The Immune SystemThe Immune System

1. The Innate System2. The Adaptive System

The Innate Immune SystemThe Innate Immune System

“Nonspecific” system– Surface Barriers– Cell and Chemical Responses

Innate Immunity: Surface BarriersInnate Immunity: Surface Barriers

Innate Immunity: Innate Immunity: Cell and Chemical DefensesCell and Chemical Defenses

• They do not target specific pathogens– They target abnormal or foreign cells

• Six categories:– Phagocytes– Natural killer (NK) cells– Inflammation response– The complement system– Interferons– Fever

PhagocytesPhagocytes

• Macrophages, neutrophils, eosinophils

1. Adherence and endocytosis2. Phagocytic endosome3. Lysosome fuses with endosome,

releases hydrolytic acids/enzymes4. Microbe is killed and digested5. Exocytosis

Natural Killer CellsNatural Killer Cells

• Lymphocytes that destroy tumor cells and cells infected with viruses

• Not phagocytes, instead release chemicals onto cell membranes– Cytolytic, perforin complexes

• The target cell lyses & nucleus disintegrates• NK cells also release substances to stimulate

inflammation

Inflammation Inflammation ResponseResponse

•Redness

•Increased Temperature

•Swelling

•Pain

The Complement SystemThe Complement System• > 20 plasma proteins • Activation triggers cascade

of chemical reactions• Molecular Complexes form:

– Membrane Attack Complex creates holes in bacterial cell membranes

– C3b marks them for phagocytes

– C3a and C5a stimulate mast cells to release histamines

InterferonsInterferons - Interfere with viral - Interfere with viral replicationreplication- Block protein synthesis - Block protein synthesis at ribosomesat ribosomes- Activate macrophages- Activate macrophages- Mobilize NK cells- Mobilize NK cells

FeverFever• When macrophages attack foreign matter,

they release chemicals called pyrogens into the blood– Endogenous: interleukins, tumor necrosis factors, macrophage

inflammatory protein, interferons– Exogenous: Lipopolysaccharides of gram-negative bacteria trigger

endogenous factors

• The hypothalamus is stimulated to increase body temperature – fever

• Liver and spleen sequester iron and zinc• High temp. unfavorable for microbes

The Adaptive Immune SystemThe Adaptive Immune System

“Specific” defense mechanisms• Three characteristics:

– recognizes & targets specific foreign substances

– protects the entire body, not a specific injury or infection site

– has a "memory" to store information from past exposures

Cell RecognitionCell RecognitionProteins, polysaccharides, glycoproteins signal the identity of the cell (host or foreign)

• Major histocompatibility complexes (MHC)– Molecular markers on host cells

• Antigens– Substances that mobilize the immune response

• Molecular markers on foreign cells, abnormal/infected or cancerous host cells

Auto-immune diseases arise when our immune system cannot differentiate “host” from “foreign” cells

Key to Adaptive Immune SystemKey to Adaptive Immune System• Lymphocytes

• Originate from stem cells in bone marrow• 30% of circulating WBCs

– B cells• mature in Bone marrow

– T cells• mature in Thymus Gland

– Both types are made in the bone marrow– Immune response may be antibody-mediated

(humoral) or cell-mediated

Antibody-mediated ImmunityAntibody-mediated Immunity• Antibodies: Y-shaped

proteins (4 polypeptides) – Made by mature B-

lymphocytes

• Binds to antigens to form antigen-antibody complex

Antibody-mediated ImmunityAntibody-mediated Immunity• Immunoglobulin classes

– IgD: antigen receptor of B cell– IgM: antigen receptor of B cell

(monomer); released by plasma cells during primary response (pentamer)

– IgG: most abundant and diverse; targets bacteria, viruses, toxins; main antibody for both primary and secondary response

– IgA: found in exocrine secretions; prevents pathogens from attaching to epithelial surface

– IgE: bound to mast cells and basophils; mediates inflammation and allergic reaction

Antibody-mediated ImmunityAntibody-mediated Immunity

Antibody-mediated Antibody-mediated ImmunityImmunity

• WBC detects a pathogen or abnormal cell– Attacks pathogen– Alerts Helper T cells and B

cells• T cells attracted by chemical

signals• B cells alerted by using the

pathogen’s own antigens

AntigenPathogen

MHC

MHC+Antigen

Signalingmolecules

Helper T cell

B cell

Macrophage

Antibody-mediated Antibody-mediated ImmunityImmunity• Antigens bind to specific

antibodies on B cell surface• Activation causes B cells to

divide rapidly– Plasma cells

• produce antibodies• 100 million antibodies/hour

– Memory B cells• Remain on “stand by” until

activated by helper T cells• Surveillance

Cell-mediated Cell-mediated ImmunityImmunity• MHC + antigen

complex waves a warning flag

• Class II MHC’s found on B cells, some T cells, and antigen-presenting cells

• Class I MHC’s found on most cells, except RBCs

Cell-mediated Cell-mediated ImmunityImmunity

AntigenPathogen

MHC

MHC +Antigen

Signalingmolecules

Signalingmolecules

Macrophage

Helper T cell

Cytotoxic T cell

ActivatedCytotoxic T cell

Memory T cell

Perforinmoleculesform poresin pathogencell membrane

• Helper T cells (CD4):– recognize class II MHC– stimulate other immune cells

• Cytotoxic T cells (CD8):– recognize class I MHC– kill infected, cancer, or foreign cells

• Memory T cells:– reactivate on re-exposure

• Suppressor T cells:– suppresses other immune cells

Cell-mediated ImmunityCell-mediated Immunity

• Helper T-cells facilitate both cell-mediated and antibody-mediated immune responses

• Cytotoxic T cells function similar to NK cells, however they only see specific MHC I + antigen complexes

Memory B and T Cells are Like…Memory B and T Cells are Like…

Immune MemoryImmune Memory• Primary immune response

– first exposure to pathogen– recognition, production of B & T cells

• 3 to 6 day lag time• antibodies peak in 10 to 12 days

– B & T memory cells created– basis for "immunity" from the disease

• Secondary immune response– Memory B & T cells immediately identify the

pathogen– faster, longer lasting, more effective than the first– at subsequent infection, new legions of B & T cells

form in a few days– often no symptoms are noticed