Normal defense mechanism

Belaynew Zemed ( MD, Assistant professor of

pediatrics and child health)
 Outline
 Objective

 Introduction

 Classification of Immune system

 Innate immunity
 Adaptive immunity
Objective
 To understand the basics of body defense
 To know the different components of immune system
 Describe the functions of each component
Introduction to immune system
Defense against infectious agents is secured through a
combination of;
 anatomic physical barriers
 skin, mucous membranes, mucous blanket, and ciliated
epithelial cells
 the components of the immune system
Introd…
the immune system is a functional system rather than a
system with discrete organs
involves multiple processes, such as identifying
pathogens, signaling other immune cells, and destroying
or neutralizing threats
parts of many organs contribute to body defense, almost
all organs in body play some role in immunity
dispersed chemicals, cells, tissues and organs
dispersal and transport via circulatory and lymphatic
systems
Classification of immune system
Classification of immune system

1. Innate (natural) immunity

is rapid and utilizes receptors encoded in the germline
include:

◦ Physical barriers

◦ Epithelial and phagocytic cell enzymes

◦ Phagocytes (neutrophils, monocytes, macrophages)

◦ soluble mediators such as complement proteins

Classification of immune system

Function

 Play role in first-line defense against invasion and

infection.
 Activation and instruction of adaptive immune responses.
 Regulation of inflammation.
Classification of immune system
A. Physical and Mechanical Barriers
Skin: Acts as a tough outer barrier, preventing pathogen
entry.
Mucous membranes: Line the respiratory, digestive,
urinary, and reproductive tracts, trapping pathogens.
Cilia: Tiny hair-like structures in the respiratory tract that
sweep away debris and pathogens.
Flushing actions: Tear flow, saliva, urine flow, and sweat
help wash away microbes.
Classification of immune system
B. Chemical Barriers
Lysozyme: Found in tears, saliva, and sweat,
breaks down bacterial cell walls.
Stomach acid: Kills ingested pathogens.
Skin oils and sweat: Create an acidic environment
that inhibits microbial growth.
Classification of immune system
C. Cellular Defenses
 Phagocytes: White blood cells like macrophages and neutrophils engulf and
destroy pathogens.
 Natural Killer (NK) Cells: Attack virus-infected cells and tumor cells without
prior sensitization.

D. Inflammatory Response

 Triggered by tissue injury or infection.

 Symptoms: Redness, swelling, heat, and pain.

 Promotes healing by increasing blood flow and recruiting immune cells

to the affected area.

Classification of immune system
2. Acquired (adaptive) immunity
 is specific to T and B cells which undergo DNA
recombination to generate receptors
 require an education process to minimize autoreactive cells.
 Needs an antigen (natural infection, or vaccination).
 Form specific antibody / activated lymphocytes that attack
specific invading organisms/ toxin.
 continually refined and adjusted throughout the lifetime.
Classification of immune system

 There are 2 types of adaptive immunity

Humoral immunity
 denotes immunologic responses that are mediated by
antibodies.

Cellular immunity
 T cells regulate the activities of B cells, T cells, and other
cells participating in immune responses.
Human Defense Mechanisms

• First line of defense Second line of defense

 Innate resistance (or Inflammatory Response
natural immunity) Phagocytes
 Includes natural barriers Natural Killer (NK) Cells

• Third line of defense Complement System

 Adaptive (acquired or Interferons

specific) immunity
 Involves “memory”
 Con’t…

Physical and mechanical barriers

 1st major level of protection from invasion and infection
 nonspecific – treats all potential pathogens the same way

• Skin, Mucous Membranes

 Protection via Sloughing off of cells, Coughing and
sneezing, Flushing from urinary system, Vomiting, Mucus
and cilia
 Con’t…

Biochemical barriers

–Enzymes synthesized and secreted in saliva, tears, ear wax,

sweat, and mucus

–Antimicrobial peptides

–Normal bacterial flora on the skin and in gut

 Con’t…
Inflammatory response

– Caused by a variety of materials

• Infection, mechanical damage, ischemia, nutrient deprivation,

temperature extremes, radiation, etc.

