IMMUNITY

Natural, or innate, immunity

• is the ability of the individual to resist infection by means of normally present body functions.

• These are considered nonadaptive or nonspecific and are the same for all pathogens or foreign substances to which one is exposed.

• No prior exposure is required, and the response does not change with subsequent exposures.

Composed of two parts

1.External defense system and

2.Internal defense system.

External defense system

• composed of structural barriers that prevent most infectious agents from entering the body.

• FIRST LINE OF DEFENSE– nonspecific

•Unbroken skin– serves as major structural barrier– Keratinization– secretes Lactic acids and fatty

acids for pH maintainance (5.6) hence inhibits growht of microorganisms

– Earwax

– mucous membranes surfaces•motion of cilia lining

the nasopharyngeal passages

•flushing action of urine•Lactic acid production

of genital tract•acidity of the stomach•Lyzosome•normal flora-hence

competetive exclusion

Internal defense system

• second part of natural immunity• one of the ways that the body resist

infection after microorganisms have penetrated the 1st line of defense.

• The internal defense system is designed to recognize molecules that are unique to infectious organisms.

• SECOND LINE OF DEFENSE

When the pathogen survive on the first defense, What happens next?

• Cellular and Humoral defense become operational.– ELEMENTS OF NATURAL RESISTANCE

• PHAGOCYTIC CELL-e.q. monocyte• COMPLEMENT-refers to a series of serum

proteins that are normally present and whose overall function is mediation of inflammation. The major functions of complement are opsonization, chemotaxis, and lysis of cells.

• ACUTE INFLAMMATORY RXN– ROBOR, TUMOR, CALOR, DOLOR

BIOCHEMICAL BARRIERS

Cellular Factors and Phagocytosis

Phagocytosis is a form of endocytosis. In the process of phagocytosis the cell changes shape by sending out projections which are called pseudpodia (false feet).

The phagocytic cell such as a macrophage may be attracted to a particle like a bacteria or virus by chemical attractant.

This process is called chemotaxis (movement toward a source of chemical attractant).

ExamplesNeutrophils are the first phagocytes in the infected area that can non-specifically phagocytize some microbes.Alveolar macrophages like neutrophils and natural killers remove particles and organisms that enter the alveoli. large lymphocytes (Natural Killer Cells)whose function is to kill undesirable cells such as tumor cells and virus infected cells.

Such microbial inhabitants are harmless for its designated part, normal flora microorganisms do not cause disease.

Can stop the growth of potentially pathogenic organisms through different mechanism such as occupying attachment sites and by producing substance against pathogenic organism.

Role of Normal Flora

Third Line of Defence

Immune Response ( Inflammatory Reaction)

one of the most effective defense mechanism in human and other animals.

vascular and cellular reaction to the presence of invading microorganisms or injury.

It is one of the most effective defense mechanism in human and other animals.

Process of inflammation may bedivided in to the following stages:

Initiation (Damage to tissue) Tissue response Leukocyte response Tissue repair (resolution) Cure.

damaged cells at the site of injury initiate the tissue response by releasing chemical factors such histamine

Then, the phagocytic cells accomplish the leukocyte response, by engulfing the microbes and damaged tissue.

Destroying and removing an injurious agent such as a microbe or its products, the inflammatory response also limits the effects of the agent or its products by confining it or walling it of from the surrounding tissues.

This is possible because blood clots around the site prevent the microbe or its products from spreading to the other part of the body.

The final stage of inflammation is tissue repair, when all harmful agents or substances have been removed or neutralized at the injury site.

Adaptive Immunity

ANA ROSE D. DE LUZON

Adaptive Immunity• also known as the acquired immune

system• body’s third line of defense• composed of highly specialized, systemic

cells and processes that eliminate or prevent pathogen growth.

• allows the body to recognize, remember and respond to specific stimulus----antigen

• can also be maladaptive when it results to autoimmunity

Adaptive Immunity• The system is highly adaptable because of :

– somatic hypermutation (a process of accelerated somatic mutations), and 

– V(D)J recombination (an irreversible genetic recombination of antigen receptor gene segments).

• This mechanism allows a small number of genes to generate a vast number of different antigen receptors, which are then uniquely expressed on each individual lymphocyte.

Adaptive Immunity• Because the gene rearrangement leads to

an irreversible change in the DNA of each cell, all of the progeny (offspring) of that cell will then inherit genes encoding the same receptor specificity, including the Memory B cells and Memory T cells that are the keys to long-lived specific immunity.

Adaptive Immunity• Functions:

– the recognition of specific "non-self" antigens in the presence of "self", during the process of antigen presentation.

– the generation of responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells.

– the development of immunological memory, in which each pathogen is "remembered" by a signature antibodies or T cell receptors, this is also known as the "anamnestic response". These memory cells can be called upon to quickly eliminate a pathogen should subsequent infections occur

Adaptive Immunity

• The cells of the acquired immune system are T and B lymphocytes (B cells & T cells-major types)

• the human body has about 2 trillion lymphocytes, constituting 20–40% of white blood cells (WBCs); their total mass is about the same as the brain or liver

Adaptive Immunity

• Active Immunity– long-term memory– acquired by natural exposure in infection

followed by B cells and T cells activation– artificially acquired by vaccination----

immunization, stimulate antibody production and memory.

Adaptive Immunity• Exogenous antigens

– antigens that have entered the body from the outside

– produced by bacteria and parasites

• Endogenous antigens– antigens that have been generated within

previously normal cells as a result of normal cell metabolism, or because of viral or intracellular bacterial infection.

