Defense against Disease

Non-specific and specific strategies

Inherent Challenges

• Constant surveillance and vigilance

• Unpredictable invaders

The Enemy

• Pathogens: microorganisms that are capable of causing disease

• Viruses

• Bacteria

• Fungi

Public Enemy #1The Viruses

•Modus Operandi

Dock with receptors on target cell surface

Insert viral DNA or RNA into host cell

Use host cell machinery to replicate new viruses

Lyse host cell and spread to nearby cells

•Lytic vs. Lysogenic life cycles

•Examples: smallpox, chickenpox, polio, HIV

Public Enemy #2Bacteria

•Modus operandi

Set up shop in tissues but remain EXTERNAL to cells

Reproduce rapidly

Secrete exotoxins or contain endotoxins as part of cell wall

•Examples: Escherichia coli, Clostridium botulinum, Salmonella

Figure from Holt Biosources

Public Enemy #3Fungi

http://www.ces.ncsu.edu/depts/pp/bluemold/

•Modus Operandi Similar to bacteria-

reproduce rapidly Damage cells directly or indirectly

by secreting enzymes•Examples: Athlete’s Foot,

Pneumocystis carinii (fungal pneumonia)

So what’s a body to do?

• First line defenses: Nonspecific anatomical barriers and secretions that prevent entry, such as skin, saliva, tears (lysozyme), mucus, stomach acid, fever

• Second line defenses: Inflammation

A nonspecific response triggered by histamine secreted by basophils when tissue is damaged

If all else fails…The Immune Response

• A highly specific, long lasting response tailored to combat pathogens

• Vocabulary:

Antigen- a molecule (usually carried on the surface of a pathogen) that is capable of eliciting an immune response

B-Lymphocytes- white blood cells that produce and secrete antibodies

T-Lymphocytes- white blood cells that serve as part of the cell-mediated immune response

Self- Nonself Recognition• Critical to appropriate immune system function• Tcells “learn” to distinguish self from non self as

they mature in the thymus• All nucleated self cells display unique Human

Leukocyte Antigens (HLA) on their Major Histocompatibility Complex (MHC) receptors

• As T cells mature, they randomly produce and display a variety of receptors

• Any T cell with receptors that bind to self MHC-HLA complexes will commit apoptosis

• Only T cells that do NOT bind to self cells should emerge from the thymus and enter circulation

The Immune Response - Overview

Immune Response- Step by Step

1. Pathogen (carrying foreign antigens) enters and survives the inflammatory response2. Some pathogens remain exposed in tissues where their antigens may be recognized by circulating B cellsOR3. Macrophages engulf pathogens and display their antigens on MHC (major histocompatibility complex) receptors. Macrophage has now become an Antigen Presenting Cell (APC)

Central Role of Helper T Cells

Humoral ImmunityB cell response

• If a circulating B cell’s receptors bind to foreign antigens, the B cell becomes activated

• Activated B cells divide into Memory B cells and Plasma B cells

• Plasma B cells rapidly produce and secrete antibodies (immunoglobulins)

• Clonal selection amplifies the production of cells that produce effective antibodies

Figure from AccessExcellence.org

Clonal Selection

Mechanism of Antibody Function• Antibodies bind to antigens

and aggregate pathogens for removal by macrophages

• Antibodies disrupt function of pathogen’s surface proteins

• Antibody-antigen complexes trigger the Complement system, a a series of enzymes carried in the bloodstream that lyse invaders

Figure from AccessExcellence.org

Cell-Mediated ImmunityT cell Response

• Helper T cells (a.k.a. TH or CD-4 T cells) constantly interact with macrophages

• When TH cell finds a macrophage that is presenting antigen (APC) it becomes activated

• Activated TH cells secrete cytokines, chemicals that stimulate both T and B cells

• Stimulated cytotoxic T cells (a.k.a. killer or CD-8 T cells) divide rapidly, bind directly to pathogen infected cells and secrete enzymes that lyse infected cells

Cytotoxic T-Cells