E

Immune response: Innate immunity (non-specific: all kind of foreign materials)) and adaptive immunity
(specific immunity: particular foreign material is recognized by lymphocytes. Also has memory cell in
addition to effector cells

Immune Cell Immunity Function

Neutrophil Innate Phagocyte
Basophil Innate Allergy (release of histamine)
Eosinophil Innate Parasitic infection
Monocyte (circulation) Innate Phagocyte to remove foreign debris and
particles
that have from the hepatic portal
↑ come
system when
passing through the liver
Become Example: Kupffer cell in liver, Microglial in brain,
Langerhans cell in skin, Alveolar macrophage in
Macrophage (tissue) lungs, Tissue macrophage in spleen/lymph
nodes/red bone marrow

11 cell
Dendritic Innate Antigen-presenting cell
Natural killer cell Innate Kill infected cell and cancer cell
B cell Adaptive Produce antibody (only B cell is converted to
plasma cell)
Extracellular pathogens (in body fluid outside
cells)
T cell
Helper T cell (CD4+) Adaptive Secrete molecule to activate B cell, cytotoxic T
cell and macrophage
Coordination of immune response
Cytotoxic T cell (CD8+) Adaptive Recognize antigen on infected cell and kill them
Intracellular pathogens, cancer cell, foreign
tissue transplant

Innate Immunity – First Line of Defense (surface barrier)

Physical barrier
Skin & mucous membranes Physical barrier to entrance of microbes
Ciliated epithelium of the upper respiratory tract Mucus traps microbes which are swept by cilia towards the
pharynx and swallowed (trachea) or phagocytosed by
macrophages
Hairs Filter out microbes and dust in nose
Tears Dilute and wash away irritating substances and microbes
Saliva Wash microbes from surface of teeth and mucous
membranes of mouth
Urine Wash microbes from urethra
Defecation and vomiting Expel microbes from body

FEETE
Chemical barrier
Sebum Produced by sebaceous glands
Form protective acidic film over skin surface that inhibits
growth of microbes
Lysozyme Present in perspiration, tears, saliva, nasal secretions and
tissue fluids
Digest bacterial cell wall leading to lysis
Gastric acid Found in Stomach
Destroy bacteria and most toxin
Vaginal secretions Slightly acidity discourage bacterial growth

Innate Immunity – Second Line of Defense (Antimicrobial substance - Interferon)

F
Interferon:

• Released by virus-infected cells

• Important defense against infection by many virus
•
•
Do not prevent viruses from attaching to and penetrating host cells
Stop viral replication
J functions
Mechanism:

1. Virus enters cell and replicates in host cell 1 (killed by virus and produce interferon)
2. Interferon produced by host cell 1 binds on the interferon receptor of host cell 2
3. Interferon binding stimulate host cell 2 to turn on gene that encodes antiviral protein
4. When the virus enters host cell 2, the antiviral protein stop viral reproduction

Innate Immunity – Second Line of Defense (Antimicrobial substance –

Complement system)
F
Complement:

• Comprise a group of normally inactive proteins in blood plasma and on plasma membrane
• Upon activation, these proteins ‘complement’ or enhance certain immune reactions
• Cause cytolysis of microbes, promotes phagocytosis and contributes to inflammation
-
• Activated by classical pathway (antibody-antigen complex), lectin pathway (mannose binding
lectin) and alterative pathway (spontaneously activated) Y

Mechanisms: =>

1. Inactivated C3 splits into activated C3a and C3b

2. C3b binds to the surface of microbe and receptors on phagocytes (C3b receptor) attaches to C3b
➔ Enhance phagocytosis. Coating of C3b to a microbe is called(opsonization 1 makea foreigte to be phagorated
,

3. C3b also initiates a series of reactions that bring about cytolysis ➔ C3b splits C5 ➔ C5b fragment
binds to C6 and C7 which attach to plasma membrane of invading microbes. C8 and C9 molecules
join other complement proteins ➔ membrane attack complex insertion
4. Membrane attack complex insert into plasma membrane and results in cytolysis (bursting of the
microbial cell due to the inflow of extracellular fluids and exit of cell contents)
 5. C3a and C5a bind to the mast cell to release histamine ➔ increase blood vessel permeability
during the inflammation. C5a also attracts phagocytes to the site of inflammation (chemotaxis)

Innate Immunity – Second Line of Defense (Antimicrobial substance – Iron-

binding protein)
Iron:

• Assists physiological processes (e.g., DNA replication, transcription, metabolism and energy
generation via respiration)
• Without iron ➔ limit the growth of bacteria

Iron-binding protein examples:

• Reduce the availability of iron

i
• Transferrin (blood and tissue fluid)
• Lactoferrin (milk, saliva, mucus)
• Ferritin (liver, spleen, red bone marrow)

Innate Immunity – Second Line of Defense (Antimicrobial protein)

• Short peptide
• Attract dendritic cell and mast cells which participates in immune response

Examples:

'I
• Dermcidin (produced by sweat gland)

,
• Defensins and cathelicidins (produced by neutrophil, macrophages and epithelia)
• Thrombocidin (produced by platelets)

Innate Immunity – Second Line of Defense (Natural Killer cell and Phagocyte)
Natural killer cell (NK cell)
• Present in spleen, lymph node and red bone marrow
• Kill a wide variety of infected body cells and tumor
• Attack any body cells that display abnormal or unusual plasma membrane proteins

