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Normal flora

_____ organisms inhabit certain parts of the body and provide balance which if disrupted will result in disease.

Intact skin

____ is a mechinal barrier

Keratin layer

____ is thick and impermeable, but it is also continuously shedding and removing some resident bacteria to prevent over growth.

Sebaceous glands

Most resident bacteria in the skin are gram positive because _____ secrete lipids on which gram positive bacteria feed and grow. On the other hand, the end products of these lipids to gram-negitive bacterial growth.

Hair follicles

When ____ fall, they remove some resident bacteria.

Sweat

____ also has a flushing removing some bacteria, besides being acidic in pH.

Wax

____ and hairs in external ear are mechanical barriers to pathogens.

Lysozyme

____ is a natural antibacterial substance found in high concentration in tears and it can break down the peptidoglycan cell wall.

Saliva

____ in mouth contains lysozyme.

Bile

____ emulsifies lipid components in bacteria.

Cilia

Upper respiratory tract has ____ in the lining epithelium which removes pathogens. Smoking destroys these ____ and predisposes smokers to respiratory infections.

Mucociliary escalator

Cilia and goblet cell together are called _____, where cilia beat moving trapped particles proximately in the respiratory tract, to be ultimately expelled by coughing.

Alveolar macrophages

____ present in the lower respiratory system phagocytose bacteria.

Genetic defenses

Patients with sickle cell disease are immune against malaria infection. Some people are immune to HIV despite repeated exposeures. These people posses highly specialized Cytotoxin T lymphocytes that overcome HIV 1 and HIV 2 peptides.

Inflammation

_____ serves to localize the effects of injury, minimize these effects, and destroy the pathogen when possible. It also sets the stage for tissue repair.

Cardinal signs of inflammation

Redness, heat, swelling, pain, and sometimes loss of function.

Vasodilation, vascular permeability

Injury releases chemical mediators especially histamine which cause ____, increase blood flow (hyperemia), and increase in ________.

Edema

Increased permeability will allow fluid to leak from vessels into tissues and cause _____. This fluid is termed exudate.

Pain

_____ may be caused by release of some mediators, nerve irritation by toxins or pressure on nerve from edema fluid.

Phagocytic mobilization

Vasodilation and hyperemia will deliver clotting factors to the site of injury, or phagocytic cells- a process known as ______-to destroy invading pathogens. This sets the stage for repair.

Serous

Clear

Sanguinous

Blood

Purulent

Pus

Meutrophils and macrophages

_____ are the primary phagocytic cells. Eosinphils are also phagocytic to parasitic infections.

Fixed macrophages, wandering macrophages

When monocytes leave the blood and migrate to tissues, they enlarge and become macrophages. They can be either ______, located at specific sites such as Kupffer's cells in the liver, or _______ that roam in different tissues and become attracted to sites of infection or inflammation.

Lysosome

Phagocyte engulfs the miccroorganism and surrounds it completely forming a phagosome. It then uses ____ which is specialized organelle that contains digestive enzymes to break down the microorganism.

Opsonization (coating)

Antibodies or complement cover the surface of a foreign cell or particle which renders it more "recognizable" and easier to phagocytose.

Complement proteins

A group of about 30 proteins produced by the liver and circulate in the plasma in an inactivated state. They can be activated to destroy pathogens by opsonization or cytolysis. Activation occurs in a cascade manner where one complement activated another, which triggers another....

Classical pathway: specific immunity

Complement is activated by antigen antibody complex which consists of two antibody molecules attach to an antigen.

Alternate pathway: non-specific immunity

Contact between a pathogen and a complement will cause it to become activated, that leads to a cascade of other complements being activated, with the end result of a large ring shaped protein called membrane attack complex (MAC). MAC bores holes in bacteria cells and viruses.

Interferon (IFN)

Small proteins produced by virus-infected cells. They are not virus-specific. ____ enter neighboring non-infected cells and stimulate them to synthesize antiviral proteins (AVPs) that prevent viral replication. So that when the virus infects neighboring cells, it becomes "blocked" and unable to multiply.