– produced by viruses replicating w/in the host cell

Humoral-Mediated Immunity

- The recognition of foreign substance and subsequent production of antibodies to substances define immunity.

- Antibody-mediated immunity to infection can be acquired if antibodies are formed by the host or if they are received from another source;

2 types of acquired immunity:1. Active Immunity2. Passive Immunity

Active Immunity- Vaccination is an

effective method of stimulating antibody production and memory (acquired resistance) without contracting the disease.

- The selected agents should stimulate the production of antibodies, w/out clinical signs and symptoms of an Immunocompetent host (able to recognize a foreign antigen and build a specific antigen-directed antibodies) and result to be a permanent antigenic memory

Passive Immunity- Is achieved by infusion of

serum or plasma containing high concentrations of antibody.

- It provides immediate antibody protection against microorganism (e.g: Hepatitis A) by administering preformed Ab.

- Temporary; as long as the Ab persist in the circulation.

Adaptive Immunity

• Passive Immunity– usually short-term, lasting between a few days

and several months– can be acquired naturally by the fetus through

the transfer of antibodies by the maternal circulation in utero.

– Breastmilk contains antibodies that are transferred to the gut of the infants

- Immediate hypersensitivity is a subset of the body’s antibody-mediated mechanism. This subset consists of the reaction primarily mediated by IgE, a class of immunogloblins w/ unique properties.

- The most dramatic and devastating systemic manifestion hypersentivity is Anaphylapsis.

Type Mode of acquisition Production by host

Time response

Active NaturalArtificial

InfectionVaccination

YesNo

LongLong*

Passive

NaturalArtificial

Transfer in vivo/ colostrumInfusion of serum/plasma

NoNo

ShortShort

Cell-Mediated Immunity- Consist of immune activities that differ from

antibody-mediated immunity. - Is moderated by the link between T lymphocytes

and phagocytic cells (i.e., monocytes-macrophages)

- A B lymphocyte can be probably respond to a native antigenic determinant of the appropriate “fit”.

- A T lymphocyte respond to antigens presented by other cells on the context of major histocompatibility complex proteins.

- Allograft tissue from genetically different member of the same species.

- Cytokines are nonspecific soluble factors are made by or act on various elements of immune system.

- Interleukins mediators that act between leukocytes.

- Delayed hypersensitivity is often synonymously with the term cell-mediated immunity.

Cytokines- Migratory inhibitory factor (MIF) was the first

cytokine activity.- MIF performs a T-cell-derived activity that

immobilizes macrophage migration, which may cause retention and accumulation of phagocytes at sites of inflammation.

- Cytokines are synthesized and secreted by cells associated with innate and adaptive immunity response to microbial and other antigen exposure

- Cytokines is preferred name for this class of mediators. Because many cytokines are made by leukocytes and act on other leukocytes, they are also referred to by the imperfect but descriptive term interleukins (ILS)

- Cytokines are polypeptide products of activated cells that control variety of cellular response and thereby regulate the immune response.

- Colony-stimulating factors (CSF) and ILS play important roles in normal proliferation, differentiation, and activation of several hematopoetic and lymphoid lineages.

Cytokines have a variety roles in host defense.-In innate immunity:

A. Cytokines mediate early inflammatory reactions to microbial organism

B. Stimulate adaptive immune response-Adaptive immunity:

A. Stimulate proliferation B. Differentiation of antigen stimulated by

lymphocytesC. Activate specialized effector cells

Cytokines differ molecularly but share the following activities:1.Secrete cytokines in rapid bursts, synthesized in response to cellular activation.2.Bind to specific membrane receptor on target cells.3.Regulate receptor expression in T and B cells, which drives positive amplification or negative feedback.4.Act on different cell types.5.Excite the same functional effects with multiple cytokines (redundancy).6.Act close to site of synthesis either on the same cell or on a nearby cell.7.Influence the synthesis and actions of other cytokines.

-Cytokines acts on other cells by bonding to cytokine receptors on the surface of cells.

Six pathways:1. Janus kinase (JAK/STAT) pathway2. Tumor necrosis factor (TNF) receptor signaling

by TRAFs (Tumor necrosis receptor-associated factor)

3. TNF receptor signaling by death domains4. Receptor-associated tyrosine kinases5. G-protein signaling

Interleukins- These molecules modulate

inflammation and immunity by regulating growth, mobility and differentiation of lymphoid cells.

- Distinct molecule by gene cloning and sequencing

Interferons- Are group of cytokines discovered in virally

infected cultured cells.- This interference with viral replication in the

cells by another virus led to name “interferons”

- IFNs are one of the body’s natural defensive responses to foreign components.

- Active physiologic regulators, enhancing the expression of specific genes, inhibiting cell proliferation, and augmenting immune effector cells.

- IFNs to act as antiviral agents, immunomodulators and antineoplastic agents.

Type I IFNs - The early innate immune response to

viral infections. - 2 Distinct group of proteins

1. IFN-alpa2. IFN-beta

Interferon-gamma- The principal macrophage-activating

cytokine and serves a critical function in innate immunity and in specific cell mediated immunity.

Tumor Necrosis Factor

- Principal mediator of the acute inflammatory response to gram-negative bacteria and other infectious microbes.

- Responsible for many of the systemic complication of severe infections.

The principal physiologic function of TFN: 1. To stimulate the recruitment of neutrophils

and monocytes to sites of infection.2. To activate these cells to eradicate microbes.

THANK YOU FOR LISTENING

O AGUILAR, PRINCESS ALENO BUMAGAT, GIANE CARLAO CRISOLOGO, ZENAIDA GORETTIO DE LUZON, ANA