Phagocyte

11
• Phagocytosis (steps: adherence, engulfment, formation of phagolysosome, destruction of
pathogens, disposal of indigestible and residual materials)
• Ingest microbes, cellular debris
• Some microbes possess capsule ➔ difficult for engulfment
• In phagocyte: burst oxidative killing: ROS and RNS

Innate Immunity – Second Line of Defense (Inflammation and fever)

Inflammation
• Non-specific defensive response of body to tissue damage
 fi
• Caused by pathogens, abrasions, chemical irritation
• Attempt to dispose of microbes, toxins or foreign material at the site of injury
• Prevent spread to other tissue and prepare the site for tissue repair to restore homeostasis
• I
PRISH: Pain, Redness, Immobility, Swelling, Heat
• Vasodilation of arterioles (more blood flow to affected areas and help to remove microbial toxin
and dead cells)
• Increased permeability of capillaries (antibodies and clotting factors are allowed to pass from the
blood vessel)
❖ Histamine released by basophil and mast cell ➔vasodilation and increase permeability
❖ Kinin ➔ vasodilation and increase permeability, also as chemotactic agent for phagocyte)

Other chemicals:
I
❖ Prostaglandins (released by damaged cells, intensify effect of histamine and kinins and
stimulate emigration of phagocyte)
I
❖ Leukotrienes (increase permeability, as chemotactic agent, adherence of phagocyte to
pathogen), Complement
PLC ❖ Complement (stimulate histamine release, attract neutrophils by chemotaxis, promote
phagocytosis, some complement can destroy bacteria)

• Phagocyte immigration
• Tissue repair

Fever
• Abnormally high body temperature due to hypothalamic thermostat is rest
• Commonly seen in infection and inflammation
• Bacterial toxin elevate body temperature (fever causing cytokines e.g., interleukin-1)
• Intensify the effect of interferon, inhibit the growth of microbes, speed up body reaction that
aid repair

Adaptive Immunity/ Adaptive defenses

• T lymphocytes (Helper T cells CD4+ and Cytotoxic T cell CD8+) ➔ cell-mediated immunity
• B lymphocytes (B cell convert to plasma cells ➔ produce antibody ➔ antibody-mediated
immunity)
• Helper T cells help to activate CD8+, B cell and macrophage

Clonal selection: H
• Process by which a lymphocyte proliferate and differentiate in response to a specific antigen
• Formation of a population of identical cells called clones ➔ recognize the same specific antigen
as the original lymphocyte
• First exposure ➔ only a few lymphocytes are able to recognize. After clonal selection ➔
thousands of lymphocytes can respond to antigen

Major Histocompatibility Complex (MHC): Class I (CD4+ cell activation) and Class II (CD8+ cell activation)

Antigen-presenting cells:
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- fundonevenhenung !
• Example: Dendritic cell, macrophage, B cell
• Located in the place where antigens are likely to penetrate the innate defenses and enter the
body (e.g., dermis, mucous membrane that line that respiratory, gastrointestinal, urinary,
reproductive tract, lymph nodes)
• Process and present exogenous antigen. Then, migrate to lymph nodes

Cytotoxic T cells:
• Direct killing
I (form pores in the infected cells)
• Perforin
• Granzymes (enter the infected cells via the perforin pore and break down the proteins to kill ➔
initiate apoptosis)

B cells:
• Are activated and converted to plasma cell which produce antibody
• Antibody can:
❖ Neutralization of antigen and prevent attachment to body cell
❖ Opsonization ➔ promote phagocytosis
❖ Immobilization of bacteria (by binding the antigen on the flagella of motile bacteria ➔
limit the spread)
❖ Membrane attack complex formation

Immunoglobulin class: IgM, IgA, IgD, IgG, IgE MADGE

Primary immune response to antigen A: Occurs after a delay

Secondary immune response to antigen A: faster and larger

Humoral Immunity

Active Passive

Naturally acquired Infection (contact with pathogen)

Antibodies pass from mother to
fetus via placenta or to infant in
her milk
Artificially acquired Vaccination (dead or attenuated Injection of exogenous antibodies
pathogens) (e.g., gamma globulin)

Case Scenario: Individual is exposed to a new strain of influenza virus

First-line defense (Surface barriers):
• Mucus traps viruses
• Cilia sweep contaminated mucus towards the pharynx, where it is swallowed and digested

Second-line defense (Innate internal defense):

• Virus-infected cells release interferon to warn nearby uninfected cell
• Phagocytes engulf virus and sound the alarm by releasing inflammatory chemicals
• Inflammation bring more immune cell and plasma protein to area by dilating arterioles and
increasing capillary permeability
• Complement activation enhance inflammation and cause opsonization of virus particles
• Natural killer cells recognize and kill virus-infected cells

Third-line defense (Adaptive defense):

• Dendritic cells engulf virus and dead virus-infected cells
• Dendritic cell migrate to a lymph node where they activate T-lymphocyte
• Dendritic cell activates CD4 cell which forms a clone of helper T cells and memory cells
• Dendritic cell and helper T cell together activate CD8 which form a clone of cytotoxic cells and
memory cells
• Helper T cell activates B cell which form a clone of plasma cell and memory B cell T cell migrate
to the site of infection. They attack and kill the infected cells
• Plasma cell release antibodies which travel to site of infection (via blood) ➔ neutralize,
complement activation, agglutination