Natural Killer (NK) cells

These are large lymphocytes that are capable of directly destroying other cells especially virus-infected and tumor cells; they can also attack large parasites. ___ cells are not immunologically specific, i.e. they do not need to recognize a specific antigen. Once they find their target, they produce a lethal burst of chemicals called perforins that produce holes in the target cell's membrane, which will eventually cause its death.

Specificity

Activated after exposure to specific antigen, and is tailored to react against that antigen.

Memory

Keeps memory of that antigen and can react faster and greater on subsequent exposure.

Distinguishes

_____ between self and non-self

Humoral immune response: B lymphocytes (B cells)

Produce specific antibodies against specific antigens. This type of immunity defends against antigens that circulate freely in body fluids.

Cell mediated response: T lymphocytes (T cells)

____ are activated and they differentiate into several different types of _____ with specific functions. They act against pathogens located within cells, such as phagocytic cells, infected host cells, cancer cells, or transplanted tissue.

Bone marrow

Both B and T cells are produced in ______.

B cells

_____ mature in the bone marrow

T cells

_____ mature in the thymus gland.

Antigen receptors

During the process of maturation they are tagged with _____.

Immunocompetent

Mature B and T cells will migrate to lymphoid tissue such as the spleen or lymph nodes where they learn how to recognize antigens and thus become _____.

Antigen

A molecule or part of a molecule that is perceived by the body as foreign (non-self) and that has the ability to provoke or generate an immune response, hence the name immunogenic.

Foreignness

Perceived as foreign and not a normal part of the body.

Size

Larger molecular weight particles are more immunogenic.

Three-dimensional structure

More complex molecules are more immunogenic.

Proteins

Perceived as foreign and not a normal part of the body

Polysaccharides

Bacterial capsules and LPS in outer membrane.

Lipoproteins

Cell membrane...

Antigenic determination (epitope)

1) Specific region on an antigen that is immunogenic, 2) Antibodies recognize that specific site and bind to it.

Haptens

Small foreign molecules that are not immunogenic by themselves. If they bind to a large carrier molecule, they become immunogenic. E.g. Penicillin can bind to plasma proteins and become a ______.

Primary immune response

1) Initial exposure to antigen: B cells will be activated -->Plasma cells -->antibodies. 2) Takes several days to complete. 3) Major type of Ig produced is IgM which is later followed by IgG. So IgM is an indicator of current or recent infection.

Secondary immune response

1) On subsequent exposure, memory B cells will expedite the response by directly differentiating into antibody-producing plasma cells, and IgG will appear more rapidly and in larger amounts. This is called anamnestic response or immunogenic memory. 2) Less IgM is produced. 3) This concept is used in "booster dose immunization". 4) We are able to examine antibody titers to determine the state of infection of a patient. It is a measure of the quantity of immune globulins that differentiates between recent and old infections.

Structure of immune globulins (antibodies)

Simplest form called monomer is Y-shaped. Two types of polypeptide chains: heavy and light. Each chain has two parts, constant and variable. Two identical antigen-binding sites for each Ig monomer at the variable ends, where the antibody will bind to the antigen determinant. Base binds to cell surface (e.g. B cell). There is also a complement-binding site.

Antibody-Antigen Interactions

Antibodies do not directly kill antigens, but they can do different functions to either stop the effects of an antigen or facilitate its destruction by other cells.

Agglutionation

Antibodies have more than one binding site, so they can bind to several antigens at the same time causing "clumping". These clumps are more readily ingested by phagocytes. It also reduces the number of active antigens thus reducing harm to the body. IgM being a pentamer has a major role.

Neutralization

Antibodies can occupy the active site of a virus thus preventing its attachment, or the active site of a toxin and prevent it from performing its action. This is the idea behind immunization against tetanus or diphtheria to counteract their toxin.

Opsonization

Antibodies (or complement) coat antigens and facilitate their
phagocytosis.

Complement fixation

When antibody binds to a cell (e.g. bacteria), the antibody changes its shape and exposes the complement- binding site. Complement will fix in that site and is able to cause lysis to the bacterial cell.

IgG

-80% of all antibodies
-Readily crosses walls of blood vessels and enters tissues
-Crosses placenta and provides fetus with immunity

IgM

-Pentamer, large.
-First responder in primary response and consequently is an indicator of recent infection.
-Agglutination reaction.

