From Blood to Host Defense Host Defense

Gregory J. Bagby, Ph.D.gbagby@lsuhsc.eduOffice: 310 (CSRB)

From Blood to Host Defense

• Blood – Components and function– Hemostasis and clotting

• The host defense system– General overview– Innate immune system

• pathogen recognition• inflammatory response

– Adaptive immune system• Humoral immune system and antibodies• Cell-mediated immune system

The Importance of the Host Defense System?

• Immunology is the study of the host defenses by which the body (host) protects itself from nonself or altered self. In the process, it destroys or neutralizes foreign matter, microorganisms, cells that are infected, and abnormal or altered self.

• Recognition, Activation and Attack• Protects against:

– microbial infection – viral, bacterial, yeast, fungi– non-microbial substances– “altered” self-cells

• The host defense system has a memory component. That is, when it sees a foreign molecule it will retain memory of the encounter so that when it sees it again it can respond more quickly and robustly.

Where Is the Host Defense System Located?

• Skin serves as a barrier• Mucosal surfaces – lung, gastrointestinal track,

genital track – barrier, secretions, epithelial cells, and specific cells of the immune system

• Liver• Bone marrow and thymus gland• Lymphoid tissues – spleen, lymph

nodes, tonsils, lymphatic vessels• A diffuse system

What Are the Cells of the Immune System?

• Blood leukocytes – granulocytes, monocytes, lymphocytes, natural killer cells.

• Tissue-resident cells– Macrophages & dendritic cells in lung, skin, liver,

barrier tissues– Lymphocytes in mucosal tissues and lymphoid

tissues– NK cells lymphoid tissues– Mast cells in almost all tissues– All these cells can be found in other tissues

Where Are Cells of the Immune System Produced?

Cell Category Location

Granulocytes Bone marrow

Monocytes Bone marrow

Lymphocytes Bone marrow; Mature in bone marrow (B cells and NK cells) and thymus (T cells); Reside and activated in peripheral tissues and lymphoid organs

Mast cells Bone marrow, then reside in most tissues

How Are Immune Cells Related to Each Other?

General or Early Name Differentiated Name

Granulocytes Neutrophils; Basophils; Eosinophils

Monocytes Macrophages, microglial cells, Kupffer cells, dendritic cells – antigen presenting cell

T lymphocytes T helper; Cytotoxic; RegulatoryNaïve; Memory; Effector

B lymphocyte Naïve; Memory; Plasma cell; Dendritic cell

NK cell (lymphocyte derived)Mast cell

NK cellMast cell

How Do Cells of the Immune System Communicate with Each Other and with Other Cells?

• Cell to cell contact via adhesion molecules, receptors and immunoglobulins.

• Production and secretion of signaling proteins called cytokines, chemokines and growth factors, as well as immunoglobulins.

• Production of lipid mediators• Serve as autocrine, paracrine or hormone

mediators

Cytokines, Chemokines and Growth Factors

• Regulate immune cell proliferation, differentiation and function.

• Names– Interleukins 1 to >30

– Interferons (α,β,γ)

– Growth factors (e.g. granulocyte colony-stimulating factor)

– “Functional” names like tumor necrosis factor, macrophage inhibitory peptide

– CC, CXC, etc chemokines

• More than a 100 of these.

The Host Defense System Can Be Divided into Two Categories:

• Innate host defense system (nonspecific)– Includes barriers such as the skin, and the lining fluid and cells

that line the airways and gastrointestinal track.– Many cells of the innate system have receptors that bind

(recognize) limited number of foreign molecules.– Innate cells become activated and have ability to destroy foreign

body.

• Adaptive (Acquired) host defense system (specific)– Limited number of cells recognize a large array of foreign

molecules or region of molecules called an antigen.– Cells of adaptive system recognize molecular shapes that are

nonself and proliferate and become activated to mount a defense leading to destruction of the antigen or a cell infected by the antigen (nonself).

Innate vs. Acquired Immunity

Recognition(Differences btw/Inn. Vs. acq.)

Innate recognition on manycells that are capable of mounting a defense.

Specific recognition by a few cells that need to expand before an effective defense can be mounted.

Eradicationof pathogen

Innate Immunity

Adaptive Immunity

Fast

Slow

Activation

Activation

Attack

Attack

Innate

Adaptive

Innate Immunity Adaptive Immunity

Receptorsfor detection

of microorganisms

PRRs:

Encoded in the germline

TCRs / BCRs:Generated randomly by

gene recombination

Receptorrepertoire

Limited Unlimited

Cells

Monocytes / MacrophagesPolymorphonuclear

Dendritic

T & BLymphocytes

Specificity Molecular Patterns

shared by classes of microbes

Broad

Structural details (e.g., specific peptides)

Narrow

Reaction Immediate 3-5 days

Memory No Yes

How Do the Innate and Adaptive Limbs of the Immune System Interact to Defend

the Host from Foreign Invaders?

• Cells of the innate system recognize something as foreign or abnormal and initiates a host defense response – produces cytokines – kills the invader by producing toxic substances and phagocytosis– Initiates response of the adaptive system by presenting antigen

• In response to antigen specific cells of the adaptive system expand in number to recognize, attack and kill the foreign invader.

• The adaptive system calls upon cells of the innate system to help in ridding the body of the invader.

What Are the Cells of the Innate and Adaptive Immune Systems?

Category Cells

Innate immune system Monocytes/MacrophagesGranulocytesMast cellsNK cellsDendritic cells

Adaptive immune system T lymphocytes T helper cell Cytotoxic T cell T regulatory cellB lymphocytes/Plasma cell

From Blood to Host Defense

• Blood – Components and function– Hemostasis and clotting

• The host defense system– General overview– Innate immune system

• pathogen recognition• inflammatory response

– Adaptive immune system• Humoral immune system and antibodies• Cell-mediated immune system