Part 2: Lines of Defense and Antibody ProductionSarah Weinsztok

Intro: Antibodies and Pathogens•*What is a pathogen? An organism or

virus causing disease•Specific antibodies combat pathogens

when they enter the body▫B cells produce antibodies

•Antibodies bind to microbes and mark them for elimination

Immune System *Lines of Defense! First line…• The first 2 defense lines=nonspecific• 1st defense line=external

▫ *Mucus and skin• Mucus=a viscous fluid that traps microbes and

other particles▫ Ex: trachea has mucus producing cells and cilial

cells- trap microbes via cilial beatings▫ Mucus regions in body: nose, trachea, vagina,

urethra• Skin is touch, secretes lactic and fatty acids to

kill microbes▫ Skin and mucus membranes provide hostile

environments for microbes- acidic skin pH via sweat glands to prevent microbial colonization

▫ Antimicrobial proteins Ex: lysozyme- digests bacterial cell walls

Line of Defense 2: Phagocytosis• We all know phagocytosis= cellular eating

▫ Ingestion of invading microorganisms by certain types of white blood cells (aka phagocytes) which causes inflammation=prevents microbial spread

• 2nd line=internal and nonspecific• Ingest pathogens in the blood-large numbers at

an infection cite form pus• *There are 4 leucocytes (white blood cells) that

are phagocytic…

Vertebrate v Invertebrate Defenses• Exoskeletons of invertebrates

act like the skin and mucus membranes of vertebrates, providing an external barrier to prevent intruders

• Hemolymph= insect equivalent of blood▫ Contains hemocytes-some ingest

bacteria by phagocytosis, or form cellular capsules around bacteria

▫ Macrophage antimicrobial peptides similar to those in hemocytes

• However, invertebrates lack cells analogous to lymphocytes (which do acquired immunity)

4 Phagocytic Leucocytes• 1) neutrophils- most abundant (60%), attracted to and

enter infected tissue, engulfing and destroying microbes▫ Downside-they self destruct, so life span=only a few days

• 2)macrophages: more effective, large, long lived cells developing from monocytes, some migrate and some permanently set in immune system▫ More on this later in Gail’s powerpt, macrophages

surround and engulf microbe, forming a vacuole, and enzyme break down microbe, expelling it via exocytosis

• 3) eosinophils-low activity but critical defense against multicellular parasites▫ Position themselves against parasites body and

discharge destructive enzymes• 4)dendritic cells- ingest like macrophages do, but

mostly stimulate development of acquired immunity

Just another important defense mechanism to remember…•Becomes important as we move on •NK (natural killer) cells

▫Another innate defense▫Patrol body and attack virus infected body

and cancer cells Attaches and releases chemicals, which leads

to death via apoptosis Remember, apoptosis=programmed cell

death

*3rd defense line, aka “The Biggie”: Antibody Production

• 3rd and last line of defense=antibody production▫ Internal and specific, or acquired

• *Antibodies v antigens?▫ Antibodies are proteins that recognize and bind to specific

antigens▫ Antigens are foreign substances that stimulate production of

antibodies; can be a wide range of substances▫ In layman’s terms, antibodies..good!, antigens…bad

• 2 branches of immunity here▫ Humoral immune response= activation and clonal selection of

B cells▫ Cell mediated immune response= activation and selection of

cytoxic T cells▫ Different branches because they respond to different threats!▫ T cells are important, they respond to antigens in antigen

presenting cells, and in turn stimulate the activation of nearby B cells and cytoxic T cells

Helper T Cells• Helper T Cells= T cells have receptors in their

plasma membrane that bind to antigens presented by microphages▫ Recognized mostly with dendritic cells,

macrophages, and B cells Remember, there are many different types of these

lymphocytes mentioned earlier, they each recognize one specific antigen and respond by forming a clone, which secretes a specific antibody against the antigen

So, Helper T’s lead to both Humoral and Cell mediated immune responses

▫ Macrophage passes signal to helper T cell, changing it from inactive to active state

• It is specific! T cells eliminate body cells infected by viruses and other intracellular pathogens, and cancer cells