IgA

-Found mainly in secretions (tears, saliva, mucus, breast milk)
-Protects mucus membranes by preventing adherence of antigens

IgD

Stimulates B cells

IgE

-Bound to mast cells throughout the body. When mast cells are exposed to antigens (pollen), they disintegrate and release histamine.
-Role in allergic reactions (hay fever ....) and in lysis of parasitic worms.

Cell Mediated Immunity

Mediated by T lymphocytes which react specifically to a single antigen. The antigen is first processed by macrophages or APC and fragments of it are presented on the surface.

Helper T cell (TH) or CD4 cell

• Plays a central role in immune response. It recognizes antigen presented by APC or macrophages and secretes cytokines that activate other immune cells such as macrophages, CD8 cells, natural killer cells, and B lymphocytes.
• Has a surface receptor called CD4
• Most abundant type of T cells
• Suppressed by HIV

Cytotoxin T cell (Tc) or CD8 cell

• Recognizes antigen present in infected viral cells or tumor cells.
• Kills these target cells by secreting proteins called perforins which cause cell lysis.
• Has surface receptor called CD8

Delayed Hypersensitivity T cell (TD)

• Responsible for allergies that occur a long time after exposure to antigen, and for delayed response, e.g. T.B. skin test.

Suppressor T cell (Ts)

• Regulates the immune system by inhibiting the responses once the antigen is destroyed. It "turns off" the immune components when no longer needed. There is also a memory T cell that keeps memory of antigens.

Active; Natural

B and T cells are challenged by daily exposure or by infection. Immunity may be life long in some cases.

Active; Artificial

Vaccination; B and T cells are challenged.

Passive; Natural

Antibodies provided from mother to baby via placenta and breast milk

Passive, Artificial

Immune globulin injections.

Vaccination: Artificial active immunity

Antigen or part of an antigen is injected in the body to produce both a primary response and secondary anamnestic response, so that the immune system is prepared in advance for possible exposure to that specific antigen.

Killed or inactivated

Exposure of live pathogens to heat or radiation will destroy their ability to replicate but does not disrupt their basic antigenic structure. Will need booster dose E.g. Rabies and Influenza

Live attenuated

Manipulation of the pathogen in a certain way that results in removing its virulence factors. So it retains the ability to multiply, but cannot cause disease. Mimics an actual infection.
Provides longer protection (life-long sometimes), effectiveness rate is about 95%, and has less need for booster doses. Not recommended for immunocompromised individuals. E.g. MMR and Chickenpox.

Acellular (bacteria) or subunit (virus)

Only a fragment of the organism, for example part of the capsule or cell wall, is contained in the vaccine. That part contains the antigenic determinant, so it stimulates host antibodies to be formed. Safer: E.g. Pneumococcus 6 -->capsule. Hepatitis B 6 -->protein surface antigen.

Toxoid

Purified inactivated bacterial exotoxin that is used as vaccine. It will stimulate production of anti-toxin (antibodies against the toxin) by host. E.g. Diphtheria and Tetanus toxoids.

DTaP

Diphtheria-Tetanus-Pertussis

Hib

Haemophilus influenza type b meningitis

PCV

Pneumococcal pneumonia (Streptococcus pneumoniae) for children and over 65 years

Meningococcal meningitis vaccine

Against Neisseria meningitidis, given to exposed high risk people.

MMR

Measles-Mumps-Rubella

VZV

Varicella zoster vaccine against chickepox

IPV

Inactivated polio vaccine against poliomyelitis

Influenza

annual

Artificial passive immunity

Provides immediate immunity. Lasts 2-3 months only. Recommended for people at high risk because of direct exposure. Also given to patients who suffer from immune deficiency diseases.

Immune serum globulin (ISG)

Serum that contains a large amount of immune globulins that are nonspecific. E. g. ISG Measles and Hepatitis A

Specific immune globulin (SIG)

Specific antibodies against specific pathogens. E.g. SIG against Diphtheria, Botulism, Spider and snake bites.

Hypersensitivity

___ is an inappropriate increased activity of the immune system that results in damage to the host's tissue.

Immunodeficiency

____ is inadequate immune response that fails to protect the host.

Hypersensitivity-Type 1

Immediate (Anaphylactic) Hypersensitivity / Allergy. Symptoms develop rapidly within 2-30 minutes. Caused by exposure to an allergen (antigen), examples are allergy to bee sting, hay fever, asthma, and food allergy. Mostly an inherited trait.

