By : Pooja Patel & Sarah Gianopoulos. Innate immunity—nonspecific, used against many organisms: First line of defense includes barriers, such as skin.

ImmunologyBy : Pooja Patel & Sarah Gianopoulos

Innate Immunity

Innate immunity—nonspecific, used against many organisms:First line of defense includes

barriers, such as skin and molecules toxic to invaders

Second line of defense includes phagocytic cells, which ingest foreign cells and particles

Most animals use innate immunity

Adaptive Immunity

Adaptive Immmunity—specific, used to distinguish between substances that were made by the organism or if they are foreign substances: Uses antibody proteins to recognize, bind

to, assist in destroying specific bacteria and viruses

Adaptive immunity is slow to develop and long lasting

Innate immunity is much quicker to develop (0-96 hours)

Two Major Types of White Blood Cells

Phagocytes Large cells that engulf pathogens and harmful substances

Lymphocytes Include B and T cells B Lymphocytes differentiate and form

antibody producing cells and memory cells T Lymphocytes kill the virus infected cells

and regulate white blood cell activity

Immune System Proteins

Cytokines bind to cell surface receptors and alter the behavior of their target cells Some can activate or inactivate B and T cells and

macrophages Antibodies are proteins, produced by B cells

that bind specifically to nonself substances Acts as a flag to make it easier for the immune

system cells to attack the invader Destruction done by inactivating/destroying

harmful pathogens, toxins and other microorganisms

Immune System Proteins Contd.

• Major histocompatibility complex (MHC)• MHC proteins are important self-

identifying labels that make sure the appropriate type of T cell binds during immune responses.

T cell receptors are integral membrane proteins on T cells, recognize and bind to nonself molecules

Immunity: Barriers and Local Agents

Skin Rarely penetrated by bacteria Skin’s saltiness is not an ideal

environment for bacterial growth Both harmless and helpful bacteria will

have to compete for space and nutrients on the skin against pathogens and harmful substances

Barriers and Local Agents Contd.

Mucus Traps microorganisms and pathogens

and is carried away by cilia Lysozome (enzyme)

Produced by mucus membranes and cleaves on the cell walls of the bacteria, thus making the harmful cell ‘lyse’

Use of internal substances

Barriers and Local Agents Contd. Defensins (peptides)

Made by mucus membranes

Hydrophobic and toxic to several other pathogens

Insert themselves into the plasma membrane to make the it permeable to water and solutes, thus killing the harmful substances

Complex Innate Defenses

Phagocytes ingest the harmful substance and destroy it by 1 of 2 ways: Hydrolysis within lysosomes Defensins

Complex Innate Defenses Contd.

Natural Killer Cells Distinguishing between

healthy and unhealthy cells▪ Apoptosis for cancerous cells▪ For other cells, Innate and

Adaptive defenses combine by lysing antibody –labeled target cells

Complex Innate Defenses Contd.

Complement Proteins A system that activates several proteins

in sequence in order to lyse the invaded cell▪ One complement protein acts as a flag to the

phagocytes as it binds to the invaded cells▪ Next protein is activated to initiate the

inflammation response and signals to the phagocytes to the infection site▪ Then many other proteins now lyse the

invaded cell

Complex Innate Defenses Contd.

Interferons Proteins that help increase resistance of

neighboring cells to infection▪ Bind to receptors on the plasma membranes

of the uninfected cells to stimulate a pathway that inhibits viral reproduction the other cells become infected

InflammationInflammation

Isolates the infected area to stop spreading the damage

Brings in cells and molecules to kill off any remaining pathogens and initiates the healing process

Mast cells are cells adhering to skin and organ linings; release chemical signals.

Tumor necrosis factor—cytokine that kills target cells and activates immune cells

Adaptive Immunity’s 4 Key Features

Adaptive Immunity is: Specific Diverse Can distinguish between self and nonself

substances▪ Clonal deletion

Has immunological memory

Specificity

Specificity: T cell receptors and antibodies

bind to specific nonself molecules (antigens).

Specific sites on the antigens are called antigenic determinants.

The host responds to an antigen’s presence with highly specific defenses using T cell receptors and antibodies.

Distinguishing Self from Nonself

Lymphocytes are usually activated by binding to antigens to induce production of clones of B Cells and T Cells-clonal selection.

To protect Self substances: Clonal deletion—Any immature B and

T cells that show the potential to mount an immune response to self antigens undergo apoptosis.

