Immuno lec midterms

Edward Jenner

demonstrated that material from cowpox lesions could be substituted for smallpox in variolation

father of immunology

Immunology

• study of all aspects of the immune system

• helps in understanding the way by which animals gain protection from disease causing agents or pathogens

• study of the system through which infectious agents are identified as different from the “self” and defend or protect against damaging effects

Innate Immunity

the second layer of defenses that consists of preexisting or rapidly responding chemical and cellular defense mechanisms

inflammation

one key aspect is the body’s ability to focus the innate defense mechanisms on sites of microbial invasion

Components include

-Phagocytes

-Complement proteins

-Natural killer cell

Specificity

Recognize invaders, destroy them and learn from the process

Memory

Recognized and remember invaders so that when it encounters them on subsequent occasions it can respond more rapidly and effectively

In acquired immunity, it takes at least __________ to become effective

several days

The acquired immune system is a ___________- that provide ultimate defense of the body

complex and sophisticated system

What is the two major branches of types of immune response

• Humoral Immune Response (B cells)

• Cell-mediated Immune Response (T cells)

Cell-mediated Immune Response (T cells)

directed against intracellular or endogenous invaders that invade cells

Humoral Immune Response (B cells)

Directed against extracellular or exogenous invaders; antibodies destroy these

B cell (Also B lymphocyte)

Strictly, a bursa–derived cell in avian species and, by analogy, a cell derived from the equivalent of the bursa in non-avian species. B cells are the precursors of plasma cells that produce antibody.

Chemokines

low-molecular-weight protein that stimulate leukocyte movement

Epitope

Site on an antigen recognized by an antibody. Also known as an antigenic determinant

Hapten

A molecule that is not immunogenic by itself but can react with specific antibody

Macrophage

A phagocytic mononuclear cell derived from bone marrow monocyte and found in tissues and at the site of inflammation. Macrophages serve accessory roles in immunity, particularly as antigen presenting cells (APCs).

Opsonin

A substance capable of enhancing phagocytosis. Antibodies and complement are the two main opsonins

PRIMARY LYMPHOID ORGANS

organs that regulate the maturation of lymphocytes or sites of antigen-independent lymphocyte proliferation

Secondary peripheral lymphatic organs

lymphocyte proliferation and exposure to antigens

What is the basis role of lymphoid organ?

• generating lymphocytes

• regulating production of lymphocytes

• providing an environment for trapping foreign antigens

Thymus

Takes in immature T cells and puts out mature (immunocompetent) T cells

thymocytes with receptors that bind self-antigens that could cause autoimmunity are killed by __________

apoptosis (negative selection)

thymocytes with receptors that _______________ are also killed

cannot react to any processed antigen

Thymulin

a zinc-containing peptide; can partially restore T-cell function

Bursa of Fabricius

A maturation and differentiation site for the cells of the antibody-forming system (B cells)

Wha is the source of B cells in chickens?

Bursa of Fabricius

In Secondary Lymphoid Organs, arise __________ and persist in adults

late in fetal life

Secondary Lymphoid Organs

They enlarge in response to antigenic stimulation

Myeloid Lineage

• Neutrophils

• Eosinophils

• Basophils

• Monocytes

• Mast cells

• Megakaryocytes (platelets)

• Erythrocytes

Neutrophils

normally confined to blood stream but in microbial invasion, the first leave the blood stream

Once on the site of microbial invasion and inflammation, neutrophils capture and destroy foreign particles through _______

phagocytosis

Destruction of ingested bacterium occurs through generation of potent oxidants causing __________ or through release of lytic enzymes and antimicrobial peptides from intracellular granules

respiratory burst

Macrophages

Second population of cells that serve as “backup system”

What is the function of myeloperoxidase in neutrophils?

produces hypohalous acids to carry out their antimicrobial activity

What is the other term for process of engulf/phagocytosis

Potent oxidant

What is the function of macrophages?