Helper T’s help both humoral and cell mediated immune responses

Cytotoxic T Cells and Cell Mediated immune response• CD8=surface protein that enhances

interaction between target cell and T cell▫Chemokines (more info in Gail’s slides)

essentially direct the migration of phagocytes Help promote activation of T cell into a killer cell

(NK remember?)• CD8 binds to I MHC molecule (more later),

importantly it helps keep 2 cells in contact during activation of T cell

• Death of an infected cell deprives pathogen of a place to reproduce and exposes it to circulating antibodies, which leads to its disposal▫Eliminate body cells infected by viruses, cancer

cells, and transplanted cells

Cytotoxic T cell binds to antigen complex on the target cell, which leads to the activation of the cytotoxic T cells

Activated T cell releases perforin molecules, which form pores in target cell membrane, and enzymes which enter target cell via endocytosis

These enzymes initiate apoptosis within target cell, leading to fragmentation of the nucleus, release of apoptotic bodies, and cell death. The newly released cytotoxic T cell can move on to attack other target cells

Cytotoxic T Cells and Viruses• Cytotoxic T cells can work on malignant tumors by

identifying their distinctive molecules (antigens)▫ Counter Ex. Epstein Barr Virus (associated with

mononucleosis) and others actually reduce I MHC molecules-they escape T cell detection, but there is a backup NK cells can induce apoptosis in these certain viral cells

• *This shows a difference between bacteria and viruses, the reason antibiotics are not effective in viruses▫ Antibiotics=chemicals produced by microorganisms to

kill/control growth of other microorganisms. They block specific metabolic pathways found in bacteria (without causing damage to human cells because big difference in the individual cellular makeups)

▫ Viruses reproduce and perform most functions using host cell’s metabolic pathways, which are not affected by antibiotics. Viruses carry out very few processes themselves, and so are not affected by antibiotics, which block metabolic pathways in bad cells

Viruses Take Over Host Cells

B Cell Activation: Humoral Immune Response• An activated helper T cell with receptors for same antigen

can then bind to a B cell. T cells send signals to B- causing it to change from inactive to active state▫ Antigens in humoral immune response are typically proteins on

bacterial surfaces, or incompatible transplanted tissue or transfused blood cells

• Inactive B cells have antibodies in their plasma membrane, and if they match an antigen, it binds to the antibody

• Stimulated by both an antigen and cytokines, B cell proliferates and differentiates into a clone of antibody-secreting plasma cells and a clone of memory B cells▫ Plasma cells: activated B cells divide forming clones, become

active with a greater volume, large rER, they synthesize large amounts of antibody, then are excreted by exocytosis

▫ Memory cells: B and T cell combination formed at the came time as activated helper T cells and B cells, used when presented with a challenging disease, provide long-term immunity to a disease

B Cell Activation Cont’d.•When an antigen binds to receptors on

surface of B cell, cell takes in a few of foreign molecules by receptor mediated endocytosis▫Then presents cell fragments to helper T cell,

which causes T and B cell-cell interactions•T-dependent (stronger response of the two)

or T-independent antigen responses. Some antigens require helper T cells along with B cells to combat it, and the response from both is stronger

Antibody Classes•There are 5 types

of constant chains of antibodies▫Tails of Y shaped

antibodies are constant

▫Head is specific to recognize/ bind with antigen

•Polyclonal vs monoclonal (explained later)

Antibody-Antigen Binding• This binding leads to antigen disposal mechanisms:

▫ 1) viral neutralization- antibodies bind to certain proteins on a virus surface-block ability to infect host

▫ 2) opsonization- bound antibodies enhance microphage attachment to microbes, increasing phagocytosis (aka cellular eating remember..)

▫ 3)agglutination- (clumping) of bacteria or viruses can be readily phagocytosed by microphages

▫ 4)precipitation-antibodies cross-link soluble antigen molecules dissolved in bodily fluids, forming immobile aggregates, disposed of by phagocytosis

• Complement system-can form cascade system where each component activates the next

• Membrane attack complex-pore forms in membrane, swells and lyses-promote inflammation and stimulates phagocytosis

Antibody mediated mechanisms of antigen disposal