Immunological Memory

Primary Immune Response Memory Cells

Secondary Immune Response Produces a quicker

and more powerful response

3 Phases of Adaptive Immunity

• Recognition phase—the organism discriminates between self and nonself to detect a pathogen.

• Activation phase—the recognition event leads to a mobilization of cells and molecules to fight the invader.

• Effector phase—the mobilized cells and molecules destroy the invader.

Cellular Immune Response

Cytotoxic T (TC) cells power the cellular immune response.

An antigen is inserted into the membrane of an antigen-presenting cell.

The antigen is recognized by a T-helper (TH) cell, with a specific T cell receptor protein.

TH cell binding to the antigen-presenting cell causes cytokine release.

Cytokines stimulate TC cells to divide.

Humoral Immune ResponseHumoral immune response

involves B cells that make antibodies. Antigen is recognized when the it

binds to a B cell that has an antibody specific to that antigen.

Antigen binding readies a B cell for division.

The TH cell bound to the B cell secretes cytokines that stimulate the B cell to divide and form a clone.

Interaction of Two Immune Responses

The result of both types of immunities:• A clone of B cells that can produce antibodies

specific for the antigen• A clone of TC cells that express a T cell

receptor that can bind to any cell expressing the antigen on its surface

In the effector phase, B clone cells produce antibodies that bind to free antigen— results in inactivation and destruction of the antigen.

TC clone cells bind to cells bearing the antigen and destroy them.

Humoral Immunity: Antibody

B cells give rise to clones of plasma and memory cells upon activation.

Plasma cells and B Cells secrete antibodies into the blood stream. • Some bind to the antigen on surface of a

pathogen.• Some may use cross-linking function to

form large complexes to be destroyed by phagocytes.

Antibody Structure

Antibodies all contain a tetramer of four polypeptides.

In each molecule are two light chains and two heavy chains, held together by disulfide bonds.

Each polypeptide chain has a constant region and a variable region.

The constant region determines the general structure and function of an immunoglobulin.

The variable region is different for each specific immunoglobulin—responsible for antibody specificity.

Five Classes of Antibodies• IgG is secreted by B cells and

constitutes about 80 percent of circulating antibodies.

• IgD is the cell surface receptor on a B cell.

• IgM is the initial surface and circulating antibody released by a B cell.

• IgA protects mucosa on epithelia exposed to the environment.

• IgE binds to mast cells and is involved with inflammation.

B Cell

Each mature B cell can produce only one specific antibody with a specific amino acid sequence.

The B cell genome:• Each gene encoding an antibody is a

supergene assembled from many smaller genes.

During B cell development the genes are cut out and rearranged.

DNA is rearranged or mutated to create high diversity of antibodies.

Cellular Immunity: T Cells Cellular immune response involves:

• T-helper cells (TH) • Cytotoxic T cells (TC) • Histocompatibility proteins (MHC) proteins

T cells have specific membrane receptors—glycoproteins, with two polypeptide chains.

Each chain is encoded by a different gene T cell receptors can bind a piece or

fragment of an antigen, on the surface of an antigen-presenting cell.

T Cells Contd.

TC cells bind to cells carrying the antigen–MHC I protein complex.

When bound, the TC cells do two things to eliminate the antigen-carrying cell:• They produce perforin, which lyses the

bound target cell.• They stimulate apoptosis in the target

cell.

Regulatory T Cells

Regulatory T cells (Tregs) regulate the immune response.

Tregs recognize and mediate tolerance to self antigens—when activated they release the cytokine interleukin 10.

This blocks T cell activation and leads to apoptosis of TC and TH cells bound to the same antigen.

Immune Deficiency Disorders: HIV/AIDS

Immune deficiency disorders can be inherited or acquired.

T or B cells may never form, or B cells lose their ability to give rise to plasma cells

Acquired immune deficiency syndrome (AIDS) results from infection by human immunodeficiency virus (HIV).

HIV/AIDS

HIV initially infects TH cells, macrophages, and antigen-presenting dendritic cells.

Numbers of TH cells decline after infection.

HIV-infected cells activate the humoral immune system and symptoms abate.

During the dormant period, people with HIV feel fine.

HIV/AIDS Contd.

Eventually more TH cells are destroyed and the person is susceptible to opportunistic infections:• Pneumonia• Lymphoma tumors

• Drug treatments for HIV are focused on inhibiting processes necessary for viral entry, assembly, and replication.