• Sensors of invasion – they possess toll-like receptors that can detect invading bacteria and viruses and then respond by producing cytokines (IL 1 & TNF-α)

• Phagocytosis − Monocytes bind strongly to the endothelial cells and emigrate through the blood vessel walls and when these cells are within the tissues they are then called macrophages

  − Macrophages are attracted to bacterial products, products of complement activation, molecules released from damaged cells and tissues

  -Macrophages destroy bacteria by both oxidative and nonoxidative mechanisms

  − However, in contrast to neutrophils, macrophages can undertake sustained, repeated phagocytic activity

• Removal of dead and dying cells

Macrophages destroy bacteria by _____

both oxidative and nonoxidative mechanisms

However, in contrast to neutrophils, macrophages can undertake sustained, ____________

Repeated phagocytic activity

In lymphoid lineage, includes the natural killer cells by _______

Lymphoid

T helper cells (CD4), can identify the enemy in conjunction with ______

MHC class II

T helper cell (CD4) stimulates _____________

macrophages to be effective in destroying pathogens

Effector or Cytotoxic T cells (CD8), Recognize endogenous peptides with ____________

MHC class I

In effector or cytotoxic t cells (CD8), Kill their target by releasing a protein perforin

inducing apoptosis

If MCH I bind with CD4, what is the result?

nothing productive will happen—this is an incorrect or incompatible interaction in the immune system.

What is the career choices of B cell?

• Plasma cell

• Memory B cells

Plasma cells

antibody factories

reserve of antigen sensitive cells to be called on when the body is re-exposed to antigen. Most _______ experienced somatic mutation (extensive mutation that occurs in the V genes of B cells during the course of immune response)

Memory B cells

Thus, antibodies are simply soluble forms of BCR secreted into body fluids and which belong to the class of proteins called _________

Immunoglobulins

What immunoglobulin does intravenously only

IgG

Langerhans cells

pick up antigens entering the skin, transport antigen draining lymph node

In Langerhans cells, Found in ____________ that trap and process antigens that penetrate the skin

epidermis and mucous membrane

Present in the interstitium of most organs, T cell-rich areas of __________

lymph nodes, spleen, epidermis of skin

In integrating dendritic cell is present ____________

antigen to CD4+ T cells (Antigen Presenting cells)

___________ pick up antigens entering the skin, transport antigen draining lymph node

Langerhans cells

Langerhans cells

Found in epidermis and mucous membrane that trap and process antigens that penetrate the skin

Cross-reactivity

There are instances that identical or similar epitopes can be found on apparently unrelated molecules.

Epitopes or antigenic determinants

These are sites on the surface of an antigen that stimulates a specific immune response

Immunoglobulin M (IgM)

• Also produced by plasma cells in the spleen, lymph nodes and bone marrow

• Second highest concentration in serum

• The major antibody produced during a primary immune response although it is also produced during secondary immune response

• Considerably more efficient than IgG at complement activation, opsonization, neutralization of viruses and agglutination

• Due to very large size, they rarely enter tissue fluids at sites of inflammation

what is the immunoglobin that only in intravascular

IgG

Haptens

Small molecule that cannot initiate an immune response unless it is bound to an immunogenic carrier molecule

Cross-reactivity

There are instances that identical or similar epitopes can be found on apparently unrelated molecules.

Monoclonal Antibodies

antibodies specific for one antigen; produced by hybridoma (cell line derived by the fusion of a single normal B cell and an immortal B cell tumor line)

Polyclonal Antibodies

collection of antibodies from different B cells that recognize multiple epitopes on the same antigen

Immunoglobulin E (IgE)

− Also produced beneath body surfaces

− Typical Y-shaped, four-chain immunoglobulin with four constant domains in its heavy chains

− Present in extremely low concentrations in serum

− Cannot simply bind and coat antigens but triggers acute inflammation by acting as a signal transducing molecule (signaling molecule) and are found on the surface of mast cell and basophil

− Has the shortest half-life (2-3 days)

− An important immune response to parasites

The resulting hybridoma cells divide indefinitely and _____________.

produce millions of monoclonal antibodies specific to the original antigen

what type of immunity of Polyclonal Antibodies?