– Vascular response

• Vasodilation (VD), blood vessels become leaky, WBCs adhere to

inner walls of vessels & migrate through the vessels

– Local manifestations-hotness, swelling, tenderness, redness

 Con’t…

• Benefits of Inflammation
–Limit tissue damage and control the inflammatory process

–Prevent and limit infection and further damage

–Initiate adaptive immune response

–Initiate healing
 Con’t…
Complement system
 Opsonization: Complement proteins (e.g., C3b) coat pathogens, making them more
recognizable to phagocytes.
 Chemotaxis: Complement fragments (e.g., C5a) recruit phagocytes to the infection site.
 Lysis: Formation of the membrane attack complex (MAC) (C5b-C9) leads to direct
pathogen destruction.
 Enhancing Phagocytosis: Complement receptors on phagocytes bind to complement-
coated pathogens.
 Enhance Neutralization of virus by antibody
 solubilize immune complexes then removed by splenic macrophages
 promotes immune complex binding to antigen-presenting cells
 Inflammation: Attracts immune cells via anaphylatoxins (C3a, C5a).
Con’t…
 Con’t…
Cellular components
 Phagocytes (macrophages, neutrophils, dendritic cells) eliminate
pathogens through:
 Recognition: Phagocytes have receptors for antibodies (Fc receptors) and
complement (CR1, CR3).
 Engulfment: Opsonized pathogens are engulfed into a phagosome.
 Killing: Inside the phagosome, pathogens are destroyed via:
o Reactive oxygen species (ROS)
o Lysosomal enzymes
o Nitric oxide (NO)
 Con’t…
Granulocytes, monocytes, platelets, lymphocytes, Mast
cells
◦ Neutrophils & macrophages = phagocytosis
◦ Eosinophils =kill parasites
◦ Platelets = clotting sequence & release mediators
◦ Lymphocytes (NK cells) = attack virus and cancer infected cells
 Con’t…
Neutrophils
Predominate in early inflammatory responses
arrive 6-12 hr after injury
They circulate in the bloodstream for only about 6 hr
When encountering specific chemotactic signals, they
adhere to the vascular endothelium and transmigrate into
tissues.
◦ Ingest bacteria, dead cells, and cellular debris
 Con’t…
 recognizes pathogens by means of Fc immunoglobulin and
complement receptors, Toll-like receptors, fibronectin
receptors, and other adhesion molecules.
 The neutrophil ingests microbes that are coated by opsonins.
 kill pathogens by the process of
◦ degranulation and

◦ activation NADPH–dependent oxidase leading to

production of H2O2 and HOCl which are potent
microbicidal agents
 Con’t…

In addition, neutrophils secrete a wide variety of cytokines

and chemokines that;
 recruit more neutrophils to fight the infection
 attract monocytes and macrophages that possess both
microbicidal and scavenger functions, and
 promote antigen presentation to initiate the adaptive
immune response.
 Con’t…
The sequence of events as the neutrophil moves from
circulating in the blood to the encounter and destruction of
bacteria is carefully orchestrated by a series of biochemical
events, defects of which are associated with genetic
disorders of neutrophil function
 Con’t…
Monocytes and macrophages
 Monocytes - produced in bone marrow blood
inflammatory site, where they develop into macrophages
 Macrophages typically arrive at the inflammatory site 24
hours or later after neutrophils
 No human has been identified as having congenital
absence of this cell line
 Con’t…
 Macrophage Activation

 Classical activation
◦ By Th1-type and NK cells through their release of IFN-γ

◦ Phagocytosis and killing of microorganisms and tumor cells by

secreting various hydrolytic enzymes and microbicidal materials
 Alternative activation
◦ by Th2-type cells through release of IL-4 and IL-13, cytokines

◦ regulate antibody responses, allergy, and resistance to parasites.

◦ functional advantages in wound healing and immunoregulation.

 Con’t…

All macrophages have 3 major functions in common

◦ phagocytosis
◦ presentation of antigens to lymphocytes and regulate the
immune response by variety of potent cytokines
◦ induction and expression of adaptive immune responses
Con’t…
Monocytes migrate into tissues in response to localized
inflammation or injury and provide
◦ proinflammatory host defense
◦ antiinflammatory responses and
◦ promote wound healing
Con’t…

Eosinophils

–Mildly phagocytic

– Main defense against parasites and regulation of vascular

mediators from mast cells
 Con’t…
Mast Cells

 Important activator of inflammatory response

 Contain granules, located in loose CT of the Skin,

digestive lining, and respiratory tract

Release:
 Histamine, Leukotrienes, Prostaglandins
 Platelet-activating factor (PAF)
 Con’t…

Natural killer (NK) cells

–Function against cells infected with viruses and cancer

Platelets

–Activation results in degranulation

(release of serotonin) and to stop bleeding

 Con’t…

Cytokines

Cytokines are small signaling proteins secreted by various cells in the

body that play a pivotal role in cell communication.

Most cytokines are classified as:

• Interleukins (IL)

– Produced by macrophages and lymphocytes in response to a pathogen

• Interferon (INF)

– Protects against viral infections

– Produced and released by virally infected host cells

Adaptive immunity
 Con’t…
Antigens

• proteins or CHO molecules that the immune system recognizes as

foreign or non-self and bind to antibodies or receptors on B and T
cells which induces adaptive immune response.

