexed with antigen-
antibody complexes.
 Phagocytosis
Step 2. Binding and Recognition of invading microbes

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 Phagocytosis
Step 3: Ingestion and formation of phagosomes

• Following attachment, pseudopods engulf the microbe. Fusion of the

pseudopodia encloses the material within an endocytic vesicle called
a phagosome, which then enters the endocytic processing pathway.
 Phagocytosis
Step 4: Formation of phagolysosome
In this pathway, a phagosome moves toward the cell interior, where it
fuses with a lysosome to form a phagolysosome.
 Phagocytosis
Step 5: Destruction of the Pathogen

• Microorganisms are killed either by:

1. Oxygen-Dependent Killing: Activated phagocytes produce a number of reactive
oxygen intermediates (ROIs) and reactive nitrogen intermediates
2. Oxygen-Independent Killing: Activated phagocytic cells also synthesize
lysozyme, hydrolytic enzymes and a variety of antimicrobial and cytotoxic
substances
• Phagocyte also displays antigenic components on external surface of plasma
cell membrane (antigen presentation) to start immune response
Stages of Phagocytosis

activation

removal
digesting
 Complement Proteins
~30 antimicrobial proteins in plasma – ‘complements’ functions of antibodies
Opsonization Inflammation Cytolysis

Complement
Complement

Once activated, they perform C Mast cell Basophil Neutrophil Macrophage

MAC

many functions: protein

Pathogen
Pathogen
Inflammation

Macrophage

Complement (C) binds to Complement activates and attracts various cells of Complement proteins create
pathogen; acts as opsonin innate immunity. MAC to lyse cell.

• Opsonin – coats pathogen to make appear different and thus recognisable by

macrophages
• Inflammation - Activates mast cells, basophils, neutrophils, and macrophages to
increase inflammatory response
• Cytolysis – causes cell lysis (Big MAC attack)
 Interferons chemicals

• Signalling molecules (cytokines) released by viral-infected cells

• Three major types: IFN-, IFN-, IFN-

Binds receptors of neighbouring 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
 Inflammation
Acute inflammatory response
➢ immediate, local, nonspecific response -- typically lasts 8-10 days
➢ sometimes persists in process of chronic inflammation

Hallmark signs
• Redness - increased blood flow
• Heat - increased blood flow and increased metabolic activity
• Swelling - increase in fluid loss – capillaries to interstitial space, capillaries
become more permeable due to histamine and other chemicals
• Pain - stimulation of pain receptors from compression from interstitial fluid;
chemical irritation by kinins, prostaglandins, microbe substances
• Loss of function - (may occur in severe cases)
 The Inflammatory Response
Major events:

Inflammation
 Fever
• Abnormal elevation of body temperature -- at least 1°C from normal (37°C)
• May accompany inflammatory response
• Due to excess fluid loss so requires increased fluid intake to prevent
dehydration
• Results from:
➢ release of pyrogens such as interleukin 1, interferons
➢ toxins from infectious agents, drug reactions toxin
• Pyrogens released and circulate through the body
➢ target hypothalamus and cause release of prostaglandin E2
➢ raises temperature set point of hypothalamus
 Fever
Benefits of fever
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• Inhibits reproduction of bacteria and viruses
• Increases activity of adaptive immunity
• Accelerates tissue repair
• Causes migration of additional immune cells out of blood
• Recommended to leave a low fever untreated

Risks of a high fever

• High fevers are potentially dangerous above 39.4oC in children
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• Changes in metabolic pathways and denaturation of proteins
• Possible seizures, irreversible brain damage at > 41oC; death above 42.8oC
• Septic shock is a life-threatening condition caused by an overwhelming
inflammatory response