Passive immunity

What is the mutual antagonist?

IL-4 and IFN-γ

INTERLEUKINS

Cytokines that regulate the interactions between lymphocytes and other leukocytes

Numbered sequentially in order of their discovery

Interleukin 1

Key role in fever, hematopoiesis, appetite control, bone metabolism and acquired immunity

Interleukin-2

• Produced by Th1 cells and targets T cells, B cells and NK cells

• Activates helper and cytotoxic T cells and NK cells, but in order to be responsive to IL-2, antigen and IL-12 must first activate T cells and induce expression of both IL-2 and its receptor

• Triggers the T cell to proliferate and stimulates the proliferation and cytotoxicity of Th1 cells

Interleukin 4

Major importance in the development of allergic reactions by inducing B cells to switch to IgE production

Interleukin 6

Also produced by muscle cells during exercise

Interleukin 10

Inhibits the synthesis of Th1 cytokines

An immunosuppressive and anti-inflammatory cytokine that regulates inflammation as well as T cell, NK cells and macrophage function

Interleukin 12

Synergizes with TNF-α in promoting IFN-γ production

Interferon-γ

Increases MHC class I expression on tumor cells and induces the appearance of MHC class II molecules on endothelial cells, keratinocytes, myeloid cells, some dendritic cells and fibroblasts as well as on macrophages

TNF-α

• Can occur in soluble or membrane-bound forms

• Activates macrophages to increase its own synthesis

TNF-β

Produced by Th1 cells and activated CD8+ T cells

*produced by macrophages and dendritic cells

Interleukin 1

Interleukin 6

Interleukin 12

TNF-α

Toll-like receptors (TLRs)

Receptors expressed on macrophages and mast cells, as well as dendritic cells, eosinophils and epithelial cells in respiratory tract and intestine

Also recognizes molecules produced by damaged tissues such as fragments of heparan sulfate that binds to TLR4 (which then activates sentinel cells) and heat shock proteins

Mannan & glucan receptors

binds to microbial carbohydrates

Macrophages

• Does not only act as sentinel cells but also kill invading microorganisms

• Play an essential role in triggering acquired immunity

• Secrete cytokines; control inflammation

• Contribute directly to the repair of damaged tissues by removing dead, dying and damaged cells (assist healing process)

Histiocytes

in connective tissues

Kupffer cells

lining the sinusoids of the liver

Microglia

in the brain

Alveolar macrophages

in the alveoli of the lungs

Mast cells

• very large, round cells scattered throughout the body in connective tissue, under mucosal surfaces, skin and around nerves

• recognized by cytoplasm that is densely packed with large granules that stain very strongly with dyes such as toluidine blue

• connective tissue and skin mast cells are rich in histamine and heparin

• intestinal mast cells contain chondroitin sulfate and little histamine

• originate from stem cells in the bone marrow

• key role in innate immunity because they release molecules that trigger acute inflammation

the mast cell degranulation can be stimulated by _______

IgE

Histamine

Most important vasoactive released by Mast cells

Rubor

Redness

Tumor

Swelling

Calor

Heat

What is the product of OCl⁻

microbicidal

OCl-

kills bacteria by oxidizing their proteins and enhances bactericidal activities of lysosomal enzymes

Dolor

Pain

Functio laesa

Loss of function

In lectins, proteins that bind carbohydrates; most important in lectin in innate immunity is the _______- found in serum

mannose-binding lectin

Anaphylatoxins

promote histamine release from mast cells and cause blood vessel dilation and leakage

NEUTROPHILS

first cells to arrive at damaged tissues

In Phagocytosis, When triggered, they mount a ________________________

respiratory burst, release elastase, defensins and oxidants