Antibodies

• also known as immunoglobulins (Ig), are specialized proteins

produced by plasma cells (mature B cells) in response to exposure
to antigen that recognize and bind specific antigens to neutralize or
tag them for destruction.
Cellular immunity
involves T cells to recognize and respond to specific
antigens
Types of T Cells by Their Roles;

1. Cytotoxic T Cells (CD8+ T Cells)

◦ Recognize antigens presented by MHC Class I molecules.
◦ Destroy infected, cancerous, or foreign cells by:
 Releasing perforins (form pores in target cell membranes).
 Releasing granzymes (induce apoptosis, or programmed cell
death).
◦ Key in defense against viruses and intracellular pathogens.
Con’t…
2. Helper T Cells (CD4+ T Cells)
 Recognize antigens presented by MHC Class II molecules.
 Do not kill cells directly but activate other immune cells by
releasing cytokines:
◦ Stimulate B cells to produce antibodies.
◦ Enhance macrophage activity to engulf pathogens.
◦ Activate cytotoxic T cells.
 Subtypes:
◦ Th1 Cells: produce IL-2 and IFN-γ, which promote cytotoxic T-
cell or delayed hypersensitivity types of responses.
◦ Th2 Cells: produce IL-4, IL-5, IL-6, IL-13, which promote B-cell
responses and allergic sensitization
Con’t…
3. Regulatory T Cells (Tregs):
Suppress excessive immune responses to maintain immune
tolerance and prevent autoimmune diseases.
4. Memory T Cells:
Long-lived cells that "remember" a specific antigen.
Provide a faster and stronger response upon re-exposure to
the same pathogen.
Con’t…
Key Steps in Cellular Immunity
Antigen Presentation
T Cell Activation:
◦ Activated T cells proliferate and differentiate into
effector or memory T cells.
Effector Functions:
◦ Cytotoxic T cells kill infected or abnormal cells.
◦ Helper T cells activate and direct other immune cells.
Con’t…
Examples of Cellular Immunity in Action
Viral Infections
Cancer Surveillance
Intracellular Bacterial Infections: e.g., Mycobacterium
tuberculosis
 Humoral immunity
 Antibodies contribute to pathogen killing by:
◦ Neutralization: Binding to pathogens to prevent their attachment to
host cells.
◦ Opsonization: Coating pathogens to enhance recognition by
phagocytes.
◦ Complement Activation: Initiating the classical complement
pathway.
◦ Antibody dependent cellular cytotoxicity (ADCC)
 Con’t…
• Classes of antibody

– IgG - most abundant class (80-85%),

• major antibody found in fetus & newborn

– IgA – Found in mucosal areas and secretions (e.g., saliva,

tears).– IgM – largest, produced 1st in initial response to
antigen

– IgE - lowest blood concentration, allergic rxn.

– IgD – low conc. in blood, receptor on B cells

 Con’t…

• Antibody response

Primary response

– following initial exposure and characterized by latent

period.

• B cell differentiation is occurring after 5 to 7 days of an

infection and IgM antibody for a specific antigen is detected
followed by IgG response.
 Con’t…

• Secondary response
–More rapid

–Larger amounts of antibody are produced

–Rapidity is caused by the presence of memory cells

–IgM is produced in similar quantities to the primary

response, but IgG is produced in considerably greater
amount.
Con’t…
 Tips of immunity level by age of a child

 Newborn infants have increased susceptibility to infections with

gram negative organisms because IgM antibodies do not cross the
placenta and Lower C3b which are powerful opsonins that enhance
phagocytosis.
 Maternally transmitted IgG antibodies serve quite adequately for
most gram positive bacteria and viruses
 Because there is a relative deficiency of the IgG2 subclass in
infancy, antibodies to capsular polysaccharide antigens may be
deficient.
 premature infants have received less maternal IgG by the time of
birth than full term infants
 Con’t…
Maternal IgG gradually disappears during the 1st 6-8 mo
of life, while the rate of infant IgG synthesis increases until
adult concentrations of total IgG are reached and
maintained by 7-8 yr.
The serum IgG level in infants usually reaches a low point
at about 3-4 mo of postnatal life.
The capacity to produce specific antibodies to protein
antigens is intact at birth, but not to polysaccharide
antigens until after 2 yr of age unless the polysaccharide is
conjugated to a protein carrier.
 Con’t…
Thymus is largest relative to body size during fetal life and
at birth is ordinarily two-thirds of its mature weight, which
it attains during the 1st yr of life.
By 1 yr of age, all lymphoid structures are mature
histologically.
Absolute lymphocyte counts in the peripheral blood also
reach a peak during the 1st yr of life.
The mean number of Peyer patches at birth is one-half the
adult number
.

Thank you!!!