IgE

The initial encounter with an allergen may be accompanied by few signs, or more commonly pass unnoticed. But the allergen stimulates B cells to secrete large quantities of ____.

Mast cells

IgE has an affinity to ____ and basophils and binds to them.

Histamine granules

Mast cells are leukocytes that contain _____ and have a prominent role in inflammatory response.

Degranulate

Upon subsequent exposure the antigen will bind to IgE antibodies present on mast cells and basophils. This will cause the mast cells to _______ with the release of histamine and other mediators which give rise to allergy symptoms.

localized, generalized

Symptoms may be ____ such as dermatitis, allergic rhinitis or asthma, or _____ like the life-threatening anaphylaxis. In anaphylaxis there is massive release of mediators in the circulation which leads to vasodilation throughout the body resulting in shock and possibly death.

Treatment

______ is mainly by injectable epinephrine for anaphylaxis, antihistamines for milder localized allergies.

Desensitization

_______ is a method used for prevention.

Hypersensitivity-Type 2

Cytotoxic Hypersensitivity. Reaction time is variable. Occurs when either IgG or IgM antibodies attach to an antigenic cell that leads to activation of complement and phagocytosis. It is called cytotoxic because cells affected usually die.

Hypersensitivity-Type 3

Immune-complex Hypersensitivity. Reaction time is variable.
IgG and IgM antibodies attach to an antigen circulating in the serum forming a complex.

Antigen-antibody complexes

Circulating ________ initiate this type of hypersensitivity. These complexes are normally eliminated by macrophages, but when their numbers exceed the ability of macrophages to remove them, they become lodged in the capillaries of normal tissues and deposit on their basement membrane. This will provoke an inflammatory response.

Hypersensitivity-Type 4

Cell-mediated (Delayed) Hypersensitivity. Reaction time is long ranging from 12 hours to several weeks. Delayed hypersensitivity T cell (TD) is responsible for this type of hypersensitivity.

Poison ivy

Oil from the plant acts as a hapten and is bound to proteins on the epithelial cells thus becoming an antigen. On first contact TD lymphocytes become activated and proliferate into activated clones. On second contact, memory cells activate T cells to release mediators (lymphokines). These mediators stimulate macrophages which attack the antigen and cause the characteristic itch 48 hours after the exposure.

Organ transplantation

Transplants are recognized by the immune system as non-self, and accordingly attacked by T cells that directly lyse the grafted cells.

Autograft

Transplant from one part of the body to another in the same person. Skin graft for burns. No rejections

Isograft

Graft from one identical twin to the other. Bone marrow or kidney. No rejection.

Allograft

Between two unrelated human beings. Heart, kidney, liver,... Rejection prevented by immunosuppressive medication.

Xenograft

From non-human. Baboon heart (esperimental). Rejection inevitable.

Tuberculin test

Skin test to detect previous exposure to ____ where purified antigen is injected into the skin and the results are read after 48 hours. A positive test is documented if there is a red indurated round lesion that is 10 mm or more in diameter.A positive test does not indicate infection, but exposure to ___. It is followed by chest x-ray and other tests to detect for infection and determine the plan of action.

Primary immunodeficiency

Inherited abnormality in development of B or T cells or both.

B cell deficiency

agammaglobulinemia. Absence of mature B cells and antibodies.

T cell deficiency

Absent thymus gland

Combined B and T cell deficiency

Both cells are very low. An explame is serve combined immunodeficiency (SCID) the condition of the famous "bubble boy"

Secondary immunodeficiency: Infection with HIV

CD4 are membrane proteins present on Helper T cells, macrophages and monocytes. _____ viral envope binds to CD4 to enter the cell and destroys it. So ____ targets "CD4 positive cells," most important of which are Helper T cells.

Secondary Immunodeficiency: Chemotherapy

Drugs used for cancer treatment and immunosuppressive drugs to prevent graft rejection suppress the immune system.

Secondary immunodeficiency: Radiotherapy

Radiation treatment for certain cancers or chronic diseases will also suppress the immune system.

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